Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
Department of Biochemistry, National Organization for Drug Control and Research (NODCAR), 12553 Giza, Egypt.
J Ethnopharmacol. 2019 Mar 1;231:262-274. doi: 10.1016/j.jep.2018.11.026. Epub 2018 Nov 17.
Ficus is an important commercial crop not only for its nutritive value but also, for its medicinal value. Several Ficus species have been traditionally used in the Egypt, Indian and Chinese as carminative, astringent, antibacterial, hepatoprotective, and hypolipidemic agents.
To standardize and compare the possible hepatoprotective potential of the ethanolic extract of leaves of five tested Ficus species namely: Ficus mysorensis Roth ex Roem. & Schult, Ficus pyriformis Hook. & Arn., Ficus auriculata Lour., Ficus trigonata L., and Ficus spragueana Mildbr. & Burret in the intrahepatic cholestasis rat model induced by 17α-Ethinylestradiol (EE) and to explore the mechanism of action with respect to their phytochemical constituents.
Determination of the total phenolic and flavonoid contents, chromatographic examination and acute oral toxicity test were performed on the tested Ficus extracts. Animals were divided into 8 groups. Group 1, served as control for 2 weeks. Group 2, untreated cholestatic rats. Groups 3-8, pretreated with Ficus extracts (100 mg/Kg/day, p.o) or ursodeoxycholic acid (as reference drug) for 2 weeks and injected by EE in the last 5 days. Serum liver function test, 5'-nucleotidase (5'-N), total bile acids (TBA), total cholesterol (T.C) and phospholipids were assayed. Also, hepatic Na/K-ATPase, nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), hepatocyte growth factor (HGF), hemeoxygenase-1 (HO-1), and markers of oxidative stress were investigated. Furthermore, molecular docking study was performed to explore the ability of the major constituents of Ficus to interact with Farnesoid X receptor (FXR).
Four phenolic compounds (gallic, chlorogenic acid, caffeic acids and rutin) were identified. Chlorogenic acid and rutin represented the major constituents of Ficus extracts. Simultaneous administration of Ficus extracts with EE effectively: i- preserved liver function, TBA, T.C and phospholipids, ii- suppressed the pro-inflammatory cytokines (NF-κB and TNF-α), iii- enhanced hepatic regeneration (HGF) and antioxidant defense system. Furthermore, molecular docking reveals that rutin and chlorogenic acid effectively act as FXR agonists.
Among the tested extracts, Ficus spragueana Mildbr. & Burret enriched with phenolics exhibited a pronounced hepatoprotective activity and may provide a new therapeutic approach for estrogen-induced cholestasis.
榕属植物不仅因其营养价值，而且因其药用价值，是一种重要的商业作物。几种榕属植物在埃及、印度和中国传统上被用作驱风药、收敛剂、抗菌剂、保肝剂和降血脂剂。
标准化并比较五种测试的榕属植物叶乙醇提取物的可能保肝潜力，即：榕属 Mysorensis 罗斯 ex Roem。&舒尔特、榕属 Pyriformis 胡克。& Arn。、榕属 Auriculata 洛厄尔、榕属 Trigonata L. 和榕属 Spragueana Mildbr。&伯雷特在 17α-乙基雌二醇（EE）诱导的肝内胆汁淤积大鼠模型中，并探讨其与植物化学成分相关的作用机制。
对测试的榕属提取物进行总酚和类黄酮含量的测定、色谱检查和急性口服毒性试验。动物分为 8 组。第 1 组，连续 2 周作为对照。第 2 组，未治疗的胆汁淤积大鼠。第 3-8 组，用榕属提取物（100mg/Kg/天，po）或熊去氧胆酸（作为参考药物）预处理 2 周，并用 EE 在最后 5 天注射。检测血清肝功能、5'-核苷酸酶（5'-N）、总胆汁酸（TBA）、总胆固醇（T.C）和磷脂。此外，还研究了肝 Na/K-ATPase、核因子-κB（NF-κB）、肿瘤坏死因子-α（TNF-α）、肝细胞生长因子（HGF）、血红素加氧酶-1（HO-1）和氧化应激标志物。此外，还进行了分子对接研究，以探讨榕属主要成分与法尼醇 X 受体（FXR）相互作用的能力。
鉴定了四种酚类化合物（没食子酸、绿原酸、咖啡酸和芦丁）。绿原酸和芦丁是榕属提取物的主要成分。榕属提取物与 EE 同时给药可有效：i- 保护肝功能、TBA、T.C 和磷脂，ii- 抑制促炎细胞因子（NF-κB 和 TNF-α），iii- 增强肝再生（HGF）和抗氧化防御系统。此外，分子对接表明芦丁和绿原酸可有效作为 FXR 激动剂。
在测试的提取物中，富含酚类化合物的榕属 Spragueana Mildbr。&Burret 表现出明显的保肝活性，可能为雌激素诱导的胆汁淤积提供新的治疗方法。
