title: Immunohistochemistry, histopathology, and biomarker studies of swertiamarin, a secoiridoid glycoside, prevents and protects streptozotocin-induced β-cell damage in Wistar rat pancreas.
abstract: BACKGROUND
  Diabetes mellitus is globally the major cause for metabolic syndrome in STZ-induced diabetic rats, leading to mortality. Treatment of diabetes by oral hypoglycemic agents causes adverse side effects and thus treatment with natural herbal drugs like swertiamarin is promising. Swertiamarin, an active compound isolated from Enicostemma littorale possesses antidiabetic activity and enhances β cell regeneration which causes reversal of diabetes.
  
  
  OBJECTIVE
  The present study aims at the following: (1) to evaluate antidiabetic, anti-hyperlipidaemic, activity of swertiamarin in Streptozotocin- induced diabetic rats using biomarkers. (2) To assess histopathological alterations in Pancreas, Liver, Kidney, and Heart of swertiamarin-treated STZ-induced diabetic rats and confirm cytoprotective activity of swertiamarin by Immunohistochemistry and morphometric investigations.
  
  
  METHODS
  Diabetes was induced intraperitoneally in male Wistar rats by Streptozotocin (STZ 50 mg/kg). After STZ-induction, hyperglycemic rats were treated with doses of swertiamarin orally (15, 25, 50 mg/kg) each for 28 days. Glibenclamide (2.5 mg/kg), a sulphonyl urea, was used as a standard drug. The glycemic control was measured by the biochemical parameter assays. Histopathology analysis of organs and immunohistochemistry of islets were carried out.
  
  
  RESULTS
  Our study results showed that oral administration of swertiamarin at a dosage of 15, 25, 50 mg/kg bw for 28 days resulted in a significant (p < 0.01) decrease in fasting blood glucose, HbA1c, TC, TG, LDL, and increased the levels of hemoglobin, plasma insulin, TP, body weight, and HDL levels significantly (p < 0.01) when compared to STZ-induced diabetic rats, as confirmed by immunohistochemical studies. The effect of swertiamarin on Carbohydrate-metabolizing enzymes was investigated and found to have normal therapeutic activity. Histopathological studies of Pancreas of swertiamarin-treated diabetic rats showed regeneration of islets when compared to STZ-induced diabetic rats, as confirmed by immunohistochemical studies.
  
  
  CONCLUSIONS
  Our research results clearly substantiate that swertiamarin possesses antihyperglycemic, antihyperlipidemic, cytoprotective, and immune reactivity and also a broad spectrum potential of treating diabetes and other complications related to diabetes and hence can be developed into a potent oral antidiabetic drug.
authors.affiliation: Department of Biotechnology, SRM University, Kattankulathur, Chennai, 603203, Tamilnadu, India. dhanavathy.rajabala@gmail.com.
authors.forename: G
authors.initials: G
authors.lastname: Dhanavathy
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D005905:Glyburide / Q000494:pharmacology / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007150:Immunohistochemistry; D057888:Iridoid Glucosides / Q000494:pharmacology / Q000627:therapeutic use*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011753:Pyrones / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D057888:Iridoid Glucosides; D010936:Plant Extracts; D020011:Protective Agents; D011753:Pyrones; C013270:swertiamarin; D005905:Glyburide
keywords: Morphometry; Nephropathy; Neuropathy; Streptozotocin; Swertiamarin