Toppo Erenius, Darvin S Sylvester, Esakkimuthu S, Stalin A, Balakrishna K, Sivasankaran K, Pandikumar P, Ignacimuthu S, Al-Dhabi N A
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.
Chem Biol Interact. 2017 May 1;269:9-17. doi: 10.1016/j.cbi.2017.03.013. Epub 2017 Mar 25.
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.
树脂栀子（Gardenia resinifera Roth.）的树胶是印度医学体系中使用的重要药物之一，也是独特的多甲氧基黄酮的来源。本研究旨在使用体外和体内模型评估树脂栀子胶中栀子苷A（Gar-A）的抗高血脂和抗非酒精性脂肪性肝病（NAFLD）作用。Gar-A从树脂栀子胶中分离出来，并根据物理和光谱数据进行鉴定。使用MTT法评估Gar-A对HepG2细胞的毒性。通过油红O染色估计脂质水平和通过估计细胞内甘油三酯含量，评估Gar-A降低脂肪变性的能力。通过估计乳酸脱氢酶（LDH）水平来测量Gar-A对改善脂毒性的作用。体内实验的剂量通过欧文试验确定，浓度在50至100mg/kg之间，经口服途径给药。在Triton WR-1339诱导的高血脂动物中评估Gar-A的急性抗高血脂作用。在高脂饮食喂养的大鼠中评估Gar-A的慢性抗高血脂和抗NAFLD作用。对HepG2细胞系的体外实验表明，在浓度高达70μg/mL时，用Gar-A处理的细胞活力没有任何显著降低。用Gar-A处理的脂肪变性HepG2细胞在浓度为2.5至10μg/mL时，脂质积累显著减少。在Triton诱导的高血脂大鼠中，该处理在合成阶段显著降低了脂质水平。用Gar-A处理高脂饮食喂养的动物显著降低了脂肪变性和转氨酶水平。其他生化参数如总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-c）、碱性磷酸酶（ALP）和酸性磷酸酶（ACP）也显著降低。用Gar-A处理显著降低了高血脂和肝脏中的脂肪积累；需要进行详细的分子研究来确定Gar-A的抗高血脂和肝脏保护潜力。
