Download PDF
Drug Res (Stuttg) 2019; 69(04): 218-226
DOI: 10.1055/a-0665-4291
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Modulation of Oxidative Stress and Hyperglycemia by Rheum spiciformis in Alloxan Induced Diabetic Rats and Characterization of Isolated Compound

Aashiq Hussain Bhat
1   Department of Clinical Biochemistry, School of Biological Sciences, University of Kashmir, Srinagar, India
2   Department of Biochemistry, School of Biological Sciences, University of Kashmir, Srinagar, India
,
Khalid Bashir Dar
1   Department of Clinical Biochemistry, School of Biological Sciences, University of Kashmir, Srinagar, India
2   Department of Biochemistry, School of Biological Sciences, University of Kashmir, Srinagar, India
,
Mohammad Afzal Zargar
2   Department of Biochemistry, School of Biological Sciences, University of Kashmir, Srinagar, India
,
Akbar Masood
1   Department of Clinical Biochemistry, School of Biological Sciences, University of Kashmir, Srinagar, India
2   Department of Biochemistry, School of Biological Sciences, University of Kashmir, Srinagar, India
,
Showkat Ahmad Ganie
1   Department of Clinical Biochemistry, School of Biological Sciences, University of Kashmir, Srinagar, India
2   Department of Biochemistry, School of Biological Sciences, University of Kashmir, Srinagar, India
› Author Affiliations
Further Information

Publication History

received 06 February 2018

accepted 25 July 2018

Publication Date:
12 September 2018 (online)

Also available at
    Permissions and Reprints

Abstract

This study evaluates the ameliorative potential of Rheum spiciformis methanolic (RS-MeOH) extract in reducing oxidative stress and hyperglycemia in albino rats along with characterization of possible therapeutic compound(s). Groups treated with 50 and 100 mg/kg bw plant extract (RS-MeOH ) decrease blood glucose levels from 359.9±8.2 to 209.5±8.5 mg/dl (50 mg/kg bw) and 354.7±13.3 to 162.5±7.4 mg/dl (100 mg/kg bw) on the 0th and 14th day (P<0.001) respectively. This reduction in blood glucose was significant as compared to glibenclamide (20 mg/dl) which reduced glucose levels from 297.7±11.39 to 132.9±8.74 mg/dl on 0th and 14th day respectively. Biochemical parameters triglycerdies, cholesterol, low density lipoprotein (LDL) and creatinine were also reduced in a dose dependent manner. Liver marker enzymes were positively modulated by administration of RS-MeOH (P<0.001). Antioxidant enzyme profile showed an enhanced/better pattern after the administration of RS-MeOH extracts for reduced glutathione, reduced glutathione (GR), glutathione peroxidase (GPx), glutathione–S-transferase (GST) and superoxide dismutase (SOD) in both liver and pancreas. Moreover pancreatic histopathology reports revealed β-cell restorative effects with RS-MeOH, thereby potentiating its role in improving blood glucose levels. RS-MeOH purification and isolation studies involving GC-MS and NMR techniques revealed presence of emodin type compounds in RS-MeOH. Overall Rheum spiciformis showed ameliorative action on oxidative stress and hyperglycemia, however further studies to explore the mechanism of action of possible therapeutic compound in invivo clinical trials will prove beneficial for the advancement of new oral antidiabetic drug.

Key words

Anti-hyperglycemic - oxidative stress - GC-MS - NMR - Glutathione, antioxidant enzymes
 

  • References

  • 1 Lindholm D, Korhonen L, Eriksson O. et al. Recent insights into the role of unfolded protein response in ER stress in health and disease. Frontiers in cell and developmental biology 2017; 5: 1-16
    PubMedGoogle Scholar
  • 2 Bullon P, Newman HN, Battino M. Obesity, diabetes mellitus, atherosclerosis and chronic periodontitis: A shared pathology via oxidative stress and mitochondrial dysfunction?. Periodontology 2000 2014; 64: 139-153
    CrossrefPubMedGoogle Scholar
  • 3 Rajendran P, Nandakumar N, Rengarajan T. et al. Antioxidants and human diseases. Clinica chimica acta 2014; 436: 332-347
    CrossrefPubMedGoogle Scholar
  • 4 Szkudelski T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiological research 2001; 50: 537-546
    PubMedGoogle Scholar
  • 5 Saravanan R, Pari L. Antihyperlipidemic and antiperoxidative effect of Diasulin, a polyherbal formulation in alloxan induced hyperglycemic rats. BMC Complementary and Alternative Medicine 2005; 5: 14
    CrossrefPubMedGoogle Scholar
  • 6 Takamura T, Misu H, Ota T. et al. Fatty liver as a consequence and cause of insulin resistance: Lessons from type 2 diabetic liver. Endocrine Journal 2012; 59: 745-763
    CrossrefPubMedGoogle Scholar
  • 7 Saravanan G, Ponmurugan P. Ameliorative potential of S-allylcysteine: Effect on lipid profile and changes in tissue fatty acid composition in experimental diabetes. Experimental and toxicologic pathology 2012; 64: 639-644
    CrossrefPubMedGoogle Scholar
  • 8 Bailey CJ, Day C. Traditional plant medicines as treatments for diabetes. Diabetes care 1989; 12: 553-564
    CrossrefPubMedGoogle Scholar
  • 9 Mitra SK, Gopumadhavan S, Muralidhar TS. et al. Effect of a herbomineral preparation D-400 in streptozotocin-induced diabetic rats. Journal of Ethnopharmacology 1996; 54: 41-46
    CrossrefPubMedGoogle Scholar
  • 10 Chang CLT, Lin Y, Bartolome AP. et al. Herbal therapies for type 2 diabetes mellitus: Chemistry, biology, and potential application of selected plants and compounds. Evidence-Based Complementary and Alternative Medicine 2013; 2013: 1-33
    PubMedGoogle Scholar
  • 11 Ashok P, Kyada A, Subbarao P. et al. Antioxidant status of a polyherbomineral formulation (Gly-13-C) in STZ-diabetic rats. IJP-International Journal of Pharmacology 2010; 6: 157-172
    PubMedGoogle Scholar
  • 12 Lewis WH, Elvin-Lewis MPF. Medical botany: Plants affecting human health. 2003. John Wiley & Sons;
    Google Scholar
  • 13 Dillard CJ, German JB. Phytochemicals: Nutraceuticals and human health. Journal of the Science of Food and Agriculture 2000; 80: 1744-1756
    CrossrefPubMedGoogle Scholar
  • 14 Parker J, Schellenberger AN, Roe AL. et al. Therapeutic perspectives on chia seed and its oil: A review. Planta Medica 2018; 84: 606-612
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Pan SY, Pan S, Yu Z-L. et al New perspectives on innovative drug discovery: An overview. Journal of Pharmacy & Pharmaceutical Sciences 2010; 13: 450-471
    CrossrefPubMedGoogle Scholar
  • 16 Chatuphonprasert W, Lao-ong T, Jarukamjorn K. Improvement of superoxide dismutase and catalase in streptozotocin-nicotinamide induced type 2-diabetes in mice by berberine and glibenclamide. Pharmaceutical biology 2014; 52: 419-427
    CrossrefPubMedGoogle Scholar
  • 17 Amritpal S, Sanjiv D, Navpreet K. et al. Berberine: Alkaloid with wide spectrum of pharmacological activities. Journal of Natural Products (India) 2010; 3: 64-75
    PubMedGoogle Scholar
  • 18 Sharma VJ, Shah UD. Antihyperglycemic activity of flavonoids from methanolic extract of aerial parts of Scoparia dulcis in streptozotocin induced diabetic rats. International. Journal of ChemTech Research 2010; 2: 214-218
    PubMedGoogle Scholar
  • 19 Jing L, Cui G, Feng Q. et al. Evaluation of hypoglycemic activity of the polysaccharides extracted from Lycium barbarum. African. Journal of Traditional, Complementary and Alternative Medicines 2009; 6: 579-584
    PubMedGoogle Scholar
  • 20 Corson TW, Crews CM. Molecular understanding and modern application of traditional medicines: Triumphs and trials. Cell 2007; 130: 769-774
    CrossrefPubMedGoogle Scholar
  • 21 Li X-J, Zhang H-Y. Western-medicine-validated anti-tumor agents and traditional Chinese medicine. Trends in Molecular Medicine 2008; 14: 1-2
    PubMedGoogle Scholar
  • 22 Hui H, Tang G, Go VLW. Hypoglycemic herbs and their action mechanisms. Chinese Medicine 2009; 4: 11
    CrossrefPubMedGoogle Scholar
  • 23 Niehaus WG, Samuelsson B. Formation of malonaldehyde from phospholipid arachidonate during microsomal lipid peroxidation. The FEBS Journal 1968; 6: 126-130
    PubMedGoogle Scholar
  • 24 Moron MS, Depierre JW, Mannervik B. Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochimica et Biophysica Acta (BBA)-General Subjects 1979; 582: 67-78
    CrossrefPubMedGoogle Scholar
  • 25 Sharma N, Trikha P, Athar M. et al. Inhibition of benzo [a] pyrene-and cyclophoshamide-induced mutagenicity by Cinnamomum cassia. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 2001; 480: 179-188
    PubMedGoogle Scholar
  • 26 Haque R, Bin-Hafeez B, Parvez S. et al. Aqueous extract of walnut (Juglans regia L.) protects mice against cyclophosphamideinduced biochemical toxicity. Human & experimental toxicology 2003; 22: 473-480
    CrossrefPubMedGoogle Scholar
  • 27 Beauchamp C, Fridovich I. Superoxide dismutase: Improved assays and an assay applicable to acrylamide gels. Analytical biochemistry 1971; 44: 276-287
    CrossrefPubMedGoogle Scholar
  • 28 Halliwell B, Gutteridge JMC, Cross CE. Free radicals, antioxidants, and human disease: Where are we now?. The Journal of laboratory and clinical medicine 1992; 119: 598-620
    PubMedGoogle Scholar
  • 29 Yesil-Celiktas O, Girgin G, Orhan H. et al. Screening of free radical scavenging capacity and antioxidant activities of Rosmarinus officinalis extracts with focus on location and harvesting times. European Food Research and Technology 2007; 224: 443-451
    CrossrefPubMedGoogle Scholar
  • 30 Johnson R, de Beer D, Dludla PV et al. Aspalathin from Rooibos (Aspalathus linearis): A Bioactive C-glucosyl Dihydrochalcone with Potential to Target the Metabolic Syndrome. Planta medica 2018
    PubMed
  • 31 Poongothai K, Ponmurugan P, Ahmed KSZ. et al. Antihyperglycemic and antioxidant effects of Solanum xanthocarpum leaves (field grown & in vitro raised) extracts on alloxan induced diabetic rats. Asian Pacific Journal of Tropical Medicine 2011; 4: 778-785
    CrossrefPubMedGoogle Scholar
  • 32 Lipinski B. Pathophysiology of oxidative stress in diabetes mellitus. Journal of Diabetes and its Complications 2001; 15: 203-210
    CrossrefPubMedGoogle Scholar
  • 33 Matteucci E, Giampietro O. Oxidative stress in families of type 1 diabetic patients. Diabetes care 2000; 23: 1182-1186
    CrossrefPubMedGoogle Scholar
  • 34 Moradabadi L, Kouhsari SM, Sani MF. Hypoglycemic Effects of Three Medicinal plants in experimental diabetes: Inhibition of rat intestinal α-glucosidase and enhanced pancreatic insulin and cardiac Glut-4 mRNAs expression. Iranian Journal Of Pharmaceutical Research: IJPR 2013; 12: 387
    PubMedGoogle Scholar
  • 35 Ashraf H, Heidari R, Nejati V. et al. Effects of aqueous extract of Berberis integerrima root on some physiological parameters in streptozotocin-induced diabetic rats. Iranian Journal of Pharmaceutical Research: IJPR 2013; 12: 425
    PubMedGoogle Scholar
  • 36 Kasetti RB, Rajasekhar MD, Kondeti VK. et al. Antihyperglycemic and antihyperlipidemic activities of methanol: Water (4: 1) fraction isolated from aqueous extract of Syzygium alternifolium seeds in streptozotocin induced diabetic rats. Food and Chemical Toxicology 2010; 48: 1078-1084
    CrossrefPubMedGoogle Scholar
  • 37 Gurrola-Díaz CM, García-López PM, Sánchez-Enríquez S. et al. Effects of Hibiscus sabdariffa extract powder and preventive treatment (diet) on the lipid profiles of patients with metabolic syndrome (MeSy). Phytomedicine 2010; 17: 500-505
    CrossrefPubMedGoogle Scholar
  • 38 Senthilkumar R, Chandran R, Parimelazhagan T. Hepatoprotective effect of Rhodiola imbricata rhizome against paracetamol-induced liver toxicity in rats. Saudi Journal Of Biological Sciences 2014; 21: 409-416
    CrossrefPubMedGoogle Scholar
  • 39 Nguyen TTK, Laosinwattana C, Teerarak M. et al. Potential antioxidant and lipid peroxidation inhibition of Phyllanthus acidus leaf extract in minced pork. Asian-Australasian Journal Of Animal Sciences 2017; 30: 1323
    CrossrefPubMedGoogle Scholar
  • 40 Tae H-J, Park JH, Cho J-H. et al. Oenanthe javanica extract increases immunoreactivities of antioxidant enzymes in the rat kidney. Chinese Medical Journal 2014; 127: 3758-3763
    PubMedGoogle Scholar
  • 41 Arif T, Sharma B, Gahlaut A. et al. Anti-diabetic agents from medicinal plants: A review. Chem Biol Lett 2014; 1: 1-13
    PubMedGoogle Scholar
  • 42 Deutschlander MS, Lall N, Van de Venter M. et al. Hypoglycemic evaluation of a new triterpene and other compounds isolated from Euclea undulata Thunb. var. myrtina (Ebenaceae) root bark. Journal of Ethnopharmacology 2011; 133: 1091-1095
    CrossrefPubMedGoogle Scholar