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Tuesday 4 September 2012

Scientific knowledge of TID will expand in the following way – by treating people with proven medicinal plants and studying how individual patients improve knowledge will be gained, and by identifying what phytochemical compounds led to the improvement, new drugs can be derived. For example a medicinal plant study in Pakistan is currently recruiting participants, see Glycemic Response to Momordica charantia in Type 2 Diabetes (contact person- Khadija I Khawaja) http://clinicaltrials.gov/ct2/show/NCT00823953 Momordica charantia is commonly-used remedy for diabetes and should have already been approved by the FDA. The first problem is that political pressure is continuously placed on medicinal plants because profits outweigh healthcare in certain cultures. The second problem is that most studies conducted on tropical medicinal plants are not published in the top-ranked medical journals and are therefore not well-known to western diabetes researchers. In addition it is difficult to keep track of the multiple small under-powered studies being conducted with few resources in developing countries. Another factor is that multiple non-human studies are conducted on the same plants because there is no central agency that tells scientists who are not working for the major pharmaceutical companies “enough already” it’s time for human use. An exception to this took place in the Philippines when a study demonstrated that a 100 milligram per kilo dose per day of Momordica charantia leaves was comparable to 2.5 milligrams of the anti-diabetes drug Glibenclamide taken twice per day and Pascual Laboratories Inc. was given a license to manufacture, distribute and market Momordica charantia tablets as an anti-diabetic medicine under the National Integrated Research Program on Medicinal Plants (NIRPROMP). http://www.gmanews.tv/story/35962/Ampalaya-tablets-out-soon-for-diabetics The Khawaja study has a link to a database file for Momordica charantia on http://www.rain-tree.com/bitmelon.htm I propose an additional type of database – one that is more quantitative and is maintained by computers so that no human bias is included in the ranking process. A skilled statistician will be needed to provide the computer language that would allow dissimilar studies, small studies and poor quality studies to be ranked. This database will thus be different from existing systematic reviews that exclude studies for various reasons. This database should be internet-based and all researchers in all countries should be able to upload their published studies into it. The Cochrane database only contains randomised controlled trials. MEDLINE and EMBASE don’t tell scientists which medicinal plant is better than which or when to end non-human studies. A mock-database is provided below for twelve plants used to treat diabetes. Columns 3 and 7 currently have subjective numbers. This database is not a list of currently funded projects nor is it “direct and therefore obvious continuation of currently running projects”. Having a database that ranks all of the information means that patterns can be seen in how different plants achieve anti-diabetic effects, and relevant plant compounds can be identified. Table 1. Database of some medicinal plants used in the tropics for diabetes Scientific name Study population Quantitative rank based on all published studies (out of 10) /no of studies Allopathic Control used Properties Need for more non-human studies Likelihood of successful drug development (%) Reference 1 2 3 4 5 6 7 8 Annona squamosa rats 2; number of studies conducted 9 glibenclamide (0.25 mg/kg) Sugar apple aqueous extract lowered fasting plasma glucose levels (P<0.05), affected serum insulin levels, serum lipid profile, liver glycogen levels and in pancreatic TBARS levels. Yes 50 1 Bixa orellana dog 7; number of studies conducted 11 annatto responsible for the hypoglycaemic episodes seen in the oral glucose tolerance test (OGTT) There was an increase in plasma insulin concentration. no 66 2,3 Catharanthus roseus rabbits 9; number of studies conducted 23 tolbutamide Periwinkle produced dose-dependent reduction in blood glucose no 95 4 Chamaesyce hirta syn. Euphorbia hirta rats 7; number of studies conducted 11 acetazolamide Malome increased electrolyte excretion and urine output. yes 75 5, 6 Commelina elegans mice 6; number of studies conducted 15 acarbose Water grass normalized hyperglycemia yes 66 7 Desmodium adscendens isolated rat pancreatic beta-islet cells; mice 6; number of studies conducted 21 Amor seco -fasting blood glucose levels and body weight decreased significantly (p < 0.05) yes 66 8-10 Hibiscus sabdariffa people 7; number of studies conducted 61 Sorrel- significant effect on blood lipid profile in patients with diabetes no 75 11 Laportea aestuans rats 5; number of studies conducted 9 Wood nettle -significant reduction in the fasting serum glucose concentrations and lowered cholesterol yes 65 12 Momordica charantia Multiple species 8; number of studies conducted 445 bitter melon -timulating kinases involved in peripheral utilization of glucose. Can reduce LPS-induced inflammatory responses by modulating NF-κB activation no 80 13, 14, 20 Morus alba Rabbits, rats 5; number of studies conducted 7 White mulberry may protect pancreatic beta cells from degeneration and diminish lipid peroxidation yes 58 15-17 Musa sapientum Rats, mice 6; number of studies conducted 31 chlorpropamide Banana produces a significant (p < 0.001) blood glucose lowering effect no 71 18,19 Reference list 1. Shirwaikar A, Rajendran K, Dinesh Kumar C, Bodla R: Antidiabetic activity of aqueous leaf extract of Annona squamosa in streptozotocin-nicotinamide type 2 diabetic rats. J Ethnopharmacol. 2004, 91(1):171-5. 2. Russell KR, Morrison EY, Ragoobirsingh D: The effect of annatto on insulin binding properties in the dog. Phytother Res. 2005, 19(5):433-6. 3. De-Oliveira AC, Silva IB, Manhaes-Rocha DA, Paumgartten FJ: Induction of liver monooxygenases by annatto and bixin in female rats. Braz J Med Biol Res. 2003, 36(1):113-8. 4. Nammi S, Boini MK, Lodagala SD, Behara RB: The juice of fresh leaves of Catharanthus roseus Linn. reduces blood glucose in normal and alloxan diabetic rabbits. BMC Complement Altern Med. 2003, 3(1):4. 5. Johnson, P.B., Abdurahman, E.M., Tiam, E.A., Abdu-Aguye, I., Hussaini, I.M: Euphorbia hirta leaf extracts increase urine output and electrolytes in rats. J Ethnopharmacol. 1999, 65 (1): 63-9. 6. Lanhers, M-C., Fleurentin, J., Dorfman, P., Mortier, F., Pelt, J-M. 1991. Analgesic, antipyretic and anti-inflammatory properties of Euphorbia hirta. Planta Med. 1991, 57 (3): 225-31. 7. Youn JY, Park HY, Cho KH: Anti-hyperglycemic activity of Commelina communis L.: inhibition of alpha-glucosidase. Diabetes Res Clin Pract. 2004, 66 Suppl 1:S149-55. 8. Barreto GS: Effect of butanolic fraction of Desmodium adscendens on the anococcygeus of the rat. Braz J Biol. 2002, 62(2):223-30. 9. Sugimoto, K., Sakurai, N., Shirasawa, H., Fujise, Y., Shibata, K., Shimodo, K., Sakata, J: Bovine cases of urolithiasis treated with traditional herbal medicine, P-3. J Vet Med Sci. 1992, 54 (3): 579 - 582. 10. Monache, G.D., Botta, B., Vinciguerra, V., de Mello, J.F., Andrade Chiapetta de, A: Antimicrobial isoflavanones from Desmodium canum. Phytochemistry 1996, 41 (2): 537 - 544. 11. Mozaffari-Khosravi H, Jalali-Khanabadi BA, Afkhami-Ardekani M, Fatehi F: Effects of sour tea (Hibiscus sabdariffa) on lipid profile and lipoproteins in patients with type II diabetes. J Altern Complement Med. 2009, 15(8):899-903. 12. Momo CE, Oben JE, Tazoo D, Dongo E: Antidiabetic and hypolipidaemic effects of a methanol/methylene-chloride extract of Laportea ovalifolia (Urticaceae), measured in rats with alloxan-induced diabetes. Ann Trop Med Parasitol. 2006, 100(1):69-74. 13. Tongia A, Tongia SK, Dave M: Phytochemical determination and extraction of Momordica charantia fruit and its hypoglycemic potentiation of oral hypoglycemic drugs in diabetes mellitus (NIDDM). Indian J Physiol Pharmacol. 2004, 48(2):241-4. 14. Cummings E, Hundal HS, Wackerhage H, Hope M, Belle M, Adeghate E, Singh J: Momordica charantia fruit juice stimulates glucose and amino acid uptakes in L6 myotubes. Mol Cell Biochem. 2004, 261(1-2):99-104. 15. Lemus I, Garcia R, Delvillar E, Knop G: Hypoglycaemic activity of four plants used in Chilean popular medicine. Phytother Res. 1999, 13(2):91-4. 16. Oku T, Yamada M, Nakamura M, Sadamori N, Nakamura S: Inhibitory effects of extractives from leaves of Morus alba on human and rat small intestinal disaccharidase activity. Br J Nutr. 2006, 95(5):933-8. 17. Singab AN, El-Beshbishy HA, Yonekawa M, Nomura T, Fukai T: Hypoglycemic effect of Egyptian Morus alba root bark extract: effect on diabetes and lipid peroxidation of streptozotocin-induced diabetic rats. J Ethnopharmacol. 2005, 100(3):333-8. 18. Dhanabal SP, Sureshkumar M, Ramanathan M, Suresh B: Hypoglycemic effect of ethanolic extract of Musa sapientum on alloxan induced diabetes mellitus in rats and its relation with antioxidant potential. J Herb Pharmacother. 2005, 5(2):7-19. 19. Ojewole JA, Adewunmi CO: Hypoglycemic effect of methanolic extract of Musa paradisiaca (Musaceae) green fruits in normal and diabetic mice. Methods Find Exp Clin Pharmacol. 2003, 25(6):453-6. 20. Chong-Kuei Lii, Haw-Wen Chen, Wen-Tzu Yun, Kai-Li Liu: Suppressive effects of wild bitter gourd (Momordica charantia Linn. var. abbreviata ser.) fruit extracts on inflammatory responses in RAW 264.7 macrophages. Journal of Ethnopharmacology. 2009, 122 (2): 227-233.