ANTI-INFLAMMATORY DRUG RESEARCH

ANTI-INFLAMMATORY DRUG RESEARCH – A Pointer To The Better Role Of Phytochemicals From Fruits And Berries
(A Short Note)
Beldeu Singh

Billions of dollars have been spent on research and production of anti-inflammatory drugs but they are all toxic. These drugs were developed with the intention to find chemicals that will suppress the Cox-2 enzymes that are associated with the inflammatory process and promote inflammations.
Cancer cells have high cell membrane potential, having lost electrons from molecules in the cell membrane to free radicals and oxidants like the peroxynitrite (ONOO-) or heavy metals and accordingly are highly inflamed, more than cells at lesions in psoriasis and arthritis.
In the New Straits Times, today at p26 the headline reads - "small daily doses of aspirin cuts many cancer risks" - it is about research on aspirin, a drug that can destroy the cementing material that binds and holds cells together and if this is destroyed in the tissue of the intestines, it can cause intestinal bleeding. Furthermore, aspirin intereferes with and blocks the blood coagulating factors which can be dangerous, especially in the older population and in accident victims.
This short newsreport says that researchers at Oxford say that low daily doses of aspirin cuts cancer the rate of cancer deaths and suggested (quite correctly) “that it does so by blocking the enzyme Cox-2 which promotes inflammation” as cancer cells have high CMB (ie they are highly inflamed) and if aspirin can suppress the inflammatory process it prevents the initiation of the formation of cancer cells. There are several epidemiological studies that clearly show that in populations that consume traditional diets and diets with relatively high fruit and vegetable intake tend to have lower incidence of cancers, which is primarily due to the role of natural antioxidants in preventing inflammations and organic minerals (iron, copper, mnaganese, zinc) that work as catalysts with the SOD-Catalase enzyme system to effecftively and efficienctly convert the superoxide into water and oxygen and thereby prevent excess hydrogen peroxide and oxygen free radical in the body and support optimal cell function that tends to decline with age and with lowering of blood antioxidant levels with consequent lower output of citric acid from the citric acid cycle and these appear to be factors in which micro-parasites and protozoa become active. In the active stage they consume more vitamin B12, competing with the host, causing vitamin B12 depletion or deficiencies and secrete more allergens that promote the inflammatory process.
Both aspirin and sulindac have been reported to display profound antiproliferative effects on tumor cell lines, alter the cell cycle distribution, and induce apoptosis (Shiff S J, Qiao L, Tsai L L, Rigas B. J Clin Invest. 1995;96:491–503: Ricchi P, Pignata S, Di Popolo A, Memoli A, Apicella A, Zarrilli R, Acquaviva A M. Int J Cancer. 1997;73:880–884: Sheng H, Shao J, Kirkland S C, Isakson P, Coffey R J, Morrow J, Beauchamp R D, DuBois R N. J Clin Invest. 1997;99:2254–2259).
However, what they did not also say is that like other anti-inflammatory drugs, aspirin also suppresses the Cox-1 enzyme which is very important for health. COX-1 is ubiquitously expressed and appears to be a housekeeping gene, whereas COX-2 expression is inducible by growth factors and oncogenes (Prescott S M, White R L. Cell. 1996;87:783–786) and fruits like strawberry is known to suppress Cox-2 (as effectively as drugs) without suppressing Cox-1. Suppression of Cox-1 can lead to serious health problems, including thinning of the stomach lining. Cayenne contains the potent chemical capsaicin, which acts on special nerves found in the stomach lining. In two rat studies, researchers reported that stimulation of these nerves by capsaicin might protect against the damage aspirin can cause to the stomach (Abdel Salam OME, Mószik G, Szolcsányi J. Studies on the effect of intragastric capsaicin on gastric ulcer and on the prostacyclin-induced cytoprotection in rats. Pharmacol Res 1995;32:209-15: Holzer P, Pabst MA, Lippe IT. Intragastric capsaicin protects against aspirin-induced lesion formation and bleeding in the rat gastric mucosa. Gastroenterology 1989;96:1425-33). The flavonoids found in the extract of licorice known as DGL (deglycyrrhizinated licorice) are helpful for avoiding the irritating actions aspirin has on the stomach and intestines. One study found that 350 mg of chewable DGL taken together with each dose of aspirin reduced gastrointestinal bleeding caused by the aspirin (Rees WDW, Rhodes J, Wright JE, et al. Effect of deglycyrrhizinated liquorice on gastric mucosal damage by aspirin. Scand J Gastroenterol 1979;14:605-7).
Some fifty cousins of aspirin exist, most of which appeared after World War II. Together they constitute a family known as non-steroidal anti-inflammatory drugs (NSAIDs). They can interfere with physiology including the formation of prostaglandins.
Many kinds of prostaglandin exist in the body to serve a plethora of physiological functions, some of which are irritable, others beneficial. Prostaglandins are among the chemicals secreted by the body’s immune system when it fights off bacteria and other invaders in injuries. Located around wounds , these chemicals cause pain and inflammation. Aspirin inhibits the production of prostaglandins (JR. Vane, 1971, Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs, Nature, New Biology: 231: 230-235). This happens because cyclooxygenase, a Cox enzyme which participates in the production of prostaglandins and thromboxanes, is irreversibly inhibited when aspirin acetylates it (Roth GJ and Majerus PW, The mechanism of the effect of aspirin on human platelets, I: acetylation of a particulate fraction protein, J Clin Invest., 1975;56:624–632: Lecomte M et al. Acetylation of human endoperoxide synthase-2 by aspirin, J Biol Chem,. 1994;269:13207–13215). Aspirin irresversibly binds cyclooxygenase (Cox-1 and Cox-2). Thereby blocking arachidonic acid from from porstaglandins (Carol D Morris, Principles of Orthopaedic Pharmacology, 7th ed, © 2008, Lippincott Williams & Wilkins).
Aspirin inhibits both Cox-1 and Cox-2 enzymes, aspirin more slectively inhibits COX-1 activity (found predominantly in platelets) than COX-2 activity (showed in tissues follwoing an inflammatory stimuli), its ability to prevent platelet aggregation is seen at relatively low doses, compared with it's anti-inflammatory effects, which require higher doses. Low-dose long-term aspirin irreversibly blocks formation of thromboxane A2 in platelets, producing an inhibitory affect on platelet aggregation, and this blood thinning property makes it useful for reducing the incidence of heart attacks (Aspirin, Pharpedia, 28th August 2005). So, how brilliant is their research?
Aspirin taken by patients while having a heart attack significantly reduces the chance of death. For people with various risk factors for heart diseases such as diabetes, obesity, or high blood pressure, aspirin lowers the probability of a first heart attack. For healthy people without cardiovascular risks, results on the effects of aspirin are inconclusive (G. Weissman, 1997, Aspirin, Scientific American, 264(1): 84-90 (1991). D. B. Jack. A hundred years of aspirin. The Lancet, 350: 437-439).
Salicylic acid, from the bark of the willow tree, is a monohydroxybenzoic acid, is a phenolic acid and a beta hydroxy acid. This colorless crystalline organic acid is widely used in organic synthesis and functions as a plant hormone. It is derived from the metabolism of salicin. It is a compound that is chemically similar to but not identical to the active component of aspirin (acetylsalicylic acid), it is probably best known for its use in anti-acne treatments and may have anti-protozoal properties. Salicylic acid is known for its ability to ease aches and pains and reduce fevers. These medicinal properties, particularly fever relief, have been known since ancient times and it was used as an anti-inflammatory drug (Philip A. Mackowiak, 2000, "Brief History of Antipyretic Therapy". Clinical Infectious Diseases, 31: 154–156). Salicylic acid (SA) is a phenolic phytohormone and is found in plants with roles in plant growth and development, photosynthesis, transpiration, ion uptake and transport. SA also induces specific changes in leaf anatomy and chloroplast structure. SA is involved in endogenous signaling, mediating in plant defense against pathogens (S. Hayat, A. Ahmad (2007). Salicylic acid - A Plant Hormone. Springer. ISBN 1402051832).
Sodium salicylate paradoxically inhibited prostaglandin synthesis when added to intact cells (Mitchell JA, et al. Selectivity of nonsteroidal anti-inflammatory drugs as inhibitors of constitutive and inducible cyclooxygenase. Proc Natl Acad Sci U S A. 1994;90:11693–11697). Furthermore, healthy subjects taking sodium salicylate excreted a significantly lower amount of prostaglandin metabolites in urine than those not taking sodium salicylate, and their levels of inhibition were comparable to those of patients taking aspirin and indomethacin (Hamberg M. Inhibition of prostaglandin synthesis in man. Biochem Biophys Res Commun. 1972;49:720–726). Aspirin also reduces human seminal prostaglandin levels (Collies JG, Flowers RJ. Effect of aspirin on human seminal prostaglandins. Lancet. 1971;i:852–853).
Aspirin, which suppresses cyclooxygenase, has the potential to interfere with implantation. Aspirin has potential risks. Aspirin inhibits platelet function and can contribute to maternal and fetal bleeding. Aspirin crosses the placenta. Although aspirin has not been associated with other congenital anomalies, it has been associated with an increased risk of vascular disruptions, particularly gastroschisis and possibly premature closure of the ductus arteriosus. Nonetheless, large trials demonstrate low-dose aspirin's relative safety (James et al, Aspirin and Reproductive Outcomes, Obstetrical & Gynecological Survey: January 2008 - Volume 63 - Issue 1 - pp 49-57).
Immunosuppressive and anti-inflammatory agents significantly inhibited T cell proliferation, especially in viral diseases such as influenza. Aspirin has an inhibitory effect because it is an effective suppressor of adhesion molecule expression and that is the molecular basis for the notion that part of the anti-atherogenic effect of aspirin may be due to the prevention of the adhesion of sensitized T cells to stressed cells and prevents cellular interaction between them for proper immune action (see: Amberger A et al, Suppressive effects of anti-inflammatory agents on human endothelial cell activation and induction of heat shock proteins, Mol Med. 1999 Feb;5(2):117-28) and there are a few other problems of aspirin.
Aspirin as well as other non-steroidal anti-inflammatory agents, can triple the rate of excretion of Vitamin C, B1 (thiamin), folic acid, and iron, in addition to decreasing the absorption of glucose, amino acids, folate, Vitamin K, thiamin, and potassium (Substances that destroy nutrients, www.innvista.com, december, 2005).
Aspirin consumption has been associated with increased loss of vitamin C in urine and has been linked to depletion of vitamin C (Coffey G, Wilson CWM. Ascorbic acid deficiency and aspirin-induced haematemesis, BMJ 1975;I:208). In a study of people hospitalized with heart disease, those who had been taking aspirin were nearly twice as likely as nonusers to have a low or marginally low blood level of vitamin B12 (Van Oijen MGH, Laheij RJF, Peters WHM, et al. Association of aspirin use with vitamin B12 deficiency (results of the BACH study), Am J Cardiol 2004;94:975-7). Intake of 3 grams of aspirin per day has been shown to decrease blood levels of zinc (Ambanelli U, Ferraccioli GF, Serventi G, Vaona GL. Changes in serum and urinary zinc induced by ASA and indomethacin, Scand J Rheumatol 1982;11:63-4).
Zinc plays a key role in the body's physiology as it is involved in the activities of many enzymes (Dréno B and Blouin E, Acne, pregnant women and zinc salts: a literature review, Ann Dermatol Venereol. 2008 Jan;135(1):27-33). Organic zinc is a very important nutrient for the immune system. Serum zinc was significantly lower in the chronic fatigue syndrome (CFS) patients than in the normal controls. This study shows that CFS is accompanied by a low serum zinc status and that the latter is related to signs of inflammation and defects in early T cell activation pathways. There was a trend toward a significant negative correlation between serum zinc and the severity of CFS (Maes M. et al, Lower serum zinc in Chronic Fatigue Syndrome (CFS): relationships to immune dysfunctions and relevance for the oxidative stress status in CFS, J Affect Disord. 2006 Feb;90(2-3):141-7). Zinc is also a cofactor for thymulin, a thymic hormone essential for T-cell maturation (Mocchegiani E, Santarelli L, Muzzioli M, Fabris N. Reversibility of the thymic involution and of age-related peripheral immune dysfunctions by zinc supplementation in old mice. Int J Immunopharmacol. 1995;17(9):703–718). Naturally Zinc deficiency is associated with the rapid progression of AIDs (Jones CY, Tang AM, Forrester JE, et al. Micronutrient levels and HIV disease status in HIV-infected patients on highly active antiretroviral therapy in the Nutrition for Healthy Living cohort. J Acquir Immune Defic Syndr. 2006;43(4):475–482).
Since zinc is an essential micronutrient for human metabolism that catalyzes more than 100 enzymes, facilitates protein folding, and helps regulate gene expression, “zinc deficiency is associated with impaired wound healing” (Institute of Medicine (U.S.). DRI: Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press; 2001).
Formulations made from strawberries and berries will also contain natural vitamins and natural antioxidants that support and promote healthy biochemistry and are more effective in the prevention of inflammations and can play a better role in health. There should be more research in this direction, naturally, for food is better medicine than drugs. I expect India to take the lead in such research including institutions like the Tuft University in the US with China showing a keen interest. Inflammations means pain and sickness but for those with good natural answers, it is a huge market.
Ample research indicates that age-related neuronal-behavioral decrements are the result of oxidative stress that may be ameliorated by antioxidants. Our previous study had shown that rats given dietary supplements of fruit and vegetable extracts with high antioxidant activity for 8 months beginning at 6 months of age retarded age-related declines in neuronal and cognitive function. The present study showed that such supplements (strawberry, spinach, or blueberry at 14.8, 9.1, or 18.6 gm of dried aqueous extract per kilogram of diet, respectively) fed for 8 weeks to 19-month-old Fischer 344 rats were also effective in reversing age-related deficits in several neuronal and behavioral parameters including: oxotremorine enhancement of K+-evoked release of dopamine from striatal slices, carbachol-stimulated GTPase activity, striatal Ca45 buffering in striatal synaptosomes, motor behavioral performance on the rod walking and accelerod tasks, and Morris water maze performance. These findings suggest that, in addition to their known beneficial effects on cancer and heart disease, phytochemicals present in antioxidant-rich foods may be beneficial in reversing the course of neuronal and behavioral aging (James A. et al, Reversals of Age-Related Declines in Neuronal Signal Transduction, Cognitive, and Motor Behavioral Deficits with Blueberry, Spinach, or Strawberry Dietary Supplementation, The Journal of Neuroscience, September 15, 1999, 19(18):8114-8121).
The inhibitory effects of strawberry extracts on the proliferation and transformation of human and mouse cancer cells were also evaluated. Strawberries had high activities of glutathione peroxidase, superoxide dismutase, guaiacol peroxidase, ascorbate peroxidase, and glutathione reductase. Strawberry extracts inhibited the proliferation of human lung epithelial cancer cell line A549 and decreased TPA-induced neoplastic transformation of JB6 P+ mouse epidermal cells. Pretreatment of JB6 P+ mouse epidermal cells with strawberry extract resulted in the inhibition of both UVB- and TPA-induced AP-1 and NF-κB transactivation. The ability of strawberries to block UVB- and TPA-induced AP-1 and NF-κB activation may be due to their antioxidant properties and their ability to reduce oxidative stress. The oxidative events that regulate AP-1 and NF-κB transactivation can be important molecular targets for cancer prevention. The strawberries may be highly effective as a chemopreventive agent that acts by targeting the down-regulation of AP-1 and NF-κB activities, blocking MAPK signaling, and suppressing cancer cell proliferation and transformation (Shiow Y. Wang et al, Inhibitory Effect on Activator Protein-1, Nuclear Factor-KappaB, and Cell Transformation by Extracts of Strawberries (Fragaria × ananassa Duch), J. Agric. Food Chem., 2005, 53 (10), pp 4187–4193).
Strawberry (Fragaria x ananassa Duch.) fruits contain phenolic compounds that have antioxidant, anticancer, antiatherosclerotic and anti-neurodegenerative properties (Navindra P. Seeram et al, Identification of phenolic compounds in strawberries by liquid chromatography electrospray ionization mass spectroscopy, Food Chemistry, Volume 97, Issue 1, July 2006, Pages 1-11).
The effects of elevated CO2 concentrations on the antioxidant capacity and flavonoid content in strawberry fruit (Fragaria x ananassa Duch.) were studied under field conditions. Increased CO2 (300 and 600 μmol mol-1 above ambient) concentrations resulted in increases in ascorbic acid (AsA), glutathione (GSH), and ratios of AsA to dehydroascorbic acid (DHAsA) and GSH to oxidized glutathione (GSSG), and a decrease in DHAsA in strawberry fruit. High anthocyanin and phenolic content were also found in fruit of CO2 treated plants. Growing strawberry plants under CO2 enrichment conditions significantly enhanced fruit p-coumaroylglucose, dihydroflavonol, quercetin 3-glucoside, quercetin 3-glucuronide, and kaempferol 3-glucoside contents, as well as cyanidin 3-glucoside, pelargonidin 3-glucoside, and pelargonidin 3-glucoside-succinate content. Fruit of strawberry plants grown in the CO2 enrichment conditions also had high oxygen radical absorbance activity against ROO•, O2•-, H2O2, OH•, and 1O2 radicals (Shiow Y. Wang, Elevated Carbon Dioxide Increases Contents of Antioxidant Compounds in Field-Grown Strawberries, J. Agric. Food Chem., 2003, 51 (15), pp 4315–4320).
Salicylic acid is responsible for the anti‐inflammatory action of aspirin, and may cause the reduced risk of colorectal cancer observed in those who take aspirin. Yet salicylic acid and other salicylates occur naturally in fruits and plants, while diets rich in these are believed to reduce the risk of colorectal cancer. Serum salicylic acid concentrations are greater in vegetarians than non‐vegetarians, and there is overlap between concentrations in vegetarians and those taking low‐dose aspirin. We propose that the cancer‐preventive action of aspirin is due to its principal metabolite, salicylic acid, and that dietary salicylates can have the same effect. It is also possible that natural salicylates contribute to the other recognized benefits of a healthy diet (JR Paterson and JR Lawrence, Salicylic acid: a link between aspirin, diet and the prevention of colorectal cancer, Oxford Journals, Medicine,QJM: An International Journal of Medicine, Volume94, Issue8, Pp. 445-448).
At least 46 % of global disease burden and 59 % of global mortality is due to chronic diseases associated with inflammations caused by various agents including allergens from protozoa, excess free radicals and advanced glycation products (AGEs) and advanced lipoxidation products (ALEs) (Baptista, J.A.B. and Carvalho, R.C.B, 2004, Indirect determination of Amadori compounds in milk-based products by HPLC/ELSD/UV as an index of protein detorioration, Food Research International, 37, 739-747), as glycation products are known to increase free radicals that rob electrons from molecules of cell membranes leading to the development of the inflammatory condition with loss of integrity of the cell membrane. All chronic diseases are in a way related, they develop all as a result of a prolonged and exaggerated inflammation (Bengmark S, 2004a, Acute and “chronic” phase response - A mother of disease. Clin. Nutr.23, 1256-1266).

Common to those suffering from chronic disease as well as critical illness is that they suffer an increased degree of inflammation (Stig Bengmark, Cucurmin As A Dietary Modulator Of Inflammation,Institute of Hepatology, University College, London Medical School, London, United Kingdom, 63-77).

Cancer is a group of more than 100 different diseases, which manifest itself in uncontrolled cellular reproduction, tissue invasion and distant metastases (Levi et al., 2001). Behind the development of these diseases are most often exposure to carcinogens, which produce genetic damage and irreversible mutations, if not repaired. During the last fifty years attempts have been made to find or produce substances that
could prevent these processes, so called chemopreventive agents. Cancers are generally less frequent in the developing world, which has been associated both with less exposure to environmental carcinogens and to a richer supply of natural chemopreventive agents (Stig Bengmark, Cucurmin As A Dietary Modulator Of Inflammation,Institute of Hepatology, University College, London Medical School, London, United Kingdom, 63-77).

Anthocyans are polyphenols ring-based flavonoids that are widespread in fruits and vegetables with red-blue color. Culture cells were used to investigate their chemopreventive effects. In mouse epidermal cells (JB6), a model for screening anticarcinogenic compounds, anthocyans inhibited cell transformation by targeting mitogen activated protein kinase (MAPK)-mediated activator protein-1 (AP-1) pathway. In mouse macrophage cells (RAW264), a model for identifying the anti-inflammation compounds, anthocyans suppressed LPS-evoked inflammation through targeting nuclear factor kappa B (NF-ΚB), AP-1 and CCAAT/enhancerbinding protein (C/EBPδ)-mediated cyclooxygenase-2 (COX-2) expression. In human leukemia cells (HL-60), a model for testing antitumoral compounds, anthocyans induced apoptosis of cancer cells through the reactive oxygen species (ROS)/c-Jun NH2-terminal kinase (JNK)-mediated mitochondrial dysfunction pathway. The data from this study provided the first molecular and cellular basis that anthocyans might have chemopreventive effects on several key steps involved in carcinogenesis (De-Xing Hou, Anthocyans and Chemoprevention: Evidence from Cellular Investigations, ACS Symposium Series, Vol. 993, Functional Food and Health, Chapter 26, pp 308–319).

Polyphenols have in recent few years received an increasing attention for their strong chemo-preventive ability. Curcumin and many other plantderived substances are increasingly regarded as shields against disease. Curcumin is the most explored of the so called curmenoids, a family of chemopreventive substances present in the spice turmeric. Although the substance has been known for some time, it is in the most recent years that the interest has exploded, much in parallel with increasing concern for severe side effects of synthetic COX-2 inhibitors (Stig Bengmark, Cucurmin As A Dietary Modulator Of Inflammation,Institute of Hepatology, University College, London Medical School, London, United Kingdom, 63-77).

Glucocorticoids like NSAID, inhibit prostaglandin synthesis, but at an earlier step in the pathway, prior to arachidonic acid synthesis. They also block cytokine secretion and T cell activation, and inhibit COX-2 activity. Since these agents bind to almost all cells in the body, they have profound effects on physiological systems. If used in long-term therapy they can cause profound immunosuppression, with an increased risk of cancer and infection, osteoporosis, gastrointestinal ulceration, hypertension and endocrine abnormalities (Pincus T and Callahan LF. 1993, What is the natural history of rheumatoid arthritis? Rheum. Dis. Clin. North Am. 19: 123–51). Aspirin and its relatives (more than 20 related drugs) inhibit the activity of both forms of the enzyme and since COX-1 is required for the production of protective prostaglandins in the digestive tract (Rodnan GP, Benedek TG. The early history of antirheumatic drugs. Arthritis Rheum. 1970; 13: 145–65) can cause problems in patients with inflammations.

Curcumin is a potent inhibitor of TGF-β and fibrogenesis (Srinisan, P. and Libbus, B., 2004, Mining Medline for implicit links between dietary substances and diseases. Bioinformatics 20, Suppl. 1, 1290-1296, and suggested to have positive effects in fibrotic diseases in kidneys, liver, intestine (Crohn’s Disease), body cavities (prevention of fibrous adhesions) (Chang, D.M., 2001, Curcumin: A heat shock response inducer and potential cytoprotector, Crit. Care Med. 29, 2231-2232) and on conditions with lung fibrosis, including cystic fibrosis. Significant antifungal properties against various fungal, especially phytopathogenic, organisms by curcumin are also reported (Kim et al, 2003, Fungal property of Curcuma longa rhizome-derived curcumin against phytopathogenic fungi in greenhouse. J. Agr. Food Chem.,51, 1578-1581). Curcumin has very good anti-parasitic properties. Curcumin is suggested to be especially effective in Th1-mediated immune diseases as it effectively inhibits Th1 cytokine profile in CD4+ T cells by interleukin-12 production (Kang et al., 1999, Curcumin inhibits Th1 cytokine profile in CD4+ T cells by suppressing interleukin-12 production in macrophages, Br. J. Pharmacol., 128, 380-384) which may partly explain its anti-parasitic action as the chemokines from protozoa mimic human molecular action and block their action against the protozoa. Together with high doses of L-ascorbic acid, they could possibly help to activate white blood cells or improve their role in the immune system unlike the anti-inflammatory drugs that exhibit an immunosuppresive role in the human body.

“Numerous other plants contain compounds that reduce inflammation and protects against disease. Among them are several thousands of plantderived chemo-preventive agents, polyphenols and many other, most often unexplored, substances, which seem to
have potential to reduce inflammation, speed of aging, prevent degenerative malfunctions of organs and development of chronic diseases. Among them isothiocyanates in cruciferous vegetables, anthocyanins and hydroxycinnamic acids in cherries, epigallocatechin-3-gallate (EGCG) in green tee, chlorogenic acid and caffeic acid in coffee beans and also in virgin tobacco leaves, capsaicin in hot chilli peppers, chalcones in apples, euginol in cloves, gallic acid in rhubarb, hisperitin in citrus fruits, naringenin in citrus fruits, kaempferol in white cabbage, myricetin in berries, rutin and quercetin in apples and onions, resveratrol and other procyanidin dimers in red wine and virgin peanuts, various curcumenoids, the main yellow pigments in turmeric curry foods, and daidzein and genistein from the soy bean. These compounds have all slightly different functions and seem to complement each other well” (Stig Bengmark, Cucurmin As A Dietary Modulator Of Inflammation,Institute of Hepatology, University College, London Medical School, London, United Kingdom, 63-77).

To use medicinal plants and their active components is becoming an increasingly attractive approach for the treatment of various inflammatory disorders among patients unresponsive or unwilling to take standard medicines (Stig Bengmark, Cucurmin As A Dietary Modulator Of Inflammation,Institute of Hepatology, University College, London Medical School, London, United Kingdom, 63-77).