The anti-diabetic and antioxidant effects of a combination of Commiphora mukul, Commiphora myrrha and Terminalia chebula in diabetic rats

Document Type: Original Research Article

Authors

1 Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

2 Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

3 Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

4 Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran.

Abstract

Objective: Effects of Commiphora mukul and Commiphora myrrha ethanolic extracts and Terminalia chebula hydro-ethanolic extract combination were evaluated in streptozotocin (STZ)-induced diabetic rats.
Materials and Methods: Male Wistar rats (n=48) were randomly assigned into: control; diabetic; diabetic+metformin (300 mg/kg); diabetic+dose 1 of herbal combination (438 mg/kg of C. mukul+214 mg/kg of C. myrrha+857 mg/kg of T. chebula); diabetic+dose 2 (642 mg/kg of C. mukul+214 mg/kg of C. myrrha+642 mg/kg of T. chebula); and diabetic+dose 3 (857 mg/kg of C. mukul+438 mg/kg of C. myrrha+1714 mg/kg t of T. chebula). All treatments were given orally by gavage. Diabetes was induced by STZ (60 mg/kg, i.p.). At the end of study (day 28), blood glucose, insulin and lipid profile; as well as hepatic malondialdehyde (MDA) and thiol content, and superoxide dismutase (SOD) and catalase (CAT) activities were determined.
Results: In diabetic rats, plasma glucose, triglycerides (TG), total cholesterol (TC), and LDL-C, as well as hepatic MDA levels were elevated but plasma HDL-C and insulin, and hepatic thiol content and SOD and CAT activities were reduced compared to control (p<0.01-p<0.001). In diabetic+dose 3, plasma TC, TG, and LDL-C and hepatic MDA level decreased (p<0.001), while plasma HDL-C and insulin, and hepatic thiol content, and SOD and CAT activities increased compared to diabetic (p<0.01-p<0.001). Treatment with dose 1 and 2 improved such abnormalities in diabetic rats except for insulin level (p<0.05-p<0.001). The herbal combination effects were comparable to those of metformin. Metformin did not significantly change serum insulin and HDL-C levels, and hepatic SOD activity; however, serum levels of TC, TG, and LDL-C, as well as hepatic MDA levels, thiol content and CAT activity were improved compared to diabetic (p<0.05-p<0.001).
Conclusion: These results indicate that this herbal combination acts as an anti-diabetic, antioxidant and hypolipidemic agent and it may be suggested as a beneficial remedy for diabetic patients.


Keywords

Main Subjects


Aebi H. 1984. Catalase in vitro. Methods Enzymol, 105:121-126.

Ahmadi-Naji R, Heidarian E, Ghatreh-Samani K. 2017. Evaluation of the effects of the hydroalcoholic extract of Terminalia chebula fruits on diazinon-induced liver toxicity and oxidative stress in rats. Avicenna J Phytomed, 7: 454-456.               

Bellamkonda R, Rasineni K, Singareddy SR, Kasetti RB, Pasurla R, Chippada AR, Desireddy S. 2011. Antihyperglycemic and antioxidant activities of alcoholic extract of Commiphora mukul gum resin in streptozotocin induced diabetic rats. Pathophysiology, 18:255-261. 

Bhat M, Zinjarde SS, Bhargava SY, Kumar AR, Joshi BN. 2011. Antidiabetic Indian plants: a good source of potent amylase inhibitors. Evid Based Complement Alternat Med, 2011:810-815.   

Cheng H-Y, Lin T-C, Yu K-H, Yang C-M, Lin C-C. 2003. Antioxidant and free radical scavenging activities of Terminalia chebula. Biol Pharm Bull, 26:1331-1335.

Cho N, Shaw J, Karuranga S, Huang Y, da Rocha Fernandes J, Ohlrogge A,  Malanda B. 2018. IDF Diabetes Atlas: global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract, 138:271-281.

Choi M-K, Kim H-G, Han J-M, Lee J-S, Lee JS, Chung SH, Son CG. 2015. Hepatoprotective effect of Terminalia chebula against t-BHP-induced acute liver injury in C57/BL6 mice. Evid Based Complement Alternat Med, 2015:51-58.

El‐Ashmawy IM, Ashry KM, El‐Nahas AF, Salama OM. 2006. Protection by turmeric and myrrh against liver oxidative damage and genotoxicity induced by lead acetate in mice. Basic Clin Pharmacol Toxicol, 98:32-37.

El Ashry E, Rashed N, Salama O, Saleh A. 2003. Components, therapeutic value and uses of myrrh. Die Pharmazie, 58:163-168.

Francis JA, Raja SN, Nair MG. 2004. Bioactive Terpenoids and Guggulusteroids from Commiphora mukul Gum Resin of Potential Anti‐Inflammatory Interest. Chem biodiversity, 1:1842-1853.

Gao H, Huang Y-N, Xu P-Y, Kawabata J. 2007. Inhibitory effect on α-glucosidase by the fruits of Terminalia chebula Retz. Food Chem, 105:628-634.

Habeeb AF. 1972. Reaction of protein sulfhydryl groups with Ellman's reagent. Methods Enzymol, 25:457-464.

Helal EG, Mahmoud A, El-Badawy EE, Kahwash AA. 2005. Effect of Commiphora myrrha extract on some physiological parameters and histological changes in diabetic albino rats. Egypt. J Hosp Med, 20:148-162.

Hundal RS, Krssak M, Dufour S, Laurent D, Lebon V, Chandramouli V,  Inzucchi SE,  Schumann WC,  Petersen KF, Landau BR, Shulman GI. 2000. Mechanism by which metformin reduces glucose production in type 2 diabetes. Diabetes, 49:2063-2069.

Ighodaro O, A Adeosun. 2018. Vascular Complications in Diabetes Mellitus. Kidney, 4:16-19.

Jandeleit-Dahm K, Cooper ME. 2002. Hypertension and diabetes. Curr Opin Nephrol Hypertens, 11:221-228.

Kannan P, Ramadevi S, Hopper W. 2009. Antibacterial activity of Terminalia chebula fruit extract. African J Microbiol Res, 3:180-184.

Kaveh M, Eidi A, Nemati A and Boskabady MH. 2017. The extract of Portulaca oleracea and its constituent, alpha linolenic acid affects serum oxidant levels and inflammatory cells in sensitized rats. Iran J Allergy Asthma Immunol, 16:256-270.

Kim J-h, Hong C-O, Koo Y-c, Kim S-J, Lee K-W. 2011. Oral administration of ethyl acetate-soluble portion of Terminalia chebula conferring protection from streptozotocin-induced diabetic mellitus and its complications. Biol Pharm Bull, 34:1702-1709.

King GL, MR Loeken. 2004. Hyperglycemia-induced oxidative stress in diabetic complications. Histochem Cell Biol, 122:333-338.

Kumar GP S, Arulselvan P, Kumar DS, Subramanian SP. 2006. Anti-diabetic activity of fruits of Terminalia chebula on streptozotocin induced diabetic rats. J Health Sci, 52:283-291.

Lee H-S, Jung S-H, Yun B-S, Lee K-W. 2007. Isolation of chebulic acid from Terminalia chebula Retz. and its antioxidant effect in isolated rat hepatocytes. Arch Toxicol, 81:211-218.

Lee H-S, Won N. H, Kim K. H, Lee H, Jun W, Lee K-W. 2005. Antioxidant effects of aqueous extract of Terminalia chebula in vivo and in vitro. Biol Pharm Bull, 28:1639-1644.

Madesh M, Balasubramanian KA. 1997. A microtiter plate assay for superoxide using MTT reduction method. Indian J Biochem Biophys, 34:535-539.

Moussa S. 2008. Oxidative stress in diabetes mellitus. Romanian J biophys, 18:225-236.

Naik G, Priyadarsini K, Naik D, Gangabhagirathi R, Mohan H. 2004. Studies on the aqueous extract of Terminalia chebula as a potent antioxidant and a probable radioprotector. Phytomedicine, 11:530-538.

Nasri H. 2013. Toxicity and safety of medicinal plants. J HerbMed Pharm, 2:188-191.

Niethammer P, Grabher C, Look AT, Mitchison TJ. 2009. Hydrogen peroxide-curse or cure? Nature, 459:996-999.

Pfundstein B, El Desouky SK, Hull WE, Haubner R, Erben G, Owen RW. 2010. Polyphenolic compounds in the fruits of Egyptian medicinal plants (Terminalia bellerica, Terminalia chebula and Terminalia horrida): characterization, quantitation and determination of antioxidant capacities. Phytochemistry, 71:1132-1148.

Pinhas-Hamiel O, Zeitler P. 2007. Acute and chronic complications of type 2 diabetes mellitus in children and adolescents. Lancet, 369:1823-1831.

Pushparaj P, Tan C, Tan B. 2000. Effects of Averrhoa bilimbi leaf extract on blood glucose and lipids in streptozotocin-diabetic rats. J Ethnopharmacol, 72:69-76.

Racine P, Auffray B. 2005. Quenching of singlet molecular oxygen by Commiphora myrrha extracts and menthofuran. Fitoterapia, 76:316-323.

Ramesh B, Karuna R, Reddy SS, Sudhakara G, Saralakumari D. 2013. Ethanolic extract of Commiphora mukul gum resin attenuates streptozotocin-induced alterations in carbohydrate and lipid metabolism in rats. EXCLI J, 12:556-561.

Ramesh B, Karuna R, Sreenivasa RS, Haritha K, Sai MD, Sasi BRB, et al. 2012. Effect of Commiphora mukul gum resin on hepatic marker enzymes, lipid peroxidation and antioxidants status in pancreas and heart of streptozotocin induced diabetic rats. Asian Pac J Trop Biomed, 2:895-898.

Ramesh B, Saralakumari D. 2012. Antihyperglycemic, hypolipidemic and antioxidant activities of ethanolic extract of Commiphora mukul gum resin in fructose-fed male Wistar rats. J Physiol Biochem, 68:573-582.

Sasidharan I, Sundaresan A, Nisha V, Kirishna MS, Raghu K, Jayamurthy P. 2012. Inhibitory effect of Terminalia chebula Retz. fruit extracts on digestive enzyme related to diabetes and oxidative stress. J Enzyme Inhib Med Chem, 27:578-586.

Shalaby MA, Hammouda A-E.  2014. Analgesic, anti-inflammatory and anti-hyperlipidemic activities of Commiphora molmol extract (Myrrh). J Intercult Ethnopharmacol, 3:56-61.

Sharma B, Salunke R, Srivastava S, Majumder C, Roy P. 2009. Effects of guggulsterone isolated from Commiphora mukul in high fat diet induced diabetic rats. Food Chem Toxicol, 47:2631-2639.

Shen T, Li G-H, Wang X-N and Lou H-X. 2012. The genus Commiphora: a review of its traditional uses, phytochemistry and pharmacology. J Ethnopharmacol, 142:319-330.

Sheng Z, Zhao J, Muhammad I, Zhang Y. 2018. Optimization of total phenolic content from Terminalia chebula Retz. fruits using response surface methodology and evaluation of their antioxidant activities. PloS one, 13:8-14.

Shokoohi R, Kianbakht S, Faramarzi M, Rahmanian M, Nabati F, Mehrzadi S,  Huseini HF. 2017. Effects of an herbal combination on glycemic control and lipid profile in diabetic women: a randomized, double-blind, placebo-controlled clinical trial. Evid Based Complement Alternat Med, 22:798-804.

Shukla R, Sharma SB, Puri D, Prabhu K, and Murthy PS. 2000. Medicinal plants for treatment of diabetes mellitus. Indian J Clin Biochem, 15:169-177.

Singh RB, Niaz MA, Ghosh S. 1994. Hypolipidemic and antioxidant effects of Commiphora mukul as an adjunct to dietary therapy in patients with hypercholesterolemia. Cardiovasc Drugs Ther, 8:659-664.

Su S, Duan J, Chen T, Huang X, Shang E, Yu L, et al. 2015. Frankincense and myrrh suppress inflammation via regulation of the metabolic profiling and the MAPK signaling pathway. Sci Rep, 5:1366-1368.

Swanston-Flatt S, Day C, Bailey C, Flatt P. 1990. Traditional plant treatments for diabetes. Studies in normal and streptozotocin diabetic mice. Diabetologia, 33:462-464.

Turban S, Stretton C, Drouin O, Green CJ, Watson ML, Gray A, Ross FLantier LViollet BHardie DGMarette AHundal HS. 2012. Defining the contribution of AMP-activated protein kinase (AMPK) and protein kinase C (PKC) in regulation of glucose uptake by metformin in skeletal muscle cells. J Biol Chem, 287:20088-20099.

Ullah A, Khan A, Khan I. 2015. Diabetes mellitus and oxidative stress––A concise. Saudi Pharm J, 24:547-553.

Urizar NL, Liverman AB, D'nette TD, Silva FV, Ordentlich P, Yan Y, Gonzalez FJHeyman RAMangelsdorf DJMoore DD. 2002. A natural product that lowers cholesterol as an antagonist ligand for FXR. Science, 296:1703-1706.

Wei L, Ren F, Zhang X, Wen T, Shi H, Zheng S, et al. 2014. Oxidative stress promotes D-GalN/LPS-induced acute hepatotoxicity by increasing glycogen synthase kinase 3β activity. Inflamm Res, 63:485-494.

Zhou J, Massey S, Li L. 2018. (Metformin: An Old Drug with New Applications. Int J Mol Sci, 19:2863-2868.