Comparative Study of Antidiabetic Activity of Swertia chirata Extract with Metformin and Pioglitazone on Indinavir Induced Diabetes in Albino Rats

Abstract

Background: Indinavir belongs to a class of protease inhibitors, which is newlinewidely used for the treatment of AIDS. Treatment with indinavir is known to newlinecause hyperglycemia; further, prolonged treatment results in insulin resistance newline(IR), which may lead to the development of diabetes mellitus. newlineIntroduction: The drug indinavir belongs to a class of protease inhibitor, newlinewhich is an important component of highly active antiretroviral therapy. newlineTreatment with indinavir usually causes hyperglycemia, IR and diabetes newlinemellitus. The herb Swertia chirata has blood glucose lowering activity. This newlineherb has been traditionally used for the treatment of hyperglycemia and newlinediabetes mellitus. newlineAim and Objectives: To check the in-vivo efficacy of Swertia chirata over newlineindinavir-induced diabetes mellitus and IR in comparison with known standard newlineantidiabetic drugs such as metformin and pioglitazone. newlineMaterials and Methods: This study was conducted on male albino Wistar newlinerats. A graded dose-response study of indinavir was conducted to determine newlinethe dose capable of producing IR and diabetes mellitus. Animals were divided newlineinto four different groups. Each group received four different doses (36, 71, newline144, and 216 mg/kg BW/p.o.) for 15 days. Physical and biochemical newlineparameters were measured. On the evening of the 14th day, the rats were newlinexix newlinekept for fasting with free access to water. On the morning of the 15th day, newlinesoon after the administration of drug, fasting blood was collected through newlineretro-orbital sinus puncture. Subsequently, biochemical parameters were newlineestimated, and oral glucose tolerance test (OGTT) was performed. Animals newlinewere sacrificed under ketamine anesthesia. The liver and pancreas were newlinedissected out and stored in 10% formalin for histopathological procedures. newlineIndinavir at the dose of 216 mg/kg BW/p.o. was found to produces the desired newlineeffect. Therefore, this dose was selected for further study. newlineA pilot study was conducted to determine the effective dose of Swertia chirata newlineplant extracts in comparison to standard drugs such as metformin and newlinepioglitazone, which possess antidiabetic activity on indinavir-treated rats. Four newlinedifferent doses of metformin (45, 90, 135, and 180 mg/kg BW/p.o.), newlinepioglitazone (0.7, 1.35, 2.7, and 4mg/kg BW/p.o.), and Swertia chirata newlineleaf/root extracts (250, 500, 750, and 1000mg/kg BW/p.o.) were used for the newlinepilot study. The respective dose that possessed desired antidiabetic activity newlinewas as follows: metformin180 mg/kg BW/p.o., pioglitazone 4 mg/kg BW/p.o., newlineand Swertia chirata leaf/root extracts 500 mg/kg BW/p.o.. These doses were newlineselected for the main study. Thereafter, the effect of standard drugs and newlineSwertia chirata extracts were studied on indinavir-treated rats. Treatment with newlineindinavir was carried out for 15 days, whereas treatment with test and newlinestandard drugs, as well as Swertia chirata leaf/root extracts, was done from newlineDay 8 to Day 15. Physical and biochemical parameters were measured. newlineRandom glucose levels of all animals were determined at the 0th, 5th, 10th, and newline14th day. After 12hr fasting on the 15th day, blood was collected from retroorbital newlinevein under mild anesthesia with the help of capillary tubes for newlinexx newlinebiochemical estimation. This was followed by OGTT; rats were treated with newlineglucose solution at a dose of 2 gm/kg body weight. The dose was delivered newlinethrough the by oral route. Following this, blood sample was collected for newlineanalysis. IR was measured by homeostatic model assessment (HOMA) of newlineinsulin resistance (HOMA-IR), and insulin sensitivity (IS) measured by HOMAIS. newlineThe animals were sacrificed, and the liver and pancreas were dissected newlineout. The tissues (liver and pancreas) were fixed in formalin and subjected to newlinehistopathological examination. Statistical analysis was performed using oneway newlineanalysis of variance followed by Bonferroniand#8223;s multiple comparison test. newlineResults: The group treated with indinavir (216 mg/kg) showed a significant (P newlinelt 0.05) increase in biochemical parametersand also produced newlinehistopathological changescompared to the control and the group treated with newlinestandard drugs and extracts. Indinavir caused a raise in HOMA-IR and newlinedecreased HOMA-IS levels. This shows that indinavir is capable of producing newlineIR and diabetes mellitus in rats. The groups treated with Swertia chirata leaf newlineand root extracts (500 mg/kg BW/P.O.) decreased glucose and insulin levels, newlineimproved lipid levels, reduced HOMA-IR, and increased HOMA-IS. These newlineeffects are almost similar to the effect produced by the standard drug newlinemetformin and pioglitazone. newlineConclusion: Indinavir induced IR, diabetes, dyslipidemia, and steatosis. The newlinegroups treated with Swertia chirata leaf and root extracts showed improved newlineglucose, insulin, and lipid profiles in indinavir-treated rats. newline