Key Laboratory of New Animal Drug Project, Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agriculture Sciences, Lanzhou 730050, China.
College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China.
Int J Mol Sci. 2023 Nov 13;24(22):16272. doi: 10.3390/ijms242216272.
Inflammation is the host response of immune cells during infection and traumatic tissue injury. An uncontrolled inflammatory response leads to inflammatory cascade, which in turn triggers a variety of diseases threatening human and animal health. The use of existing inflammatory therapeutic drugs is constrained by their high cost and susceptibility to systemic side effects, and therefore new therapeutic candidates for inflammatory diseases need to be urgently developed. Natural products are characterized by wide sources and rich pharmacological activities, which are valuable resources for the development of new drugs. This study aimed to uncover the alleviating effect and potential mechanism of natural product (LAH) on LPS-induced inflammatory responses in macrophages. The experimental results showed that the optimized conditions for LAH ultrasound-assisted extraction via response surface methodology were an ethanol concentration of 72%, a material-to-solvent ratio of 1:37 g/mL, an extraction temperature of 73 °C, and an extraction power of 70 W, and the average extraction rate of LAH total flavonoids was 0.3776%. Then, data of 1666 components in LAH ethanol extracts were obtained through quasi-targeted metabolomics analysis. The ELISA showed that LAH significantly inhibited the production of pro-inflammatory cytokines while promoting the secretion of anti-inflammatory cytokines. Finally, combined with the results of network pharmacology analysis and protein expression validation of hub genes, it was speculated that LAH may alleviate LPS-induced inflammatory responses of macrophages through the AKT1/RELA/PTGS2 signaling pathway and the MAPK3/JUN signaling pathway. This study preliminarily revealed the anti-inflammatory activity of LAH and the molecular mechanism of its anti-inflammatory action, and provided a theoretical basis for the development of LAH as a new natural anti-inflammatory drug.
炎症是免疫细胞在感染和创伤组织损伤时的宿主反应。失控的炎症反应会导致炎症级联反应，进而引发各种威胁人类和动物健康的疾病。现有炎症治疗药物的使用受到其高成本和易产生全身副作用的限制，因此需要紧急开发新的炎症疾病治疗候选药物。天然产物具有广泛的来源和丰富的药理活性，是开发新药的宝贵资源。本研究旨在揭示天然产物（LAH）对 LPS 诱导的巨噬细胞炎症反应的缓解作用及其潜在机制。实验结果表明，通过响应面法优化的 LAH 超声辅助提取条件为乙醇浓度 72%、料液比 1:37 g/mL、提取温度 73°C、提取功率 70 W，LAH 总黄酮的平均提取率为 0.3776%。然后，通过准靶向代谢组学分析获得了 LAH 乙醇提取物中 1666 种成分的数据。ELISA 结果表明，LAH 能显著抑制促炎细胞因子的产生，同时促进抗炎细胞因子的分泌。最后，结合网络药理学分析和关键基因蛋白表达验证的结果，推测 LAH 可能通过 AKT1/RELA/PTGS2 信号通路和 MAPK3/JUN 信号通路缓解 LPS 诱导的巨噬细胞炎症反应。本研究初步揭示了 LAH 的抗炎活性及其抗炎作用的分子机制，为开发 LAH 作为新型天然抗炎药物提供了理论依据。
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