Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA, Puncak Alam Campus, Bandar Puncak Alam, 42300 Selangor, Malaysia.
Integrative Pharmacogenomics Institute (iPROMISE), Universiti Teknologi MARA, Puncak Alam Campus, Bandar Puncak Alam, 42300 Selangor, Malaysia; Department of Biomedical Science, Faculty of Medicine and Health Sciences,Universiti Putra Malaysia UPM, 43400 Serdang, Selangor, Malaysia.
J Ethnopharmacol. 2015 May 26;166:109-18. doi: 10.1016/j.jep.2015.03.016. Epub 2015 Mar 16.
Muntingia calabura L. has been used in Southeast Asia and tropical America as antipyretic, antiseptic, analgesic, antispasmodic and liver tonic. This study aims to determine the acute toxicity and the metabolic pathways involved in the hepatoprotective mechanism of M. calabura.
CCl4-induced hepatotoxic rat model was developed and a dose dependent effect of M. calabura was conducted. Body weight, food and water consumption were measured every day and rats were sacrificed to collect the serum samples at the end of the 10-days treatment. Liquid chromatography-mass spectrometry quadrapole time of flight (LC/MS-QTOF) combined with principal component analysis (PCA) were used to determine differentially expressed metabolites due to treatment with CCl4 and M. calabura extracts. Metabolomics Pathway Analysis (MetPA) was used for analysis and visualization of pathways involved.
Body weight, food and water consumption were significantly decreased and histopathological study revealed steatosis in CCl4-induced rats. PCA score plots show distinct separation in the metabolite profiles of the normal group, CCl4-treated group and extract of M. calabura (MCME) pre-treated groups. Biomarkers network reconstruction using MetPA had identified 2 major pathways which were involved in the protective mechanism of MCME. These include the (i) biosynthesis of the primary bile acid, (ii) metabolism of arachidonic acid.
This study has successfully isolated 2 major pathways involved in the hepatoprotecive effect of MCME against CCl4-induced liver injury using the LC/MS Q-TOF metabolomics approach. The involvement of archidonic acid and purine metabolism in hepatoprotection has not been reported previously and may provide new therapeutic targets and/or options for the treatment of liver injury.
Muntingia calabura L. 在东南亚和热带美洲被用作退热、防腐、镇痛、抗痉挛和肝脏滋补剂。本研究旨在确定 M. calabura 的急性毒性和参与其肝保护机制的代谢途径。
建立了 CCl4 诱导的大鼠肝损伤模型，并进行了 M. calabura 的剂量依赖性效应研究。每天测量体重、食物和水的消耗，在 10 天治疗结束时处死大鼠以收集血清样本。液相色谱-质谱四极杆飞行时间（LC/MS-QTOF）结合主成分分析（PCA）用于确定由于 CCl4 和 M. calabura 提取物处理而导致的差异表达代谢物。代谢组学途径分析（MetPA）用于分析和可视化所涉及的途径。
体重、食物和水的消耗明显减少，组织病理学研究显示 CCl4 诱导的大鼠发生脂肪变性。PCA 得分图显示正常组、CCl4 处理组和 M. calabura 提取物（MCME）预处理组的代谢物图谱有明显分离。使用 MetPA 进行的生物标志物网络重建确定了涉及 MCME 保护机制的 2 个主要途径。这些途径包括（i）初级胆汁酸的生物合成，（ii）花生四烯酸的代谢。
本研究成功地使用 LC/MS Q-TOF 代谢组学方法分离了参与 MCME 对 CCl4 诱导的肝损伤的 2 个主要途径。花生四烯酸和嘌呤代谢在肝保护中的参与以前没有报道过，可能为肝损伤的治疗提供新的治疗靶点和/或选择。
