Category: phospholipid

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Brain cells and aging

Within the majority of the brain the type of brain cells that send nerve signals generally do not get replaced, however they also generally don’t lose function. Dementia – loss of memory and other cognitive skills – is not a normal part of healthy aging. Age related forgetfulness has to do with loss of the connections between brain cells but the brain cells remain functional – so continuing to take part in learning and social activities may help prevent dementia and forgetfulness by helping to maintain current connections between brain cells and add new connections formed during learning or socializing. 

And yet Alzheimer’s dementia now “afflicts 5% to 10% of the U.S. population over the age of 65 and as much as 45% of the population over 85.” (page 694, Neuroscience, 6th. edition, 1)

Research for medications for Alzheimer’s treatment have focused on reducing the levels of certain types of protein that collect in the damaged areas of the brain of a patient with the condition, however even if successful at reducing the amount of the protein the medications have not been found very helpful for restoring the patient’s cognitive health. (previous post) People with normal brain function also can have excess of the protein and it is also found in the brains of people with autism disorder – confusing, yes. Adequate quality sleep may help the brain waste removal system keep the levels of excess protein from building up to damaging amounts. (previous post on sleep and the glymphatic system)

Things that may increase risk include chronic stress and the excess cortisol and inflammatory oxidative stress chemicals production. Moderate exercise may help reduce stress and promote detoxification of inflammatory chemicals. Staying socially and mentally active also may be protective of brain function. Prevention is the best medicine for conditions that cause irreversible degenerative changes such as the damage in Alzheimer’s Disease. Learning about new foods and recipes and then making healthy meals to share with others can be a way to combine physical and mental activity and gain from nutrients that help detoxify inflammatory oxidative stress chemicals. (previous post, Foods for beneficial T-cells) – (Nrf2 promoting foods)

T cells are a type of blood cell with immune system functions. Beneficial T cells can help clear excess protein found in Alzheimer’s (2) while other types can increase inflammation and the types can transform based on the level of oxidative stress chemicals that are present so having antioxidants and other phytonutrients in daily meals can help signal the T-cells to take the beneficial forms instead of the inflammatory forms. (The non euphoria producing endogenous cannabinoid 2-AG (acts at the CB2 receptor, somewhat similar to CBD) may also help signal T cells towards the less inflammatory type, and reduce migration of them. page 96)

Nrf2 is a gene and protein that help promote the more beneficial types of T cells and help the immune system in other ways and also promote our own production of antioxidants for reducing the oxidative stress chemicals that are a natural waste product left from energy metabolism – when blood sugar is turned into a usable form of energy.

The long story is complicated, the short story remains,

  • include moderate exercise most days of the week,
  • have adequate sleep, 6-8 hours/night, ideally with complete darkness, blackout curtains and cover the light from an electric bedside alarm clock (put it in a nearby drawer or cover it with something),
  • get some natural sunshine or full spectrum light during the day if possible (may help with vitamin D, bioactive sulfate, and circadian rhythm metabolism within the body which includes production of melatonin,
  • stay mentally and socially active,
  • reduce stress when possible and/or practice relaxation techniques,
  • drink adequate water and regularly eat a good variety of colorful fresh produce, whole grains, nuts, beans, seeds, and include omega 3 fatty acid sources on a daily or weekly basis.
  • Clean air quality is also important. Formaldehyde (from secondhand smoke or even excessive use of decorative candles), and other air pollutants (released by plastics or new carpeting/flooring for example) can collect in poorly ventilated buildings. See this post for more information about formaldehyde sources and ways to reduce it: Formaldehyde: Health Risks, and Environmental and Dietary Sources.(effectiveselfcare.info)
  • Adequate water, not getting dehydrated regularly, is important enough to repeat because dehydration allows toxins within the body, including formaldehyde, to collect, instead of being removed by the glymphatic/lymphatic and vascular system, and to then be excreted by the kidneys. Brain Formaldehyde is Related to Water Intake Behavior, Ting Li, et al, 2016, (PubMed) A discussion of how much water is typically needed for health each day, and how much protein to eat for basic needs without being too much for long term kidney health, is available in a previous post: Make Every Day Kidney Appreciation Day. (effectiveselfcare.info)

More of the long story – the Cannabinoid Receptor Type 2 is also activated by a phytonutrient called beta-caryophyllene (BCP) which is found in many aromatic herbs and spices including: oregano, cinnamon,  clove , rosemary,  thyme, black pepper, (4), and copaiba oil. (5) Benefits may include reducing inflammation and pain, anti-anxiety, anti-cancer, (4), and protection of the brain by helping reduce increased activity after brain trauma which can lead to scar like tissue walling off the area of trauma instead healing.(5)

The problem in Alzheimer’s may not be the protein itself but instead the cells that over-actively making it in response to inflammatory signals so the solution would be not trying to remove excess protein but to stop the production of excess protein by signaling the overactive cells that all is well again, stop walling off the supposed injury. Formalin, a more dilute buffered form of formaldehyde was the toxin used to create inflammation in an animal based study of the potential benefits of beta-caryophyllene. A dose of 5 mg/Kg purified beta-caryophyllene essential oil given by mouth (rather than by an injection) was found to help reduce inflammatory pain from the formalin. (4) For a 75 kilogram adult that would be a capsule with 375 milligrams of the purified oil.

The herb rosemary is pine needle like plant that has been used as a pain killer in traditional folk medicine for arthritis pain and was thought of a s a memory aid. Studies more recently have found the essential oil beneficial for improving memory. (6)  **Use care when purchasing essential oils, some are intended only for external use either on the skin when diluted in a small amount of milder oil such as almond oil for massage or topical pain relief, or as an aromatic for scent (example, put a few drops on a cotton ball that is attached to a fan or on the outlet of a humidifier to circulate the aroma through a room).

/Disclosure: This information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes./

  1.  Neuroscience, 6th Edition, Editors D. Purves, G.J. Augustine, D. Fitzpatrick, W.C. Hall, A.S. LaMantia, R.D. Mooney, ML. Platt, L.E. White, (Sinauer Associates, Oxford University Press, 2018, New York) (Barnes&Noble)
  2. Anna Mietelska-Porowska and Urszula Wojda, “T Lymphocytes and Inflammatory Mediators in the Interplay between Brain and Blood in Alzheimer’s Disease: Potential Pools of New Biomarkers,” Journal of Immunology Research, vol. 2017, Article ID 4626540, 17 pages, 2017. https://doi.org/10.1155/2017/4626540. https://www.hindawi.com/journals/jir/2017/4626540/
  3. edited by Karsten Sauer, Klaus Okkenhaug, Lipid Signaling in T Cell Development and Function, Frontiers Media SA, Nov 12, 2015 page 96
  4. A.-L.Klauke, I.Racz, B.Pradier, et al., The cannabinoid CB2 receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain. European Neuropsychopharmacology, Vol. 24, Issue 4, April 2014, Pages 608-620, https://www.sciencedirect.com/science/article/pii/S0924977X13003027
  5. Guimarães-Santos A, Santos DS, Santos IR, et al. Copaiba Oil-Resin Treatment Is Neuroprotective and Reduces Neutrophil Recruitment and Microglia Activation after Motor Cortex Excitotoxic Injury. Evidence-based Complementary and Alternative Medicine : eCAM. 2012;2012:918174. doi:10.1155/2012/918174. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3291111/
  6. Rachel Hosie, Surge in Rosemary Sales as Aromatic Herb Found to Boost Memory, May 19, 2017, independent.co.uk,  https://www.independent.co.uk/life-style/health-and-families/rosemary-sales-surge-herb-boost-memory-holland-barrett-a7745231.html
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Endocannabinoids, retrograde signaling, and learning.

The endocannabinoid system is involved in our ability to learn. Use of medical marijuana, in quantity, is known to reduce short term memory but it may also be helping the body form long term memories. However our natural endocannabinoid system wouldn’t primarily use the equivalent to the euphoria forming THC called anandamide. That is used to reduce nerve cell signaling. It is the non euphoria causing 2AG that is used within our brains to cause stronger nerve cell signals – practice more and the cells are more active in a certain order and that pathway is strengthened so next the cells will fire in that order more easily. (Endocannabinoids Performance through Retrograde Signaling).

More information about nerve signaling between brain cell synapses see Neuroscience, 6th Edition, pages 85-112, 169-189, and 571-593, (1), or summary information and short video explanations are available online for the previous edition: Synaptic Transmission, Synaptic Plasticity, Modification of Brain Circuits as a Result of Experience.

2AG is more similar to the non-euphoric cannabidiol (CBD) that is found in varying amounts in certain strains of medical marijuana. Both 2AG and CBD can activate both the Cannabinoid Receptor 1 and the Cannabinoid Receptor 2. It can have pain relieving and anxiety relieving benefits. (About the Endocannabinoid System)

Phospholipids and cannabinoids can be found in some legally and commonly available foods in addition to medical marijuana or the non-euphoric hemp kernel or hemp seed oil. See this post for more information about the nutrient group and other important nutrients, our bodies need all or most of them on a daily basis: Macro- and Micro-nutrients: Description and Food Sources.

Happy learning!

Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes.

  1. Reference: pp 169-189 “Synaptic Plasticity“, pp 571-593 “Experience-Dependent Plasticity in the Developing Brain“, pp 85-112, “Synaptic Transmission,” Neuroscience, 6th Edition, Editors D. Purves, G.J. Augustine, D. Fitzpatrick, W.C. Hall, A.S. LaMantia, R.D. Mooney, ML. Platt, L.E. White, (Sinauer Associates, Oxford University Press, 2018, New York) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4326841/ (Barnes&Noble)
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Pumpkin seeds – rich in zinc

Pumpkin seed kernels, raw, unsalted.

Pumpkin seed kernels are a good source of protein, essential fats, fiber, magnesium and other vitamins and minerals – and a great source of zinc which may be lacking in vegetarian or vegan diets. (Pumpkin Seeds – Benefits, nutrition and dietary tips.) (Other vegetarian sources of zinc.)

Work is progressing on the development of pumpkin seed flour for use as a food thickening substance for use in gravies or other sauces or stews. It would increase the protein, essential fatty acids, and other trace nutrient content of the resulting foods. (10) The use of pumpkin seeds in the diet may also prove to be protective against cancer and liver or kidney injury; and as a good source of antioxidants such as carotenoids (vitamin A family of nutrients) the use of pumpkin seeds in the diet may prove to be helpful against many conditions that involve excess oxidative stress. (4, 5, 6, 7, 8, 9) They are also a source of vitamin E (tocopherols), other phytosterols, and linoleic acid, a beneficial polyunsaturated fat. Pumpkin seed oil may be helpful in wound healing. (15) Pumpkin seeds are also a good source of phospholipids, (16), which are important for skin and membrane health.

Pumpkins are considered a drought tolerant plant for gardeners. Adequate water is needed to grow larger pumpkin and squash but the vines can survive limited water conditions. The seeds of other summer and winter squash are also nutrient rich and also may be more drought tolerant plants. (11, 12) Enough but not too much water at the right times are critical. Flooding or severe drought may both harm the garden yield. Mulching and drip irrigation or other watering methods applied at optimal stages of growth can be the water thrifty solution for best yield. (13, 14)

The seeds of butternut squash and some types of winter squash can be collected when trimming the squash and later toasted and eaten as a crunchy nutritious snack. India grocery markets may also have shelled squash seeds available for sale. They are slightly smaller and paler in color than the shelled pumpkin kernels in the image above.

Magnesium is one of the beneficial nutrients found in pumpkin seeds. It is a mineral that is needed in greater quantity during pregnancy and high blood pressure/hypertension can be a symptom of deficiency. Preeclampsia and the more severe eclampsia are complications characterized by high blood pressure and edema/swelling that can occur during pregnancy. Toxins collect in the excess fluid buildup and can risk a brain condition similar to hypertension encephalopathy in the more severe eclampsia. Seizure activity can result and death for the woman and expected infant are risks. Magnesium is used as an intravenous or intramuscular injection to reduce risk of the seizures during eclampsia. The mineral seems to help protect the blood brain barrier and reduce swelling in the brain during eclampsia. It’s role as an antioxidant to reduce free radical toxins may be involved but the exact mechanism for its benefit in eclampsia is not known. (2, page 139)

More information about preclampsia is available in a previous post, and more information about food sources and supplement sources of magnesium is also available in a previous post.

I have several writing projects in draft mode however they overlap – pumpkin seeds, a good source of magnesium and zinc, helped my previous prenatal clients who had a history of preeclampsia or high blood pressure in a previous pregnancy prevent a reocurrence of the problem. Why? Possibly because of the magnesium and other beneficial nutrients which could be protecting the blood brain barrier and might then also be helpful for preventing harm to oligodendrocytes and protect against demyelination – a risk that can occur with some types of encephalopathy (3).

Disclaimer: Opinions are my own and the information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes.

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4827242/Megan Ware, What are the health benefits of pumpkin seeds?, July 24, 2018, https://www.medicalnewstoday.com/articles/303864.php
  2. Mehmet Kaya, Bulent Ahishali, Chapter 9: The role of magnesium in edema and blood brain barrier disruption, page 139, in the book edited by Robert Vink, Mihai Nechifor, Magnesium in the Central Nervous System, University of Adelaide Press, 2011, adelaide.edu.au, free ebook pdf, https://www.adelaide.edu.au/press/titles/magnesium/magnesium-ebook.pdf  (2) 
  3. S. Love, Demyelinating Diseases, J Clin Pathol. 2006 Nov; 59(11): 1151–1159.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1860500/ (3)
  4. Scientific Studies collection on a commercial website by Pepo Farms, https://pepofarms.com.au/scientificstudies/ (4) which includes:
  5. M. Gossell-Williams, A. Davis, N. O’Connor, Inhibition of Testosterone-Induced Hyperplasia of the Prostate of Sprague-Dawley Rats by Pumpkin Seed Oil. Jun 2006, Vol. 9, No. 2 : 284 -286. 
  6. C. Z. Nkosi, A. R. Opoku, S. E. Terblanche, Antioxidative effects of pumpkin seed (Cucurbita pepo) protein isolate in CCl4-Induced liver injury in low-protein fed rats.
  7. Fahim AT Abd-el Fattah AA Agha AM Gad MZ
    Effect of pumpkin-seed oil on the level of free radical scavengers induced during adjuvant-arthritis in rats.
    In: Pharmacol Res (1995 Jan) 31(1):73-9 ISSN: 1043-6618
  8. Suphakarn VS Yarnnon C Ngunboonsri P, The effect of pumpkin seeds on oxalcrystalluria and urinary compositions of children in hyperendemic area. In: Am J Clin Nutr (1987 Jan) 45(1):115-21 ISSN: 0002-9165
  9. Matus Z Molnar P Szabo LG [Main carotenoids in pressed seeds (Cucurbitae semen) of oil pumpkin (Cucurbita pepo convar. pepo var. styriaca)] Olajtok (Cucurbita pepo convar. pepo var. styriaca) magjabol nyert presmaradek ossz-karotinoid-tartalmanak es karotinoid-osszetetelenek meghatarozasa. In: Acta Pharm Hung (1993 Sep) 63(5):247-56 ISSN: 0001-6659 (Published in Hungarian)  * The main carotenoids included per the Pepo Farms site: “The main components of the press-residue were lutein [3,3′-dihydroxy-alpha-carotene = (3R,3’R,6’R)-beta,epsilon-carotene-3,3′-diol; 52.5%] and beta- carotene (beta,epsilon-carotene; 10.1%). In addition to the above- mentioned pigments it was successful to reveal the presence of violaxanthin, luteoxanthin, auroxanthin epimers, lutein epoxide, flavoxanthin, chrysanthemaxanthin, 9(9′)-cis-lutein, 13(13′)-cis- lutein, 15-cis-lutein (central-cis)-lutein, alpha-cryptoxanthin, beta- cryptoxanthin and alpha-carotene (beta,epsilon-carotene) in small quantities.”  (4)
  10. Initial food technology research on the preparation and use of pumpkin seed flour for use in more nutritious gravy type sauces: Sharma G, Lakhawat S., Development, Quality Evaluation and Acceptability of Pumpkin Seed Flour Incorporated in Gravy. J Nutr Food Sci 7:613. doi: 10.4172/2155-9600.1000613      https://www.omicsonline.org/open-access/development-quality-evaluation-and-acceptability-of-pumpkin-seed-flourincorporated-in-gravy-2155-9600-1000613.php?aid=91345
  11. EllenB, Growing Drought Tolerant Vegetables, June 9, 2009, ThriftyFun.com, https://www.thriftyfun.com/Growing-Drought-Tolerant-Vegetables.html (11)
  12. Troy Scott, Drought Tolerant Vegetables for your Garden, July 9 2018, HeavenlyGreens.com http://www.heavenlygreens.com/blog/drought-tolerant-vegetables-for-your-garden (12)
  13. Joan Morris, Vegetable Gardening in a Drought, mercurynews.com, April 1, 2015,  https://www.mercurynews.com/2015/04/01/vegetable-gardening-in-a-drought/ (13)
  14. Extension Utah State University, Vegetable Irrigation: Squash and Pumpkin, Horticulture/Vegetables/2015-4,   https://digitalcommons.usu.edu/cgi/viewcontent.cgi?article=1744&context=extension_curall (14)
  15. Bardaa S, Ben Halima N, Aloui F, et al. Oil from pumpkin (Cucurbita pepo L.) seeds: evaluation of its functional properties on wound healing in rats. Lipids in Health and Disease. 2016;15:73. doi:10.1186/s12944-016-0237-0. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4827242/ (15)
  16. Zh.Y. Petkova, G.A. Antova, Changes in the composition of pumpkin seeds (Cucurbita moschata) during development and maturation. Grassas Y Aceites, 66 (1), Jan–March 2015, e058. http://grasasyaceites.revistas.csic.es/index.php/grasasyaceites/article/viewFile/1523/1658 (16)
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Pomegranate extract update – has similar mechanism to NSAIDs

Update, 8/18/2018, for anyone interested in phytonutrient biochemistry or herbal medicinal foods: Wintergreen and wintergreen berries are also a natural source of a painkiller in the NSAID group – aspirin. The plant can also be a source of phytonutrients that activate TRPA1 channels which can affect fluid balance and other symptoms. Winterberries are in the cranberry family and have a minty flavor. They are in season currently and eating more of them seems to increase my symptoms of inflammation and swelling more than the pomegranate extract or pomegranate seeds. Having too many variables in an experiment makes it unclear which factor might be a cause or if both may be involved. Experimental method tries to narrow variables to one factor at a time. Stopping both pomegranate products and wintergreen berries helped but other symptoms got worse, adding pomegranate back to my diet didn’t make the inflammation/swelling symptoms much different but more recently adding the wintergreen berries back into my diet did make the symptoms of lower leg inflammation/swelling and pain worse.

An excerpt from one of my other websites, G3.6.1.5: People with overactive TRPA1 channels may be sensitive to:

  • “(Winter-green),” (G3.67); Wintergreen is a natural flavoring herb in the mint family. It is typically used as an essential oil as a flavoring in many foods and other types of products. It has medicinal benefits related to it containing the chemical that acts as the pain killing ingredient of aspirin.(G3.73) (effectivecare.info, G3)

My ongoing self study of pomegranate extract for my mental and physical health symptoms has led me to use a fairly small dose, daily though is still best. Missing even a few days seems to increase mood and anxiety problems but using a very large serving has some side effects. Lower leg and foot swelling is associated with some physical health problems but it can also be a side effect of NSAIDs pain killers such as ibuprofen. (7) Pomegranate extract has been shown to reduce pain and inflammation by the same mechanism as NSAIDS – inhibition of cyclooxygenase enzymes (COX1 and COX2,  with more inhibition of COX2 than COX1). It also may have an anti-inflammatory effect by reducing inflammatory cytokines that signal increase in production of Nitric Oxide (NO) and Prostaglandin E2 (PGE2). (1) Prostaglandin E2 is made from arachidonic acid and is involved in the inflammation associated with rheumatoid arthritis and osteoarthritis. (2) Nitric oxide can be beneficial but it can also transform into reactive oxidative species and add to the antioxidant burden of metabolism. (5) (9) Other studies including an animal study on obesity found pomegranate extract reduced inflammatory biomarkers and increased nitric oxide, which might make it helpful for Metabolic Syndrome. (6)

Pomegranate extract was found helpful in a dose related level against mammary tumerogenesis in an animal study, (0.2-5 gram/Kg body weight was used). Reducing COX2, heat shock protein 90 (HSP90), nuclear factor-κB (NF-κB) pathways, and increasing Nrf2 pathways were found to be part of the mechanism for benefit. (4) That amount could be quite a lot. Equivalent amounts for a 75 kilogram/165 pound human would be 15-375 grams per day or roughly one tablespoon (15 grams approximately)-13.4 ounces/27 tablespoons per day. (Mammary tumerogenesis means the initial onset of breast cancer tumors.)

It helps to prop my feet when sitting or even lay down with my feet above my heart. I’m getting better at typing while laying down. Better mood and having feeling in my fingertips is worth it. There may some other health or diet issues affecting the leg swelling. Heart or kidney or vein problems can be a cause. (7) I do have vein problems and may have heart issues, which can be an increased risk with hyperthyroidism. Cutting back on salt, daily exercise, and elevating the lower legs above the level of the heart several times per day for a half an hour is recommended, wearing compression socks is also a recommendation and that makes me feel old. (7) Maybe 52 is old.

Lymphedema – lower leg swelling due to reduced drainage from vein problems may be the best fit for my personal history, and lack of stretching exercises lately may be part of the reason the problem has become worse lately. Physical therapists explain the problem and provide exercise, massage and compression wrapping suggestions in a free video available online. (8) The exercise routine is similar to what I generally do when I do stretching exercises – so that seems like a good habit to return to my daily schedule.

Lower leg swelling has been a symptom for me at various stages of previous ill health and with some other medications I’ve used in the past, but currently it does seem worse when I use larger amounts of the pomegranate extract. One teaspoon a day helps with the stable mood and I haven’t had numbness in my fingertips in months with the ongoing daily use of pomegranate extract in larger amounts, 2-3 tablespoons was typical. I stopped use of it altogether when the leg swelling became a problem to see if the swelling would get better but the mood symptoms got worse again after having seemed fine for quite a while – quite a while while using pomegranate extract daily and the leg swelling didn’t get a lot better. Being not well is unpleasant and some side effects can be better than being unwell.

Breast cancer treatments currently may cause hair loss, severe vomiting and may leave the patient with cognitive decline afterwards, and pomegranate extract doesn’t cause any of those symptoms in the amounts that I’ve tried. It is a diuretic and causes increased urination which I cope with by drinking extra fluids and using the pomegranate extract early in the day rather than at night. I may be preventing breast cancer tumor development (4) while drinking extra fluid and urinating in increased amounts – getting old isn’t great but the alternative isn’t better. I may go buy my first pair of compression socks and feel young at heart if not in body.

Industry math – one pomegranate peel makes about six cups of extract by my method which would provide 288 teaspoons/96 tablespoons. It may have improved somewhat but the worsening in mood was more obvious.  From an industry perspective getting 288 servings of a mood and nerve treatment from one pomegranate peel seems like it could be profitable. Dehydrating one teaspoon into a capsule serving also seems possible. Side effects with psychiatric medications are unfortunately common and can include swelling/edema of the lower legs or more severe edema including facial edema.

/Disclaimer: This information is provided for educational purposes within the guidelines of fair use. While I am a Registered Dietitian this information is not intended to provide individual health guidance. Please see a health professional for individual health care purposes./  

  1. Shukla, Meenakshi & Gupta, Kalpana & Rasheed, Zafar & A Khan, Khursheed & Haqqi, Tariq. (2008). Bioavailable constituents/metabolites of pomegranate (Punica granatum L) preferentially inhibit COX-II activity ex vivo and IL-1beta-induced PGE2 production in human chondrocytes in vitro. Journal of inflammation (London, England). 5. 9. 10.1186/1476-9255-5-9.
  2. Jean Y. Park, Michael H. Pillinger, Steven B. Abramson, Prostaglandin E2 synthesis and secretion: The role of PGE2 synthases, Clinical Immunology, Vol 119, Iss 3, 2006, pp 229-240, ISSN 1521-6616, https://doi.org/10.1016/j.clim.2006.01.016.
    https://www.sciencedirect.com/science/article/pii/S1521661606000453 (2)
  3. Arachidonic Acid – an overview, ScienceDirect, https://www.sciencedirect.com/topics/neuroscience/arachidonic-acid (3)
  4. Mandal A, Bhatia D, Bishayee A. Anti-Inflammatory Mechanism Involved in Pomegranate-Mediated Prevention of Breast Cancer: the Role of NF-κB and Nrf2 Signaling Pathways. Nutrients. 2017;9(5):436. doi:10.3390/nu9050436. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5452166/ (4) From Abstract: “Mammary tumor samples were harvested from our previous chemopreventive study in which PE (0.2–5.0 g/kg) was found to reduce mammary tumorigenesis in a dose-dependent manner. The expressions of COX-2, HSP90, NF-κB, inhibitory κBα (IκBα) and Nrf2 were detected by immunohistochemical techniques. PE decreased the expression of COX-2 and HSP90, prevented the degradation of IκBα, hindered the translocation of NF-κB from cytosol to nucleus and increased the expression and nuclear translocation of Nrf2 during DMBA-induced mammary tumorigenesis.” From Introduction:”During the last decade, pomegranate fruit has been gaining a widespread reputation as a dietary supplement as well as a functional food due to emerging scientific evidence on potential health benefits, including prevention and/or treatment of cardiovascular ailments, neurological disorders, oncologic diseases, dental problems, inflammation, ulcer, arthritis, microbial infection, obesity, diabetes, acquired immune deficiency syndrome and erectile dysfunction [,,,,,]. Pomegranate fruit contains phytochemicals, including flavonoids (e.g., anthocyanins and catechins), flavonols (e.g., kaempferol and quercetin), flavones (e.g., apigenin and luteolin), conjugated fatty acids, hydrolyzable tannins and related compounds which are thought to be responsible for various biological and pharmacological activities [,,,,,]. Based on preclinical and clinical studies conducted by various laboratories worldwide, pomegranate-derived substances, such as juice, extracts and phytoconstituents exhibited cancer preventive and therapeutic effects against colon, liver, lung, prostate and skin cancer [,,,,]. Various extracts, fractions and phytochemicals from pomegranate fruit, peel, seed and flower demonstrated cytotoxic, antiproliferative, proapoptotic, antiangiogenic, anti-invasive, and antimetastatic properties against estrogen receptor-positive and ‑negative breast cancer cells [,,,,,,,,,,,,,]” (4)
  5. Matsubara K, Higaki T, Matsubara Y, Nawa A. Nitric Oxide and Reactive Oxygen Species in the Pathogenesis of Preeclampsia. Miller FJ, ed. International Journal of Molecular Sciences. 2015;16(3):4600-4614. doi:10.3390/ijms16034600. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394437/ (5)
  6. Filomena de Nigris, Maria Luisa Balestrieri, Sharon Williams-Ignarro, Francesco P. D’Armiento, Carmela Fiorito, Louis J. Ignarro, Claudio Napoli,
    The influence of pomegranate fruit extract in comparison to regular pomegranate juice and seed oil on nitric oxide and arterial function in obese Zucker rats, Nitric Oxide, Volume 17, Issue 1, 2007, pp 50-54, ISSN 1089-8603, https://doi.org/10.1016/j.niox.2007.04.005.
    (http://www.sciencedirect.com/science/article/pii/S1089860307000432) (6)
  7. Swollen Legs: Causes and Treatments, WebMD, https://www.webmd.com/dvt/why-legs-puffy#1 (7)

  8. Bob Schrupp, Brad Heineck, 10 Exercises for Leg Lymphedema (Swelling or Edema of the Lower Extremities). physicaltherapyvideo, https://www.youtube.com/watch?v=3t8Kp99e50k&feature=youtu.be (8)

  9. Aouache R, Biquard L, Vaiman D, Miralles F. Oxidative Stress in Preeclampsia and Placental Diseases. International Journal of Molecular Sciences. 2018;19(5):1496. doi:10.3390/ijms19051496.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983711/ (9)