Studies Force New View on Biology of Flavonoids-Science Daily (Mar. 5, 2007) -Report

Posted on August 29, 2011 by Bio-gen Extracts

Science Daily (Mar. 5, 2007) — Flavonoids, a group of compounds found in fruits and vegetables that had been thought to be nutritionally important for their antioxidant activity, actually have little or no value in that role, according to an analysis by scientists in the Linus Pauling Institute at Oregon State University.

  • However, these same compounds may indeed benefit human health, but for reasons that are quite different — the body sees them as foreign compounds, researchers say, and through different mechanisms, they could play a role in preventing cancer or heart disease.
  • Based on this new view of how flavonoids work, a relatively modest intake of them — the amount you might find in a healthy diet with five to nine servings of fruits and vegetables — is sufficient. Large doses taken via dietary supplements might do no additional good; an apple a day may still be the best bet.
  • A research survey and updated analysis of how flavonoids work and function in the human body were recently published in Free Radical Biology and Medicine, a professional journal.
  • “What we now know is that flavonoids are highly metabolized, which alters their chemical structure and diminishes their ability to function as an antioxidant,” said Balz Frei, professor and director of the Linus Pauling Institute. “The body sees them as foreign compounds and modifies them for rapid excretion in the urine and bile.”
  • Flavonoids are polyphenolic compounds with some common characteristics that are widely found in fruits and vegetables and often give them their color — they make lemons yellow and certain apples red. They are also found in some other foods, such as coffee, tea, wine, beer and chocolate, and studies in recent years had indicated that they had strong antioxidant activity — and because of that, they might be important to biological function and health.
  • “If you measure the activity of flavonoids in a test tube, they are indeed strong antioxidants,” Frei said. “Based on laboratory tests of their ability to scavenge free radicals, it appears they have 3-5 times more antioxidant capacity than vitamins C or E. But with flavonoids in particular, what goes on in a test tube is not what’s happening in the human body.”
  • Research has now proven that flavonoids are poorly absorbed by the body, usually less than five percent, and most of what does get absorbed into the blood stream is rapidly metabolized in the intestines and liver and excreted from the body. By contrast, vitamin C is absorbed 100 percent by the body up to a certain level. And vitamin C accumulates in cells where it is 1,000 to 3,000 times more active as an antioxidant than flavonoids.
  • The large increase in total antioxidant capacity of blood observed after the consumption of flavonoid-rich foods is not caused by the flavonoids themselves, Frei said, but most likely is the result of increased uric acid levels.
  • But just because flavonoids have been found to be ineffectual as antioxidants in the human body do not mean they are without value, Frei said. They appear to strongly influence cell signaling pathways and gene expression, with relevance to both cancer and heart disease.
  • “We can now follow the activity of flavonoids in the body, and one thing that is clear is that the body sees them as foreign compounds and is trying to get rid of them,” Frei said. “But this process of gearing up to get rid of unwanted compounds is inducing so-called Phase II enzymes that also help eliminate mutagens and carcinogens, and therefore may be of value in cancer prevention.
  • “Flavonoids could also induce mechanisms that help kill cancer cells and inhibit tumor invasion,” Frei added.
  • It also appears that flavonoids increase the activation of existing nitric oxide synthase, which has the effect of keeping blood vessels healthy and relaxed, preventing inflammation, and lowering blood pressure — all key goals in prevention of heart disease.
  • Both of these protective mechanisms could be long-lasting compared to antioxidants, which are more readily used up during their free radical scavenging activity and require constant replenishment through diet, scientists say.
  • However, Frei said, it’s also true that such mechanisms require only relatively small amounts of flavonoids to trigger them — conceptually, it’s a little like a vaccine in which only a very small amount of an offending substance is required to trigger a much larger metabolic response. Because of this, there would be no benefit — and possibly some risk — to taking dietary supplements that might inject large amounts of substances the body essentially sees as undesirable foreign compounds.
  • Numerous studies in the United States and Europe have documented a relationship between adequate dietary intake of flavonoid-rich foods, mostly fruits and vegetables, and protection against heart disease, cancer and neurodegenerative disease, Frei said.
  • http://www.sciencedaily.com/releases/2007/03/070305140834.htm

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Microbial pigments (carotene) new source of natural antioxidants

Posted on April 6, 2011 by Bio-gen Extracts

There is an increased evidence for the participation of free radicals in the etiology of various diseases like cancer, diabetes, cardiovascular diseases, autoimmune disorders, neurodegenerative diseases, aging1 etc. A free radical is defined as any atom or molecule possessing unpaired electrons. The primary oxygen derived free radicals are superoxide anion (O2·), hydroxyl (OH·), hydroperoxyl (OOH·), peroxyl (ROO·) and alkoxyl (RO·) radicals and non free radicals are hydrogen peroxide (H2O2), hypochlorous acid (HOCl), ozone (O3) and singlet oxygen (1/2O2). These reactive intermediates are collectively termed as reactive oxygen species (ROS). Similarly, reactive nitrogen species (RNS) are mainly nitric oxide (NO·), peroxynitrite (ONOO·) and nitrogen dioxide (NO2). Free radicals can cause a wide range of toxic oxidative reactions like initiation of the peroxidation of the membrane lipids leading to the accumulation of lipid peroxides, direct inhibition of mitochondrial respiratory chain enzymes, fragmentation or random cross linking of molecules like DNA, enzymes and proteins which ultimately leads to cell death12. ROS can be formed in living organisms by both endogenous and exogenous sources. Endogenous sources of free radicals include normal aerobic respiration, peroxisomes and stimulation of polymorphonuclear leucocytes and macrophages. The exogenous sources include ionizing radiation, tobacco smoke, pollutants, pesticides and organic solvents18. Antioxidants are agents which scavenge the free radicals and prevent the damage caused by them. They can greatly reduce the damage due to oxidants by neutralizing the free radicals before they can attack the cells and prevent damage to lipids, proteins, enzymes, carbohydrates and DNA5. Antioxidants can be classified into two major classes i.e., enzymatic and non-enzymatic. The enzymatic antioxidants are produced endogenously and include superoxide dismutase, catalase, and glutathione peroxidase. The non-enzymatic antioxidants include tocopherols, carotenoids, ascorbic acid, flavonoids and tannins which are obtained from natural plant. A wide range of antioxidants from both natural and synthetic origin has been proposed for use in the treatment of various human diseases3. There are some synthetic antioxidant compounds such as butylated hydroxytoluene, butylated hydroxyanisole and tertiary butylhydroquinone which are commonly used in processed foods. However, it has been suggested that these compounds have shown toxic effects like liver damage and mutagenesis8. Flavonoids and other phenolic compounds of plant origin have been reported as scavengers of free radicals7. Hence, nowadays search for natural antioxidant source is gaining much importance.

A considerable number of bacteria produce non photosynthetic coloured compounds known as Pigments. This is especially true of the strictly aerobic species. Many colour are produced covering the entire range of the chromatic spectrum40. Subsequent studies of the S. aureus pigment have unraveled an elaborate biosynthetic pathway that produces a series of carotenoids41. Similar carotenoids produced in dietary fruits and vegetables are well recognized as potent antioxidants by virtue of their free-radical scavenging properties and exceptional ability to quench singlet oxygen42. We hypothesized. That S. aureus could utilize its golden carotenoid pigment to resist oxidant-based clearance mechanisms of the host innate immune system.

An increasing number of investigations have been carried out to find antioxidative drugs, which not only prolong the shelf life of food products but also participate as radical scavengers in living organism’s .As with other synthetic food additives, commercial antioxidants have been criticized, mainly due to possible toxic effects. Therefore, there is an increasing interest in the antioxidative activity of natural compounds. They can be an alternative to the use of synthetic compounds in food and pharmaceutical technology or serve as lead compounds for the development of new drugs with the prospect of improving the treatment of various disorders.

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2. Cao, G., Sofic, E. and Prior, R.L. (1997). Antioxidant and pro-oxidant behaviour of flavonoids: structure activity relationships. Free Radic. Biol. Med., 22: 749-760.

3. Cuzzocrea, S., Riley, D.P., Caputi, A.P. and Salvemini, D. (2001). Antioxidant therapy: A new pharmacological approach in shock, inflammation and ischemia/reperfusion injury. Pharmacol. Rev., 53: 135-159.

4. Duh, P.D., Tu, Y.Y. and Yen. (1999). Antioxidant activty of water extract of harng Jyur (Chrysanthemum morifolium Ramat). Lebens. Wiss. U. Technol., 32: 269-277.

5. Fang, Y., Yang, S. and Wu, G. (2002). Free radicals, antioxidants and nutrition. Nutrition, 18: 872-879.

6. Fejes, S., Blazovics, A., Lugasi, A., Lemberkovics, E., Petri, G. and Kery, A. (2000). In vitro antioxidant activity of Anthriscus cerefolium L. (Hoffm.) extracts. J. Ethnopharmacol., 69: 259-265.

7. Formica, J.V. and Regelson, W. (1995). Review of the biology of quercetin and related bioflavonoids. Food Chem. Toxicol., 33: 1061-1080.

8. Grice, H.C. (1986). Safety evaluation of butylated hydroxytoluene (BHT) in the liver, lung and gastrointestinal tract. Food Chem. Toxicol., 24: 1127-1130.

9. Gulcin, I., Oktay, M., Kufrevioglu, I. and Aslam, A. (2002). Determination of antioxidant activity of lichen Cetraria islandica (L) Ach. J. Ethnopharmacol., 79: 325-329.

10. Gutierrez, R.M.P., Luna, H.H. and Garrido, S.H. (2006). Antioxidant activity of Tagates erecta essential oil. J. Chil. Chem. Soc., 51: 883-886.

11. Halliwell, B. (1991). Reactive oxygen species in living systems: Source, biochemistry and role in human disease. Am. J. Med., 91: 14-22.

12. Halliwell, B. and Gutteridge, J.M.C. (1999). Free radicals in Biology and Medicine, 3rd ed. Oxford University Press, Oxford, pp. 23-27.

13. Halliwell, B., Gutteridge, J.M.C. and Arouma, O.I. (1987). The deoxyribose method: a simple test tube assay for the determination of rate constants for reactions of hydroxyl radicals. Anal.Biochem., 165: 215-219.

14. Hsu, C. (2006). Antioxidant activity of extract from Polygonum aviculare L. Biol. Res., 39: 281-288.

15. Huang, D., Ou, B. and Proir, R.L. (2005). The chemistry behind the antioxidant capacity assays. J.Agric. Food Chem., 53: 1841-1856.

16. Huang, S. and Kuo, J.C. (2000). Concentrations and antioxidant activity of Anserine and Carnosine in poultry meat extracts treated with demineralization and papain. Proc. Natl. Sci. Counc. ROC. (B)., 24(4): 193-201.

17. Ilavarasan, R., Mallika, M. and Venkataraman, S. (2005). Anti-inflammatory and antioxidant activities of Cassia fistula Linn. bark extracts. Afr. J. Trad. CAM., 2 (1): 70-85.

18. Irshad, M. and Chaudhuri, P.S. (2002). Oxidant-antioxidant system: Role and significance in human body. Indian J. Exp. Biol., 40: 1233-1239.

19. Jayaprakasha, G.K., Jena, B.S., Negi, P.S. and Sakariah, K.K. (2002). Evaluation of antioxidant activities and antimutagenicity of turmeric oil: A byproduct from curcumin production. Z. Naturforsch., 57c: 828-835.

20. Kirthikar, K.R. and Basu, B.D. (1987). Indian Medicnal Plants, 2nd ed. International Book Distributors, Dehradun, pp. 1151-1154.

21. Lee, J., Koo, N. and Min, D.B. (2004). Reactive oxygen species, aging and antioxidative nutraceuticals. CRFSFS., 3: 21-33.

22. Liu, F. and Ng,T.B. (2000). Antioxidative and free radical scavenging activities of selected medicinal herbs. Life Sci., 66: 725-735. 73

23. Marcocci, P.L., Sckaki, A. and Albert, G.M. (1994). Antioxidant action of Ginkgo biloba extracts EGP761. Methods Enzymol., 234: 462-475.

24. Meir, S., Kanner, J., Akiri, B. and Hadar, S.P. (1995). Determination and involvement of aqueous reducing compounds in oxidative systems of various senescing leaves. J. Agric. Food Chem., 43: 1813-1817.

25. Mensor, L.L., Menezes, F.S., Leitao, G.G., Reis, A.S., dos Santos, T.C. and Coube, C.S. (2001). Screening of Brazilian plant extracts for antioxidant activity by the use of DPPH free radical method. Phytother. Res., 15:127-130.

26. Nanjo, F., Goto, K., Seto, R., Suzuki, M., Sakai, M. and Hara, Y. (1996). Scavenging effects of tea catechins and their derivatives on 1,1-diphenyl-2-picryl hydrazyl radical. Free Radic. Biol. Med., 21: 895-902.

27. Ng, T.B., Liu, F., Lu, Y., Cheng, C.H.K. and Wang, Z. (2003). Antioxidant activity of compounds from the medicinal herb Aster tataricus. Compar. Biochem. Physiol. Part C., 136: 109-115.

28. Oktay, M., Gulcin, I. and Kufrevioglu. (2003). Determination of in vitro antioxidant activity of fennel (Foeniculum vulgare) seed extracts. Lebensm.-Wiss. U.-Technol., 33: 263-271.

29. Prieto, P., Pineda, M. and Aguilar, M. (1999). Spectrophotometric quantitation of antioxidant capacity through the formation of a phosphomolybdenum complex: specific application to the determination of vitamin E. Anal. Biochem., 269: 337-341.

30. Rice-Evans, C.A., Miller, N.J. and Paganga, G. (1997). Antioxidant properties of phenolic compounds. Trends Plant Sci. Rev., 2: 152-159.

31. Sreejayan, N. and Roa, M.N.A. (1997). Nitric oxide scavenging by curcuminoids. J. Pharm. Pharmacol., 49: 105-107.

32. Umamaheswari, M., Asokkumar, K., Somasundaram, A., Sivashanmugam, T., Subhadradevi, V. and Ravi, T.K. (2007). Xanthine oxidase inhibitory activity of some Indian medical plants. J. Ethnopharmacol., 109: 547-551.

33. Venkateswaran, S. and Pari, L., 2003. Effect of Coccinia indica leaves on antioxidant status in streptazotocininduced diabetic rats. J. Ethnopharmacol., 84(2-3):163-168.

34. Wasantwisut, E. and Viriyapanich, T. (2003). Ivy gourd (Coccinia grandis Voigt, Coccinia cardifolia, Coccinia indica) in human nutrition and traditional applications. In: Simopoulous, A.P., Gopalan, C., eds. Plants in Human Health and Nutrition Policy: World Reviews of Nutrition and Dietics. Karger, Basel, pp. 60-66.

35. Wichi, H.P. (1988). Enhanced tumour development by butylated hydroxyanisole (BHA) from the prospective of effect on forestomach and oesophageal squamous epithelium. Food Chem. Toxicol., 26: 717-723.

36. Yamaguchi, F., Ariga, T., Yoshimara, Y. and Nakazawa, H. (2000). Antioxidant and antiglycation of carcinol from Garcina indica fruit rind. J. Agric. Food Chem., 48: 180-185.

37. Yen, G.C., Duh, P.D. and Tsai, C.L. (1993). Relationship between antioxidant activity and maturity of peanut hulls. J. Agric. Food Chem., 41: 67-70.

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39. Yildrim, A., Oktay, M. and Bilaloglu, V. (2001). The antioxidant activity of the leaves of Cydonia vulgaris. Turk. J. Med. Sci.,31:23-27.

40. Salle A.J. (1974)”Fundamental Principle of Bacteriology” TMH ED

41. Altas R. M. Porks L.C. (1993), “Handbook of Microbiological Media” CRC Press Inc.London.

42. John h. Marshall* and Gregory j wilmoth “pigments of staphylococcus aureus, a series of triterpenoid carotenoids” journal of bacteriology, sept. 1981, p. 900-913

43. Krinsky, N.I. 1993. Actions of carotenoids in biological systems. Annu. Rev. Nutr. 13:561–587.

44. Sibeyn et. al. “process for the recovery of crystalline beta carotene and Lycopene from B. trispora” US 2002/0025548A1, feb28 2002

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Natural Extracts to Nutraceuticals – The New Demands of New Consumers

Posted on April 4, 2011 by Bio-gen Extracts

The Indian pharmaceutical market is one of the most exciting in the world. According to a recent McKinsey report, India will become one of the top 10 pharmaceutical markets in the world by 2015. Healthcare consumption in the country is expected to increase three times riding on prosperity, better healthcare infrastructure, insurance regulations and health awareness. The same report goes on to predict that by 2015, millions more will suffer from chronic, costly to treat diseases such as diabetes, respiratory illnesses and cancer.

The pharmaceutical industry’s contribution to therapeutics, healthcare, well-being, disease prevention and disease cure has been outstanding. The importance of this contribution cannot be highlighted more than by the fact that pharmaceuticals are a 1,043 billion dollar market worldwide. While pharmaceutical companies are spending almost a billion dollars per molecule on the drug discovery process and much more on merger and acquisition transactions to populate their drug pipelines, the number of new molecules being registered has not kept up with growth.

Many conditions that make humans sick are still being treated symptomatically. Often, such diseases and conditions those are chronic in nature like hypertension, arthritis and cardiovascular disease seek solutions in related forms of medicine like Ayurveda, Chinese or herbal medicine. In order to address these issues: the lack of known cause for the disease, absence of cure, maintenance of the disease by treatment and other issues like iatrogenesis or the side effects related to pharmaceutical use; natural extract processing has undergone a transformation with the use of pharmaceutical technology. The important end product of this process is the group of therapeutic substances that we recognize as nutraceuticals.

Nutraceuticals have become a significant part of a pharmaceutical company’s portfolio. A nutraceutical is any substance that as a food or a part of food that provides medical or health benefits, including the prevention and/or treatment of disease.  The use of nutraceuticals, as an attempt to accomplish desirable therapeutic outcomes with reduced side effects as compared with other therapeutic agents has met with great monetary success. While the pharmaceutical industry continues to grow at a healthy 9%, the nutraceuticals industry in India has grown at a CAGR of 18% over the last few years.

Traditional nutraceuticals, whole foods with new information about their potential health qualities like lycopene in tomatoes and non-traditional nutraceutical foods, foods that result from adding ingredients to boost their nutritional value (like fortified foods) are finding traction amongst consumers.

Since nutraceuticals are most often natural whole foods, they do not fall under the regulations that govern pharmaceutical manufacturing. The FDA regulates nutraceuticals as it regulates all foods. In order to meet with consumer expectations of transparency, information and safety as are related to pharmaceutical consumption, the Indian government passed the Food Safety and Standard Act in 2006, to integrate and streamline the many regulations covering nutraceuticals, foods and dietary supplements.

Cosmetics, women’s health, therapeutics, functional foods, nutritional foods and dietary supplements are some of the industries that make regular use of nutraceuticals in their product offerings.

Carotino® is an anti-oxidant rich premium red cooking oil that has natural carotenes. The oilis a combination of canola oil & red palm fruit extract. The premium cooking oil is cholesterol free and rich in natural beta-carotenes, vitamin E, omega-3, 6 essential fatty acids, co-enzyme Q10 and lycopene sans harmful trans-fatty acids. Carotenes and Vitamin E in the oil act as scavengers of damaging free radicals and play a protective role in ageing, atherosclerosis and cancer. Many research papers on the efficacy of red palm oil in increasing serum retinol and beta-carotene levels in children have been published to encourage the use of the oil. The Singapore Health Promotion Board (HPB) has even certified the food as a ‘Healthier Choice Symbol’,given as a label to foods that meet the nutritional standards set by the Singapore Heart Association.

Carotino® ismanufactured by the J C Chang Group in Malaysia and is marketed all over the world including India.

Omega 3 Fatty Acids (DHA), are potent controllers of inflammatory processes, maintain brain function and reduce cholesterol deposition. We can now freely avail of vegetarian sources of Omega-3 fatty acids from microalgae. Food fortified with DHA has now made an appearance on the shelves of daily consumables like breads, cereal and milk. Bread fortified with DHA is already available to Indian consumers and is popular with people following cosmopolitan lifestyles in the larger cities and metros.

Japan and China have been large consumers of green tea. It has become part of tradition and culture of the land, with ceremonies and celebrations built around its preparation. It comes as no surprise that these countries consume green tea in other forms of food as well, be it flavoring of soy bean drinks, health drinks, cold beverages and in medicinal preparations. Japan is the second largest market for nutraceuticals in the world with 47% of its population consuming nutraceuticals. Continue reading →

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