Abstract：
Chuanwang xiaoyan capsules (CWXYC) have anti-inflammatory and detoxification effect, are used in the treatment of acute and chronic tonsillitis, pharyngitis and other inflammation-related diseases clinically. However, the anti-inflammatory mechanisms have not been elucidated. This study aimed to investigate the anti-inflammatory mechanisms of CWXYC using cell metabolomics and network pharmacology strategy. Specifically, CWXYC could efficiently reduce the content of nitric oxide (NO), the cytokines Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in LPS-induced RAW264.7 cells. Furthermore, metabolomics was performed to achieve 23 differential metabolites and 9 metabolic pathways containing glutamate metabolism, glutathione metabolism, arginine and proline metabolism, urea cycle, malate-aspartate shuttle, phosphatidylcholine biosynthesis, transfer of acetyl groups into mitochondria, cysteine metabolism and ammonia recycling. The results of network pharmacology showed that CWXYC could treat inflammation through 10 active components, 10 key targets and 55 pathways. Then the results of molecular docking also approved that there existed strong binding energy between the active components and the key targets. Finally, metabolomics and network pharmacology were integrated to get core targets AKT1, SRC and EGFR. Western blot experiments verified that CWXYC could exert anti-inflammatory effect by down-regulating the activated Akt1 and Src proteins. This study demonstrated that CWXYC exerted effects against inflammation, and the potential mechanisms were elucidated. These novel findings will provide an important basis for further mechanism investigations.
摘要：
川旺消炎胶囊（CWXYC）具有抗炎解毒作用，用于治疗急性和慢性扁桃体炎，咽炎和其他临床炎症相关疾病。然而,抗炎机制尚未阐明.本研究旨在通过细胞代谢组学和网络药理学策略探讨CWXYC的抗炎机制。具体来说,CWXYC可以有效降低一氧化氮（NO）的含量，细胞因子白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）在LPS诱导的RAW264.7细胞中的作用。此外，进行代谢组学以获得23种差异代谢物和9种含有谷氨酸代谢的代谢途径，谷胱甘肽代谢，精氨酸和脯氨酸代谢，尿素循环,苹果酸-天冬氨酸穿梭,磷脂酰胆碱生物合成，将乙酰基转移到线粒体中，半胱氨酸代谢和氨再循环。网络药理学结果显示,CWXYC可通过10种活性成分治疗炎症,10个关键靶标和55个途径。然后分子对接的结果也证明了活性成分与关键靶标之间存在很强的结合能。最后,整合代谢组学和网络药理学以获得核心靶标AKT1，SRC和EGFR。Westernblot实验证实CWXYC可通过下调活化的Akt1和Src蛋白发挥抗炎作用。这项研究表明，CWXYC对炎症产生影响，并阐明了潜在的机制。这些新发现将为进一步的机制研究提供重要依据。
