Pomegranate, neuroinflammation, antimicrobial, metal chelator.

Pomegranate and its various products all have been found to have beneficial phytonutrients. The antioxidant power of the peel is strong enough to protect metal from rusting. The juice also includes polyphenol antioxidants that can enter the blood brain barrier (1, 4) and help detoxify oxidative stress chemicals within the brain (1 4), – anti-corrosive for the brain.

A metabolite (UA) of the pomegranate polyphenols was measured in brain tissue and blood plasma during an animal study. (4) “The concentration of UA in the brain was 1.68 ± 0.25 ng/g tissue and in plasma 18.75 ± 3.21 ng/mL. ” (4) It also seemed to increase activity of an anti-inflammatory enzyme (“GPx activity“) which would increase our own antioxidant production and helped reduce levels of the amyloid-β protein that is thought to be involved in Alzheimer’s dementia . (4)

  • It seems that PJ [pomegranate juice] caused down-regulation of α-synuclein protein expression since in rats treated alone with the juice, the levels of α-synuclein oligomers was decreased while the ratio of this fraction to monomeric was higher than in Control. This effect is likely to be involved in the improvement of neuronal cell survival, which was also reported for other natural preparations [42,62]. ” (4)

Pomegranate extract helped reduce/improve the balance of levels of the amyloid-β proteins involved in Alzheimer’s dementia in an animal model of the disease. (2) “The mice (age 24-30 mo) received either PE [pomegranate extract] (at 100 & 200 mg/kg) or a control solution daily for three weeks” (2)

What is standardized pomegranate extract? And how might you calculate a human dose?

It is hard to know and dose might vary with the type of pomegranate extract. Whether the seed, juice or peel, or the whole fruit is used to make the pomegranate extract might vary – read each article for details. Pomegranate Peel Extract (PPE) is used regularly in research regarding the medical uses.

  • Doses of 100 or 200 mg/kg of “a standardized pomegranate extract (PE)” was used in a study of an aged Alzheimer’s disease animal model. Ratios of the amyloid-beta proteins thought to be involved in Alzheimer’s disease were improved. (2) “Our findings support a specific anti-amyloidogenic mechanism of a pomegranate extract in this aged AD animal model. ” (2)
  • Pomegranate seeds (PGSE) were used to make the extract for an animal study of ischemic stroke damage to the brain. Doses of 100 or 200 mg/kg were found protective against oxidative damage. (1) An upper tolerance dose was trialed at 800 mg/kg but it did not cause toxic effects.
    • No toxicity was observed even with high-dose PGSE consumption (800 mg/kg, for 14 days). ” (1)

Without knowing how the extract was made, roughly an adult size amount (for a person weighing 70 kilograms/154 pounds) might be 7-14 grams per day (approximately 2-4 teaspoons).

I found 1-2 tablespoons (3-6 teaspoons) of my whole peel extract to be a beneficial amount for my symptoms. It can have diuretic side effects, use early in the day and have some extra nondiuretic fluids. Using only the inner white part of the peel can reduce the diuretic effects without losing other health benefits – the ratio of phytonutrients is slightly different for the inner and outer part of the peel, with both containing some of the hyrolyzable tannins that have healing, and diuretic effects. For directions/recipe and more information see: G13. Pomegranate Benefits and Preparation.

Pomegranate juice also was found neuroprotective in an Alzheimer’s animal model study. “Commercial 6-fold concentrated pomegranate juice (PJ) […] The total polyphenols content expressed as g of ellagic acid (EA) equivalents per L of juice was 18.90 ± 0.96 g/L. (4)

For humans eight ounces of pomegranate juice daily for four weeks was found beneficial for memory and changes in blood tests suggested it was being absorbed in an amount sufficient to help against inflammation.

In older subjects with age-associated memory complaints, who drank 8 ounces of pomegranate juice for four weeks, a significant improvement in verbal and visual memory as well as an increase in plasma Trolox-equivalent antioxidant capacity was observed. Noteworthily, individuals drinking pomegranate juice represented an increased level of a metabolite of pomegranate ellagitannins—urolithin A glucuronide—in plasma [15]. It is believed that pomegranate’s neuroprotective effects are mediated by urolithins—the colonic microbiota ellagitannins (ETs)-derived metabolites [8].” (4)

From my own use I have found about four ounces per day beneficial for mood and four ounces twice a day was helpful on a bad day. The fresh seeds, 1/3-1/2 cup also helped my anxiety symptoms in a similar way. Dried pomegranate seeds, anardana, are available in markets with foods from India, about 2-3 tablespoons might be an equivalent serving.

Pomegranate extracts may also have healing benefits when used topically, for wound care in this study:

  • Whole fruit extract was used topically, diluted to 7.5% was mentioned in an animal based study on wound healing. “…whole fruit extract of pomegranate (P. granatum Linn.) standardized with 40% ellagic acid produced by Xi’an Bio-Technology Co., Ltd.,…” (3)

Regarding CoV19 & pomegranate peel

In the case of SARS-CoV-2/COVID-19 there may be a problem with the virus suppressing the normal immune response of interleuken I and III (ref) Inflammatory interleuken 1 and 6, IL-1 and IL-6, can become elevated in patients with severe illness. Pomegranate peel or whole fruit extract has been found to have significant anti-inflammatory and immune-modulating effects. In different studies it has been shown to have benefits by inhibiting levels of IL-1, (7) , and IL-6. (5)

  • PGPE consumption […] prevent the instigation of a low-grade inflammatory status compared to OVX Control animals, through the down-regulated expression of CCL2 (0.33-fold; p < 0.05) & IL1-R1 (0.64-fold; p < 0.001) and the up-regulated expression of IL1-Rn (1.89-fold; p < 0.001)” (7)
    • IL1-Rn= “IL-1 receptor antagonist allows unopposed IL-1 activation” (6)
  • In another study, we demonstrated that PFE significantly inhibited the excessive production of IL-6 and IL-8 via suppression of the JNK-, extracellular signal-regulated kinases (ERK)- MAPKs and NF-κB-signaling events. (19)  ” (5)

*preliminary version.

Disclaimer: This information is provided for educational purposes within the guidelines of Fair Use. It is not intended to provide individual guidance. Please seek a health care provider for individualized health care guidance.

Reference List

  1. Sarkaki A, Rezaiei M, Gharib Naseri M, Rafieirad M. Improving active and passive avoidance memories deficits due to permanent cerebral ischemia by pomegranate seed extract in female rats. Malays J Med Sci. 2013;20(2):25–34. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3743996/
  2. Ahmed AH, Subaiea GM, Eid A, et al., Pomegranate extract modulates processing of amyloid-β precursor protein in an aged Alzheimer’s disease animal model. Curr Alzheimer Res. 2014;11(9):834-43. https://ncbi.nlm.nih.gov/pubmed/25274111
  3. Yuniarti WM, Primarizky H, Lukiswanto BS. The activity of pomegranate extract standardized 40% ellagic acid during the healing process of incision wounds in albino rats (Rattus norvegicus). Vet World. 2018;11(3):321–326. doi:10.14202/vetworld.2018.321-326 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891847/
  4. Kujawska M, Jourdes M, Kurpik M, et al. Neuroprotective Effects of Pomegranate Juice against Parkinson’s Disease and Presence of Ellagitannins-Derived Metabolite-Urolithin A-In the Brain. Int J Mol Sci. 2019;21(1):202. Published 2019 Dec 27. doi:10.3390/ijms21010202 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981883/Commercial 6-fold concentrated pomegranate juice (PJ) was obtained from Alter Medica (Żywiec, Poland). The product was manufactured in accordance with the principle of HACCP (hazard analysis and critical control point) and fruit ingredients are fully compliant with the Code of Practice of the European Fruit juice Association (AIJN). Since pomegranate’s ellagitannins and their hydrolysis product—ellagic acid—have been demonstrated to be precursors of potentially neuroprotective urolithins, including urolithin A [8], which we detected in this study, we identified these phenolics in the tested juice. The ellagitannin composition of PJ was as follows: Galloyl-hexoside, ellagic acid-hexoside, 3-bis-HHDP-hexoside (pedunculagin), 4-galloyl-bis-HHDP-hexoside (casuarinin), and ellagic acid (Figure S1). The total polyphenols content expressed as g of ellagic acid (EA) equivalents per L of juice was 18.90 ± 0.96 g/L. ” *so full strength juice might have a sixth or approximately 3 grams/L of ellagic acid.
  5. Rasheed Z. Intake of Pomegranate Prevents the Onset of Osteoarthritis: Molecular Evidences. Int J Health Sci (Qassim). 2016;10(2):V‐VIII. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4825888/In another study, we demonstrated that PFE significantly inhibited the excessive production of IL-6 and IL-8 via suppression of the JNK-, extracellular signal-regulated kinases (ERK)- MAPKs and NF-κB-signaling events. (19) “
  6. IL1RN interleukin 1 receptor antagonist [ Homo sapiens (human) ], Gene ID: 3557, updated on 17-Apr-2020 https://ncbi.nlm.nih.gov/gene/3557
  7. Mélanie Spilmont, Laurent Léotoing, Marie-Jeanne Davicco, et al., Pomegranate Peel Extract Prevents Bone Loss in a Preclinical Model of Osteoporosis and Stimulates Osteoblastic Differentiation in Vitro, Nutrients 2015, 7(11), 9265-9284; https://doi.org/10.3390/nu7115465 https://www.mdpi.com/2072-6643/7/11/5465/htm
  8. **helped “encephalitis lethargica symptoms during ME(ME/CFS) ” anecdotal.

Today, it is well-known that the TRPA1, TRPC5, TRPM2, TRPM7, TRPV1, TRPV3, and TRPV4 cation channels are activated by ROS and reactive nitrogen species (RNS) [2932].” (Nazıroğlu 2015)

Anemia of Inflammation, IL-6, Hepcidin, Iron and Vitamin C.

During bacterial infections iron is shifted out of hemoglobin production and into ferritin and intracellular storage. (Iron and Anemia of Chronic Inflammation, post) If amounts of the free iron overloads the cell capacity and antioxidant capacity then cell death may result and other damage. The shift of iron involves an increase in the inflammatory cytokine IL-6 (Interleucon-6) which causes an increase in hepcidin, which causes the removal of iron from hemoglobin. (5)

Having extra antioxidants in the diet can help the body cope with the sudden increase in free iron – think of rust – iron oxidizes and the body doesn’t want rust anymore than you want it on your car. Antioxidants like vitamin A and C and bioflavonoids can all help stabilize the chemically active iron. The anti-malarial herbal extract called artemisinin may help by binding some of the excess free iron stores. (4)

ACE2 receptors are likely more prevalent in the lung cells of smokers (1) and COPD patients, (3), and people living in air pollution because it has a protective effect against lung injury. It helps decrease levels of the inflammatory cytokine IL-6. (2) Which suggests that extra vitamin C and bioflavonoids, and other nutrients may also help reduce the risk of anemia of chronic inflammation and other lung and heart risks from chronic hypoxia (low oxygen levels in the blood).

The COVID-19 illness may have a risk of sudden death due to cardiovascular problems upon relapse/reinfection (6) because of the shift in iron and resulting risk of cell death due to excess free iron. The use of iron chelators or artemisinin and continuing the use of extra antioxidants such as vitamin C and bioflavonoids might help prevent excess coagulation and reverse the shift of iron atoms from hemoglobin molecules to ferritin and free iron within cells. Infectious microbes need iron too so it is a self defense strategy that may become excessive in the case of severe COVID-19 illness.

There is more about bioflavonoids, vitamin C, and coagulation risks of SARS-CoV-2 infection in this post: Bitter Taste Receptors in the Lungs – Hesperidin’s Decongestant Properties.

Reference List

  1. SJ Brake, K Barnsley, Wenying Lu, et al., Smoking Upregulates Angiotensin-Converting Enzyme-2 Receptor: A Potential Adhesion Site for Novel Coronavirus SARS-CoV-2 (Covid-19). J. Clin. Med.20209(3), 841; https://doi.org/10.3390/jcm9030841 https://www.mdpi.com/2077-0383/9/3/841/htm
  2. Lin CI, Tsai CH, Sun YL, Hsieh WY, Lin YC, Chen CY, Lin CS. Instillation of particulate matter 2.5 induced acute lung injury and attenuated the injury recovery in ACE2 knockout mice. Int J Biol Sci 2018; 14(3):253-265. doi:10.7150/ijbs.23489. Available from http://www.ijbs.com/v14p0253.htm air pollution studies – ACE2 would be protective against ACE->IL-6 “Increased ACE levels cause the activation of AT1R by Ang II, consequently inducing the expression of the inflammatory cytokines IL-6, TNF-α and TGF-β1 [17]. ACE2 counter-regulates the effects produced by Ang II by converting Ang II to Ang-(1-7), activates Mas to repress the signaling pathways of STAT3 and extracellular signal-regulated kinases (ERK) [18], and acts as an anti-inflammatory factor [19].
  3. ACE-2 Expression in the Small Airway Epithelia of Smokers and COPD Patients: Implications for COVID-19. https://erj.ersjournals.com/content/early/2020/03/26/13993003.00688-2020
  4. Inhibitory effect of novel iron chelator, 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1) and green tea extract on growth of Plasmodium falciparum https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4590262/Artemisinin found in the Chinese medicinal plant (Artemisia annua) binds iron to form ferric-dihydroartemisinin complex, resulting in reactive oxygen species (ROS)-mediated potent anti-malarial activity against ring and late stage of CQ-resistant P. falciparum malaria parasites [5]. “
  5. Covid-19 – Liver – iron overload – lung cascade – coagulation a forum topic on peakprosperity.com with links to research, excerpts and discussion re COVID-19 – Liver – iron overload – lung cascade – coagulation. https://www.peakprosperity.com/forum-topic/covid-19-liver-iron-overload-lung-cascade-coagulation/
  6. Jules Quartly, Exclusive: Chinese doctors say Wuhan coronavirus reinfection even deadlier. Feb 14, 2020, TaiwanNews.com, https://www.taiwannews.com.tw/en/news/3876197

Phytonutrients that may help against SARS-CoV-2.

  • Anthemis hyalina, a medicinal daisy like herb, carvocrol and alpha-pinene were main components. It was most potent at preventing coronavirus replication in a cell based study compared with Nigella sativa oil and citrus peel extract, however citrus peel is easier to find at the grocery store. (1, 2)
  • Citrus peel (peel of Citrus sinensis – standard oranges) contains potent phytonutrients with antiviral & decongestant properties. (1, post)
  • Nigella sativa/Black Seed Oil/Black Cumin Seed, (1), contains “thymoquinone (TQ) (30- 48%), flavonoids, anthocyanins, alkaloids and essential fatty acids, particularly linoleic and oleic acid.” Thymoquinone/Nigella sativa oil has been found to promote the beneficial Nrf2 pathway and inhibits the inflammatory NfKb pathway in addition to acting as an antioxidant. It also has been found to help protect liver and kidney health in the presence of a variety of chemical and pathogenic toxins. (3)

Citrus peel, Black Seed oil, and a medicinal daisy are fairly specific foods or herbal supplements however there are ten other phytonutrients found in many different foods, that are also suspected of having antiviral benefits against the SARS-CoV-2 virus. Computer modeling of the chemical shapes of the nutrients and the virus was used to estimate potential bond strength of the Spike portion of the virus and the phytonutrients and the medication hydroxychloroquine. The phytonutrients were estimated to be more effective at bonding with and inhibiting the virus at the Spike protein compared to the medication hydroxychloroquine, (a lower number – more negative in this case- indicates a stronger bond energy):

Among these phytochemicals, flavonoids and non-flavonoids have been found to be the active source of different anti-microbial agents. Recently, studies have shown that these phytochemicals have essential anti-viral activities.”

Kamferol, curcumin, pterostilbene, and HCQ [hydroxychloroquine] interact with the C-terminal of S1 domain with binding energies of -7.4, -7.1, -6.7 and -5.6 Kcal/mol, respectively.”

Fisetin, quercetin, isorhamnetin, genistein, luteolin, resveratrol and apigenin on the other hand, interact with the S2 domain of spike protein with the binding energies of -8.5, -8.5, -8.3, -8.2, -8.2, -7.9, -7.7 Kcal/mol, respectively.”

*The lower the number, the stronger the molecular bonding is estimated to be – energy required to break the molecular bond between phytonutrient or medication and the viral protein – the C-terminal of the S1 domain of the Spike protein on the SARS-CoV-2 virus or the S2 domain. Note that the binding energy of hydroxychloroquine is the weakest (closest to zero).

(Rane et al., 2020)(4)

The phytonutrients are found in wide range of foods, some in many foods, and others may be found in a few specific foods – the variety may be adding up to health. These nutrients and others in whole foods can help reduce the risk of Metabolic Syndrome or improve it. Having Metabolic Syndrome, obesity, and/or Type 2 diabetes has been associated with greater risk of more severe symptoms if sick with COVID19. (20)

Given the speed at which health markers for metabolic disease improve from dietary interventions, an equally strong if not more significant population health message should now be to “eat real food, protect the NHS and save lives.””

Covid 19 and the Elephant in the Room, (20).

Phytonutrients that may inhibit the Spike protein of the SRS-CoV-2 virus and block entry into cells.

  • Kamferol – is a flavonoid found in similar green veggies as quercetin, including kale, leeks, onions, broccoli, and also is in blueberries, strawberries, kiwi, and other fruits and berries, (myintakepro), and cinnamon. (23) (The camphor in cough drops that helps as a decongestant is different, it is a terpene, and is extracted from a couple tree species. It is also found in the herb rosemary. (wikipedia.org/Camphor)
  • Curcumin is an extract of turmeric root which is used in curry spice mixes. It is a vitamin D analog, and active hormone D is essential for a healthy immune response, some is essential but too much D can also be harmful.
    • Curcumin and catechins have been found to be active at the coronavirus Spike protein and human ACE2 receptor where the virus enters cells. (7)
  • Catechins are also flavonoids, and are found in green & black tea, apples, blackberries, dark chocolate, red wine, cherries, guava, pears, sweet potatoes & purple potatoes. (8, 7)
  • Pterostilbene is found in almonds & Vaccinium berries – blueberries, cranberries, also in grape leaves/grapes but doesn’t last through the wine making process. It is chemically similar to resveratrol which can be found in grapes & wine. (9)
  • Resveratrol is found in grapes/grape skins/wine, and in “peanuts, pistachios, grapes…wine, blueberries, cranberries…dark chocolate.” (10)
    It is an estrogen receptor modulator/analog & estrogen can have anti-inflammatory effects for health. (11)
  • Genistein is found in soybeans, soy products like tofu, tempeh & miso, also is in chickpeas/other legumes, in smaller amounts. It is an estrogen receptor analog/modulator (like resveratrol) and estrogen can have anti-inflammatory effects. (12)
    • While men tend to have more ACE2 receptors and that is thought a possible reason for a higher rate of mortality for men than women from COVID19, may be estrogen is having a protective effect also.
  • Fisetin– is a “flavonoid found in…(strawberries, apples, mangoes, persimmons, kiwis, & grapes), vegetables (tomatoes, onions, and cucumbers), nuts, & wine that has shown strong anti-inflammatory, anti-oxidant, anti-tumorigenic, anti-invasive, anti-angiogenic” properties. (13)
  • Quercetin – is in onions, garlic, green leafy veg, citrus peel, figs, and is a focus of several recent posts: Citrus Fig jam: (14), Hesperidin & quercetin content in citrus peel: (15), Decongestant properties of hesperidin/citrus peel: (16).
  • Isorhamnetin is a flavonol, and a derivative of quercetin. It is found in “parsley, green bell peppers, and dills and in a lower concentration in garden cress, black chokeberries, and honey,” (17), and in cinnamon. (23)
  • Luteolin is a flavonoid “found in celery, thyme, green peppers, and chamomile tea,” (18) and “chrysanthemum flowers, sweet bell [green/red/orange] peppers, carrots, onion leaves, broccoli, and parsley [7 8]. (21)
  • Apigenin is a flavonoid found in “grapefruit, plant-derived beverages and vegetables such as parsley, onions, oranges, tea, chamomile, wheat sprouts and in some seasonings.” (19)
    • Intake of more dietary flavonoids on average was associated with a reduced cancer risk. (19)

During the past two decades, plant-derived bioactive compounds have been reported as novel health-giving agents for prevention and/or mitigation of different human diseases such as cancer, inflammation, cardiovascular, and neurodegenerative diseases [5]. Among these compounds, more than 5000 flavonoids have been identified and are distributed in a wide range of plants. On the basis of their chemical structures, these flavonoids have been grouped into 10 categories, 6 of which including:  flavonesflavanonesanthocyanidinsflavonols

isoflavones, and catechins, are commonly present in the human diet.” *

(Imran, et al., 2019) (21) *links are to ScienceDirect topic pages.

Many of these phytonutrients and others found in plant foods help our bodies to have enough of an immune response without having an overactive autoimmune or allergy type of response, acting as immunomodulators. They also help the body switch from inflammatory chemical pathways, that are more typical of daytime hours of our circadian cycle, to anti-inflammatory pathways more typical of sleep hours.

Pitch blackness at night and some full spectrum daylight during wake hours of an individual’s circadian 24 hour day can also help the body to stop the day time stress response inflammatory chemistry and start the nighttime anti-inflammatory healing activity. More on this topic is available in a book that is in very early stages of being written/rewritten from work I’ve completed elsewhere: Tipping the Circadian Clock Towards Health.

Some other tips for lifestyle changes that can help protect health and may even help promote growth of new brain cells in the hippocampus, (the area of the brain that is damaged in Alzheimer’s dementia). 22

Anti-inflammatory Phytonutrients/nutrients from a previous post; promote p53 or inhibit NLRP3:

Other phytonutrients including quercetin which is found in citrus peel, also can help inhibit production or activity of the inflammatory NLRP3 inflammasome which has been found to be elevated during more severe COVID19 illness. Sulfarophane (broccoli, etc), resveratrol (grape skins, etc), EGCG (green tea, pomegranate peel), curcumin (turmeric/curry powder), gensenoside (ginseng), emodin (aloe vera gel), mangiferin (mango) and genipin (from a fruit used as a Traditional Chinese Medicinal) are also phytonutrients that may reduce activity or production of NLRP3 inflammasomes. (17*) **

Increasing activity of a protein called p53 seems to help inhibit the production or activity of the NLRP3 inflammasome. Phytonutrients and nutrients that may promote p53 activity also include zinc, artemisinin (wormwood herb), goldenseal (berberine, also found in a few other herbs), Black seed oil (Nigella sativa), ginger (6-gingerol), feverfew, chamomile, and cordyceps mushrooms. (18*)** Replication of human coronaviruses and the SARS-CoV-1,(2003 strain) virus has been found to be inhibited by p53 and have also been found to cause the production of an additional protein that leads to breakdown of the p53 protein which may help explain the dysfunction of immune function in more severe infections. (21*, 22*)**

Inactivating the NLRP3 inflammasome seems to have anti-inflammatory benefits (17) that may help prevent age related changes. It is an area of research being pursued for pharmaceutical development. (11*)** Sleep masks/pitch blackness during sleep, with the alarm clock and light leaking in the window covered, could help your body inactivate the NLRP3 inflammasome on a nightly basis with no ongoing copay. **(See the post Bitter Taste Receptors… for references 11*, 17*, 18*, 21*, 22*)

Options exist and are worth trying in an order of least toxicity risk to greater toxicity risk – foods and herbs and spices or herbal supplements are generally low toxicity and would taste too strong as an indicator of an excess being used. First-aid/self care type of treatments can include the bowl of hot and sour spicy soup or orange with the pith layer left on, or a cup of hot steamy green tea or herbal tea with slippery elm powder, (a mucilaginous/water soluble fiber source, see the post ACE2, Diarrhea… for more food mucilaginous foods and food sources of hydrolyzable tannins, both groups can be beneficial for inflammatory bowel/diarrhea types of conditions or symptoms).

Mix it up – and it may add up to health, have some healthy ingredients along with whatever favorite foods you may also love. Experiment with adding more herbs and spices to favorite foods, gradually, and taste preferences can adapt and new discoveries may become old favorites eventually.

Disclaimer: This information is provided for educational purposes within the guidelines of Fair Use. It is not intended to provide individual guidance. Please seek a health care provider for individualized health care guidance.

Reference List

  1. Ulasli M, Gurses SA, Bayraktar R, et al. The effects of Nigella sativa (Ns), Anthemis hyalina (Ah) and Citrus sinensis (Cs) extracts on the replication of coronavirus and the expression of TRP genes family. Mol Biol Rep. 2014;41(3):1703–1711. doi:10.1007/s11033-014-3019-7 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933739/
  2. Abdolhossein Rustaiyan, Shiva Masoudi, Laleh Ezatpour, Elmira Danaii, Mahboubeh Taherkhani & Zahra Aghajani (2011) Composition of the Essential Oils of Anthemis Hyalina DC., Achillea Nobilis L. and Cichorium intybus L. Three Asteraceae Herbs Growing Wild in Iran, Journal of Essential Oil Bearing Plants, 14:4, 472-480, DOI: 10.1080/0972060X.2011.10643603 https://www.tandfonline.com/doi/abs/10.1080/0972060X.2011.10643603
  3. Desai S D, Shaik Hussain Saheb, Kusal K Das, Haseena S, Phytochemical Analysis of Nigella sativa and Its Antidiabetic Effect. J. Pharm. Sci. & Res. Vol. 7(8), 2015, 527-532 https://www.jpsr.pharmainfo.in/Documents/Volumes/vol7Issue08/jpsr07081506.pdf
  4. Rane, Jitendra Subhash; Chatterjee, Aroni; Kumar, Abhijeet; Ray, Shashikant (2020): Targeting SARS-CoV-2 Spike Protein of COVID-19 with Naturally Occurring Phytochemicals: An in Silco Study for Drug Development. ChemRxiv. Preprint. https://doi.org/10.26434/chemrxiv.12094203.v1 https://chemrxiv.org/articles/Targeting_SARS-CoV-2_Spike_Protein_of_COVID-19_with_Naturally_Occurring_Phytochemicals_An_in_Silco_Study_for_Drug_Development/12094203
  5. Kaempferol Rich Foods, myintakepro.com, https://myintakepro.com/blog/kaempferol-rich-foods/
  6. Camphor, wikipedia.com, https://en.wikipedia.org/wiki/Camphor
  7. Atala B. Jena, Namrata Kanungo, Vinayak Nayak et al. Catechin and Curcumin interact with corona (2019-nCoV/SARS-CoV2) viral S protein and ACE2 of human cell membrane: insights from Computational study and implication for intervention, 08 April 2020, PREPRINT (Version 1) available at Research Square https://doi.org/10.21203/rs.3.rs-22057/v1 https://researchsquare.com/article/rs-22057/v1
  8. 10 Ways to Get Your Catechin Fill, cleaneatingmag.com, https://www.cleaneatingmag.com/clean-diet/10-ways-to-get-your-catechin-fill
  9. What is Pterostilbene?, elysiumhealth.com, https://www.elysiumhealth.com/en-us/science-101/what-is-pterostilbene
  10. Resveratrol Offers Health Boost, health.harvard.edu, https://www.health.harvard.edu/blog/diet-rich-resveratrol-offers-health-boost-201405157153
  11. Resveratrol, ScienceDirect.com, https://sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/resveratrol
  12. Sutrisno Sutrisno, Hardianti Aprin, Happy Marthalena Simanungkalit, et al., Genistein modulates the estrogen receptor and suppresses angiogenesis and inflammation in the murine model of peritoneal endometriosis. J Trad & Comp Med, 8;2, April 2018, pp 278-281, https://doi.org/10.1016/j.jtcme.2017.03.002 sciencedirect.com, https://www.sciencedirect.com/science/article/pii/S2225411017300366
  13. Pal HC, Pearlman RL, Afaq F, et al., Fisetin and Its Role in Chronic Diseases. Adv Exp Med Biol. 2016;928:213-244. https://ncbi.nlm.nih.gov/pubmed/27671819
  14. Citrus Fig Marmalade Jam, transcendingsquare.com, https://transcendingsquare.com/2020/04/12/citrus-fig-marmalade-jam/
  15. Hesperidin & quercetin content in citrus peel, transcendingsquare.com, https://transcendingsquare.com/2020/04/14/hesperidin-and-quercetin-content-in-citrus-peel/
  16. Bitter Taste Receptors in the Lungs – Hesperidin’s Decongestant properties, transcendingsquare.com, https://transcendingsquare.com/2020/04/07/bitter-taste-receptors-in-the-lungs-hesperidins-decongestant-properties/
  17. Showing Compound Isorhamnetin (FDB000604) foodb.ca https://foodb.ca/compounds/FDB000604
  18. USDA/Agricultural Research Service, Luteolin stars in study of healthful plant compounds. July 16, 2010, ScienceDaily.com, https://www.sciencedaily.com/releases/2010/07/100708141622.htm
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  21. Imran M, Rauf A, Abu-Izneid T, et al., Luteolin, a flavonoid, as an anticancer agent: A review. Biomed Pharmacother. 2019 Apr;112:108612. doi: 10.1016/j.biopha.2019.108612 https://www.sciencedirect.com/science/article/pii/S0753332218367180?via%3DihubDuring the past two decades, plant-derived bioactive compounds have been reported as novel health-giving agents for prevention and/or mitigation of different human diseases such as cancer, inflammation, cardiovascular, and neurodegenerative diseases [5]. Among these compounds, more than 5000 flavonoids have been identified and are distributed in a wide range of plants. On the basis of their chemical structures, these flavonoids have been grouped into 10 categories, 6 of which including  flavonesflavanonesanthocyanidinsflavonolsisoflavones, and catechins are commonly present in the human diet.
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