[Mechanism of Huanglian Wendan Decoction in ameliorating feeding imbalance induced by olanzapine in mice based on NLRP3-mediated neuroinflammation and leptin resistance].
摘要
This study aims to investigate the mechanism of Huanglian Wendan Decoction(HLWDD) in ameliorating the feeding imbalance induced by olanzapine in mice. Female C57BL/6J mice were randomly divided into a blank group, a model group(olanzapine, 3 mg·kg~(-1)·d~(-1)), HLWDD groups(24, 12, and 6 g·kg~(-1)·d~(-1), respectively), and a metformin group(300 mg·kg~(-1)·d~(-1)). The model group was orally administered olanzapine for five weeks, while the HLWDD group was simultaneously given the corresponding dose of HLWDD via gavage. Body weight and food intake were monitored regularly during the administration period. Serum leptin, interleukin-1β(IL-1β), and interleukin-18(IL-18) were detected by enzyme-linked immunosorbent assay. Immunofluorescence staining was used to measure the expression of hypothalamic pro-opiomelanocortin(POMC), proto-oncogene c-FOS, and phosphorylated signal transducer and activator of transcription 3(p-STAT3), and real-time quantitative polymerase chain reaction and Western blot analysis were performed to quantify the expression of neuropeptide Y(NPY), POMC, suppressor of cytokine signaling 3(SOCS3), leptin receptor(LEPR), NOD-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein(ASC), N-terminal fragment of gasdermin D(GSDMD-N), cleaved caspase-1, and IL-1β. The results showed that compared with the blank group, the model group showed significantly increased body weight, cumulative food intake, and levels of serum leptin, IL-1β, and IL-18. Besides, the model group showed a significantly increased degree of leptin resistance in mice, as evidenced by significantly increased food intake and significantly decreased p-STAT3~+ and POMC~+/c-FOS~+cell ratio in the arcuate nucleus 24 hours after leptin injection. Compared with those of the model group, the body weight, cumulative food intake, and serum leptin, IL-1β, and IL-18 levels, as well as leptin resistance showed varying degrees of decrease in the HLWDD groups at all doses and the metfo