COURSE PROJECT

Plants to Improve Cardiovascular and Respiratory Health

Instructions

In this project, you will connect information on how different types of plants affect the body, and how they may be used to support or improve the functioning of particular body systems. First, you will evaluate some plants that may be used to improve the functioning of the cardiovascular system, in either a prophylactic or a restorative capacity. Then, you will examine how medicinal plants may help to relieve breathing difficulties that have a variety of causes. By completing this project, you will be better prepared to evaluate when and how these types of plants may be integrated into a personal health plan.

Except as indicated, use this document to record all your project work and responses to any questions. At a minimum you will need to turn in a digital copy of this document to your instructor as part of your project completion. You may also have additional supporting documents that you will need to submit. Your instructor will provide feedback to help you work through your findings

Note: Though your work will only be seen by those grading the course and will not be used or shared outside the course, you should take care to obscure any information you feel might be of a sensitive or confidential nature.

Complete each project part as you progress through the course. Wait to submit the project until all parts are complete. Begin your course project by completing Part One below. A submit button can be found on the final Course Project assignment page. Information about the grading rubric is available on any of the course project assignment pages online. Do not hesitate to contact your instructor if you have any questions about the project

Part One

Boost the Cardiovascular System

When people hear the ‘cardiovascular system’, they typically think about the heart. However, there are other structures that are involved in moving chemicals throughout the body, and all of them can potentially benefit from the support of medicinal plants. For each of the questions below, demonstrate some key learnings from this course as you answer in the space provided, and, where appropriate, referring to plants that have been covered in the videos, readings, and other course documents.

1. Give three examples of plant-based remedies used in traditional medicine for heart diseases, and explain for each, their mechanism of action.

Example 1, the hawthorn tree genus (also called hedge thorn, crataegus, crataegus, kratos akis, sharp strenght, quickthorn, thornapple, may-tree, may tree, whitethorn, hawberry, shan zha, meidoorn, haagdoorn and steendoorn) e.g. crataegus sp. plant is part of a group of trees and shrubs in the rosaceae family (also called rozenfamilie) which is used for its fruits which are eaten raw, or made into jams, and for the plant the leaves, berry, and flower are used which nutrients are useful for diseases of the heart and blood vessels (i.e. cardiovascular diseases) like chest pain [1, 2], congestive heart failure because the flavonoids in hawthorn inhibit myocardial sodium/potassium ATPase, which slow and strengthen the heartbeat by increasing the strength of the cardiac muscle contraction and decreasing blood pressure which results in protection against congestive heart failure. [1, 2], to strengthen cardiovascular function because the flavonoids in hawthorn inhibit myocardial sodium/potassium ATPase, which slow and strengthen the heartbeat by increasing the strength of the cardiac muscle contraction [1], reduce irregular heartbeat [1, 2], to treat both low and high blood pressure because the flavonoids in hawthorn inhibit myocardial sodium/potassium ATPase, which slow and strengthen the heartbeat by increasing the strength of the cardiac muscle contraction and decreasing blood pressure [1], reduce the hardening of the arteries [1, 2], and reduce high cholesterol [1, 2] because it may lower cholesterol by increasing the secretion of bile and reducing the formation of cholesterol [1].

>Its main bioactive compounds significant in interfering with cardiovascular function for cardiovascular diseases are polyphenols of which flavonoids [1].

> More than 30 cardiac glycosides (also called digitalisglycosiden, cardioglycosides and hartglycosiden) are contained in the leaves of digoxin and digitoxin are the most significant of use in treating cardiovascular diseases which both 1) Increase strength of the contraction in the heart by forcing the heart to beat thus increasing cardiac output resulting in more blood pumped through the body; 2) Lower heart rate, improve circulation, decrease edema, increase kidney output

[2]

>The flavonoids in hawthorn interferes with the transmission of electrical signals through the heart inhibiting myocardial sodium/potassium ATPase by inhibiting Na–K ion pumps in the heart cell membranes, causing a rise in the concentration of sodium and calcium ions inside these cells which larger Ca2+ concentration results in a stronger force of contraction, which in turn slows (slows by interfering with the transmission of electrical signals through the heart) and strengthens the heartbeat by increasing the strength of the cardiac muscle contraction and decreasing blood pressure which results in increased exercise tolerance and protection against congestive heart failure.

>They also seem to cause a relaxing of blood vessels farther from the heart, which results in lowered blood pressure [1].

Source references

[1] CALS154_course-transcript 2021

[2] a lecture of Giulia Friso at Cornell University, course PLBIO2100 Medical Ethnobotany lecture 24 titled “Plants used in the treatment of disorders of the cardiovascular systems”.

Example 2, aspirin.

The following text I wrote for this assignment will be about aspirin’s bioactive compound salicylic acid because of special interest by me hence I made it myself in a laboratory back in 2017. This text might be a little longer than expected but please bear with me because I want to share the full story as I know it which could possibly contain some interesting information for you yourself as well.

[salicylic acid - sources BELOW]

The salicylate carbonic acid aspirin (also called acetylsalicylzuur, acetosal, aspirine, acetylsalicylic acid, acetyl salicylic acid and ASA) which contains the phytonutrient bioactive metabolite compound salicylic acid (also called salicylzuur and SA) which can among others plants be found in the willow (also called sallows, sealh, osiers, wilg, wilgen, salix and sallis, sal meaning 'near' and lis meaning 'water’ because the plant often grows nearby water streams) tree plant species of the genus salix of the salicaceae family (salicin from the willow is where the semi-synthetic, i.e. outside of the human body made, derivates salicylic acid and acetyl salicylic acid, which acetyl salicylic acid is chemically adding an acetyl group (CH3-CH2-) to salicylic acid, were first originally derived in 1897 by Felix Hoffmann) which is used for its 1) analgesic properties to relieve pain because salicylic acid suppresses cyclooxygenase (COX) enzymes (e.g. COX-1 and/or COX-2 and/or others but not sure which because they COX-1 and COX-2 both can lead to prostaglandin formation but possibly both COX-1 and COX-2 because I learned about this at Eindhoven University of Technology in the pharmacology course I took in 2019 that salicylic acid non-reversibly inhibits both enzymes by covalently binding to them which is also the reason that aspirin would not be approved if it was discovered today because it would not pass most western countries governmental safety regulations today because non-reversible inhibition is not preferential for safety reasons) which take the pro-inflammatory omega-6 fatty-acid arachidonic acid our body makes or we get directly via diet (primarily from eating chicken and eggs) turning it into the inflammatory mediators prostaglandins causing inflammation which is thus diminished by salicylic acid causing less inflammation thus less pain, swelling, and fever; and is used for its 2) anti-inflammatory properties because it suppresses the cyclooxygenase (COX) 1 (COX-1 also called COX1) enzymes that take the pro-inflammatory omega-6 fatty-acid arachidonic acid compounds our body makes, and/or we acquire via diet and turns it into inflammatory mediators, such as thromboxane which produces thrombotic blood clots and prostaglandins which cause inflammation [2]; and is used for its 3) possible anti-coagulant ability of the compound to slow blood clotting and to decrease the size of forming blood clots by halting/inhibiting/stopping the prostaglandin (PGs) thromboxane (TX) type A2 (TXA2) production which makes platelets to become less sticky and thus less likely to plug up an artery decreasing vasoconstriction enhancing blood flow and therefore helpful in a situation of a heart attack (also called myocardial infarction) as it can help during a heart attack because the mechanism is relatively remarkable fast increasing survival rate, and also after a heart attack it is used in which case it may help prevent a second heart attack [1, 21]; 4) and the compound salicylic acid significantly suppresses on a genetic level the expression of the inflammatory cyclooxygenase enzyme (COX-2 also called COX2) causing less prostaglandins formation which dilates the lymphatic tubes inside tumors allowing cancer cells to spread throughout the human body, which is the reason why cancer tries to boost COX activity so it can increase its spread [14]. Intake of salicylic acid via aspirin could possibly cause reduced mortality risk by suppressing the growth and spread of cancerous tumors that already exist thus extending people’s life which was demonstrated in randomized controlled trials in which aspirin appeared to cut the risk of metastases in half, particularly in the case of adenocarcinomas like colorectal (colon) cancer [15]. Furthermore, salicylic acid possibly may work prophylactically to reduce cancer risk [16]. In an ex-vivo study using umbilical cord vein endothelial cells and foreskin fibroblast cells it was demonstrated that relatively low levels of salicylic acid caused by dietary consumption such as a smoothie significantly suppressed the expression the previously mentioned COX-2 on a genetic level, which dietary intake could be favorable as I will discuss in more detail below [17].

I think it should only be recommendable to take aspirin in appropriate relatively low dosing when the potential death by cardiovascular disease benefit outweighs the risk of gastrointestinal digestive tract ulcers and bleeding thereof by damaging the gastroduodenal mucosa linings of our stomachs increasing the risk for major gastrointestinal bleeding leading to hospitalization and severe extracranial brain bleeding leading to hospitalization [3, 5]. Current hemorrhagic bleeding complication hazards possibly aspirin-induced because aspirin increases risk could be considered an underestimated concern [4]. These are also the reasons why European guidelines do not recommend aspirin for the general population anymore [6].

Another risk of aspirin is, while often done by people, taking it with, before or after alcohol consumption because both acts as “blood thinners” (blood thinners do not actually thin your blood, but they inhibit blood clots from forming or growing larger via the mechanism described above by thromboxane type A2 TXA2 thus anti-coagulant would be a better word instead of blood thinner) and mutually contribute to an increased risk of severe gastrointestinal stomach hospitalization by heavy bleeding of ulcers. Furthermore, higher alcohol consumption could be associated with a possible general higher blood pressure over time which could contribute to heavier and more frequent ulcer disruption caused by aspirin supplements [18].

Better would be to prevent or reverse cardiovascular disease by a special form of a whole food plant and fungi-based diet to get the benefitting potential avoiding of cardiovascular disease without the risks associated with aspirin supplement but I will not go into other benefits except salicylic acid over here in this discussion panel now [7].

Salicylates can (because they act as plant hormones [22]) also be found in a high amount of plant species next to the willow including berry fruits such as blackberries, but also white onions, green apples, green beans, herbs and spices, which is the reason the active ingredient in aspirin, i.e. salicylic acid, is found normally in the bloodstream of human animals even though people not taking aspirin supplement, of which people who generally consume more fruits and vegetables generally have a higher level salicylic acid in the bloodstream of which vegetarians possibly having the same level of aspirin in their blood and possibly peeing out the same amount as some people actually taking aspirin supplements (of course this is dependent on the dosing amount and frequency of people taking supplement but this showcases the bioavailability potential through nutrition) [8, 9, 10, 11]. Red chili powder, paprika powder, turmeric powder and cumin powder contain a lot of salicylates of which cumin’s mass is about one percent salicylic acid which is why people and populations of people that incorporate substantial amounts of spices in foods may have higher daily intakes of salicylates which break down in the body to salicylic acid which is why it has been suggested as reason for the India having the lowest incidence of colorectal (colon) cancer in the world [19].

Concluding that getting salicylic acid through diet seems optimal because it is like having the benefits without the risks since plant based nutritional products that contain salicylic acid also contain gut-protective nutrients to balance the otherwise only pro-ulcerative effects of aspirin supplements leading to both vegetarian non-aspirin supplementary women and men human animals to appear to have a significantly lower risk of ulcers thus bleeding thereof [12, 13]. Salicylic acid could thus be considered an important nutrient, but I would not call it a “vitamin S” such as some researchers do but that might also be because I am against the “vitamin” category altogether because I think that it does not rightly inform people about nutrition [20].

Source references:

[1] a lecture of Giulia Friso at Cornell University, course PLBIO2100 Medical Ethnobotany lecture 2 titled “Medical Ethnobotany & Botanical Legends”.

[2] Duthie GG, Wood AD. Natural salicylates: foods, functions and disease prevention. Food Funct. 2011 Sep;2(9):515-20. doi: 10.1039/c1fo10128e. Epub 2011 Aug 30. PMID: 21879102. https://pubmed.ncbi.nlm.nih.gov/791988/ ; https://pubs.rsc.org/en/content/articlelanding/2011/FO/c1fo10128e

[3] Park K, Bavry AA. Aspirin: its risks, benefits, and optimal use in preventing cardiovascular events. Cleve Clin J Med. 2013 May;80(5):318-26. doi: 10.3949/ccjm.80a.12146. Erratum in: Cleve Clin J Med. 2013 Jul;80(7):435. PMID: 23636924. https://pubmed.ncbi.nlm.nih.gov/23636924/ ; https://www.ccjm.org/content/80/5/318.long

[4] Siller-Matula JM. Hemorrhagic complications associated with aspirin: an underestimated hazard in clinical practice? JAMA. 2012 Jun 6;307(21):2318-20. doi: 10.1001/jama.2012.6152. PMID: 22706838. https://pubmed.ncbi.nlm.nih.gov/22706838/ ; https://jamanetwork.com/journals/jama/article-abstract/1172021

[5] Ge L, Niu G, Han X, Gao Y, Wu Q, Wu H, Zhang Y, Guo D. Aspirin treatment increases the risk of cerebral microbleeds. Can J Neurol Sci. 2011 Nov;38(6):863-8. doi: 10.1017/s0317167100012440. PMID: 22030424. https://pubmed.ncbi.nlm.nih.gov/22030424/ ; https://www.cambridge.org/core/product/identifier/5X28V717114124K7/type/journal_article

[6] https://www.aspirin-foundation.com/scientific-information/guidelines/european-guidelines-aspirin/

[7] Esselstyn CB Jr, Gendy G, Doyle J, Golubic M, Roizen MF. A way to reverse CAD? J Fam Pract. 2014 Jul;63(7):356-364b. PMID: 25198208. https://pubmed.ncbi.nlm.nih.gov/25198208/ ; https://www.mdedge.com/familymedicine/article/83345/cardiology/way-reverse-cad

[8] Swain AR, Dutton SP, Truswell AS. Salicylates in foods. J Am Diet Assoc. 1985 Aug;85(8):950-60. PMID: 4019987. https://pubmed.ncbi.nlm.nih.gov/4019987/

[9] Paterson JR, Blacklock C, Campbell G, Wiles D, Lawrence JR. The identification of salicylates as normal constituents of serum: a link between diet and health? J Clin Pathol. 1998 Jul;51(7):502-5. doi: 10.1136/jcp.51.7.502. PMID: 9797725; PMCID: PMC500801. https://pubmed.ncbi.nlm.nih.gov/9797725/ ; https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/9797725/ ; https://jcp.bmj.com/content/51/7/502.long

[10] Rinelli S, Spadafranca A, Fiorillo G, Cocucci M, Bertoli S, Battezzati A. Circulating salicylic acid and metabolic and inflammatory responses after fruit ingestion. Plant Foods Hum Nutr. 2012 Mar;67(1):100-4. doi: 10.1007/s11130-012-0282-4. PMID: 22392497. https://pubmed.ncbi.nlm.nih.gov/22392497/ ; https://link.springer.com/article/10.1007%2Fs11130-012-0282-4

[11] Hare LG, Woodside JV, Young IS. Dietary salicylates. J Clin Pathol. 2003 Sep;56(9):649-50. doi: 10.1136/jcp.56.9.649. PMID: 12944545; PMCID: PMC1770049. https://pubmed.ncbi.nlm.nih.gov/12944545/ ; https://jcp.bmj.com/content/56/9/649.long ; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770049/

[12] Knutsen SF. Lifestyle and the use of health services. Am J Clin Nutr. 1994 May;59(5 Suppl):1171S-1175S. doi: 10.1093/ajcn/59.5.1171S. PMID: 8172119. https://pubmed.ncbi.nlm.nih.gov/8172119/ ; https://academic.oup.com/ajcn/article-abstract/59/5/1171S/4732581?redirectedFrom=fulltext

[13] McCarty MF. Dietary nitrate and reductive polyphenols may potentiate the vascular benefit and alleviate the ulcerative risk of low-dose aspirin. Med Hypotheses. 2013 Feb;80(2):186-90. doi: 10.1016/j.mehy.2012.11.025. Epub 2012 Dec 21. PMID: 23265354. https://pubmed.ncbi.nlm.nih.gov/23265354/ ; https://linkinghub.elsevier.com/retrieve/pii/S0306-9877(12)00506-3

[14] Chan AT, Ogino S, Fuchs CS. Aspirin and the risk of colorectal cancer in relation to the expression of COX-2. N Engl J Med. 2007 May 24;356(21):2131-42. doi: 10.1056/NEJMoa067208. PMID: 17522398. https://pubmed.ncbi.nlm.nih.gov/17522398/ ; https://www.nejm.org/doi/10.1056/NEJMoa067208?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0www.ncbi.nlm.nih.gov

[15] Rothwell PM, Wilson M, Price JF, Belch JF, Meade TW, Mehta Z. Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials. Lancet. 2012 Apr 28;379(9826):1591-601. doi: 10.1016/S0140-6736(12)60209-8. Epub 2012 Mar 21. PMID: 22440947. https://pubmed.ncbi.nlm.nih.gov/22440947/ ; https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(12)60209-8

[16] Thun MJ, Jacobs EJ, Patrono C. The role of aspirin in cancer prevention. Nat Rev Clin Oncol. 2012 Apr 3;9(5):259-67. doi: 10.1038/nrclinonc.2011.199. PMID: 22473097. https://pubmed.ncbi.nlm.nih.gov/22473097/ ; https://www.nature.com/articles/nrclinonc.2011.199

[17] Xu XM, Sansores-Garcia L, Chen XM, Matijevic-Aleksic N, Du M, Wu KK. Suppression of inducible cyclooxygenase 2 gene transcription by aspirin and sodium salicylate. Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5292-7. doi: 10.1073/pnas.96.9.5292. PMID: 10220459; PMCID: PMC21857. www.pnas.org/cgi/pmidlookup?view=long&pmid=10220459 ; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC21857/

[18] Puddey IB, Parker M, Beilin LJ, Vandongen R, Masarei JR. Effects of alcohol and caloric restrictions on blood pressure and serum lipids in overweight men. Hypertension. 1992 Oct;20(4):533-41. doi: 10.1161/01.hyp.20.4.533. PMID: 1356922. https://pubmed.ncbi.nlm.nih.gov/1356922/ ; https://www.ahajournals.org/doi/10.1161/01.hyp.20.4.533?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

[19] Paterson JR, Srivastava R, Baxter GJ, Graham AB, Lawrence JR. Salicylic acid content of spices and its implications. J Agric Food Chem. 2006 Apr 19;54(8):2891-6. doi: 10.1021/jf058158w. PMID: 16608205. https://pubmed.ncbi.nlm.nih.gov/16608205/ ; https://pubs.acs.org/doi/10.1021/jf058158w

[20] Duthie GG, Wood AD. Natural salicylates: foods, functions and disease prevention. Food Funct. 2011 Sep;2(9):515-20. doi: 10.1039/c1fo10128e. Epub 2011 Aug 30. PMID: 21879102. https://pubmed.ncbi.nlm.nih.gov/21879102/ ; https://pubs.rsc.org/en/content/articlelanding/2011/FO/c1fo10128e

[21] a lecture of Giulia Friso at Cornell University, course PLBIO2100 Medical Ethnobotany lecture 24 titled “Plants used in the treatment of disorders of

the cardiovascular systems”.

[22] Yeasmin, F., & Choi, H. W. (2020). Natural Salicylates and Their Roles in Human Health. International journal of molecular sciences, 21(23), 9049. https://doi.org/10.3390/ijms21239049 ; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731389/ ; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731389/pdf/ijms-21-09049.pdf

Example 3, the sweet small annual herb stevia rebaudiana (also called stevia or ka'a he'e) in the asteraceae plant family (also called the sunflower family) which leaves or leave powder extracts are used as a sugar substitute as sweetener and may help to regulate blood pressure which is why they are often used in a tea (e.g. it is used in yerba mate tea) to help regulate high blood pressure. [1].

> taken by mouth to treat high blood pressure, diabetes, high uric acid levels in the blood, for weight loss, and to stimulate heart rate [1].

>The primary active ingredients in stevia are two glycosides, stevioside and rebaudioside, which are 200 to 400 times sweeter than sugar [1].

>The effects of these glycosides are still unclear, although they are believed to act as calcium channel antagonists [1].

>Stevia glycosides have been shown to also help to regulate the blood sugar and increase insulin sensitivity in animal studies [1].

Source references:

[1] CALS154_course-transcript 2021

Example 4, the sweet yellow clover relatively drought-tolerant herb plant melilotus officinalis (also called yellow melilot, ribbed melilot and common melilot) in the fabaceae family (also called legume family), not to be confused with red clover because of different properties although it is member of the same family, is used for its potentially anticoagulant and cholesterol-lowering properties and used as livestock feed.

>It's used to relieve symptoms of poor blood circulation, including leg pain and heaviness, varicose vein, nerve pain, and fluid retention or edema [1].

>Its main bioactive compounds are phenolic and flavonoids including coumarin [1].

>Coumarin can be converted into the powerful anticoagulant dicoumarol when the plants become wet and moldy which can poison livestock [1].

>Coumarin itself does not play a role in blood coagulation, however dicoumarol does [1].

>Dicoumarol competitively inhibits the vitamin K epoxide reductase enzyme by binding to it preventing the recycling of vitamin K into active vitamin K, which is necessary for the formation of coagulant enzymes such as coagulation factor II prothrombin responsible for blood clotting [1].

This led to the discovery of currently in 2021 one of the most used of mass-produced anticoagulant pharmaceuticals called Warfarin [1].

Source references:

[1] CALS154_course-transcript 2021

Example 5, the woody climbing vines with cat's claw-shaped (also called kattenklauw and katteklauw) thorns plants in the genus uncaria in the rubiaceae family (also called coffee family) include about 40 species of which the species uncaria tomentosa which are used as treatment to help regulate blood pressure [1].

> used for regulating blood pressure [1].

> It has many active compounds including alkaloids, glycoside, terpenoids, sterols and saponines [1].

> The bark of the vine and/or the roots have been used in for centuries to treat hypertension [1]

> It’s mechanism of action includes that it interacts with anticoagulants [1].

Source references:

[1] CALS154_course-transcript 2021

Example 6,

I also very much like to share the following about flax seeds because it is next to for example turmeric and salicylic acid for me amongst the most interesting plant compounds I am enthusiastic about and discovered about through learning and in accordance with this course part of playing a role in treatment of cardiovascular diseases. Furthermore, I would very much like everyone to know more about flax seeds including you 😊.

>the relatively in proportion high phytoestrogen lignan precursors containing which are metabolized in the lignans in the human body by gut bacteria which we can then absorb [39] and relatively high alpha-linolenic acid ALA containing dietary brown-golden hard hulled (that keeps them fresh) raw ground/grinded/milled/crushed (to make sure our body can use it an such that they do not pass right through us) flax seeds (also called linseeds, vlaszaad, vlas, FX, FS and lijnzaad) and not just the flax seed oil from the flax seed plant linum usitatissimum in the family linaceae (also called vlasfamilie and flax family) are usable as

>Antihypertensive for people with relatively hypertensive elevated blood pressure because it is one of the most potent antihypertensive effects ever achieved by a dietary intervention [1, 6]. The action mechanism is that dietary flaxseed reduces central aortic blood pressure without cardiac involvement but through changes in a group of fatty acid metabolites involved in inflammation in the bloodplasma as pro-inflammatoire called the long chain omega-6 fatty acid arachidonic acid (which is relatively highly prevalent in body damaging foods such as a relative high amount of animal food products and culinary oils) derived pro-inflammatoire oxylipins leukotoxin diols which may be by inhibiting the enzyme and thus the lowering the activity of the enzyme that makes these pro-inflammatory oxylipins which in turn may lower blood pressure [2, 3, 4, 5]. This is possibly by molecular compounds including the precursor of the cardioprotective long-chain n-3 fatty acids alpha-linolenic acid (ALA) present in flax seed which effect was independelty shown in a 12-week long dietary intervention placebo-controlled trial study of people with dyslipidaemic significantly lowering systolic and diastolic blood pressure as compared to safflower oil, in which systolic blood pressure rose and diastolic blood pressure stayed about the same [19].

A 6 (six) month prospective double-blinded placebo-controlled randomized trial for potential hypertension alleviation showed that eating ground flax seeds every day dropped their systolic blood pressure number about 10 (ten) points and their diastolic blood pressure number by about 7 (seven) points dropping cutting brain stroke risk almost in half by 46 [%], lowering risk of coronary heart disease with 29 [%], and for those persons who started out with a systolic blood pressure number far over 140 got a 15-point drop [6]. This is more than 2 (two) times better than and thus more than comparable to powerful angiotensin converting enzyme (ACE) inhibiting drugs like enalapril (also called kadril, vasotec, renitec, and enacard), which may drop pressures as follows: systolic blood pressure number only by 5 (five) and diastolic blood pressure number only by 2 (two) points; and amlodipine (also called norvasc and amlor) which may drop pressures as follows: systolic blood pressure number by 8 (eight) and diastolic blood pressure number only by 3 (three) points; and cardizem (also called diltiazem, diltiazem hydrochloride and tildiem) which may drop pressures as follows: systolic blood pressure number by 8 (eight) and diastolic blood pressure number only by 3 (three) points [7].

These drugs have an enormous amount of side effects while flax seeds are almost without any side effects except possibly a bit more flatulent when the body is not yet acclimated to a higher level of dietary fibrous food. Better is of course to prevent relatively high blood pressure in the first place, which is possible through dietary changes, following the axiom that any avoidable risk is unacceptable.

>It can also blunt the blood sugar spike after a meal [8].

>It may help against “high cholesterol” because Canada allows a health claim on the labels of products with flax seeds saying that they know with sufficient certainty that flax seeds does indeed help with lowering cholesterol levels [31]. It may be used as treatment to lower LDL cholesterol levels because a yearlong double-blind randomized placebo-controlled trial study showed that the dietary flax seed group saw a 15 [%] reduction in LDL cholesterol as early as one month into the trial, but only fell significantly lower than the whole wheat group in those on cholesterol-lowering drugs. In those off drugs, the whole wheat group’s cholesterol went down too, diminishing the efficacy of the flax in comparison. So, it could help but that it is just not visible because it is so hard to create a good enough placebo for the control group in such a study [32]. Furthermore, an 8 (eight) week randomized double-blind, placebo-controlled study with the lignan secoisolariciresinol diglucoside (SDG) which precursors are in flax seed in a relatively high-level present (which are metabolized in the human animal body by gut bacteria which we can then absorb) shows that may decrease plasma cholesterol and glucose concentrations but this of course is only one of the compounds present in flax seeds and could have a different working when isolated [18, 39].

>It could also be for treatment against diabetes because an open-label study, i.e. a study in which the study group is being aware that they are being studied as compared to blind study, showed that of a tablespoon of ground flax seeds every day for a month compared to the control group led to a significant drop in fasting blood sugars of glucose, triglycerides, cholesterol, and a drop in A1C level which is an indicator used by physicians for determining if someone is type 2 diabetic [9]. However, if one’s glucose blood sugars are already well-controlled then there may be no additional benefit in the sense of lowering glucose blood sugar levels [10].

>It may also help against body mass gain since no weight gain was reported in type 2 diabetic people adding a quarter cup (about 60 [ml]) of ground flax a day to their diets for three months, as compared to the opposite happing in the other groups since the flax group ended up with a slimmer waist than the flax seed oil control group. Even up to nearly a half cup (about 120 [ml]) a day there was still no significant weight gain, though this was only after a month [10]. A different and open-label study, i.e. the study group is being aware that they are being studied as compared to a blind study, in which overweight patients were for a 12-week long period randomly assigned to receive either lifestyle advice and daily ground flax seeds or as control group just the lifestyle advice alone without the daily ground flax seed showed body weight, waist circumference, and body mass index decreasing significantly in both groups (even without the lifestyle advice just enrolling people in a study where you know they are going to keep weighing you can get people to lose weight) though there was a significantly greater reduction in the flax seed group, and not just by a little. The control group that got lifestyle advice over the 12-week period lost on average nearly 7 (seven) [pounds] (i.e. a bit more than 3 (three) [kg]), and about 1 (one) [inch] (i.e. 2,5 (two and a half) [cm]) off their waist. But the group that got the same advice plus a spoon of ground flax a day, so in effect given more food to eat, lost over 20 [pounds] (i.e. about 9 (nine) [kg]) on average over the same period and cut nearly 4 (four) [inches] (i.e. about 10 (ten) [cm]) off their waist. Nutrionally speaking those are to be called extraordinary numbers for an intervention that adds rather than actively removed calories from a diet [33].

A systematic review and meta-analysis of 45 randomized placebo-controlled trial studies of the connection between flax seeds and weight loss showed study [33] and [34] to be outliers and that most of those studies do not show significant weight loss, but putting all the studies together and hoping studies [33] and [34] are not in some way flawed and thus flukes for body mass loss skewing the meta-analysis results you do see a significant reduction in body weight, BMI, and waistlines following flax seed consumption. Body weight cutting by about 2 (two) [pounds] (about 1 (one) [kg]) could then be more expected than 20 [pounds] (i.e. about 9 (nine) [kg]) [35].

>It may also help in treatment for obesity and its caused liver disease since the obesity epidemic now very prevalent most common liver disease non-alcoholic fatty liver disease NAFLD recognized as a major public health problem for humans all around the world with high-fat diet as the most common cause, because in a randomized open labeled controlled pilot study in which lifestyle modification advice with or without flax seeds was given body weight went down, along with liver inflammation, and scarring and fat inside the liver in both groups (when you know they are going to keep weighing you can get people to lose weight), but better in the flax seed group. And again, just as in study [33] an extraordinary 20 [pounds] (i.e. about 9 (nine) [kg]) weight loss telling people to add something to their diet thus actively adding to instead of removing calories from a diet [34]. A systematic review and meta-analysis of 45 randomized placebo-controlled trial studies of flax seeds and weight loss showed study [33] and [34] to be outliers and that most of those studies do not show significant weight loss, but putting all the studies together and hoping studies [33] and [34] are not in some way flawed and thus flukes for body mass loss skewing the meta-analysis results, you do see a significant reduction in body weight, BMI, and waistlines following flax seed consumption. Body weight cutting by about 2 (two) [pounds] (about 1 (one) [kg]) could then be more expected than 20 [pounds] (i.e. about 9 (nine) [kg]) [35]. It may also help in improving insulin sensitivity and thus resistency in obese people with glucose intolerance. The action mode could include that after 12 weeks of there was a small significant drop in insulin resistance, possibly related to the drop in oxidant stress given the antioxidant qualities of flax seed phytonutrients [11].

>It may also be especially helpful for human women against ovarian disfunction, possibly because they have an incredibly powerful at dampening the effects of estrogen which may be the action mechanism by inhibiting estrogen receptors as is the case with breast cancer [42], since eating a single tablespoon of ground flax seeds a day could results in improved ovarian function lengthening the woman’s menstrual cycle by extending the luteal phase delaying one’s next period not the menses (the regular discharge of blood and mucosal tissue from the inner lining of the uterus through the vagina) itself, but the whole month-long cycle by an average of about one day slowing the menstrual cycle and resulting in fewer disturbances in their ovulatory cycles by fewer anovulatory cycles i.e. failed ovulations not being able to pregnant because there is no egg to be fertilized. [12]. Vegetarian women have fewer disturbances in their cycles and vegan women never failed to ovulate at all which could be attributed to their more plant-based diets because those that eat lots of plants, vegetarians, have about 8 (eight) times the phytoestrogen lignan precursor intake compared to omnivores, and the ones that ate the most plants, the vegans, about 32 times [13, 14, 25].

>It may also help in decreasing hot flash activity because a study following women not taking estrogen therapy showed significant decrease of hot flashes (also known as opvliegers) [43].

> It may also be especially helpful for human women against breast pain because a 6 (six) months double-blindly randomized study in flaxseed for severe cyclical mastalgia menstrual breast pain significantly concluded greater reduction in reported breast pain, breast swelling, and breast lumpiness in the flax seed group thus being effective in relieving symptoms of cyclical mastalgia without significant side effects except flatulent a bit more flatulent when the body is not yet acclimated to a higher level of dietary fibrous containing food [15].

>And It may also be especially helpful for human women because it may help against breast cancer for prevention and for treatment since women with breast cancer who ate the most phytoestrogen lignan precursors appear to live longer [24], and because lignans have showed ex vivo in a petri dish to not only have direct anticancer growth activity against human breast cancer cells by suppressing them but also prevent their migration [26], and because high lignan precursor intake was associated with reduced breast cancer risk [27]. This supports the current educated guess hypothesis about why women with frequent bladder urinary tract infections (UTIs) may be at higher and thus increased risk for breast cancer, because every time they take antibiotic for UTIs (which they repeatedly do when they have frequent infections) may be wiping out a lot of the colorectal (colon) gut bacteria, thus inhibiting/stymying/hampering their ability to take full advantage of all the plants the humans were eating turning them into anticancer lignans, as a few days on antibiotics dramatically drops your gut bacteria’s and thus indirectly diminishes your body’s ability to make the anticancer lignan compounds from the plants we eat after which it can take weeks for our gut bacteria to recover [26, 40, 41]. So, eating flax, one of the world’s best sources of lignans may in this manner indeed help prevent breast cancer. Just like the chemotherapy drug tamoxifen, ground flax seed consumption boosts the levels of angiogenesis inhibitors, like the protein endostatin the body makes to try to starve tumors of their blood supply because it makes them less able to hook on blood tubes. The chemotherapy drug tamoxifen is used by a technique called micro-dialysis in which you stick a catheter into a woman’s breast and kind of suck out some of the fluid bathing the breast cells. A study showed that when you give women tamoxifen for 6 (six) weeks, the levels of endostatin within the breast tend to go up which same thing happens when you instead add a little under a quarter cup (which is about 60 [ml]) of ground flax seeds to their daily diet. The flax seed did not seem as powerful as the chemotherapy drug, but further study was according to the researchers warranted [16]. A randomized double-blind placebo-controlled clinical trial of flax seeds in breast cancer patients showed that tumor samples before and after 5 (five) weeks with or without flax seed consumption on average showed that people consuming flax seeds had their tumor cell proliferation go down, cancer cell death to go up, and their c-erbB2 score of c-erbB-2 protein which is a marker of cancer aggressiveness and potential for forming metastases thus spreading to go down concluding that it has the potential to reduce tumor growth in patients with breast cancer and if the therapeutic index seen in this relatively short-term study can be sustained over a long-term period the inexpensive and readily available flax seed may be a potential dietary alternative or adjunct to currently used breast cancer drugs [17]. The action mechanism could be that the molecules in the phytonutrient class called lignans (e.g. the lignan secoisolariciresinol diglucoside (SDG)) which precursors are phytoestrogens and metabolized in the human animal body by gut bacteria which we can then absorb are present in relatively high level in flax seed [39] lower the expression of a proliferation biomarker associated with cancer called Ki-67 in a yearlong study by the U.S.A. government’s federal National Cancer Institute (NCI) of women at high risk for breast cancer (meaning they had a suspicious breast biopsy (showing either precancerous changes, or carcinoma in situ) and women that already had breast cancer taking a biopsy and feeding them a teaspoon of ground flaxseeds every day for a yearlong leading to Ki-67 going up in 9 (nine) of the 45 women, but in the other about 80 [%] of the women it went down while overall on average finding less cellular proliferation in breast tissue and fewer precancerous changes in all the women [18]. A study matching 3’000 women with breast cancer to 3’000 women without breast cancer found that consumption of flaxseed alone was associated with a 20–30 [%] reduction in breast cancer risk [28]. The mechanism of action for flaxseeds in possibly playing a role in preventing and treating breast cancer could also be that it boosts the activity of the protective anti-inflammatory inhibitor interkeukin-1 receptor antagonist which our body produces to inhibit the inflammatory molecule called interleukin-1 IL-1 (which may help tumors feed, grow, and invade) by binding to the IL-1 receptor blocking the action of IL-1 just like the drug tamoxifen but then just by eating ground flax seeds which on a diet with one month of a few spoonfuls of ground flax was able to increase the anti-inflammatory inhibitor levels by over 50 [%] which is even better than the drug’s boost of 40 [%] [29]. Concluding as a part of a healthy lifestyle through a healthy diet they might help to reduce breast cancer risk in the general population [30].

>It may also be especially helpful for human men because it appears to be effective against prostate cancer because a study interested in why there is a huge disparity in prostate cancer prevalence (the incidence of malignant prostate cancer is highest in African Americans, some 30 times greater than in Japanese men, and 120 times greater than in Chinese men) showed that higher levels of phytonutrients in the prostate fluids of human men were found in countries with relatively low rates of prostate cancer [20].

Ex vivo in vitro studies have shown lignans can slow the growth of prostate cancer cells in a petri dish [21], therefore a pilot intervention study was launched on flaxseed supplementation in men with prostate cancer as a short-term dietary intervention 1 (one) month before surgical removal of their prostates and started them on a relatively low-fat diet with 3 (three) tablespoons of ground flax seed a day to see what effect that might have on the growth of their tumors. Just within those few weeks they found significantly lower cancer proliferation rates and significantly higher rates of apoptotic cancer cell commonly called “suicide” deaths. However, this was not a randomized controlled comparison [22]. A later pilot study comprised men with early-stage prostate cancer prostatic intraepithelial neoplasia (PIN) and/or atypia who acted as their own control group because these were men that just got their prostates biopsied (biopsy i.e. the removal of tissue from any part of the body to examine it for disease) to make sure the cancer was not spreading and were scheduled to get a repeat biopsy in 6 (six) months’ time. After the first biopsy they reduced the fat in their diet and put them on ground flax seeds to see if it made their repeat biopsy look any different. They found a significant drop in the prostate-specific antigen (PSA) blood test levels which is a biomarker of prostate cell growth, furthermore a drop in cholesterol which is what is expected with a lower-fat diet and the added extra dietary fiber, and most importantly a significant decrease in the cellular proliferation rates in their prostates. 2 (two) of the men’s PSA levels dropped so much that they did not even have to go through with the second biopsy at all as it was considered not necessary anymore because of the good outlook [23]. However, given the composite nature of the intervention of both a lower-fat diet and flaxseeds it is unknown whether the effects can be attributed to flaxseed supplementation, a fat-restricted diet, or both factors working together mutually which might be synergistically [23]. To figure that out, a study was designed in which 161 men with prostate cancer at least 21 days before their prostate removal surgery were randomly assigned splitted into four groups (a control group; a flaxseed-only group; a lower-fat-only group; and a flaxseed-and-lower-fat group) concluding that it was apparently the ground flax seeds and not dietary fat restriction alone that reduced prostate cancer proliferation rates in men pre-surgery because whether they were eating their usual or lower-fat diet, it was the men eating the ground flax seed that saw their tumor proliferation rates significantly drop. Though, if you look at what they ate, the “low-fat diet” groups never got down to the target 20 [%] calories from fat. They did drop their fat intake, but you could hardly call a 25-28 [%] calories from fat a low-fat diet. Still, the lower-fat groups were the only ones who saw a significant drop in cholesterol and body weight, so there are certainly benefits [36].

Bottom-line, further studies are needed before we can definitively support flaxseed supplementation as a proven complementary therapy for prostate cancer. To date, however, the evidence suggests that flaxseed is a good and low-cost source of nutrition which is safe to use. So, why not give it a try?

>It also appears helpful against prostate enlargement benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (also called LUTS, and lagere urineweg symptomen) which is a collective term for complaints of the lower urinary tract (such as the bladder, prostate, urethra) as a 4 (four) month randomized double-blind placebo-controlled clinical trial study with flax seed lignan precursor extract of 33 [%] secoisolariciresinol diglucoside (SDG) was compared on the International Prostate Symptom Score (IPSS) developed for categorizing LUTS to commonly used leading pharmacological treatment interventions such as alpha1A (α1a) adrenoceptor blockers and 5alpha (5α) reductase inhibitors (also known as 5-ARIs and dihydrotestosterone (DHT) blockers) such as the relatively selective alpha1 receptor antagonist tamsulosin hydrochloride (also called flomax, omnic, tamsulosin HCl, tamsulosin and tamsulosine) used for enlarged prostates. The study found that flax phytonutrients not only alleviate BPH symptoms, but their efficacy appeared and thus may be comparable to the commonly used leading billion dollar standard prescription drugs drug costing about $300, - a year versus only about $10,- a year for daily flax. This study found they both work just as well as each other but in case of the flax seed without all the negative side effects except possibly a bit more flatulent when the body is not yet acclimated to a higher level of dietary fibrous food [37, 38].

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[29] Abrahamsson A, Morad V, Saarinen NM, Dabrosin C. Estradiol, tamoxifen, and flaxseed alter IL-1β and IL-1Ra levels in normal human breast tissue in vivo. J Clin Endocrinol Metab. 2012 Nov;97(11):E2044-54. doi: 10.1210/jc.2012-2288. Epub 2012 Aug 28. PMID: 22930784. https://pubmed.ncbi.nlm.nih.gov/22930784/ ; https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2012-2288

[30] Saarinen NM, Wärri A, Airio M, Smeds A, Mäkelä S. Role of dietary lignans in the reduction of breast cancer risk. Mol Nutr Food Res. 2007 Jul;51(7):857-66. doi: 10.1002/mnfr.200600240. PMID: 17576639. https://pubmed.ncbi.nlm.nih.gov/17576639/ ; https://onlinelibrary.wiley.com/doi/10.1002/mnfr.200600240

[31] Summary of Health Canada's Assessment of a Health Claim about Ground Whole Flaxseed and Blood Cholesterol Lowering. Bureau of Nutritional Sciences, Food Directorate, Health Products and Food Branch. Jan 2014. https://www.canada.ca/en/health-canada/services/food-nutrition/food-labelling/health-claims/assessments/ground-whole-flaxseed-blood-cholesterol-lowering-nutrition-health-claims-food-labelling.html

[32] Edel AL, Rodriguez-Leyva D, Maddaford TG, Caligiuri SP, Austria JA, Weighell W, Guzman R, Aliani M, Pierce GN. Dietary flaxseed independently lowers circulating cholesterol and lowers it beyond the effects of cholesterol-lowering medications alone in patients with peripheral artery disease. J Nutr. 2015 Apr;145(4):749-57. doi: 10.3945/jn.114.204594. Epub 2015 Feb 18. PMID: 25694068. https://pubmed.ncbi.nlm.nih.gov/25694068/ ; https://academic.oup.com/jn/article/145/4/749/4644334

[33] Yari Z, Rahimlou M, Poustchi H, Hekmatdoost A. Flaxseed Supplementation in Metabolic Syndrome Management: A Pilot Randomized, Open-labeled, Controlled Study. Phytother Res. 2016 Aug;30(8):1339-44. doi: 10.1002/ptr.5635. Epub 2016 May 6. PMID: 27151322. https://pubmed.ncbi.nlm.nih.gov/27151322/ ; https://onlinelibrary.wiley.com/doi/10.1002/ptr.5635

[34] Yari Z, Rahimlou M, Eslamparast T, Ebrahimi-Daryani N, Poustchi H, Hekmatdoost A. Flaxseed supplementation in non-alcoholic fatty liver disease: a pilot randomized, open labeled, controlled study. Int J Food Sci Nutr. 2016 Jun;67(4):461-9. doi: 10.3109/09637486.2016.1161011. Epub 2016 Mar 17. PMID: 26983396. https://pubmed.ncbi.nlm.nih.gov/26983396/ ; https://www.tandfonline.com/doi/abs/10.3109/09637486.2016.1161011?journalCode=iijf20

[35] Mohammadi-Sartang M, Mazloom Z, Raeisi-Dehkordi H, Barati-Boldaji R, Bellissimo N, Totosy de Zepetnek JO. The effect of flaxseed supplementation on body weight and body composition: a systematic review and meta-analysis of 45 randomized placebo-controlled trials. Obes Rev. 2017 Sep;18(9):1096-1107. doi: 10.1111/obr.12550. Epub 2017 Jun 21. PMID: 28635182. https://pubmed.ncbi.nlm.nih.gov/28635182/ ; https://onlinelibrary.wiley.com/doi/10.1111/obr.12550

[36] Demark-Wahnefried W, Polascik TJ, George SL, Switzer BR, Madden JF, Ruffin MT 4th, Snyder DC, Owzar K, Hars V, Albala DM, Walther PJ, Robertson CN, Moul JW, Dunn BK, Brenner D, Minasian L, Stella P, Vollmer RT. Flaxseed supplementation (not dietary fat restriction) reduces prostate cancer proliferation rates in men presurgery. Cancer Epidemiol Biomarkers Prev. 2008 Dec;17(12):3577-87. doi: 10.1158/1055-9965.EPI-08-0008. PMID: 19064574; PMCID: PMC2703189. https://pubmed.ncbi.nlm.nih.gov/19064574/ ; https://cebp.aacrjournals.org/content/17/12/3577.long ; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2703189/

[37] Parsons JK. Lifestyle factors, benign prostatic hyperplasia, and lower urinary tract symptoms. Curr Opin Urol. 2011 Jan;21(1):1-4. doi: 10.1097/MOU.0b013e32834100c9. PMID: 21045705. https://pubmed.ncbi.nlm.nih.gov/21045705/ ; https://journals.lww.com/co-urology/Abstract/2011/01000/Lifestyle_factors,_benign_prostatic_hyperplasia,.2.aspx

[38] Zhang W, Wang X, Liu Y, Tian H, Flickinger B, Empie MW, Sun SZ. Effects of dietary flaxseed lignan extract on symptoms of benign prostatic hyperplasia. J Med Food. 2008 Jun;11(2):207-14. doi: 10.1089/jmf.2007.602. PMID: 18358071. https://pubmed.ncbi.nlm.nih.gov/18358071/ ; https://www.liebertpub.com/doi/10.1089/jmf.2007.602?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed ; https://www.liebertpub.com/doi/epdf/10.1089/jmf.2007.602

[39] Singh KK, Mridula D, Rehal J, Barnwal P. Flaxseed: a potential source of food, feed and fiber. Crit Rev Food Sci Nutr. 2011 Mar;51(3):210-22. doi: 10.1080/10408390903537241. PMID: 21390942. https://pubmed.ncbi.nlm.nih.gov/21390942/ ; https://www.tandfonline.com/doi/abs/10.1080/10408390903537241?journalCode=bfsn20

[40] Knekt, P., Adlercreutz, H., Rissanen, H., Aromaa, A., Teppo, L., & Heliövaara, M. (2000). Does antibacterial treatment for urinary tract infection contribute to the risk of breast cancer?. British journal of cancer, 82(5), 1107–1110. https://doi.org/10.1054/bjoc.1999.1047 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2374435/

[41] Velicer CM, Lampe JW, Heckbert SR, Potter JD, Taplin SH. Hypothesis: is antibiotic use associated with breast cancer? Cancer Causes Control. 2003 Oct;14(8):739-47. doi: 10.1023/a:1026323424792. PMID: 14674738. https://pubmed.ncbi.nlm.nih.gov/14674738/

[42] McCann SE, Kulkarni S, Trevisan M, Vito D, Nie J, Edge SB, Muti P, Freudenheim JL. Dietary lignan intakes and risk of breast cancer by tumor estrogen receptor status. Breast Cancer Res Treat. 2006 Oct;99(3):309-11. doi: 10.1007/s10549-006-9196-x. Epub 2006 Mar 16. PMID: 16541305. https://pubmed.ncbi.nlm.nih.gov/16541305/ ; https://link.springer.com/article/10.1007%2Fs10549-006-9196-x

[43] Pruthi S, Thompson SL, Novotny PJ, Barton DL, Kottschade LA, Tan AD, Sloan JA, Loprinzi CL. Pilot evaluation of flaxseed for the management of hot flashes. J Soc Integr Oncol. 2007 Summer;5(3):106-12. doi: 10.2310/7200.2007.007. PMID: 17761129. https://pubmed.ncbi.nlm.nih.gov/17761129/

2. Give three examples of plant species used in traditional medicine for cardiovascular diseases, and explain for each, their mechanism of action.

Example 1, the nerium oleander plant is a shrub or a small tree in the apocynaceae family (also called dogbane family, dog-away family and maagdenpalmfamilie) is used as 1) garden plant for which it is one of the most poisonous garden plants for human animals in terms of amounts and furthermore all parts of the plant including the flowers are poisonous to human animals [1]; 2) tool to commit suicide [1]; 3) oleander's seed and leaves are used for heart conditions, asthma, epilepsy, cancer, painful menstrual periods, malaria, ringworm, indigestion, and venereal diseases [1]; 4) used to cause abortion [1]; 5) it’s used topically to treat skin problems and warts [1].

>Oleander contains several cardiac glycosides like oleandrin and oleandrogenin that work in the same way as those in foxglove and hawthorn, with the same results of slowing and strengthening the heartbeat [1].

>Its main bioactive compounds significant in interfering with cardiovascular function for cardiovascular diseases are polyphenols of which flavonoids [1].

[3]

>They also seem to cause a relaxing of blood vessels farther from the heart, which results in lowered blood pressure [1].

Source references

[1] CALS154_course-transcript 2021

[2] William Withering in 1785 in the text An Account of the Foxglove and Some of its Medical Uses

[3] a lecture of Giulia Friso at Cornell University, course PLBIO2100 Medical Ethnobotany lecture 24 titled “Plants used in the treatment of disorders of the cardiovascular systems”.

Example 2, the foxglove (foxglove because Scandinavian legend says that the faeries taught foxes to ring foxglove bells to warn each other of approaching hunters, but also called witch glove plant, foxes glofa plant, vingerhoedjesplant, fairy finger plant, thimble-shaped flower fairy finger capped plant, fairy finger capped plant, folks glove referring to faerie folk and glove of the fox because its flower looks like the finger of a glove) is the common name for the about 20 flower plant species in the genus digitalis (digitalis comes from the word digitanus, meaning finger for the thimble-shaped flowers that look like you could fit your finger right Inside) in the plantaginaceae family such as the most common species in this genus which is foxglove digitalis purpurea which leaves are used for cardiac diseases such as arrhythmia, congestive heart failure and dropsy [1],

>used for dropsy as herb ingredient in a tea foxglove has a long history for dropsy in the United Kingdom originating with Mother Hutton who experimented with foxglove in teas, which working was demonstrated with clinical trials by William Withering documenting the effects, side effects, successes, and failures using the plant extracts using a scientific approach [1, 2].

> in the United Kingdom it has a long history used for heart problems because it helps slow and strengthen heartbeats [1].

> foxglove can be used to treat edema, congestive heart failure, and arrhythmia [1, 2]

>Foxglove contains more than 30 cardiac glycosides of which digoxin and digitoxin work kind of in the same way as those in oleander (oleandrin and oleandrogenin) and hawthorn (digoxin and digitoxin), with the same results of slowing and strengthening the heartbeat [1].

>Its main bioactive compounds significant in interfering with cardiovascular function for cardiovascular diseases are polyphenols of which flavonoids [1].

[3]

>They also seem to cause a relaxing of blood vessels farther from the heart, which results in lowered blood pressure [1].

Source references

[1] CALS154_course-transcript 2021

[2] William Withering in 1785 in the text An Account of the Foxglove and Some of its Medical Uses

[3] a lecture of Giulia Friso at Cornell University, course PLBIO2100 Medical Ethnobotany lecture 24 titled “Plants used in the treatment of disorders of the cardiovascular systems”.

Example 3, the fruit of the olive tree plant olea europaea (also known as European olive) in the oleaceae family is used as for its potentially anticoagulant and cholesterol-lowering properties and used as food for human animals

>The fruit is the main product of interest, but the root is also highly valuable [1].

> the leaves, fruit, and seeds are commonly used to treat heart disease, high cholesterol, and high blood pressure [1].

>According to the reader 1) fatty acids and phenolics in olive oil (also called oleum and oleic) and olive leaves seem to decrease cholesterol levels and lower blood pressure [1] 2) olive is used to promote lower cholesterol level and lower hypertension [1]. 3) One of those phenolics called oleocanthal works in a similar way to non-steroidal anti-inflammatory drugs by reducing the effect of enzymes that cause inflammation [1].

But I would consider this as wrong because these studies measure something different. These studies that have suggested endothelial benefits after olive oil consumption have measured ischemia-induced dilation as opposed to flow-mediated dilation of which for ischemia-induced dilation there is not good evidence that that’s actually an index of endothelial function, which is what predicts heart disease [3]. Hundreds of studies have shown that these ischemia-induced dilation tests can give a false negative result [3].

It should furthermore be noted that the Mediterranean diet is healthier than other diets in spite of olive oil instead of olive oil. Olive oil even extra-virgin olive oil (which because extra virgin olive oil retains a fraction of the anti-inflammatory phytonutrients found in the olive fruit does appear to induce a lower spike in inflammatory markers than the spike caused by regular olive oil [5, 6]) is not helpful for your body because it may deleteriously impair endothelial function’s ability to relax and dilate thus impairing the function of the lining of our blood tubes [2, 4]. Extra-virgin olive oil might be better than fractionate omega-6-rich oils and saturated fats but may still show adverse effects thus it may be worse than just empty calories. Preparing food baking with water instead of oil is surprisingly easy and should be considered as superior in use for increasing and maintaining cardiovascular health.

Source references:

[1] CALS154_course-transcript 2021

[2] Vogel RA. Brachial artery ultrasound: a noninvasive tool in the assessment of triglyceride-rich lipoproteins. Clin Cardiol. 1999 Jun;22(6 Suppl):II34-9. doi: 10.1002/clc.4960221407. PMID: 10376195; PMCID: PMC6656162. https://pubmed.ncbi.nlm.nih.gov/10376195/ ; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6656162/

[3] Gori T. Olive oil and ischemic reactive hyperemia in hypercholesterolemic patients. J Am Coll Cardiol. 2006 Jul 18;48(2):414; author reply 414-5. doi: 10.1016/j.jacc.2006.04.051. Epub 2006 Jun 22. PMID: 16843199. https://pubmed.ncbi.nlm.nih.gov/16843199/ ; https://www.sciencedirect.com/science/article/pii/S0735109706011211?via%3Dihub

[4] Vogel RA, Corretti MC, Plotnick GD. The postprandial effect of components of the Mediterranean diet on endothelial function. J Am Coll Cardiol. 2000 Nov 1;36(5):1455-60. doi: 10.1016/s0735-1097(00)00896-2. PMID: 11079642. https://pubmed.ncbi.nlm.nih.gov/11079642/ ; https://www.sciencedirect.com/science/article/pii/S0735109700008962?via%3Dihub

[5] Bogani P, Galli C, Villa M, Visioli F. Postprandial anti-inflammatory and antioxidant effects of extra virgin olive oil. Atherosclerosis. 2007 Jan;190(1):181-6. doi: 10.1016/j.atherosclerosis.2006.01.011. Epub 2006 Feb 20. PMID: 16488419. https://pubmed.ncbi.nlm.nih.gov/16488419/ ; https://linkinghub.elsevier.com/retrieve/pii/S0021-9150(06)00040-2

[6] Esposito K, Nappo F, Giugliano F, Giugliano G, Marfella R, Giugliano D. Effect of dietary antioxidants on postprandial endothelial dysfunction induced by a high-fat meal in healthy subjects. Am J Clin Nutr. 2003 Jan;77(1):139-43. doi: 10.1093/ajcn/77.1.139. PMID: 12499333.

https://pubmed.ncbi.nlm.nih.gov/12499333/ ; https://academic.oup.com/ajcn/article/77/1/139/4689644

Example 4, the Indian snakeroot rauwolfia serpentina of the apocynaceae plant family is used against chest pain caused by the angina pectoris condition marked by severe pain in the chest caused by an inadequate blood supply to the heart of which the mode of action may be that the main bioactive alkaloid is the indole alkaloid reserpine present in the root of the plant first isolated in 1952 which blocks Vesicular Monoamine Transporters (VMAT) inhibiting the release of catecholamines (which are substances involved in controlling heart rate, force of cardiac contraction and nervous system) leading to a loss of neurotransmitters catecholamines (i.e. adrenaline and dopamine) from the nervous tissue (synaptic vesicles) leaving neurotransmitters in the cytoplasm where they are destroyed causing relaxation of vessels and output of the heart, reducing blood pressure thus useful for treatment of angina pectoris [1, 2]; and against hypertension as antihypertensive of

which the mode of action may be that the main bioactive alkaloid is the indole alkaloid reserpine present in the root of the plant first isolated in 1952 which blocks Vesicular Monoamine Transporters (VMAT) inhibiting the release of catecholamines (which are substances involved in controlling heart rate, force of cardiac contraction and nervous system) leading to a loss of neurotransmitters catecholamines (i.e. adrenaline and dopamine) from the nervous tissue (synaptic vesicles) leaving neurotransmitters in the cytoplasm where they are destroyed causing relaxation of vessels and output of the heart, reducing blood pressure by having sedative tranquillizing effects (tranquillize effects is emotion calmness without producing hypnosis) reducing blood pressure [1, 2].

Source references:

[1] a lecture of Giulia Friso at Cornell University, course PLBIO2100 Medical Ethnobotany lecture 16 titled “Indian Traditional Medicine”.

[2] a lecture of Giulia Friso at Cornell University, course PLBIO2100 Medical Ethnobotany lecture 24 titled “Plants used in the treatment of disorders of the cardiovascular systems”.

3. What are some of the uses of garlic in traditional medicine? Which of its active compounds seems to contribute to its effect on cardiovascular diseases? What is the proposed mode of action?

The cloves in the bulbs of the in multiple climates growing spear-shaped leek garlic (also called nectar of the gods, camphor of the poor, da-suan, la-suan and stinking rose) herb plant allium sativum in the amaryllidaceae family (also called amaryllis family) and previously part of the lily family (also called leliefamilie and Liliaceae) before a classification change (which family includes onions, leeks, chives, and shallots) and is part of the genus allium, which is the same genus as the onion, are used as for culinary purposes in the kitchen as an ingredient in savory foods [1]; as ornamentals [1]; and has anticoagulant and cholesterol-lowering properties [1].

> garlic was believed to increase their strength and endurance; therefore, the ancient Greeks gave garlic to Olympic athletes so that they could be stronger and more resilient [1].

>In Chinese garlic tea is recommended as treatment for fever and headache [1].

>In Japan, mixing soup with garlic is used against the common cold, fever, headache, and sore throat [1].

> Louis Pasteur demonstrated in the 1800s that garlic is antibacterial because it could kill bacteria. Due to its strong antibacterial activity, garlic was one of the most effective antidotes during the black plague caused by the plague bacteria yersinia pestis [1].

>Today, garlic is widely recognized for its health enhancing effect, and used for its cardiovascular, antimicrobial, or antioxidant properties [1].

>Garlic uses include strengthen the immune system, and treat or prevent the common cold, fever, cough, and stomachache [1].

>Garlic is used for mental health because it contains vitamin B which boosts mood [1].

>It can also help to regulate blood sugar and can be applied to skin to treat fungal or bacterial infection [1].

>It also works as an insect repellent. When diseases caused by mosquito bites were considered "the touch of the vampire," garlic came in handy as a mosquito repellent [1].

> garlic is held in high regard as an aphrodisiac and for its ability to increase semen [1].

>Garlic is antihypercholesterolemic, meaning it will lower blood cholesterol, and hypolipidemic, meaning it will also lower the other lipids in the blood.

>It also has hypotensive activity and blood thinning property [1].

>As an antioxidant, it can protect cells from oxidized LDL damage and protect DNA from free radical-mediated damage and mutation [1].

> (crushed) garlic is also an excellent insecticide [1].

>garlic when placed in the soil around plants will deter slugs and other pests [1]. Garlic is also a natural pesticide against mosquito larvae [1].

>Garlic bulbs contain more than 100 bioactive compounds including glucosinolates sulfur-containing molecules allicin and alliin, which glucosinolates sulfur-containing molecules are majorily contributing to the smell and taste of garlic [1].

>Allicin, the other active ingredient in garlic can inhibit atherosclerosis by different mechanisms, lipoprotein modification and degradation by macrophages [1].

Source references:

[1] CALS154_course-transcript 2021

4. You are working in the emergency department, and a 25-year-old man presents with a three-day history of stomach upset, visual halos, dizziness, abnormal heartbeats, and chest discomfort. His symptoms had started a few hours after eating lunch, beginning with generalized weakness and fatigue, then he noticed that his pulse was also slow. What herbal remedy could he have ingested which may cause these symptoms?

Probably foxglove because foxglove is unsafe to take by mouth without being properly informed by proper advice because there's a fine line between the therapeutic and toxic dose of digitalis [1].

>The primary concern with using this plant is that the full therapeutic dose is very close to the dose at which toxic effects develop which means very exacting dosage is required [1].

The symptoms as described in this question “stomach upset, visual halos, dizziness, abnormal heartbeats, chest discomfort, weakness, fatigue, and slow pulse” are equitable to the symptoms of foxglove:

>A toxic dose will cause nausea, vomiting, and diarrhea, an abnormal heartrate, and eventually collapse, tremors, seizures, and death by cardiac arrest. Also, seeing of haloes like drawn in Gogh's “yellow period” is a major sign [1].

>Digitalis will interact with quinine, which also affects the heart, and many medications including antibiotics, stimulant laxatives such as Senna, diuretics, antacid, antifungal medication should not be taken in combination with this medication. Also, taking digitalis extract together with digoxin or digitoxin can increase the effect of digoxin or digitoxin and increase the risk of side effects [1].

Source references:

[1] CALS154_course-transcript 2021

5. Select one plant species from the ‘Additional Plants to Improve Cardiovascular Health’ tool that could be beneficial for an individual suffering from arrhythmia. Explain why you would recommend that particular plant, including the major safety considerations that the individual should be aware of and the mode of action of the compounds that have the beneficial effects. You should refer back to the ‘Resources for Evaluating Herbal Supplements’ Tool from the first course in this series to find more information about the plants.

A plant from the ‘Additional Plants to Improve Cardiovascular Health’ tool beneficial for an individual suffering from arrhythmia would be:

The broom-like shaved grass resembling shrub ephedra sinica spp. (also called ma huang and ephedra equisetina) in the plant family ephedraceae which is used because it stimulates the heart rate.

It contains the alkaloids ephedrine, pseudoephedrine, norephedrine, methylephedrine.

The mechanism of action would be that the cardiac stimulant bioactive alkaloid compound ephedrine prevents dangerous drops in blood pressure.

The alkaloids ephedrine and pseudoephedrine influence the C.N.S. leading to constriction of peripheral blood vessels, but in high doses they also raise blood pressure which may lead to other cardiovascular adverse reactions such as heart attack stroke.

Major safety considerations would be that high doses over long periods of time leads to hypertension and cardiovascular events [1]. It contains the cardiac stimulant bioactive alkaloid compound ephedrine which is used and abused as a performance enhancer and weight-loss agent of which it is thought to have contributed to many deaths which is one of the reasons that in 2004 the U.S.A. government’s FDA decided to severely restrict selling this compound [1]. The risks associated with using it may outweigh any benefits gained, certainly when there are substitutes available, but it may be useful in the case of preventing dangerous drops in blood pressure [1].

Source references:

[1] a lecture of Giulia Friso at Cornell University, course PLBIO2100 Medical Ethnobotany lecture 21 titled “Plants used in the treatment of disorders of

respiratory Systems”.

Part Two

Strengthening and Healing the Respiratory System

Despite the fact that everyone breathes about 20,000 times per day, we typically don’t spend much time thinking about it unless something goes wrong. But without it, life stops. Taking care of your respiratory system is just as important as taking care of other body systems. In this module, you examined a variety of plants that can help in this area. For each of the questions below, demonstrate some key learnings from this course as you answer in the space provided, and, where appropriate, referring to plants that have been covered in the videos, readings, and other course documents.

1. Give three examples of plant-based remedies used in traditional medicine as expectorants and decongestants and explain for each the main mechanism of action.

Example 1, the in warm temperature regions camphor compound producing camphor tree

(the leaves have a glossy, waxy appearance and smell of camphor when crushed [2]) plant the camphor cinnamomum camphora in the lauraceae tree plant family is used the help with breathing [2], as a bronchodilator and/or decongestant because it increases the expansion of bronchial tubes and/or reduces congestion [1] and it is an expectorant and/or mucolytic because it promotes the secretion of mucus from lungs, bronchi and trachea by the air passages, used especially to treat coughs [1].

There are a variety of bioactive ingredients in the camphor plant, mainly terpene derivatives [2].

The largest fraction of terpene derivatives the bioactive component and strong aromatic odoring terpenoid (also called terpene, terpen and terpenen) camphanon (also called camfora, kafur, karpūra, kapur, camphre, camphor, kamfer and 1,7,7-trimethylbicyclo[2.2.1]heptaan-2-on) characterizable by a white glossy waxy appearance which is a crystalline solid that can be obtained from resin but it also present in bark and leaves (smell of camphor when crushed), which is extracted from both the wood and leaves by steam distillation [2] but camphor can also be made synthetically i.e. by humans outside of the human body in a laboratory from turpentine[2].

Camphor is a substance that is the active ingredient in decongestants [2]. Camphor is an ingredient in Vicks VapoRub for its expectorant and antimicrobial properties and in Tiger Balm as analgesic and anti-inflammatory [2].

Camphor oil works as bronchodilators or decongestants as the terpenoids increase the expansion of the bronchial tube and reduce congestion. At the same time, the antiseptic property has to prevent the growth of pathogenic microorganisms [2].

Source references:

[1] a lecture of Giulia Friso at Cornell University, course PLBIO2100 Medical Ethnobotany lecture 21 titled “Plants used in the treatment of disorders of

respiratory Systems”.

[2] CALS154_course-transcript 2021

Example 2, the “aromatic”, in the sense of fragrantly odored not necessarily in the sense of Huckel’s rule, short to medium height spreading perennial herbs plants in the mentha (also called mint) genus, which genus has around 13-24 members in the lamiaceae family (also called mint family and sage family), e.g. mentha spp which is a bronchodilator and/or decongestant because it increases the expansion of bronchial tubes and/or reduces congestion [1] and it is an expectorant and/or mucolytic because it promotes the secretion of mucus from lungs, bronchi and trachea by the air passages, used especially to treat coughs [1].

There are many bioactive compounds identified in mint, but the main bioactive compounds are the terpenoid menthol, essential oils menthone, limonene, cineol, and azulene and flavonoids [1, 2]. One of the compounds identified in mint, azulene, appears to reduce inflammation [2].

It is used as decongestant in nasal spray inhalers against the common cold flu [1].

Mint is used as leaf extract e.g. in tea, as essential oil, as herbal supplements for the treatment of cold and flu symptoms and as a decongestant using nasal spray and inhalers [2].

Mint has several modes of action: It acts as demulcent, relieving irritation of the mucous membrane in the respiratory tract by forming a protective film. It can help to relax the muscles of the respiratory tract, easing breathing in people with cough. It helps digestion by blocking calcium ion channels, which causes the relaxation of the gastrointestinal smooth muscle. Mint has antibacterial properties effective against several types of bacteria strains. It can also selectively activate certain opioid receptors, which causes an analgesic effect [2].

Another mode of action could be that it has the ability to chemically trigger the cold sensitive receptors in the skin which is responsible for the cooling sensation it provokes when inhaled (but also when eaten and applied to the skin) thus this helping with common cold symptoms such as slime congestion in nose and throat [1].

Source references:

[1] a lecture of Giulia Friso at Cornell University, course PLBIO2100 Medical Ethnobotany lecture 21 titled “Plants used in the treatment of disorders of

respiratory Systems”.

[2] CALS154_course-transcript 2021

Example 3, the broom-like shaved grass resembling shrub ephedra sinica spp. (also called ma huang) in the plant family ephedraceae is a bronchodilator and/or decongestant because it increases the expansion of bronchial tubes and/or reduces congestion [1].

Ephedra dilates the bronchial passages of the lungs and relieves asthma and respiratory problems [1].

It’s above ground and root parts have been used in Traditional Chinese Medicine (TCM) used for more than 5000 years primarily to treat asthma, bronchitis, and hay fever used for nasal decongestion in the form of nasal drops [1].

Furthermore, native Americans and Mormon pioneers drank a tea brewed from Ephedra species, called "Mormon tea" to promote health [1].

While ephedrine is banned in for as sports supplements, but it is still commonly used to treat allergic disorders such as bronchial asthma or colds [1]. It is also used in certain medical procedures involving anesthesia to prevent dangerous drops in blood pressure [1].

The pure herb plant extract used for the use in tea containing ephedrine is still sold legally in the U.S.A. to relieve stuffy nose, watery eyes, other cold and allergy symptoms [1].

It contains the alkaloids ephedrine, pseudoephedrine, norephedrine, methylephedrine [1].

The mechanism of action would be that the bioactive alkaloid compounds ephedrine and pseudoephedrine can be used as decongestants because they influence the C.N.S. leading to constriction of peripheral blood vessels, furthermore ephedra’s anti-asthmatic effect arises from its ability to relax bronchial smooth muscle [1].

Source references:

[1] a lecture of Giulia Friso at Cornell University, course PLBIO2100 Medical Ethnobotany lecture 21 titled “Plants used in the treatment of disorders of

respiratory Systems”.

2. Give two examples of plant species used in traditional medicine as cough suppressants, and explain for each the main mechanism of action.

Example 1, the colorless strong sweet woody scented eucalyptus liquid oil from the relatively fast-growing evergreen flowering shrub plant eucalyptus globulus spp. of the eucalyptus genus (which genes contains more than 700 species) in the “aromatic”, in the sense of fragrantly odored not necessarily in the sense of Huckel’s rule, myrtaceae tree plant family (which family also includes plants such as bay tree and clove) extracted from the leaves which are steam distilled to extract eucalyptus oil is used as a bronchodilator and/or decongestant because it increases the expansion of bronchial tubes and/or reduces congestion [1] and it is an expectorant and/or mucolytic because it promotes the secretion of mucus from lungs, bronchi and trachea by the air passages, used especially to treat coughs [1].

It is one of the most used plants to treat respiratory tract disorders and it 1) reduces inflammation [1], 2) helps to breathe better [1] and 3) it stimulates the release of saliva and helps loosen cough [1].

It is used for respiratory tract disorders to reduce symptoms of coughs, colds, congestion and respiratory illnesses in mouthwash, cough suppressants, bronchitis and asthma because of its mucolytic and anti-inflammatory effect [1, 2].

The mechanism of action includes the primary parts used which are the leaves that contain terpenoids (e.g. the terpene eucalyptol), essential oil, antioxidants flavonoids (i.e. flavonoids with antioxidant properties) and tannins which may help to reduce inflammation and they also exert mucolytic effects meaning they can dissolve thick mucus and help relieve respiratory difficulties by breaking down the chemical bond between molecules in the mucus lowering the viscosity of the mucus and allow it to more easily be expelled or reabsorbed by the body [1, 2].

Eucalyptus oil suppresses cough, possibly by inhibiting the cough center in the brain elevating the threshold for coughing [2].

Source references:

[1] a lecture of Giulia Friso at Cornell University, course PLBIO2100 Medical Ethnobotany lecture 21 titled “Plants used in the treatment of disorders of

respiratory Systems”.

[2] CALS154_course-transcript 2021

Example 2, the wide pink-redly flowering herb opium poppy papaver somniferum (somniferum means sleep-bringing, referring to is sedative property due to the presence of opiates) of the papaveraceae family (which has over 700 species) is used as an aid for the respiratory system as an antitussive to prevent and relieve cough because it can help to suppress the coughing reflex [1, 2].

Opium contains more than 50 opiate alkaloid molecules including the analgesics alkaloids morphine, codine (also called codeine) and thebaine, as well as the non-analgesic alkaloids papaverine and noscapine. Morphine (named after Morpheus the Greek god of dreams) is the most active alkaloid. It thus contains the bioactive component opium analgesic alkaloid codeine [1].

It is used to treat respiratory problems including a stubborn cough [2].

Almost full citation:

“The mode of action of opioid alkaloids has been extensively studied. Opiates produce pharmacological action such as analgesia and hallucination by activating receptors located on the neural cell membrane. These receptors are distributed throughout the central nervous system, but also in the respiratory, gastrointestinal, and cardiovascular system. Opioid analgesics, codeine in particular, are among the most effective drugs for suppression of cough, primary via the μ-opioid receptor in the central nervous system. The κ-opioid receptor also seems to contribute partly to the production of antitussive effects of the drug, elevating the threshold for cough. Opiates are used to treat severe or acute pain or persistent strong cough for short period of time, or for people that may not respond well to other pain medication” [2].

Part of the mechanism of action is that it probably works by inhibiting the cough center in the brain, elevating the threshold for coughing. The exact mechanism is still poorly understood [1].

Source references:

[1] a lecture of Giulia Friso at Cornell University, course PLBIO2100 Medical Ethnobotany lecture 21 titled “Plants used in the treatment of disorders of

respiratory Systems”.

[2] CALS154_course-transcript 2021

3. What are some plants with antimicrobial properties used in respiratory disorders? Which type of active compounds seems to contribute to their effect? What is the speculated mode of action?

Example 1, the shrub papery white barked tea tree species melaleuca alternifolia (alternifolia means having leaves that grow on alternate sides of stems and alternate i.e. alternating over the stem) in the melaleuca genus (melaleuca comes from a combination of the Greek ‘melamelas’ (black) and ‘leukos’ (white), referring to the characteristic black trunk and young white branches) of the myrtaceae family (which includes bay, clove, and eucalyptus) is used for its antimicrobial properties [1].

More than 15 compounds have been isolated from tea tree oil, mainly terpenoids that have a fresh, camphor-like smell. For modern uses, the oil is extracted by steam distillation of the tea tree leaves [1].

The oil can also be inhaled to ease the effects of a cough and may inhibit the growth of bacteria that causes sinus infection and respiratory disorders. Tea tree is also a potent insect and lice repellent [1].

Arthur Penfold found that tea tree essential oil was 13 times stronger than the at that time frequently used antiseptic carbolic acid [1]. By World War II, tea tree was a popular remedy, and Australian soldiers carried it in their first aid kits. However, it was not until the 1970s that mass-scale commercial production of tea tree essential oil began spreading to lots of places all over the world [1].

The crushed leaves are boiled, and the steam inhaled, the paste is applied to wounds and cuts as antimicrobial and to accelerate healing, and its leaves are brewed to make a tea for throat illnesses [1].

For the mechanism of action, the terpenoid called terpinen-4-ol is the main component of tea tree oil and has been identified as a responsible for the antifungal and antimicrobial activity because it has been shown to inhibit growth of pathogen organisms such as candida, e. coli, staphylococcus aureus, and pseudomonas aeruginosa [1, 2].

Terpen-4-ol has also been shown to suppress inflammatory mediator production of activated human monocytes. A tea tree oil concentrate prevented the influenza virus from entering host cells by disturbing the normal viral membrane fusion procedure.

The text below is to show more about its antimicrobial properties as mentioned in the question but not necessarily for respiratory disorders.

Tea tree oil is used for its anti-fungus properties for hair dandruff (also called haarroos and roos) which is caused by a fungus that lives and feeds on the human animal scalp [13]. A hundred and twenty-six men and women randomized to daily use of a 5% tea tree oil shampoo or placebo for a month showed that the placebo worked a little bit, decreasing dandruff severity by about 10%, but the tea tree oil shampoo worked better with about a 40% drop with only one patient in the tea tree oil group actually achieving a complete response, though one in the placebo group did as well. Thus, it appears that the tea tree oil shampoo would require ongoing application for control of dandruff [14].

It is also used for athlete’s food fungus treatment (also called tinea pedis and voetschimmel) but might not be effective in treating the underlying cause but only treating the symptoms. A hundred patients randomized into one of three groups, a 10 [%] tea tree oil cream, tinactin (an antifungal drug), or a placebo cream. A month later, the fungus was wiped out in 85 [%] of the drug group, but only about a quarter of the placebo and tea tree oil groups. This is somewhat surprising, since tea tree oil can kill off the fungus in a petri dish but apparently not on toes [15]. From a mycological cure standpoint, i.e. a fungus cure standpoint, tea tree oil didn’t really do any better than placebo. But though the drug wiped out the fungus in 85 [%] of cases, in some of those cases, the patients actually didn’t notice an improvement in symptoms, or they actually felt worse after the drug—probably a reflection of tinactin’s irritant side effects. If instead of mycological cure, you looked at symptom improvement, tea tree oil works as well as the drug. So, this may be the basis for the popular use of tea tree oil in the treatment of athlete’s foot. But people should realize that it’s just symptomatic relief, and they’re not necessarily eliminating the underlying cause [16]. Furthermore, if you go with not a 10 [%] cream, but up to 25 [%] or 50 [%], you can get mycological cure rates above that of placebo, but still not as good as when compared to a commonly used drug. And, at those high concentrations, some of the patients applying tea tree oil developed moderate to severe dermatitis meaning they broke out in a rash. But if you have a patient that doesn’t want to use the medicated creams, then a 25 [%] tea tree oil application has a decent chance of knocking it out without being too risky. But the standard over-the-counter antifungal creams may work better [17].

And its anti-fungus properties are also use for nail fungus, a double-blind randomized controlled trial study head-to-head comparing tea tree oil with a common antifungal drug with twice-daily application of either the drug or pure tea tree oil on the nail for 6 months with debridement (the removal of damaged tissue or foreign objects from a wound) every few months concluded that after six months, the drug tea tree oil did just as well wiping the fungus out completely in about one in 10 cases, with for the majority of patients the situation looked better either from the doctor’s assessment or the patient’s with partial or full resolution of the appearance [9]. The two preparations were comparable in efficacy of cure, clinical assessment, and subjective improvement. Even their cost was comparable. So, for patients desiring a ‘natural’ treatment for athlete’s foot or nail fungus, topical tea tree oil is a reasonable alternative to prescription or over-the-counter antifungals [10]. One potential reason for the poor long-term benefits of any therapy for nail fungus is that it may be treating only a manifestation of underlying disease, such as generalized immune suppression or peripheral micro- or macrovascular disease. Maybe fungal nail infections are just a manifestation of poor peripheral blood circulation that would normally allow your body’s natural defenses to keep the fungus from taking root in the first place [10]. Evidently, there was a non-English language study of 400 patients that looked at the “relationship between blood circulation of the skin and the development of fungus disease [11] and found a greater than 50% reduction in blood flow in patients with athlete’s foot and nail fungus compared with patients without these disorders. So, if fungal nail infections are “just a symptom of an underlying process, then treatment aimed at eradication of a pathogen may be unrealistic. No wonder it just grows right back. A more appropriate goal may then be to just give up and live with it. Or if it’s a circulation problem, why not try to instead improve the circulation? It is known since the 1950s that you can effectively switch peripheral artery circulation on and off, like a light switch, within days by switching people between a low-fat plant-based diet and the more conventional diet that contributed to the problem in the first place [12].

>Tea tree oil is anti-viral because applying straight tea tree oil topically on virus caused hand finger warts for five days caused all warts to considerably reduce in size, and in another week, they were all gone. And they didn’t come back. Without negative side effects—only affecting the warts, in contrast to the standard acid treatments, which can damage the surrounding tissue also causing a lot of pain [3].

>Tea tree oil is anti-inflammatory and works better than drugs used for skin inflammation such as zinc oxide ointment and moderate potency prescription steroid cream of clobestason butyrate, but without the side effects [4].

>Tea tree oil is anti-bacterial for suppressing the acne causing bacteria [5, 6, 7, 8]. “In a randomized, double-blind, placebo-controlled trial of a 5% topical tea tree oil gel in mild-to-moderate acne the following was concluded: After six weeks in the tea tree oil group, a 40% drop in whiteheads and blackheads, a 40% drop in red and tender acne bumps, and a 47% drop in pus-filled pimples, compared to comparatively little change in the control group. Overall, in terms of total lesion count, the tea tree oil gel was three and a half times more effective than placebo, i.e. three and a half times more effective than essentially doing nothing. But most people don’t do nothing for their pimples so how does tea tree oil compare to the gold standard, benzoyl peroxide? Benzoyl peroxide is by far the most popular over-the-counter acne therapy despite its side effects. It can be irritating, causing redness, dryness, peeling, stinging, or burning. However, the prescription option, the long-term use of topical and oral antibiotics, is discouraged due to the development and spread of antibiotic resistance. As a result, attention has turned to non-antibiotic products such as tea tree oil. The benzoyl peroxide did cause more side effects—dryness, itching, stinging, redness, burning— but it worked better too, cutting the number of inflamed pimples by two-thirds within three months, versus only by half in the tea tree oil group, though the most recent study found them to be more comparable. Tea tree oil products not only beat out placebo but approximate more standard regimens like benzoyl peroxide or topical antibiotics, suggesting tea tree oil products may be an appropriate option for treating mild-to-moderate acne [5, 6, 7, 8].

Source references:

[1] CALS154_course-transcript 2021

[2] May J, et al. Time-kill studies of tea tree oils on clinical isolates. J Antimicrob Chemother 2000;45:639-43. https://pubmed.ncbi.nlm.nih.gov/10797086/ ; https://academic.oup.com/jac/article/45/5/639/746736

[3] Millar BC, Moore JE. Successful topical treatment of hand warts in a paediatric patient with tea tree oil (Melaleuca alternifolia). Complement Ther Clin Pract. 2008 Nov;14(4):225-7. doi: 10.1016/j.ctcp.2008.05.003. Epub 2008 Jul 11. PMID: 18940708. https://pubmed.ncbi.nlm.nih.gov/18940708/ ; https://www.sciencedirect.com/science/article/abs/pii/S1744388108000595?via%3Dihub

[4] Wallengren J. Tea tree oil attenuates experimental contact dermatitis. Arch Dermatol Res. 2011 Jul;303(5):333-8. doi: 10.1007/s00403-010-1083-y. Epub 2010 Sep 24. PMID: 20865268.

https://pubmed.ncbi.nlm.nih.gov/20865268/ ; https://link.springer.com/article/10.1007/s00403-010-1083-y

[5] Enshaieh S, Jooya A, Siadat AH, Iraji F. The efficacy of 5% topical tea tree oil gel in mild to moderate acne vulgaris: a randomized, double-blind placebo-controlled study. Indian J Dermatol Venereol Leprol. 2007 Jan-Feb;73(1):22-5. doi: 10.4103/0378-6323.30646. PMID: 17314442. https://pubmed.ncbi.nlm.nih.gov/17314442/

[6] Bassett IB, Pannowitz DL, Barnetson RS. A comparative study of tea-tree oil versus benzoylperoxide in the treatment of acne. Med J Aust. 1990 Oct 15;153(8):455-8. doi: 10.5694/j.1326-5377.1990.tb126150.x. PMID: 2145499. https://pubmed.ncbi.nlm.nih.gov/2145499/ ; https://onlinelibrary.wiley.com/doi/abs/10.5694/j.1326-5377.1990.tb126150.x

[7] Despuig E, Domingo P, Feliciano K, et al. A comparative study of the effectiveness of tea tree oil and benzoyl peroxide in the treatment of acne vulgaris among Filipino teenagers and adults in Metro Manila. UERM Health Sciences Journal. 2016; 5(1):20-24. https://ejournals.ph/article.php?id=11302

[8] Bagherani N, Smoller BR. Role of tea tree oil in treatment of acne. Dermatol Ther. 2015 Nov-Dec;28(6):404. doi: 10.1111/dth.12235. Epub 2015 May 14. PMID: 25818124.

https://pubmed.ncbi.nlm.nih.gov/25818124/ ; https://onlinelibrary.wiley.com/doi/10.1111/dth.12235

[9] Buck DS, Nidorf DM, Addino JG. Comparison of two topical preparations for the treatment of onychomycosis: Melaleuca alternifolia (tea tree) oil and clotrimazole. J Fam Pract. 1994;38(6):601-5. https://pubmed.ncbi.nlm.nih.gov/8195735/

[10] Bergstrom KG. Tea tree oil: panacea or placebo? J Drugs Dermatol. 2009 May;8(5):494-6. PMID: 19537376. https://pubmed.ncbi.nlm.nih.gov/19537376/

[11] Forck G. Beziehungen zwischen Hautdurchblutung und der Entstehung von Pilzkrankheiten [Relations between the blood circulation of the skin and the development of fungus diseases]. Zentralbl Bakteriol Orig. 1970;212(2):544-53. German. PMID: 4245766. https://pubmed.ncbi.nlm.nih.gov/4245766/

[12] KUO PT, WHEREAT AF, HORWITZ O. The effect of lipemia upon coronary and peripheral arterial circulation in patients with essential hyperlipemia. Am J Med. 1959 Jan;26(1):68-75. doi: 10.1016/0002-9343(59)90328-6. PMID: 13606154. https://pubmed.ncbi.nlm.nih.gov/13606154/ ; https://linkinghub.elsevier.com/retrieve/pii/0002-9343(59)90328-6

[13] Shuster S. The aetiology of dandruff and the mode of action of therapeutic agents. Br J Dermatol. 1984 Aug;111(2):235-42. doi: 10.1111/j.1365-2133.1984.tb04050.x. PMID: 6235835.

https://pubmed.ncbi.nlm.nih.gov/6235835/ ; https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2133.1984.tb04050.x?sid=nlm%3Apubmed

[14] Satchell AC, Saurajen A, Bell C, Barnetson RS. Treatment of dandruff with 5% tea tree oil shampoo. J Am Acad Dermatol. 2002 Dec;47(6):852-5. doi: 10.1067/mjd.2002.122734. PMID: 12451368. https://pubmed.ncbi.nlm.nih.gov/12451368/ ; https://www.jaad.org/article/S0190-9622(02)00313-4/pdf

[15] Tong MM, Altman PM, Barnetson RS. Tea tree oil in the treatment of tinea pedis. Australas J Dermatol. 1992;33(3):145-9. doi: 10.1111/j.1440-0960.1992.tb00103.x. PMID: 1303075.

https://pubmed.ncbi.nlm.nih.gov/1303075/ ; https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1440-0960.1992.tb00103.x?sid=nlm%3Apubmed

[16] Tong MM, Altman PM, Barnetson RS. Tea tree oil in the treatment of tinea pedis. Australas J Dermatol. 1992;33(3):145-9. doi: 10.1111/j.1440-0960.1992.tb00103.x. PMID: 1303075. https://pubmed.ncbi.nlm.nih.gov/1303075/ ; https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1440-0960.1992.tb00103.x?sid=nlm%3Apubmed

[17] Satchell AC, Saurajen A, Bell C, Barnetson RS. Treatment of interdigital tinea pedis with 25% and 50% tea tree oil solution: a randomized, placebo-controlled, blinded study. Australas J Dermatol. 2002 Aug;43(3):175-8. doi: 10.1046/j.1440-0960.2002.00590.x. PMID: 12121393.

https://pubmed.ncbi.nlm.nih.gov/12121393/ ; https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1440-0960.2002.00590.x?sid=nlm%3Apubmed

Example 2, The aromatic in the sense of flagrant odored substance frankincense (also called olibanum and franc encens meaning 'high-quality incense') present in and thus extractable from the resinous dried sap behind the bark of the biblical frankincense tree e.g. boswellia sacra and boswellia serrata species in the boswellia genus of the de burseraceae plant family (which is the same family as commiphora myrrha myrrh burseraceae) is anti-microbial thus anti-bacterial and anti-viral according to [1]. It has been used as disinfectant [2].

>Boswellic acid, the major constituent of Boswellia, is thought to contribute to most of the herb's pharmacological activities [1].

>Used in traditional medicine for similar effect as myrrh: an allergenic, antimicrobial, anti-inflammatory, and to soothe respiratory conditions as an expectorant and cough suppressant [1].

However, I can not find in literature that it is antimicrobial like said in this course. What I can find is that it may be bacteriostatic i.e., capable of inhibiting the growth or reproduction of bacteria. But not anti-microbial.

Source references:

[1] a lecture of Giulia Friso at Cornell University, course PLBIO2100 Medical Ethnobotany lecture 3 titled “African Traditional Medicine”.

[2] CALS154_course-transcript 2021

Example 3, nutmeg made from the seed from the medium to tall evergreen tree plant species called myristica fragrans (also called nutmeg, nootmuskaat and muskaatnoot) in the myristicaceae family [1].

Active compounds in nutmeg include the phenolic myristicin and several terpenoids and essential oils. In traditional medicine, nutmeg is used as an antimicrobial anti-inflammatory, to treat respiratory disorders, as a relaxant, to relieve symptoms of asthma and cough [1].

Citation:

“The phenolic compounds found in nutmeg may have activity against the bacteria that are associated with the respiratory infection. Myristicin, the main active component of nutmeg, has anticholinergic activity and works as bronchodilator, blocking the parasympathetic nerve reflexes that cause the airway to constrict, which allow air passages to remain open. Anticholinergic bronchodilators can be therefore used to treat chronic obstructive pulmonary disease and asthma” [1].

Source references:

[1] CALS154_course-transcript 2021

4. Select one plant species from the ‘Additional Plants to Improve Respiratory Health’ tool that could be beneficial for an individual suffering from the common cold. Explain why you would recommend that particular plant, including the major safety considerations that the individual should be aware of and the mode of action of the compounds that have the beneficial effects. You should refer back to the ‘Resources for Evaluating Herbal Supplements’ Tool from the first course in this series to find more information about the plants.

I want to start of that I find none of the four plant species of choice significantly helpful in treating the common cold.

Centella asiatica

Eleutherococcus senticosus

Uncaria tomentosa

Withania somnifera

Therefore, I have provided below this assignment information about the Chinese gooseberry kiwi fruit, especially the golden kiwi fruit actinidia chinensis ‘Hort16A’ variety which does significantly help with treating the common cold, and would be next to salt gurgling my first stop suggestion to help anyone with the common cold.

Furthermore, another plant in the tool is the leaves and aboveground parts of the herbaceous perennial common yarrow achillea millefollium of the achillea genus in the asteraceae family (also called daisy family) which is an (respiratory) immunostimulant because it stimulates the immuno-response [1] and a demulcent and/or emollient because it relieves irritation of the mucous and/or softens the skin [1]. It contains polyphenols, flavonoids, and sterols [2].

Source references:

[1] a lecture of Giulia Friso at Cornell University, course PLBIO2100 Medical Ethnobotany lecture 21 titled “Plants used in the treatment of disorders of respiratory Systems”.

[2] CALS155_course-transcript 2021 but have to track this down with research to know if the claims are true and to what extend they are true.

However, if I have to choose from this my answer would be the following:

The plant that I would recommend from the ‘Additional Plants to Improve Respiratory Health’ tool that for an individual suffering from the common cold would be centella asiatica gotu kola which could be is used to treat inflammation associated with the common cold.

Research about the mode of action of the beneficial bioactive compounds is lacking.

Laboratory experiments suggest that gotu kola can reduce inflammation, but human data are lacking [1]. Very few studies have been conducted in humans but part of the mechanism of action could be that laboratory studies have found a range of effects including improved wound healing and anti-inflammatory effects [1]. Studies in humans have

suggested that gotu kola can decrease venous pressure in people with venous insufficiency and may be able to relieve anxiety [1].

Major safety considerations would be that it could potentially lead to contact dermatitis when applied topically [17] and to hepatotoxicity [18, 26].

[1] a lecture of Giulia Friso at Cornell University, course PLBIO2100 Medical Ethnobotany lecture 16 titled “Indian Traditional Medicine”.

[17] Gomes J, Pereira T, Vilarinho C, Duarte Mda L, Brito C. Contact dermatitis due to Centella asiatica. Contact Dermatitis. 2010 Jan;62(1):54-5.

[18] Jorge OA, Jorge AD. Hepatotoxicity associated with the ingestion of Centella asiatica. Rev Esp Enferm Dig. 2005 Feb;97(2):115-24.

[26] Dantuluri S, North-Lewis P, Karthik SV.Gotu Kola induced hepatotoxicity in a child - need for caution with alternative remedies. Dig Liver Dis. 2011 Jun;43(6):500.

Plant used in discussion 2 on Canvas to add to this portfolio:

This is a graded discussion: 10 points possible

due Dec 18

General Respiratory System Support

7 7 unread replies. 7 7 replies.

Discussion topic:

In this module, you have examined many plants to support the respiratory system. For many of the body's systems, it may be easier to prevent illness, rather than trying to recover from it. For someone in overall good health, what plant-based medicines might be helpful to avoid respiratory ailments? You can discuss one plant that has been discussed in the course, but you should find an additional one that was not discussed. In your answer, include potential interactions and side effects. You may want to refer back to the Resources for Evaluating Herbal Supplements (Links to an external site.) tool to help you find more information from reliable sources. Make sure to include where you found your information in your answer.

Instructions:

You are required to participate meaningfully in all course discussions.
Limit your comments to 200 words.
You are strongly encouraged to post a response to at least two of your peers' posts.

To participate in this discussion:

Click Reply to post a comment or reply to another comment. Please consider that this is a professional forum; courtesy and professional language and tone are expected. Before posting, please review eCornell's policy regarding plagiarism (the presentation of someone else's work as your own without source credit).

To the question “for someone in overall good health, what plant-based medicines might be helpful to avoid respiratory ailments”, my choice of preference would be the Chinese gooseberry kiwi fruit, especially the golden kiwi fruit actinidia chinensis ‘Hort16A’ variety helps with the common cold flu-like symptoms because it extremely significantly improves immune system function reducing the severity and duration of certain upper respiratory tract infection symptoms such as severity and duration of head congestion, and the duration of sore throat [1]. It also makes people significantly less susceptible to respiratory infections meaning not only significantly improving the symptoms of those that got sick, but fewer people on kiwi fruit get sick in the first place. Those in the banana control group who got an upper-respiratory-tract infection suffered for about five days with a sore throat and congestion, compared to the kiwifruit eaters who felt better after just a day or two [2].

It significantly improves sleep onset, duration, and efficiency using both subjective and objective measurements [4].

It significantly helps preventative against DNA damage because of the phytonutrient antioxidants it contains [5] and it furthermore also significantly helps against oxidative DNA damage upregulating our DNA restorative repair enzymes [6].

It also helps with irritable bowel syndrome IBS from which about 10-20 [%] of the people of the general population suffer. Two kiwifruits a day seem to significantly improve bowel function in people having irritable bowel syndrome with constipation by shortening colon transit time, increasing defecation frequency and improving bowel function without deleterious effects on psychological functioning which are prevalent with the use of tegaserod (also called zelnorm and zelmac) which was the most frequently prescribed drug for irritable bowel until it was pulled from the market by the U.S.A. government’s FDA in 2007 out of concern it was killing people by increasing risk of heart attack and stroke [8].

However, care should be taken with consumption because kiwi allergy is a very prevalent allergy because about 1 in 130 people may be allergic to kiwifruit, which may rank kiwis as the third-most common food allergen second only to milk and eggs [3].

Source references:

[1] Hunter DC, Skinner MA, Wolber FM, Booth CL, Loh JM, Wohlers M, Stevenson LM, Kruger MC. Consumption of gold kiwifruit reduces severity and duration of selected upper respiratory tract infection symptoms and increases plasma vitamin C concentration in healthy older adults. Br J Nutr. 2012 Oct;108(7):1235-45. doi: 10.1017/S0007114511006659. Epub 2011 Dec 15. PMID: 22172428. https://pubmed.ncbi.nlm.nih.gov/22172428/ ; https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/consumption-of-gold-kiwifruit-reduces-severity-and-duration-of-selected-upper-respiratory-tract-infection-symptoms-and-increases-plasma-vitamin-c-concentration-in-healthy-older-adults/21FADFCDA9B1CE84BF9FE2476B1A2AC4

[2] Skinner, M.A. (2012) "Wellness foods based on the health benefits of fruit: Gold kiwifruit for immune support and reducing symptoms of colds and influenza," Journal of Food and Drug Analysis: Vol. 20 : Iss. 1 , Article 29. Available at: https://doi.org/10.38212/2224-6614.2095

[3] Rancé F, Grandmottet X, Grandjean H. Prevalence and main characteristics of schoolchildren diagnosed with food allergies in France. Clin Exp Allergy. 2005 Feb;35(2):167-72. doi: 10.1111/j.1365-2222.2005.02162.x. PMID: 15725187. https://pubmed.ncbi.nlm.nih.gov/15725187/ ; https://onlinelibrary.wiley.com/doi/10.1111/j.1365-2222.2005.02162.x

[4] Lin HH, Tsai PS, Fang SC, Liu JF. Effect of kiwifruit consumption on sleep quality in adults with sleep problems. Asia Pac J Clin Nutr. 2011;20(2):169-74. PMID: 21669584. https://pubmed.ncbi.nlm.nih.gov/21669584/ ; https://apjcn.nhri.org.tw/server/APJCN/20/2/169.pdf

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