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: Prostaglandins: Prostaglandins were first discovered in the 1930's by a Swedish scientist and are contained in almost every cell in the body with over 36 Prostaglandins identified to date. Prostaglandins are hormone-like regulators and messengers. Each cell needs to maintain the materials needed to make each prostaglandin as a second messenger in the intra-cellular communication system. Prostaglandins are fatty acids of a diverse group known as eicosanoids, all of which contain 20-carbon atoms. This group includes the fish oils EPA and DHA, which can be made in small quantities in the body from plant-source Omega-3 fatty acids. Prostaglandins' main structure is a 5-carbon ring, which may be the carrier of an M-state mineral. Prostaglandins and other eicosanoids are referred to as local or intra-cellular hormones. Prostaglandins alter the activity of the cells in which they are synthesized, and also affect nearby cells. Prostaglandins regulate important functions like blood flow, inflammation, fever, and transport across cell membranes.
Most anti-inflammatory drug therapies try to block pro-inflammatory physiological pathways. Prednisone, which can cause glaucoma, is used in high doses to block the liberation of arachidonic acid, the precursor of the pro-inflammatory prostaglandins. This can often be more safely acheived with supplementation of the safer steroids DHEA (or 7-Keto) or its precursor pregnenolone, as well as immune-modulating plant-analog phytosterols. Drugs that inhibit prostaglandin synthesis by blocking enzymes that convert arachidonic acid to prostaglandins include aspirin, NSAIDs and acetaminophen. In contrast, EPA provides a substrate for the anti-aggregatory, anti-inflammatory and vasodilating prostaglandin -3 series. Other effective alternatives for relief of pain and inflammation include a highly absorbable water soluble quercetin (Pain Guard forte'). Studies on omega-3 fatty acid metabolism show:
The anterior uvea synthesizes PGE3 and PGD3 in human, monkey, and rabbit and may play a role in lowering intraocular pressure. Cyclooxygenase
and lipoxygenase pathways in anterior uvea and conjunctiva. Lewith, G., Kenyon, J., Lewis, P. Complementary Medicine: An Integrated Approach 1996, pp. 108-9. New York: Oxford University Press. Plant sources such as flax seed, hemp seed, chia seed, and walnut provide the precursor Omega-3 fatty acid: Alpha-linolenic acid that the human body converts, though inefficiently, to the longer chain EPA and DHA fatty acids needed for anti-inflammatory prostaglandin formation, neuro-visual development and performance (e.g. DHA for visual acuity) and other cellular needs. Soy and rape seed (Canola from Canadian Oil Company) also contain ALA but are not recommended as sources by Remission Foundation. DHA is the #1 fatty acid in the central nervous system. Fish oils contain the Omega-3 fatty acids in their physiologically active EPA and DHA forms for health benefits as immediate PG3 prostaglandin precursors, saving the time and energy of the inefficient enzymatic steps necessary to process Alpha-linolenic acid into the biologically active forms. In many health situations, these enzyme pathways limit the amount of eicosanoids the body can produce to much less than the levels requisite for optimal health and performance. Nutrients required for the anti-inflammatory EFA pathways to function include:
Enzymes: delta-6-desaturase, delta-5-desaturase, elongase, cyclo-oxygenase and oxygenase convert alpha-linolenic acid into the beneficial, anti-inflammatory PGE3 series prostaglandins (see chart). Omega-3 Pathway:
Omega-6 Pathway:
Several investigators have demonstrated that PGE 2 and PGF 2 alpha in low doses, lower intraocular pressure in all species studied, including human, but while PGF 2 promotes inflammation that could aggravate glaucoma, PGE 2 has anti-inflammatory effects. PGF 2 derivatives are used to medically lower IOP by affecting the FP receptor. These include latanoprost (Xalatan), travoprost (Travatan), bimatoprost (Lumigan) and unoprostone isopropyl (Rescula). Forskolin (Colforsin) works on the complementary IOP-lowering but anti-inflammatory PGE 2 pathway via the c-AMP-mediated EP 2, EP 3 and EP 4 receptors. Ginger (Zingiber officinalis) inhibits prostaglandin and leukotriene biosynthesis while increasing cyclic AMP. Gingerols and diarylhepatanoids have been identified as active anti-prostaglandin compounds. Another constituent, (6)-shogaol, may act as an analgesic by inhibiting the release of the immunoreactive substance P. Ginger root is known in the Ayurvedic tradition as vishwabhesaj, meaning universal medicine. Bupleurum root (Bupleurum chinense), a native of China, is used in the treatment of chronic hepatitis, enlarged liver or spleen, chemical liver damage, liver stasis or liver congestion, depression, and irregular menstruation. Bupleurum root contains saikosaponins that help maintain liver health and support immune function. Bupleurum reduces inflammation by inhibiting prostaglandin production. Bupleurum root also increases cyclic AMP. Prostaglandins are named after the prostate gland. Prostaglandins such as PGE2 and leukotrienes (leukotriene B4, LTB4) are known inflammatory mediators produced by inflammatory cells which infiltrate the prostate gland in BPH Robinnette, C.L. 1988 Sex-Hormone-Induced Inflammation and Fibromuscular Proliferation in the Rat Lateral Prostate. Prostate, 12 : 271-286. Theyer, G., Kramer, G., and Assmann, I. 1992 Phenotypic Characterization of Infiltrating Leukocytes in Benign Prostatic Hyperplasia. Lab Invest, 66 : 96-107. Other researchers report that Saw Palmetto extracts inhibit the enzymes that make these substances and that constituents of Saw Palmetto extracts that concentrate in the prostate also inhibit these enzymes. Chaudry, A.A., Wahle, K.W., McClinton, S., and Moffat, L.E. 1994 Arachidonic Acid Metabolism in Benign and Malignant Prostate Tissue in vitro: Effects of Fatty Acids and Cyclooxygenase Inhibitors. Int. J. Cancer, 57 : 176-180. Paubert-Braquet, M., Mencia Huerta, J-M., Cousse, H., and Braquet, P. 1997 Effect of the Lipidic Lipidosterolic Extract of Serenoa repens (Permixon) on the Ionophore A23187-Stimulated Production of Leukotriene B4 (LTB4) from Human Polymorphonuclear Neutrophils. Prostaglandins Leukotrienes Essen. Fatty Acids ,57 : 299-304. Most salicylates, e.g. aspirin, inhibit cyclooxygenase, the first enzyme involved in the steps between arachidonic acid and prostaglandins. Platelets cannot regenerate cyclooxygenase, so that aspirin can inhibit platelet cyclooxygenase for the life of the platelet (8-11 days). Unlike aspirin, salicylic acid, from botanicals like White Willow (Salix alba) and Black Cohosh (Cimicifuga racemosa), has no acetylating activity. It does have capacity to reduce the synthesis of prostaglandins through another pathway, but almost no activity against cycloxygenase. Hamberg, M. Inhibition of prostaglandin synthesis in man. Biochem. Biophys. Res. Comm. , 1972,49, 720-726. PGE-2 is high in every animal tumor, in every cancer cell system, and in every human biopsy of tumor in which prostaglandin E-2 was assayed. PGE-2 is linked to tumor promotion. PGE-2 is also the major pain-transmitting neurochemical in the body. Aspirin inhibits the production of PGE-2 by blocking access to the active site of the enzyme, prostaglandin H2 synthase, and has some anti-carcinogenic effects in some studies, but the damage it does limits its usefulness. New York Times, August 1, 1995 Fortunately some safe botanicals also inhibit PGE-2:
HerbalGram. 1991;25:24-27; American Botanical Council Prostaglandins in Plants:
Plant enzymes responsible for synthesis of Prostaglandins:
Prostaglandin precursors in Plants
Unsaturated Polyhydroxy Fatty acids with PG-like activity:
Prostaglandin-like Compounds:
Abstract Prostaglandins (PG's) have been detected in many different plants and certain microorganisms. A few prostaglandin-like compounds have also been shown to occur in plants such as flax, Chromolaena morii, and aquatic sedge; and direct precursors (arachidonic acid, di-homo-(-linolenic acid and eicosapentaenoic acid) have been detected in a variety of plants and microorganisms, including certain red algae, brown algae, green algae and saltwater diatoms. Furthermore, arachidonic acid has been found in mosses and a liverwort. It has been also reported that arachidonic acid occurs in certain angiosperms namely poplar (Populus balsamifera), wheat germ oil, Aloe vera and Allium sativum (garlic). In our studies on the possible physiological effects of prostaglandins we found that a prostaglandin possibly has an effect on the flowering of the short-day plant Pharbitis nil. It has hastened flower formation by 28 days as compared with controls under inductive conditions (short days), and certain inhibitors of PG-biosynthesis inhibited flowering to a greater or lesser extent. In other physiological studies of prostaglandins it was found that they have an effect on such aspects as GA3 controlled responses in barley endosperm, inhibition of crown gall tumor formation on potato discs and certain electron flow reactions in isolated chloroplasts. In corn-leaf segments it has an effect on photosynthesis, nucleic acid metabolism and protein synthesis. The effect on four plant bioassay systems was negligible. It has also been reported that PG's play a role in the regulation of cell membrane permeability. Groenewald van der Westhuizen, E. G. and A. J.. Prostaglandins and Related Substances in Plants, in The Botanical Review 63(3) 199-220. Additional-References: Lindsey, K. et al. Screening of plants used by Southern African traditional healers in the treatment of dysmenorrhoea for prostaglandin-synthesis inhibitors and uterine relaxing activity. Journal of Ethnopharmacology 1999; 61(1): 9-14. Dunstan, C. A., Y. Noreen, G. Serrano, P. A. Cox, P. Perera, L. Bohlins. 1997. Evaluation of some Samoan and Peruvian medicinal plants by prostaglandin biosynthesis and rat ear oedema assays. Journal of Ethnopharmacology 57: 35-56. |
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