ABSTRACT
OBJECTIVE: The present study was aimed to enumerate the role of metformin-associated H2S release against lipopolysaccharide (LPS) induced neuroinflammation. MATERIALS AND METHODS: Five groups of animals were subjected to treatment as control (normal saline), toxic control (LPS, 125 µg/kg, i.p.), and three separate groups treated with 6.25, 12.5, and 25 mg/kg of metformin along with LPS for a period of 28 days. LPS was administered on 1st, 2nd, 3rd, 4th, 23rd, 24th, 25th and 26th day. The animals were evaluated for behavioral (elevated plus maze, rotarod and actophotometer); biochemical (plasma and tissue H2S, COX, LOX and NO), antioxidant (TBARS, SOD, catalase, protein carbonyl and GSH) and liver toxicity (SGOT and SGPT) markers. The brain tissues were further evaluated histopathologically, free fatty acid profile and NF-κB expression. RESULT: The LPS could not hasten any significant behavioral, biochemical, antioxidant and histopathological changes in the brain tissue. LPS also failed to modify the free fatty acid profile and NF-κB expression in the brain tissue. The LPS demarcated a well-defined peripheral inflammation as perceived through the plasma H2S, NO, SGOT and SGPT. Metformin administration demonstrated a marked effect on the peripheral inflammation induced by LPS. CONCLUSION: The LPS (i.p.) administration is devoid of any neuroinflammatory effects; however, precipitates peripheral inflammatory reactions and the same can could be attributed to the fact that LPS is devoid of/confined by very minimal permeability across the blood brain barrier. Metformin demonstrated a significant effect on peripheral inflammatory reactions precipitated through LPS.
Subject(s)
Hydrogen Sulfide/metabolism , Hypoglycemic Agents/therapeutic use , Inflammation Mediators/metabolism , Lipopolysaccharides/toxicity , Metformin/therapeutic use , Animals , Hypoglycemic Agents/pharmacology , Inflammation/chemically induced , Inflammation/drug therapy , Inflammation/metabolism , Inflammation Mediators/antagonists & inhibitors , Male , Maze Learning/drug effects , Maze Learning/physiology , Metformin/pharmacology , Oxidative Stress/drug effects , Oxidative Stress/physiology , Random Allocation , Rats , Rats, WistarABSTRACT
Objective: To assess in-vitro antioxidant activity of different fraction and perform high performance thin layer chromatography fingerprint analysis of most active fraction of Rumexvesicarius L. (R. vesicarius). Methods: In the present study, acetone, ethyl acetate, n-butanol, and methanol extracts of R. vesicarius were evaluated for radical scavenging activity by studying the inhibition of the level of lipid peroxidation induced by Fe(++)/ascorbate, DNA sugar damage, scavenging of hydrogen peroxide, diphenylphosphine DPPH radical scavenging activity, total phenolic content, total flavonoids content and total proanthocyanidin. High performance thin layer chromatography finger print profiling of R. vesicarius L. was also done. Results: Lipid peroxidation induced by the iron/ascorbate system, hydrogen peroxide, diphenylphosphine and DNA sugar damage were inhibited by the addition of different extract ofR. vesicarius. Among them, methanolic extract showed maximum efficacy. The methanolic extract showed the highest total phenolic, total flavonoids and total proanthocyanidin contents.Conclusions:The results suggest that the extracts can be a vital source of phytochemical antioxidants.
