Pharmacological Evaluation and Investigation of Mechanism of Action of Gallic Acid in Dyslipidemia

Abstract

Aim and Objectives: Dyslipidemia is a disorder of lipoprotein metabolism, including lipoprotein overproduction. The aim of the present study is to elucidate whether gallic acid have beneficial effects in dyslipidemia and to find out its mechanism of action on peroxisome proliferated activate receptors. Materials and Methods: Docking studies were performed on the Peroxisome proliferated activated receptor (PPAR) using SurFlex Do.ck module from SYBYL X 1.3. Developed by Tripos, USA. During this study affinity and interactions of gallic acid towards the PPARα was compared with clofibric acid. Pharmacological evaluations were carried out using high fat diet induced hyperlipidemic animal model. Hyperlipidemia was induced by feeding high fat diet. Wistar rats (200-250 gm) were divided into six groups. Treatment was carried out for 21 days as follows. (1) Normal control (2) Disease control fed on high fat diet (3) Normal control treated with Clofibric acid (10mg/kg/day) (p.o.) (4) Disease control treated with Clofibric acid (10mg/kg) (5) Normal control group treated with gallic acid 50mg/kg gallic acid (6) Disease control group treated gallic acid (50mg/kg): At the end of treatment blood samples were collected from retro orbital plexus. Serum was separated and biochemical estimations like glucose, cholesterol, triglyceride, high density lipoproteins (HDL), low density lipoproteins (LDL) and very low density lipoproteins (VLDL) were carried out. Whole blood collected was utilized for the determination of Glucose-6- phosphte dehydrogenase. Later on animals were sacrificed on the next day and livers were collected. These livers were used for the determination of HMG-Co-A reductase. Results: Dyslipidemic animals treated with clofibric acid and gallic acid showed statistically significant (p<0.05) reduction in serum glucose levels when compared with dyslipidemic group. Serum lipid parameters such as cholesterol, triglyceride, LDL and VLDL were found to decrease significantly (p<0.05) in disease control group treated with clofibric acid and gallic acid compared disease control group. But when compared to normal control group there is no statistically significant change in the serum. There was no statistically significant (p<0.05) change in the activity of HMG-Co-A reductase was observed in disease control group treated with gallic acid when compared to disease control group. When it comes to the activity of glucose-6-phosphate dehydrogenase, disease control group treated with clofibric acid and gallic acid showed statistically significant (p<0.05) decrease in the activity of glucose-6-phosphate dehydrogenase activity as compared to disease control group. Conclusion Our data suggest that gallic acid shows beneficial effect in dyslipidemia. The activity of gallic acid appears to be produced by decreasing the serum glucose, cholesterol, triglyceride, LDL and VLDL levels. It seems that gallic acid might have worked through its interactions with PPARα as it was found through docking studies. Further gallic acid found to decrease G6PD activity which is an important enzyme that is regulated by the PPAR. Therefore on the basis of present observations gallic acid could be projected as a probable drug for the treatment of dyslipidemia owing to its action on PPARα.