Mechanism of action of natural products used in the treatment of diabetes mellitus

Pranav Kumar Prabhakar; Mukesh Doble

doi:10.1007/s11655-011-0810-3

Your Location：

Home >

Browse articles >

Mechanism of action of natural products used in the treatment of diabetes mellitus

OriginalPaper | Updated：2021-08-27

- Mechanism of action of natural products used in the treatment of diabetes mellitus
- Mechanism of action of natural products used in the treatment of diabetes mellitus
- 中国结合医学杂志（英文版） 2011年17卷第8期页码：563-574
- Affiliations：
  
  Department of Biotechnology, Indian Institute of Technology Madras,Chennai,India
- Author bio：
- Funds：
- DOI：10.1007/s11655-011-0810-3
  中图分类号：
- 纸质出版日期：2011，
  
  网络出版日期：2011-8-9，
Scan for full text
Prabhakar, P.K., Doble, M. Mechanism of action of natural products used in the treatment of diabetes mellitus., Chin. J. Integr. Med. 17, 563 (2011). https://doi.org/10.1007/s11655-011-0810-3

Pranav Kumar Prabhakar, Mukesh Doble. Mechanism of action of natural products used in the treatment of diabetes mellitus[J]. Chinese Journal of Integrative Medicine, 2011,17(8):563-574.
Prabhakar, P.K., Doble, M. Mechanism of action of natural products used in the treatment of diabetes mellitus., Chin. J. Integr. Med. 17, 563 (2011). https://doi.org/10.1007/s11655-011-0810-3 DOI：

Pranav Kumar Prabhakar, Mukesh Doble. Mechanism of action of natural products used in the treatment of diabetes mellitus[J]. Chinese Journal of Integrative Medicine, 2011,17(8):563-574. DOI： 10.1007/s11655-011-0810-3.

摘要

Diabetes mellitus (DM) is a metabolic disorder caused by insufficient or inefficient insulin secretary response and it is characterized by increased blood glucose levels (hyperglycemia). DM is a heterogonous group of syndromes. Glucose is the main energy source for the body

and in the case of DM

management of glucose becomes irregular. There are three key defects in the onset of hyperglycemia in DM

namely increased hepatic glucose production

diminished insulin secretion

and impaired insulin action. Conventional drugs treat diabetes by improving insulin sensitivity

increasing insulin production and/or decreasing the amount of glucose in blood. This article provides a comprehensive review of the mode of action of most popular hypoglycemic herbs

such as ginseng

bitter melon

fenugreek

banaba

Gymnema sylvestre and Coptis chinensis. The herbs act by increasing insulin secretion

enhancing glucose uptake by adipose and skeletal muscle tissues

inhibiting intestinal glucose absorption and inhibiting hepatic glucose production. Although evidence from animals and humans consistently supports the therapeutic effect of these phytomedicines

multicenter large-scale clinical trials have not been conducted to evaluate the safety and efficacy of these herbal medicines and their interaction with conventional drugs when administered simultaneously.

Abstract

and in the case of DM

management of glucose becomes irregular. There are three key defects in the onset of hyperglycemia in DM

namely increased hepatic glucose production

diminished insulin secretion

and impaired insulin action. Conventional drugs treat diabetes by improving insulin sensitivity

increasing insulin production and/or decreasing the amount of glucose in blood. This article provides a comprehensive review of the mode of action of most popular hypoglycemic herbs

such as ginseng

bitter melon

fenugreek

banaba

Gymnema sylvestre and Coptis chinensis. The herbs act by increasing insulin secretion

enhancing glucose uptake by adipose and skeletal muscle tissues

inhibiting intestinal glucose absorption and inhibiting hepatic glucose production. Although evidence from animals and humans consistently supports the therapeutic effect of these phytomedicines

关键词

hyperglycemiamedicinal plantsginsengbitter melonfenugreekbanaba

Keywords

hyperglycemiamedicinal plantsginsengbitter melonfenugreekbanaba

references

Lin Y, Sun Z. Current views on type 2 diabetes. J Endocrinol 2010;204:1–11.

King H, Aubert RE, Herman WH. Global burden of diabetes, 1995–2025: prevalence, numerical estimates, and projections. Diabetes Care 1998;21:1414–1431.

Marx J. Unraveling the causes of diabetes. Science 2002;296:686–689.

Mohler ML, He Y, Wu Z, Dong JH, Miller DD. Recent and emerging anti-diabetes targets. Med Res Rev 2009;29:125–195.

Bagust A, Hopkinson PK, Maier W, Currie CJ. An economic model of the long-term health care burden of type 2 diabetes. Diabetologia 2001;44:2140–2155.

Harris MI, Flegal KM, Cowie CC, Eberhardt MS, Goldstein DE, Little RR, et al. Prevalence of diabetes, impaired fasting glucose, and impaired glucose tolerance in U.S. adults. The Third National Health and Nutrition Examination Survey, 1988–1994. Diabetes Care 1998;21:518–524.

Gupta RK, Kesari AN, Murthy PS, Chandra R, Tandon V, Watal G. Hypoglycemic and antidiabetic effect of ethanolic extract of leaves of Annona squamosa L. in experimental animals. J Ethnopharmacol 2005;99:75–81.

Alarcon-Aguilara FJ, Roman-Ramos R, Perez-Gutierrez S, Aguilar-Contreras A, Contreras-Weber CC, Flores-Saenz JL. Study of the anti-hyperglycemic effect of plants used as antidiabetics. J Ethnopharmacol 1998;61:101–110.

Prabhakar PK, Doble M. A target based therapeutic approach towards diabetes mellitus using medicinal plants. Curr Diabetes Rev 2008;4:291–308.

Modi P. Diabetes beyond insulin: review of new drugs for treatment of diabetes mellitus. Curr Drug Discov Technol 2007;4:39–47.

Hui H, Zhao X, Perfetti R. Structure and function studies of glucagon-like peptide-1 (GLP-1): the designing of a novel pharmacological agent for the treatment of diabetes. Diabetes Metab Res Rev 2005;21:313–331.

Garber AJ, Spann SJ. An overview of incretin clinical trials. J Fam Pract 2008; 57(Suppl 9):S10–S18.

Prabhakar PK, Doble M. Mechanism of action of medicinal plants towards diabetes mellitus—a review. In: Govil JN, Singh VK, Bhardwaj R, eds. Recent progress in medicinal plants. Vol 22. LLC, USA: Studium Press; 2008:187–210. LLC, USA: Studium Press; 2008:187–210.

Hui H, Dotta F, Di Mario U, Perfetti R. Role of caspases in the regulation of apoptotic pancreatic islet beta-cells death. J Cell Physiol 2004;200:177–200.

Kameswararao B, Kesavulu MM, Apparao C. Evaluation of antidiabetic effect of Momordica cymbalaria fruit in alloxandiabetic rats. Fitoterapia 2003;74:7–13.

Middleton E, Kandaswami C, Theoharides TC. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev 2000;52:673–751.

Grover JK, Vats V. Shifting the paradigm from conventional to alternative medicines: an introduction on traditional Indian medicines. Asia Pacific Biotech News 2001;5:28–32.

Ernst E. Herbal medicines: where is the evidence? BMJ 2000;321:395–396.

Wood AJJ, De Smet PAGM. Herbal Remedies. N Engl J Med 2002;347:2046–2056.

Inamdar N, Edalat S, Kotwal V, Pawar S. Care with nature’s cure: herbal drugs. Pharmacognosy Rev 2007;1:361–368.

Liu RH. Potential synergy of phytochemicals in cancer prevention: mechanism of action. J Nutr 2004;134(Suppl 12):3479S–3485S.

Kawase M, Wang R, Shiomi T, Saijo R, Yagi K. Antioxidative activity of (−)-epigallocatechin-3-(3″-O-methyl) gallate isolated from fresh tea leaf and preliminary results on its biological activity. Biosci Biotechnol Biochem 2000;64:2218–2220.

Kim K, Kim HY. Korean red ginseng stimulates insulin release from isolated rat pancreatic islets. J Ethnopharmacol 2008;120:190–195.

Kim EK, Kwon KB, Lee JH, Park BH, Park JW, Lee HK, et al. Inhibition of cytokine-mediated nitric oxide synthase expression in rat insulinoma cells by scoparone. Biol Pharm Bull 2007;30:242–246.

Chung SH, Choi CG, Park SH. Comparisons between white ginseng radix and rootlet for antidiabetic activity and mechanism in KKAy mice. Arch Pharm Res 2001;24:214–218.

Vuksan V, Sievenpiper JL, Koo VY, Francis T, Beljan-Zdravkovic U, Xu Z, Vidgen E. American ginseng (Panax quinquefolius L.) reduces postprandial glycemia in nondiabetic subjects and subjects with type 2 diabetes mellitus. Arch Intern Med 2000;160:1009–1013.

Kimura M, Kimura I, Chem FJ. Combined potentiating effects of Byakko-ka-ninjin-to, its constituents, rhizomes of Anemarrhena asphodeloides, timosaponin A-III, and calcium on pilocarpine-induced saliva secretion in streptozocindiabetic mice. Biol Pharm Bull 1996;19:926–931.

Sievenpiper JL, Arnason JT, Leiter LA, Vuksan V. Variable effects of American ginseng: a batch of American ginseng (Panax quinquefolius L.) with a depressed ginsenoside profile does not affect postprandial glycemia. Eur J Clin Nutr 2003;57:243–248.

Banz WJ, Iqbal MJ, Bollaert M, Chickris N, James B, Higginbotham DA, et al. Ginseng modifies the diabetic phenotype and genes associated with diabetes in the male ZDF rat. Phytomedicine 2007;14:681–689.

Wu Z, Luo JZ, Luo L. American ginseng modulates pancreatic beta cell activities. Chin Med 2007;2:11.

Hwang JT, Lee MS, Kim HJ, Sung MJ, Kim HY, Kim MS, et al. Antiobesity effect of ginsenoside Rg3 involves the AMPK and PPAR-gamma signal pathways. Phytother Res 2009;23:262–266.

Lee WK, Kao ST, Liu IM, Cheng JT. Increase of insulin secretion by ginsenoside Rh2 to lower plasma glucose in Wistar rats. Clin Exp Pharmacol Physiol 2006;33:27–32.

Xiang YZ, Shang HC, Gao XM, Zhang BL. A comparison of the ancient use of ginseng in traditional Chinese medicine with modern pharmacological experiments and clinical trials. Phytother Res 2008;22:851–858.

Kiefer D, Pantuso T. Panax ginseng. Am Fam Physician 2003;68:1539–1542.

McCarty MF. Does bitter melon contain an activator of AMP-activated kinase? Med Hypotheses 2004;63:340–343.

Krawinkel MB, Keding GB. Bitter gourd (Momordica charantia): a dietary approach to hyperglycemia. Nutr Rev 2006;64:331–337.

Harinantenaina L, Tanaka M, Takaoka S, Oda M, Mogami O, Uchida M, et al. Momordica charantia constituents and antidiabetic screening of the isolated major compounds. Chem Pharm Bull (Tokyo) 2006;54:1017–1021.

Rathi SS, Grover JK, Vikrant V, Biswas NR. Prevention of experimental diabetic cataract by Indian Ayurvedic plant extracts. Phytother Res 2002;16:774–777.

Shibib BA, Khan LA, Rahman R. Hypoglycaemic activity of Coccinia indica and Momordica charantia in diabetic rats: depression of the hepatic gluconeogenic enzymes glucose-6-phosphatase and fructose-1,6-bisphosphatase and elevation of both liver and red-cell shunt enzyme glucose-6-phosphate dehydrogenase. Biochem J 1993;292(Pt1):267–270.

Chao CY, Huang C. Bitter gourd (Momordica charantia) extract activates peroxisome proliferator-activated receptors and upregulates the expression of the acyl CoA oxidase gene in H4IIEC3 hepatoma cells. J Biomed Sci 2003;10(6 Pt 2):782–791.

Chuang CY, Hsu C, Chao CY, Wein YS, Kuo YH, Huang CJ. Fractionation and identification of 9c, 11t, 13t-conjugated linolenic acid as an activator of PPAR-alpha in bitter gourd (Momordica charantia L.). J Biomed Sci 2006;13:763–772.

Tan MJ, Ye JM, Turner N, Hohnen-Behrens C, Ke CQ, Tang CP, et al. Antidiabetic activities of triterpenoids isolated from bitter melon associated with activation of the AMPK pathway. Chem Biol 2008;15:263–273.

Basch E, Ulbricht C, Kuo G, Szapary P, Smith M. Therapeutic applications of fenugreek. Altern Med Rev 2003;8:20–27.

Chen Q, Chan LL, Li ET. Bitter melon (Momordica charantia) reduces adiposity, lowers serum insulin and normalizes glucose tolerance in rats fed a high fat diet. J Nutr 2003;133:1088–1093.

Cefalu WT, Ye J, Wang ZQ. Efficacy of dietary supplementation with botanicals on carbohydrate metabolism in humans. Endocr Metab Immun Disord Drug Targets 2008;8:76–81.

Yu R, Hui H, Shlomo M, eds. Insulin secretion and action. Endocrinology (2nd ed). Humana Press; 2005:311–319.

Lee YS, Kim WS, Kim KH, Yoon MJ, Cho HJ, Shen Y, et al. Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states. Diabetes 2006;55:2256–2264.

Zhou JY, Zhou SW, Zhang KB, Tang JL, Guang LX, Ying Y, et al. Chronic effects of berberine on blood, liver glucolipid metabolism and liver PPARs expression in diabetic hyperlipidemic rats. Biol Pharm Bull 2008;31:1169–1176.

Zhou L, Wang X, Shao L, Yang Y, Shang W, Yuan G, et al. Berberine acutely inhibits insulin secretion from beta-cells through 3′, 5′-cyclic adenosine 5′-monophosphate signaling pathway. Endocrinology 2008;149:4510–4518.

Kong WJ, Zhang H, Song DQ, Xue R, Zhao W, Wei J, et al. Berberine reduces insulin resistance through protein kinase C-dependent up-regulation of insulin receptor expression. Metabolism 2009;58:109–119.

Liu WH, Hei ZQ, Nie H, Tang FT, Huang HQ, Li XJ, et al. Berberine ameliorates renal injury in streptopzotocin-induced diabetic rats by suppression of both oxidative stress and aldose reductase. Chin Med J (Engl) 2008;121:706–712.

Turner N, Li JY, Gosby A, To SW, Cheng Z, Miyoshi H, et al. Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex i: a mechanism for the action of berberine to activate AMP-activated protein kinase and improve insulin action. Diabetes 2008;57:1414–1418.

Yin J, Xing H, Ye J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism 2008;57:712–717.

Yin J, Zhang H, Ye J. Traditional Chinese medicine in treatment of metabolic syndrome. Endocr Metab Immun Disord Drug Targets 2008;8:99–111.

Judy WV, Hari SP, Stogsdill WW, Judy JS, Naguib YM, Passwater R. Antidiabetic activity of a standardized extract (Glucosol™) from Lagerstroemia speciosa leaves in type II diabetics: a dose-dependence study. J Ethnopharmacol 2003; 87:115–117.

Sauvaire Y, Petit P, Broca C, Manteghetti M, Baissac Y, Fernandez-Alvarez J, et al. 4-hydroxyisoleucine: a novel amino acid potentiator of insulin secretion. Diabetes 1998;47:206–210.

Madar Z, Abel R, Samish S, Arad J. Glucose-lowering effect of fenugreek in non-insulin dependent diabetics. Eur J Clin Nutr 1988;42:51–54.

Broca C, Manteghetti M, Gross R, Baissac Y, Jacob M, Petit P, et al. 4-hydroxyisoleucine: effects of synthetic and natural analogues on insulin secretion. Eur J Pharmacol 2000;390:339–345.

Devi BA, Kamalakkannan N, Prince PS. Supplementation of fenugreek leaves to diabetic rats: effect on carbohydrate metabolic enzymes in diabetic liver and kidney. Phytother Res 2003;17:1231–1233.

Preet A, Siddiqui MR, Taha A, Badhai J, Hussain ME, Yadava PK, et al. Long-term effect of Trigonella foenum graecum and its combination with sodium orthovanadate in preventing histopathological and biochemical abnormalities in diabetic rat ocular tissues. Mol Cell Biochem 2006;289:137–147.

Siddiqui MR, Moorthy K, Taha A, Hussain ME, Baquer NZ. Low doses of vanadate and trigonella synergistically regulate Na+/K+-ATPase activity and GLUT4 translocation in alloxandiabetic rats. Mol Cell Biochem 2006;285:17–27.

Kochhar A, Nagi M. Effect of supplementation of traditional medicinal plants on blood glucose in non-insulin-dependent diabetics: a pilot study. J Med Food 2005;8:545–549.

Annida B, Stanely Mainzen Prince P. Supplementation of fenugreek leaves reduces oxidative stress in streptozotocin-induced diabetic rats. J Med Food 2005;8:382–385.

Flammang AM, Cifone MA, Erexson GL, Stankowski LF Jr. Genotoxicity testing of a fenugreek extract. Food Chem Toxicol 2004;42:1769–1775.

Shanmugasundaram ER, Rajeswari G, Baskaran K, Rajesh Kumar BR, Radha Shanmugasundaram K, Kizar Ahmath B. Use of Gymnema sylvestre leaf extract in the control of blood glucose in insulin-dependent diabetes mellitus. J Ethnopharmacol 1990;30:281–294.

Shanmugasundaram ER. Antidiabetic effect of a leaf extract from Gymnema sylvestre in non-insulin-dependent diabetes mellitus patients. J Ethnopharmacol 1990;30:295–300.

Khan A, Safdar M, Ali Khan MM, Khattak KN, Anderson RA. Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care 2003;26:3215–3218.

Crawford P. Effectiveness of cinnamon for lowering hemoglobin A1c in patients with type 2 diabetes: a randomized, controlled trial. J Am Board Fam Med 2009;22:507–512.

Anderson RA, Broadhurst CL, Polansky MM, Schmidt WF, Khan A, Flanagan VP, et al. Isolation and characterization of polyphenol type-A polymers from cinnamon with insulin-like biological activity. J Agric Food Chem 2004;52:65–70.

Anderson RA. Chromium and polyphenols from cinnamon improve insulin sensitivity. Proc Nutr Soc 2008;67:48–53.

Jarvill-Taylor KJ, Anderson RA, Graves DJ. A hydroxychalcone derived from cinnamon functions as a mimetic for insulin in 3T3-L1 adipocytes. J Am Coll Nutr 2001;20:327–336.

Baker WL, Gutierrez-Williams G, White CM, Kluger J, Coleman CI. Effect of cinnamon on glucose control and lipid parameters. Diabetes Care 2008;31:41–43.

Hsu CH, Liao YL, Lin SC, Hwang KC, Chou P. The mushroom Agaricus blazei Murill in combination with metformin and gliclazide improves insulin resistance in type 2 diabetes: a randomized, double-blinded, and placebo-controlled clinical trial. J Altern Complement Med 2007;13:97–102.

Grover JK, Vats V, Yadav S. Effect of feeding aqueous extract of Pterocarpus marsupium on glycogen content of tissues and the key enzymes of carbohydrate metabolism. Mol Cell Biochem 2002;241:53–59.

Penumathsa SV, Thirunavukkarasu M, Zhan L, Maulik G, Menon VP, Bagchi D, et al. Resveratrol enhances GLUT-4 translocation to the caveolar lipid raft fractions through AMPK/AKT/eNOS signaling pathway in diabetic myocardium. J Cell Mol Med 2008;12:2350–2361.

Singh SS, Pandey SC, Srivastava S, Gupta VS, Patro B, Ghosh AC. Chemistry and medicinal properties of Tinospora cordifolia (Guduchi). Indian J Pharmacol 2003;35:83–91.

Chattopadhyay RR. A comparative evaluation of some blood sugar lowering agents of plant origin. J Ethnopharmacol 1999;67:367–372.

Mukherjee PK, Maiti K, Mukherjee K, Houghton PJ. Leads from Indian medicinal plants with hypoglycemic potentials. J Ethnopharmacol 2006;106:1–28.

Ng TB, Wong CM, Li WW, Yeung HW. Insulin-like molecules in Momordica charantia seeds. J Ethnopharmacol 1986;15:107–117.

Yu BC, Hung CR, Chen WC, Cheng JT. Antihyperglycemic effect of andrographolide in streptozotocin-induced diabetic rats. Planta Med 2003;69:1075–1079.

Sugihara Y, Nojima H, Matsuda H, Murakami T, Yoshikawa M, Kimura I. Antihyperglycemic effects of gymnemic acid IV, a compound derived from Gymnema sylvestre leaves in streptozotocin-diabetic mice. J Asian Nat Prod Res 2000;2:321–327.

Ohnishi M, Matuo T, Tsuno T, Hosoda A, Nomura E, Taniguchi H, et al. Antioxidant activity and hypoglycemic effect of ferulic acid in STZ-induced diabetic mice and KK-Ay mice. Bio Factors 2004;21:315–319.

Vessal M, Hemmati M, Vasei M. Antidiabetic effects of quercetin in streptozocin-induced diabetic rats. Comp Biochem Physiol C Toxicol Pharmacol 2003;135C:357–364.

Hii CS, Howell SL. Effects of flavonoids on insulin secretion and 45Ca2+ handling in rat islets of langerhans. J Endocrinol 1985;107:1–8.

Mezei O, Banz WJ, Steger RW, Peluso MR, Winters TA, Shay N. Soy isoflavones exert antidiabetic and hypolipidemic effects through the PPAR pathways in obese Zucker rats and murine RAW 264.7 cells. J Nutr 2003;133:1238–1243

Waltner-Law ME, Wang XL, Law BK, Hall RK, Nawano M, Granner DK. Epigallocatechin gallate, a constituent of green tea, represses hepatic glucose production. J Biol Chem 2002;277:34933–34940.

Chakravarthy BK, Gupta S, Gambhir SS, Gode KD. The prophylactic action of (−)-epicatechin against alloxan induced diabetes in rats. Life Sci 1981;29:2043–2047.

Rizvi SI, Zaid MA. Insulin-like effect of (−)epicatechin on erythrocyte membrane acetylcholinesterase activity in type 2 diabetes mellitus. Clin Exp Pharmacol Physiol 2001;28:776–778.

Cherian S, Augusti KT. Antidiabetic effects of a glycoside of leucopelargonidin isolated from Ficus bengalensis Linn. Indian J Exp Biol 1993;31:26–29.

Cooper EJ, Hudson AL, Parker CA, Morgan NG. Effects of the beta-carbolines, harmane and pinoline, on insulin secretion from isolated human islets of langerhans. Eur J Pharmacol 2003;482:189–196.

Sheela CG, Augusti KT. Antidiabetic effects of S-allyl cysteine sulphoxide isolated from garlic Allium sativum Linn. Indian J Exp Biol 1992;30:523–526.

Sheela CG, Kumud K, Augusti KT. Anti-diabetic effects of onion and garlic sulfoxide amino acids in rats. Planta Med 1995;61:356–357.

Mathew PT, Augusti KT. Hypoglycaemic effects of onion, Allium cepa Linn. on diabetes mellitus: a preliminary report. Indian J Physiol Pharmacol 1975;19:213–217.

Kumari K, Mathew BC, Augusti KT. Antidiabetic and hypolipidemic effects of S-methyl cysteine sulfoxide isolated from Allium cepa Linn. Indian J Biochem Biophys 1995;32:49–54.

Prabhakar PK, Doble M. Synergistic effect of phytochemicals in combination with hypoglycemic drugs on glucose uptake in myotubes. Phytomedicine 2009;16:1119–1126.

Prabhakar PK, Doble M. Interaction of phytochemicals with hypoglycemic drugs on glucose uptake in L6 myotubes. Phytomedicine 2010;18:285–291.

FULL TEXT LINK

More>

浏览量

1330

Downloads

CSCD

文章被引用时，请邮件提醒。

Submit

工具集

关联资源

Time-effect relationship of extracts from ginseng, notoginseng and chuanxiong on vascular endothelial cells senescence

Treatment of neuropathic pain with plant medicines

The effect of Baihu Decoction (白虎汤) on blood glucose levels in treating systemic inflammatory response syndrome

Effects of hydro-alcoholic extract of Launaea acanthodes on serum gonadotropin and testosterone levels and the structure of seminiferous tubules in hyperglycemic rats

The application of biotechnology in medicinal plants breeding research in China