HanseMerkur Center for Traditional Chinese Medicine at the University Medical Center Hamburg-Eppendorf, Breitenfelder Straße 15, D-20251 Hamburg, Germany.
Swiss Federal Institute of Technology, ETH Zürich, Institute of Food Nutrition and Health, Schorenstr. 16, CH-8603 Schwerzenbach, Switzerland.
Phytomedicine. 2019 Nov;64:153075. doi: 10.1016/j.phymed.2019.153075. Epub 2019 Aug 23.
Obesity is one of the major health problems worldwide. The induction of brown adipocyte formation and activity represents a promising therapeutic option by increasing energy expenditure. Asian herbs have the potential to treat obesity, however, pharmacological effects should be well documented at the molecular level first.
A novel hypothesis-driven screening approach identified the root of Pueraria montana var. lobata (Willd.) Sanjappa & Pradeep (PLR) to have potential effects on obesity by stimulating brown adipocytes.
This study explored the metabolic effects of PLR water extract (PLRE) in a high-fat diet-induced obesity mouse model and characterized its secondary metabolite composition.
Animals were orally treated daily for two weeks and the bioactivity of PLRE evaluated by measuring various parameters including body weight, circulating metabolites, energy expenditure and insulin sensitivity. The chemical composition of the mains components was obtained by HPLC-MS-ELSD-PDA. Based on the dereplication results and semi-quantitative estimation, pure molecules were selected for tests on adipocytes in vitro.
PLRE induces brown adipocyte activity and triggers the formation of brown-like cells in inguinal fat tissue, weight loss, and improved glucose metabolism. These effects are primarily caused by cell-autonomous activation of brown adipocytes and not by autonomic nervous system regulation. Even though the analysis of PLRE revealed puerarin as the most abundant secondary metabolite, it showed no effect on brown adipocyte formation and function. Brown adipocyte activity was induced dose-dependently by two other isoflavones, daidzein, and genistein. Daidzein is present in a very small amount in PLRE, but various glycosidic isoflavones, including puerarin, may release daidzein after metabolism.
This approach demonstrated the positive effects of PLRE on a diet-induced obesity mouse model and provided clues on the mode of action of PLRE at the molecular level.
肥胖是全球主要健康问题之一。诱导棕色脂肪细胞的形成和活性是一种很有前途的治疗方法，可通过增加能量消耗来实现。亚洲草药具有治疗肥胖的潜力，然而，首先应在分子水平上充分记录其药理学作用。
一种新的基于假说的筛选方法发现，野葛 Pueraria montana var. lobata（Willd.）Sanjappa & Pradeep（PLR）的根具有通过刺激棕色脂肪细胞来治疗肥胖的潜在作用。
本研究在高脂肪饮食诱导的肥胖小鼠模型中探讨了 PLR 水提取物（PLRE）的代谢作用，并对其次生代谢产物组成进行了表征。
动物每天口服治疗两周，通过测量包括体重、循环代谢物、能量消耗和胰岛素敏感性在内的各种参数来评估 PLRE 的生物活性。通过 HPLC-MS-ELSD-PDA 获得主要成分的化学组成。基于去重复结果和半定量估计，选择纯分子进行体外脂肪细胞测试。
PLRE 可诱导棕色脂肪细胞活性并触发腹股沟脂肪组织中棕色样细胞的形成，从而减轻体重和改善葡萄糖代谢。这些作用主要是通过棕色脂肪细胞的自主激活引起的，而不是通过自主神经系统调节引起的。尽管 PLRE 的分析表明，葛根素是最丰富的次生代谢物，但它对棕色脂肪细胞的形成和功能没有影响。两种其他异黄酮，大豆苷元和染料木黄酮，可剂量依赖性地诱导棕色脂肪细胞活性。大豆苷元在 PLRE 中的含量非常少，但各种糖苷异黄酮，包括葛根素，在代谢后可能会释放出大豆苷元。
该方法证明了 PLRE 对饮食诱导肥胖小鼠模型的积极作用，并为 PLRE 在分子水平上的作用机制提供了线索。
