Antihyperlipidemic and hepatoprotective effects of Gardenin A in cellular and high fat diet fed rodent models.

Abstract

The gum of Gardenia resinifera Roth., is one of the important drugs used in the Indian system of medicine and a source of unique polymethoxylated flavones. This study was aimed to evaluate the antihyperlipidemic and anti-NAFLD effects of Gardenin A (Gar-A) from G. resinifera gum using in vitro and in vivo models. Gar-A was isolated from G. resinifera gum and was identified on the basis of the physical and spectral data. Toxicity of Gar-A to HepG2 cells was evaluated using MTT assay. The ability of Gar-A to reduce steatosis was assessed using oleate-palmitate induced HepG2 cell lines by estimating the lipid levels by ORO staining and by estimating the intracellular triglyceride content. Effect of Gar-A on amelioration of lipotoxicity was measured by estimating the LDH levels. The doses for in vivo experiments were fixed by Irwin test, between 50 and 100 mg/kg concentrations, through oral route. The acute antihyperlipidemic effect of Gar-A was assessed in Triton WR-1339 induced hyperlipidemic animals. The chronic antihyperlipidemic and anti-NAFLD effects of Gar-A were evaluated in HFD fed rats. In vitro experiments with HepG2 cell line indicated that the cells treated with Gar-A did not show any significant reduction in the viability up to 70 μg/mL concentration. Steatotic HepG2 cells treated with Gar-A showed a significant reduction in lipid accumulation at 2.5-10 μg/mL concentrations. In triton induced hyperlipidemic rats, the treatment significantly reduced the lipid levels at the synthesis phase. The treatment with Gar-A to the HFD fed animals significantly lowered the steatosis and transaminase levels. The other biochemical parameters such as TC, TG, LDL-c, ALP and ACP were also decreased significantly. Treatment with Gar-A significantly lowered the hyperlipidemia and fat accumulation in the liver; detailed molecular investigations are necessary to establish the antihyperlipidemic and hepatoprotective potentials of Gar-A.

• Authors: Erenius Toppo, S Sylvester Darvin, S Esakkimuthu, A Stalin, K Balakrishna, K Sivasankaran, P Pandikumar, S Ignacimuthu, N A Al-Dhabi
• Journal: Chemico-biological interactions (Chem Biol Interact) Vol. 269 Pg. 9-17 (May 01 2017) ISSN: 1872-7786 [Electronic] Ireland
• PMID: 28351695 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical References

• Flavones
• Hypolipidemic Agents
• Lipids
• Palmitates
• Protective Agents
• gardenin A
• Oleic Acid
• Polyethylene Glycols
• tyloxapol

Topics

• Animals
• Cell Survival (drug effects)
• Diet, High-Fat
• Flavones (chemistry, pharmacology, therapeutic use)
• Gardenia (chemistry, metabolism)
• Hep G2 Cells
• Humans
• Hyperlipidemias (chemically induced, drug therapy, pathology)
• Hypolipidemic Agents (chemistry, pharmacology, therapeutic use)
• Lipids (blood)
• Liver (drug effects, metabolism)
• Male
• Non-alcoholic Fatty Liver Disease (metabolism, pathology, prevention & control)
• Oleic Acid (toxicity)
• Palmitates (toxicity)
• Polyethylene Glycols (toxicity)
• Protective Agents (chemistry, pharmacology, therapeutic use)
• Rats
• Rats, Wistar