Homeopathy 2013; 102(03): 160-171
DOI: 10.1016/j.homp.2013.05.002
Original Paper
Copyright © The Faculty of Homeopathy 2013

Effect of homeopathic preparations of Syzygium jambolanum and Cephalandra indica on gastrocnemius muscle of high fat and high fructose-induced type-2 diabetic rats

Sathish Sampath
1   Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Sekkizhar Campus, Taramani, Chennai 600 113, India
Akilavalli Narasimhan
1   Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Sekkizhar Campus, Taramani, Chennai 600 113, India
Raveendar Chinta
2   Central Council for Research in Homeopathy, 61-65, Institutional Area, Opp. D-Block, Janakpuri, New Delhi 110 058, India
K.R. Janardanan Nair
2   Central Council for Research in Homeopathy, 61-65, Institutional Area, Opp. D-Block, Janakpuri, New Delhi 110 058, India
Anil Khurana
2   Central Council for Research in Homeopathy, 61-65, Institutional Area, Opp. D-Block, Janakpuri, New Delhi 110 058, India
Debadatta Nayak
2   Central Council for Research in Homeopathy, 61-65, Institutional Area, Opp. D-Block, Janakpuri, New Delhi 110 058, India
Alok Kumar
2   Central Council for Research in Homeopathy, 61-65, Institutional Area, Opp. D-Block, Janakpuri, New Delhi 110 058, India
Balasubramanian Karundevi
1   Department of Endocrinology, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Sekkizhar Campus, Taramani, Chennai 600 113, India
› Author Affiliations

Subject Editor:
Further Information

Publication History

Received21 October 2012
revised30 April 2013

accepted07 May 2013

Publication Date:
20 December 2017 (online)

Background: Homeopathy is a holistic method of treatment that uses microdoses of natural substances originating from plants, minerals, or animal parts. Syzygium jambolanum and Cephalandra indica are used in homeopathy for treatment of type-2 diabetes. However, the molecular mechanisms responsible for such effects are not known.

Methods: Homeopathic preparations of S. jambolanum and C. indica in mother tincture, 6c and 30c were used to examine the molecular mechanism of antidiabetic effects in the skeletal muscle of rats with high fat and fructose-induced type-2 diabetes mellitus. After 30 days treatment, fasting blood glucose, serum insulin and insulin signaling molecules in the skeletal muscle (gastrocnemius) were measured.

Results: Diabetic rats showed a significant decrease in serum insulin and lipid profile as well as low levels of insulin receptor (IR), v-akt murine thymoma viral oncogene homolog (Akt), p-Aktser473 and glucose transporter-4 (GLUT4) protein expression (p < 0.05) with a significant increase in fasting blood glucose level (p < 0.05) compared to the control group. Treatment with homeopathic remedies significantly increased the serum insulin and expression of these proteins (p < 0.05) with a significant decrease in fasting blood glucose (p < 0.05) compared to diabetic rats.

Conclusions: In the present study homeopathic preparations of S. jambolanum and C. indica, including ultramolecular dilutions exhibit antidiabetic effects, improving insulin action through activation of insulin signaling molecules in skeletal muscle of type-2 diabetic rats.

  • References

  • 1 Wild S., Roglic G., Green A., Sicree R., King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004; 27: 1047-1053.
  • 2 Ginsberg H.N. Insulin resistance and cardiovascular disease. J Clin Invest 2000; 106: 453-458.
  • 3 Saini V. Molecular mechanisms of insulin resistance in type 2 diabetes mellitus. Insulin 2010; 1 (03) 68-75.
  • 4 Bennett W.L., Odelola O.A., Wilson L.M. et al. Evaluation of guideline recommendations on oral medications for type 2 diabetes mellitus: a systematic review. Ann Intern Med 2012; 156: 27-36.
  • 5 Khuda-Bukhsh A.R. Laboratory research in homeopathy: pro. Intregr Cancer Ther 2006; 5 (04) 320-332.
  • 6 Khuda-Bukhsh A.R., Pathak S. Homeopathic drug discovery: theory update and methodological aspect. Expert Opin Drug Discov 2008; 3 (08) 979-990.
  • 7 Teut M., Lüdtke R., Schnabel K., Willich S.N., Witt C.M. Homeopathic treatment of elderly patients – a prospective observational study with follow-up over a two year period. BMC Geriatr 2010 Feb 22; 10: 10.
  • 8 De A., Das A., Dutta S., Chakraborty D., Boujedaini N., Khuda-Bukhsh A.R. Potentized homeopathic drug Arsenium Album 30C inhibits intracellular reactive oxygen species generation and up-regulates expression of arsenic resistance gene in arsenine-exposed bacteria Escherichia coli . J Chin Integr Med 2012; 10 (02) 210-227.
  • 9 Linde K., Clausius N., Ramirez G. et al. Are the clinical effects of homeopathy placebo effects? A meta-analysis of placebo-controlled trials. Lancet 1997; 350: 834-843.
  • 10 Eisenberg D.M., Davis R.B., Ettner S.L. et al. Trends in alternative medicine use in the United States, 1990–1997: results of a follow-up national survey. JAMA 1998; 280: 1569-1575.
  • 11 Oxford University Press US. Whorton J.C. Nature Cures: The History of Alternative Medicine in America. 2004. New York: Oxford University Press; 18-52.
  • 12 Altunc U., Pittler M.H., Ernst E. Homeopathy for childhood and adolescence ailments: systematic review of randomized clinical trials. Mayo Clinic Proc 2007; 82 (01) 69-75.
  • 13 Vijayakumar S. Alternative medicine: homeopathy – a review. Inter J of Pharm 2012; 2 (02) 57-69.
  • 14 Bellavite P., Conforti A., Piasere V., Ortolani R. Immunology and homeopathy. 1. Historical background. Evid Based Complement Alternat Med 2005; 2 (04) 441-452.
  • 15 Chikramane P.S., Suresh A.K., Bellare J.R., Kane S.G. Extreme homeopathic dilutions retain starting materials: a nanoparticulate perspective. Homeopathy 2010; 99 (04) 231-242.
  • 16 Sharma B., Viswanath G., Salunke R., Roy P. Effects of flavonoid-rich extract from seeds of Eugenia jambolana (L.) on carbohydrate and lipid metabolism in diabetic mice. Food Chem 2008; 110: 697-705.
  • 17 Panda D.K., Ghosh D., Bhat B., Talwar S.K., Jaggi M., Mukherjee R. Diabetic therapeutic effects of ethyl acetate fraction from the roots of Musa paradisiaca and seeds of Eugenia jambolana in streptozotocin-induced male diabetic rats. Methods Find Exp Clin Pharmacol 2009; 31 (09) 571-584.
  • 18 Helmstädter A. Antidiabetic drugs used in Europe prior to the discovery of insulin. Pharmazie 2007; 62 (09) 717-720.
  • 19 Kurpad A.V., Raj R. The effect of Ivy Gourd (Coccinia cordifolia) extract on diabetic patients. Bull Nutr Foundation India 2008; 29: 1-8.
  • 20 Balaraman A.K., Singh J., Dash S., Maity T.K. Antihyperglycemic and hypolipidemic effects of Melothria maderaspatana and Coccinia indica in Streptozotocin induced diabetes in rats. Saudi Pharm J 2010; 18: 173-178.
  • 21 Nampurath G.K., Mathew S.P., Khanna V. et al. Assessment of hypolipidaemic activity of three thiazolidin-4-ones in mice given high-fat diet and fructose. Chem Biol Interact 2008; 171 (03) 363-368.
  • 22 Gonzalez C.G., Alonso A., Balbin M., Diaz F., Fernandez S., Patterson A.M. Effects of pregnancy on insulin receptor in liver, skeletal muscle and adipose tissue of rats. Gynecol Endocrinol 2002; 16: 193-205.
  • 23 Selvaraj J., Sathish S., Mayilvanan C., Balasubramanian K. Excess aldosterone-induced changes in insulin signaling molecules and glucose oxidation in gastrocnemius muscle of adult male rat. Mol Cell Biochem 2013; 372 (1–2): 113-126.
  • 24 Liu Y., Wan Q., Guan O., Gao L., Zhao J. High-fat diet feeding impairs both the expression and activity of AMPKa in rats skeletal muscle. Biochem Biophy Res Commun 2006; 339: 701-707.
  • 25 Dombrowski L., Roy D., Mareotte B., Marette A. A new procedure for the isolation of plasma membrane, T-tubules and internal membranes from skeletal muscles. Am J Physiol Endocrinol Metab 1996; 270: 667-676.
  • 26 Nevado C., Valverde A.M., Benito M. Role of insulin receptor in the regulation of glucose uptake in neonatal hepatocytes. Endocrinology 2006; 147 (08) 3709-3718.
  • 27 Lowry O.H., Rosebrough N.J., Farr A.L., Randall R.J. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193: 265-275.
  • 28 Centers for Disease Control and Prevention. National Diabetes Fact Sheet: National Estimates and General Information on Diabetes in the United States. Revised edn. Atlanta, GA: Centers for Disease Control and Prevention; 1998.
  • 29 Bagai U., Rajan A., Kaur S. Antimalarial potential of Nosode 30 and 200 against Plasmodium berghei infection in BALB/c mice. J Vector Borne Dis 2012; 49 (02) 72-77.
  • 30 Dhanabal S.P., Koate C.K., Ramanathan M., Elango K., Suresh B. The hypoglycemic activity of Coccinia indica Wight & Arn. and its influence on certain biochemical parameters. Indian J Pharmacol 2004; 36: 249-250.
  • 31 Schossler D.R., Mazzanti C.M., Luz S.C.A. et al. Syzygium cumini and the regeneration of insulin positive cells from the pancreatic duct. Braz J Vet Res Anim Sci 2004; 41: 236-239.
  • 32 Mallick C., Chatterjee K., GuhaBiswas M., Ghosh D. Antihyperglycemic effects of separate and composite extract of root of Musa paradisiaca and leaf of Coccinia indica in streptozotocin-induced diabetic male albino rat. Afr J Tradit Complement Altern Med 2007; 4 (03) 362-371.
  • 33 Grover J.K., Yadav S., Vats V. Medicinal plants of India with anti-diabetic potential. J Ethnopharmacol 2002; 81 (01) 81-100.
  • 34 Akhtar M.A., Rashid M., Wahed II M. et al. Comparison of long-term antihyperglycemic and hypolipidemic effects between Coccinia cordifolia (Linn.) and Catharanthus roseus (Linn.) in alloxan-induced diabetic rats. Res J Med Med Sci 2007; 2 (01) 29-34.
  • 35 Sahana D.A., Shivaprakash G., Baliga R. et al. Effect of Eugenia jambolana on plasma glucose, insulin sensitivity and HDL-C levels: preliminary results of a randomized clinical trial. J Pharm Res 2010; 3: 1268-1270.
  • 36 Ravi K., Sivagnanam K., Subramanian S. Anti-diabetic activity of Eugenia jambolana seed kernels on streptozotocin-induced diabetic rats. J Med Food 2004; 7 (02) 187-191.
  • 37 Umamaheswari M., Chatterjee T.K. In vitro antioxidant activities of the fractions of Coccinia grandis L. leaf extract. Afr J Tradit Complement Altern Med 2008; 5 (01) 61-73.
  • 38 Khandagale A.N., Shanbhag D.A. Application of HPTLC in the standardization of a homoeopathic mother tincture of Syzygium Jambolanum . J Chem Pharm Res 2011; 3 (01) 395-401.
  • 39 Morton J. Fruits of warm climates. Miami: Julia Morton Winterville North Carolina; 1987: 281-286.
  • 40 Rastogi R.M., Mehrotra B.N. Lucknow, India: Central Drug Research Institute; Compendium of Indian Medicinal Plants. 1 1990: 388-389.
  • 41 Ravi K., Ramachandran B., Subramanian S. Protective effect of Eugenia jambolana seed kernel on tissue antioxidants in streptozotocin induced diabetic rats. Biol Pharm Bull 2004; 27 (08) 1212-1217.
  • 42 Ravi K., Ramachandran B., Subramanian S. Effect of Eugenia jambolana seed kernel on antioxidant defense system in streptozotocin induced diabetes in rats. Life Sci 2004; 75 (22) 2717-2731.
  • 43 Bajpai M., Pande A., Tewari S.K., Prakash D. Phenolic contents and antioxidant activity of some food and medicinal plants. Int J Food Sci Nutr 2005; 56 (04) 287-291.
  • 44 Sagrawat H., Mann A., Kharya M. Pharmacological potential of Eugenia jambolana: a review. Pharmacog Mag 2006; 2 (06) 96-105.
  • 45 Afify M.R., Fayed S.A., Shalaby E.A., El-Shemy H.A. Syzygium cumini (pomposia) active principles exhibit potent anticancer and antioxidant activities. Afr J Pharm Pharmacol 2011; 5 (07) 948-956.
  • 46 Singh G., Gupta P., Rawat P., Puri A., Bhatia G., Maurya R. Antidyslipidemic activity of polyprenol from Coccinia grandis in high-fat diet-fed hamster model. Phytomedicine 2007; 14 (12) 792-798.
  • 47 Bhakuni D.S., Srivastava S.N., Sharma V.N., Kaul K.N. Chemical examination of the fruits of Coccinia indica . J Sci Ind Res Sect B Phys Sci 1962; 21B: 237-238.
  • 48 Basu K., Ghosh B.K. Chemical investigation of Coccinia indica . Trans Bose Res Inst (Calcutta) 1972; 35 (02) 43-44.
  • 49 Deokate U.A., Khadabadi S.S. Pharmacology and phytochemistry of Coccinia indica-review. J Pharmaco Phyto 2011; 3 (11) 155-159.
  • 50 Chandira M., Vankateswarlu B.S., Gangwar R.K. et al. Studies on anti-stress and free radical scavenging activity of whole plant of Coccinia Indica Linn. Int J Pharm Sci 2010; 01 (01) 50-55.
  • 51 Ravi K., Rajasekaran S., Subramanian S. Antihyperlipidemic effect of Eugenia jambolana seed kernel on streptozotocin-induced diabetes in rats. Food Chem Toxicol 2005; 43 (09) 1433-1439.
  • 52 Schoenfelder T., Warmlin C.Z., Manfredini M.S. et al. Hypoglycemic and hypolipidemic effect of leaves from Syzygium cumini (L.) Skeels, Myrtaceae in diabetic rats. Braz J Pharmacog 2010; 20 (02) 222-227.
  • 53 Eshrat M.H. Effect of Coccinia indica (l.) and Abroma augusta (l.) on glycemia, lipid profile and on indicators of end-organ damage in streptozotocin induced diabetic rats. Indian J Clin Biochem 2003; 18: 54-63.
  • 54 Evans J.L., Goldfine I.D., Maddux B.A., Grodsky G.M. Are oxidative stress activated signaling pathways mediators of insulin resistance and β-cell dysfunction?. Diabetes 2003; 52: 1-8.
  • 55 Ceriello A., Motz E. Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arterioscler Thromb Vasc Biol 2004; 24: 816-823.
  • 56 White M.F., Yenush L. The IRS-signaling system: a network of docking proteins that mediate insulin and cytokine action. Curr Top Microbiol Immunol 1998; 228: 179-208.
  • 57 Taylor S.I. Deconstructing type 2 diabetes. Cell 1999; 97 (01) 9-12.
  • 58 Bhattacharya S., Dey D., Roy S.S. Molecular mechanism of insulin resistance. J Biosci 2007; 32: 405-413.
  • 59 Leontowicz H., Gorinstein S., Lojek A., Leontowicz M., Ciz M., Soliva-Fortuny R. Comparative content of some bioactive compounds in apples, peaches and pears and their influence on lipids and antioxidant capacity in rats. J Nutr Biochem 2002; 13 (10) 603-610.
  • 60 Guo L., Hu W.R., Lian J.H., Ji W., Deng T., Qian M. Anti-hyperlipidemic properties of CM 108 (a flavone derivative) in vitro and in vivo . Eur J Pharmacol 2006; 551: 80-86.
  • 61 Tamilselvan N., Thirumalai T., Elumalai E.K., Balaji R., David E. Pharmacognosy of Coccinia grandis: a review. Asian Pac J Trop 2011; 5: S299-S302.
  • 62 Khuda-Bukhsh A.R. Towards understanding molecular mechanisms of action of homeopathic drugs: an overview. Mol Cell Biochem 2003; 253: 339-345.
  • 63 Abdelli S., Bonny C. JNK3 maintains expression of the insulin receptor substrate 2 (IRS2) in insulin-secreting cells: functional consequences for insulin signaling. PLoS One 2012; 7 (05) e35997.
  • 64 Hur E.M., Zhou F.Q. GSK3 signalling in neural development. Nat Rev Neurosci 2010; 11: 539-551.
  • 65 Manning B.D., Cantley L.C. AKT/PKB signaling: navigating downstream. Cell 2007; 129: 1261-1274.
  • 66 Deprez J., Vertommen D., Alessi D.R., Hue L., Rider M.H. Phosphorylation and activation of heart 6-phosphofructo-2-kinase by protein kinase B and other protein kinases of the insulin signaling cascades. J Biol Chem 1997; 272: 17269-17275.
  • 67 Gottlob K., Majewski N., Kennedy S., Kandel E., Robey R.B., Hay N. Inhibition of early apoptotic events by Akt/PKB is dependent on the first committed step of glycolysis and mitochondrial hexokinase. Genes Dev 2001; 15: 1406-1418.
  • 68 Armoni M., Harel C., Bar-Yoseph F., Milo S., Karnieli E. Free fatty acids repress the GLUT4 gene expression in cardiac muscle via novel response elements. J Biol Chem 2005; 280: 34786-34795.
  • 69 Tappy L., Le K. Metabolic Effects of Fructose and the Worldwide Increase in Obesity. Physiol Rev 2010; 90: 23-46.
  • 70 Kaneto H., Katakami N., Matsuhisa M., Matsuoka T. Role of reactive oxygen species in the progression of type 2 diabetes and atherosclerosis. Mediators Inflamm 2010; 2010: 1-11.
  • 71 Sano H., Kane S., Sano E. et al. Insulin stimulated phosphorylation of Rab GTPase activating protein regulates GLUT4 translocation. J Biol Chem 2003; 278: 14599-14602.
  • 72 Nie Y., Ma R.C., Chan J.C., Xu H., Xu G. Glucose-dependent insulinotropic peptide impairs insulin signaling via inducing adipocyte inflammation in glucose-dependent insulinotropic peptide receptor-overexpressing adipocytes. FASEB J 2012; 26: 2383-2393.
  • 73 Karnieli E., Armoni M. Transcriptional regulation of the insulin-responsive glucose transporter GLUT4 gene: from physiology to pathology. Am J Physiol Endocrinol Metab 2008; 295: E38-E45.
  • 74 Zaubair Q.M., Ahmad M.M., Ahmad W. Effect of mother tinctures of Gymnema sylvestre and Cephalendra indica on diabetes type II. Pakistan J Med Res 2002; 41 (03) 1-6.
  • 75 Kanchana G., Malini P., Murugan R. Antibiabetic efficacy of ellagic acid in streptozotocin induced diabetes mellitus in albino wistar rats. Asian J Pharm Clin Res 2011; 4 (03) 124-128.