中药药理与临床2025，Vol.41Issue(5)：14-21,8.
四味藏木香调控SRC/AKT信号通路介导解热镇痛作用
Siweizangmuxiang Exerts Antipyretic and Analgesic Effects via SRC/AKT Signaling Pathway
摘要
Abstract
Objective:This study aims to evaluate the antipyretic,analgesic,and anti-inflammatory effects of the Tibetan medicine formula Siwei-zangmuxiang(四味藏木香,SWZMX)in powder form and syrup form based on the Tibetan medical theory.Additionally,we explored their mechanisms of action through network pharmacology to support dosage form reform and preparation development of Tibetan medicines.Meth-ods:A lipopolysaccharide(LPS)-induced fever model was established to evaluate the antipyretic effects of SWZMX in powder and syrup forms.The hot plate and acetic acid-induced writhing tests were performed to assess their analgesic effects.The croton oil-induced paw edema model was used to evaluate anti-inflammatory effects.TCMSP was employed to predict the active ingredients and targets of SWZMX.Disease-related targets were obtained from databases such as GeneCards.STRING and Cytoscape were employed to establish the protein-protein inter-action network and screen the core targets.DAVID and Metascape were used for GO function and KEGG pathway enrichment analyses,and a"disease-drug component-target-pathway"network was established.Western blot was employed to verify the effects of SWZMX on the core signaling pathways in LPS-induced BV2 microglial cells.Molecular docking was conducted for active components and core targets.Finally,the core targets in LPS-induced BV2 microglial cells treated with SWZMX were detected by RT-PCR to explain the pharmacological mecha-nisms of the antipyretic and analgesic effects.Results:Compared with the normal control group,the model group showed a rise in body tem-perature(P<0.05 or P<0.01).Compared with the model group,the 0.19 g/kg SWZMX powder group showed a decline in body tempera-ture(P<0.05 or P<0.01),which fluctuated near 37.3℃,while the syrup form did not show antipyretic effect.In analgesic experiments,compared with the model group,SWZMX in both forms increased the pain threshold and decreased the writhing times of mice(P<0.05 or P<0.01),which indicated certain analgesic effect,with the syrup form outperforming the powder form.In anti-inflammatory effect experi-ments,neither form showed significant effect compared with the model group.Network pharmacology screened out 23 core targets including TP53,AKT1,and IL6.GO enrichment analysis revealed associations of the antipyretic and analgesic effects of SWZMX with signal transduc-tion,protein kinase activity,and kinase binding pathways.KEGG pathway enrichment analysis indicated associations with the cAMP,PI3K-AKT,and calcium signaling pathways for the antipyretic and analgesic effects of SWZMX.The cell experiments demonstrated that SWZMX activated AKT phosphorylation in LPS-induced BV2 cells.Molecular docking results indicated that SWZMX might target the SRC protein.RT-PCR experiments confirmed that SWZMX suppressed the up-regulation of SRC expression in LPS-induced BV2 cells.Conclusion:Differ-ent forms of SWZMX exhibited varying pharmacological activities.The syrup form showed superior analgesic effects over the powder form,possibly due to the addition of white sugar as the medicinal usher.The syrup form showed no antipyretic effect,whereas the powder form ex-hibited antipyretic effect,maintaining body temperature fluctuating around 37.3℃.It aligns with Tibetan medical theory of promoting matu-ration and stabilizing body temperature during early stage of warm diseases,and white sugar is not suitable to be added as the medicinal usher for season-related diseases.SWZMX may exert its antipyretic and analgesic effects through targeting SRC,as well as activating the PI3K-AKT signaling pathway.These findings provide pharmacodynamic and mechanism support for the dosage form reform and clinical application of SWZMX in clinical practice.关键词
四味藏木香/解热/镇痛/抗炎/网络药理学/蛋白激酶/磷脂酰肌醇3激酶Key words
Siweizangmuxiang/Antipyretic/Analgesic/Anti-inflammatory/Network pharmacology/Protein kinase/Phosphatidylinositol 3-kinase(PI3K)引用本文复制引用
索朗吉拉,旦增尼玛,陈嘉逸,许天姝,王子婧,次松拉姆,塔德合,才航吉,边巴坚参,强桂芬..四味藏木香调控SRC/AKT信号通路介导解热镇痛作用[J].中药药理与临床,2025,41(5):14-21,8.基金项目
西藏藏医药大学藏医药"十四五"规划内涵建设项目(编号:2023ZYYGH03) （编号:2023ZYYGH03）
西藏自治区藏医药管理局局级课题(编号:JJKT2023003). （编号:JJKT2023003）
