Zhu Mengmeng, Zhang Baixia, Zhang Jinghui, Ge Shaoqin, Liu Meiyun
College of Chinese Medicine, Hebei University, Baoding, Hebei 071000, China.
General Hospital of Xuzhou Mining Group, Xuzhou, Jiangsu 221006, China.
Evid Based Complement Alternat Med. 2022 Apr 28;2022:5494224. doi: 10.1155/2022/5494224. eCollection 2022.
As the major type of obesity in clinical, simple obesity has gained increasing attention in recent years. Depending on the etiology and pathogenesis of simple obesity and combined with clinical practice experience, Huaji Jianpi decoction (HJJPD) was established to invigorate the spleen and eliminate dampness; however, the underlying molecular mechanism is yet unclear.
A simple obesity mouse model was established by feeding a high-fat diet to the animals, and the related indexes were analyzed. The mice were divided into the normal, positive control (orlistat), and HJJPD high-dose, medium-dose, and low-dose groups. After 6 weeks of administration, the curative effect of HJJPD was observed. Simple obesity is associated with leptin resistance. The leptin signal transduction pathways mainly include the JAK2-STAT3, AMPK-ACC, LepRb-IRS-PI3K-PDE3B-cAMP, and LepRb-SHP2-MAPKs (ERK1/2) pathways. Therefore, the networks of HJJPD acting on these four pathway-related targets were constructed using the network pharmacology method, and the key nodes were identified.
After 6 weeks of drug intervention, we found a good therapeutic effect of HJJPD on simple obesity in the mouse model. The biological network analysis showed that HJJPD plays a role in treating leptin resistance in simple obesity by acting on multiple targets in the JAK2-STAT3 pathway via various components. Also, HJJPD can improve leptin resistance in mice by enhancing the binding force of LEP and LEPRB and activating the LEP-mediated JAK2-STAT3 signaling pathway.
In this study, animal experiments, network pharmacology, and molecular biology were combined to establish a mouse model of simple obesity, confirm the role of HJJPD in the treatment of simple obesity, and preliminarily reveal the related mechanism. Relevant research results will provide a basis for the treatment of simple obesity and the drug discovery.
单纯性肥胖作为临床上主要的肥胖类型，近年来受到越来越多的关注。根据单纯性肥胖的病因病机，并结合临床实践经验，创立了化积健脾汤（HJJPD）以健脾祛湿；然而，其潜在的分子机制尚不清楚。
通过给动物喂食高脂饮食建立单纯性肥胖小鼠模型，并分析相关指标。将小鼠分为正常组、阳性对照组（奥利司他）以及HJJPD高剂量组、中剂量组和低剂量组。给药6周后，观察HJJPD的疗效。单纯性肥胖与瘦素抵抗有关。瘦素信号转导途径主要包括JAK2-STAT3、AMPK-ACC、LepRb-IRS-PI3K-PDE3B-cAMP和LepRb-SHP2-MAPKs（ERK1/2）途径。因此，采用网络药理学方法构建HJJPD作用于这四条途径相关靶点的网络，并确定关键节点。
药物干预6周后，我们发现HJJPD对小鼠模型中的单纯性肥胖具有良好的治疗效果。生物网络分析表明，HJJPD通过其多种成分作用于JAK2-STAT3途径中的多个靶点，从而在治疗单纯性肥胖的瘦素抵抗中发挥作用。此外，HJJPD可通过增强LEP与LEPRB的结合力并激活LEP介导的JAK2-STAT3信号通路来改善小鼠的瘦素抵抗。
本研究将动物实验、网络药理学和分子生物学相结合，建立了单纯性肥胖小鼠模型，证实了HJJPD在治疗单纯性肥胖中的作用，并初步揭示了相关机制。相关研究结果将为单纯性肥胖的治疗和药物研发提供依据。
