School of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, PR China.
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, PR China.
Biomed Pharmacother. 2016 Dec;84:1891-1898. doi: 10.1016/j.biopha.2016.10.099. Epub 2016 Nov 8.
Valeriana jatamansi Jones, a plant with heart-shaped leaves in the Valeriana genus of Valerianaceae, is widely used in Chinese folk medicine. Iridoid is an important constituent of V. jatamansi that contributes to the pharmacological efficacy of the herb. This study aims to investigate the regulation of lipid metabolism and its mechanism of the iridoids rich fraction in V. jatamansi (IRFV). A high fat diet was used to establish the hyperlipidemia rat model, with 2mg/kg/d of simvastatin as a positive control, fed with 7.5, 15, and 30mg/kg/d of IRFV for 20days to investigate the lipid regulation activity and mechanism of IRFV. Body weight, liver index, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in both serum and liver, as well as total bile acid (TBA), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in serum were measured. The lipoprotein lipase (LPL) and hepatic lipase (HL) activities and the apoprotein A5 (ApoA5), peroxisome proliferator-activated receptor α (PPAR-α), sterol regulatory element-binding proteins (SREBP-1c), and liver X receptor α (LXR-α) protein expressions were observed. Liver pathology was described through hematoxylin-eosin (HE) staining. Compared with the model group, three different IRFV dosages can slow down the weight gain of rats, reduce the contents of TG, and increase the contents of HDL-C in serum. Low IRFV dosage can significantly reduce the AST and ALT contents in serum, liver index, and the TG contents in liver, enhance LPL activity. Medium IRFV dosage can significantly decrease the TG and LDL-C contents in liver. High IRFV dosage can significantly reduce LDL-C, TBA, AST, and ALT contents in serum, and enhance HL activity. Three different IRFV dosages can significantly increase the ApoA5 and PPAR-α protein expression and decrease the SREBP-1c protein expression. Furthermore, the LXR-α protein expression decreased in low- and high-dose groups. Liver tissue pathological observation showed that IRFV can improve cell degeneration to a certain extent. These results strongly suggest that IRFV play significant roles in regulating lipid metabolism, the mechanism may be related to the increased ApoA5 protein expression.
缬草，败酱科缬草属植物，其叶片呈心形，广泛应用于中国民间医学。裂环烯醚萜类化合物是缬草中的一种重要成分，对该草药的药理功效有贡献。本研究旨在探讨缬草裂环烯醚萜类化合物（IRFV）对脂代谢的调节作用及其机制。采用高脂饮食建立大鼠高脂血症模型，以 2mg/kg/d 的辛伐他汀作为阳性对照，分别给予 7.5、15 和 30mg/kg/d 的 IRFV 进行 20 天治疗，以研究 IRFV 的脂质调节活性及其作用机制。检测血清和肝脏中体重、肝指数、总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）和高密度脂蛋白胆固醇（HDL-C），以及血清中总胆汁酸（TBA）、天门冬氨酸氨基转移酶（AST）和丙氨酸氨基转移酶（ALT）的含量。观察脂蛋白脂肪酶（LPL）和肝脂肪酶（HL）的活性以及载脂蛋白 A5（ApoA5）、过氧化物酶体增殖物激活受体 α（PPAR-α）、固醇调节元件结合蛋白-1c（SREBP-1c）和肝 X 受体 α（LXR-α）蛋白的表达。通过苏木精-伊红（HE）染色描述肝组织病理学变化。与模型组相比，三种不同剂量的 IRFV 可减缓大鼠体重增加，降低血清 TG 含量，增加 HDL-C 含量。低剂量 IRFV 可显著降低血清 AST 和 ALT 含量、肝指数和肝 TG 含量，增强 LPL 活性。中剂量 IRFV 可显著降低肝 TG 和 LDL-C 含量。高剂量 IRFV 可显著降低血清 LDL-C、TBA、AST 和 ALT 含量，增强 HL 活性。三种不同剂量的 IRFV 可显著增加 ApoA5 和 PPAR-α 蛋白表达，降低 SREBP-1c 蛋白表达。此外，LXR-α 蛋白表达在低剂量和高剂量组中降低。肝组织病理学观察表明，IRFV 可在一定程度上改善细胞变性。这些结果强烈表明，IRFV 在调节脂代谢方面发挥着重要作用，其机制可能与 ApoA5 蛋白表达增加有关。
