Division of Ethnopharmacology, Entomology Research Institute, Loyola College, Chennai, Tamil Nadu 600 034, India.
Division of Biotechnology, Entomology Research Institute, Loyola College, Chennai, Tamil Nadu 600 034, India.
Biomed Pharmacother. 2018 Nov;107:979-988. doi: 10.1016/j.biopha.2018.08.019. Epub 2018 Aug 23.
The prevalence of Non Alcoholic Fatty Liver Disease (NAFLD) is increasing globally. Terminalia arjuna W. & Arn. (Combretaceae) is an endemic tree found in India and Sri Lanka and used traditionally for its cardioprotective and hepatoprotective effects. Arjunolic acid (AA) is an oleanane triterpenoid found mainly in the heartwood of T. arjuna. This study was aimed to evaluate the hepatoprotective effect of AA using cellular and rodent models of NAFLD. AA was isolated from the ethyl acetate extract of the heartwood of T. arjuna. The structure of AA was confirmed by physical and spectroscopic data. Steatosis was induced in HepG2 cells using palmitate-oleate mixture and the effects of AA on triglyceride accumulation and lipotoxicity were assessed. In vivo effect of AA on NAFLD was assessed using HFD fed rats. The treatment with AA did not affect the cell viability upto 100 μM and showed GI value of 379.9 μM in HepG2 cells. The treatment with AA significantly lowered the ORO concentration by 35.98% and triglyceride accumulation by 66.36% at 50 μM concentration (P < 0.005) compared to the vehicle treated group. The treatment with AA also reduced the leakage of ALT and AST by 61.11 and 48.29% in a significant manner (P < 0.005). The in vivo findings clearly demonstrated that the animals treated with AA at 25 and 50 mg/kg concentrations showed a significant decrease in the levels of transaminases, phosphatase and GGT (P < 0.005). In the liver, the expression of PPARα and FXRα expressions were upregulated, while PPARγ expression was downregulated by the treatment with AA. The liver histology of the animals showed reduction in steatosis and MNC infiltration. These preliminary evidences suggested that AA might be a promising lead to treat NAFLD. Future robust scientific studies on AA will lead to tailoring it for the treatment of NAFLD.
非酒精性脂肪性肝病（NAFLD）的患病率在全球范围内呈上升趋势。Terminalia arjuna W. & Arn.（使君子科）是一种在印度和斯里兰卡发现的特有树种，传统上用于其心脏保护和肝脏保护作用。Arjunolic acid（AA）是一种主要存在于 Terminalia arjuna 心材中的齐墩果烷三萜。本研究旨在使用 NAFLD 的细胞和啮齿动物模型评估 AA 的肝脏保护作用。AA 是从 Terminalia arjuna 心材的乙酸乙酯提取物中分离得到的。通过物理和光谱数据确定了 AA 的结构。使用棕榈酸-油酸混合物在 HepG2 细胞中诱导脂肪变性，并评估 AA 对甘油三酯积累和脂毒性的影响。使用高脂肪饮食喂养的大鼠评估 AA 对 NAFLD 的体内作用。AA 的治疗对细胞活力的影响在 100 μM 以下，在 HepG2 细胞中 GI 值为 379.9 μM。在 50 μM 浓度下，AA 处理可使 ORO 浓度降低 35.98%，甘油三酯积累降低 66.36%（P<0.005），与载体处理组相比。AA 处理还可使 ALT 和 AST 的漏出量分别显著降低 61.11%和 48.29%（P<0.005）。体内研究结果清楚地表明，用 25 和 50mg/kg 浓度的 AA 治疗的动物肝转氨酶、磷酸酶和 GGT 水平显著降低（P<0.005）。在肝脏中，AA 处理可上调 PPARα 和 FXRα 的表达，而下调 PPARγ 的表达。动物肝脏组织学显示脂肪变性和 MNC 浸润减少。这些初步证据表明，AA 可能是治疗 NAFLD 的有希望的先导化合物。对 AA 的未来强大科学研究将使其适用于治疗 NAFLD。
