title: 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.affiliation: Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai, Tamil Nadu 600 034, India.
authors.forename: Erenius
authors.initials: E
authors.lastname: Toppo
authors.affiliation: Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai, Tamil Nadu 600 034, India.
authors.forename: S Sylvester
authors.initials: SS
authors.lastname: Darvin
authors.affiliation: Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai, Tamil Nadu 600 034, India.
authors.forename: S
authors.initials: S
authors.lastname: Esakkimuthu
authors.affiliation: Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai, Tamil Nadu 600 034, India.
authors.forename: A
authors.initials: A
authors.lastname: Stalin
authors.affiliation: Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai, Tamil Nadu 600 034, India.
authors.forename: K
authors.initials: K
authors.lastname: Balakrishna
authors.affiliation: Division of Taxonomy & Biodiversity, Entomology Research Institute, Loyola College, Chennai, Tamil Nadu 600 034, India.
authors.forename: K
authors.initials: K
authors.lastname: Sivasankaran
authors.affiliation: Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai, Tamil Nadu 600 034, India. Electronic address: pkr_eri@hotmail.com.
authors.forename: P
authors.initials: P
authors.lastname: Pandikumar
authors.affiliation: Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai, Tamil Nadu 600 034, India; Division of Taxonomy & Biodiversity, Entomology Research Institute, Loyola College, Chennai, Tamil Nadu 600 034, India; International Scientific Partnership Program, King Saud University, Post Box 2455, Riyadh 11451, Saudi Arabia. Electronic address: eriloyola@hotmail.com.
authors.forename: S
authors.initials: S
authors.lastname: Ignacimuthu
authors.affiliation: Addiriyah Chair for Environmental Studies, Department of Botany and Microbiology, College of Science, King Saud University, Post Box 2455, Riyadh 11451, Saudi Arabia.
authors.forename: N A
authors.initials: NA
authors.lastname: Al-Dhabi
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D059305:Diet, High-Fat; D047309:Flavones / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D032062:Gardenia / Q000737:chemistry / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D006949:Hyperlipidemias / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D000960:Hypolipidemic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D019301:Oleic Acid / Q000633:toxicity; D010168:Palmitates / Q000633:toxicity; D011092:Polyethylene Glycols / Q000633:toxicity; D020011:Protective Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
chemical_list: D047309:Flavones; D000960:Hypolipidemic Agents; D008055:Lipids; D010168:Palmitates; D020011:Protective Agents; C000589472:gardenin A; D019301:Oleic Acid; D011092:Polyethylene Glycols; C016811:tyloxapol
keywords: Adipocyte hypertrophy; FXRα; Fatty Liver; Gardenia lucida; Gardenia resinifera