Li Quan, Chen Juan, Wang Meng-Meng, Cao Li-Ping, Zhang Wei, Yang Zhi-Zhou, Ren Yi, Feng Jing, Han Xiao-Qin, Nie Shi-Nan, Sun Zhao-Rui
Department of Intensive Care Unit, Suqian First Hospital, Suqian, Jiangsu Province, 223800, China.
Department of Emergency Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, China.
Chin J Integr Med. 2024 Dec 5. doi: 10.1007/s11655-024-3769-6.
To explore the potential effects and mechanisms of Liang-Ge-San (LGS) for the treatment of acute respiratory distress syndrome (ARDS) through network pharmacology analysis and to verify LGS activity through biological experiments.
The key ingredients of LGS and related targets were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. ARDS-related targets were selected from GeneCards and DisGeNET databases. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using the Metascape Database. Molecular docking analysis was used to confirm the binding affinity of the core compounds with key therapeutic targets. Finally, the effects of LGS on key signaling pathways and biological processes were determined by in vitro and in vivo experiments.
A total of LGS-related targets and 496 ARDS-related targets were obtained from the databases. Network pharmacological analysis suggested that LGS could treat ARDS based on the following information: LGS ingredients luteolin, wogonin, and baicalein may be potential candidate agents. Mitogen-activated protein kinase 14 (MAPK14), recombinant V-Rel reticuloendotheliosis viral oncogene homolog A (RELA), and tumor necrosis factor alpha (TNF-α) may be potential therapeutic targets. Reactive oxygen species metabolic process and the apoptotic signaling pathway were the main biological processes. The p38MAPK/NF-κ B signaling pathway might be the key signaling pathway activated by LGS against ARDS. Moreover, molecular docking demonstrated that luteolin, wogonin, and baicalein had a good binding affinity with MAPK14, RELA, and TNF α. In vitro experiments, LGS inhibited the expression and entry of p38 and p65 into the nucleation in human bronchial epithelial cells (HBE) cells induced by LPS, inhibited the inflammatory response and oxidative stress response, and inhibited HBE cell apoptosis (P<0.05 or P<0.01). In vivo experiments, LGS improved lung injury caused by ligation and puncture, reduced inflammatory responses, and inhibited the activation of p38MAPK and p65 (P<0.05 or P<0.01).
LGS could reduce reactive oxygen species and inflammatory cytokine production by inhibiting p38MAPK/NF-κ B signaling pathway, thus reducing apoptosis and attenuating ARDS.
通过网络药理学分析探讨凉膈散（LGS）治疗急性呼吸窘迫综合征（ARDS）的潜在作用及机制，并通过生物学实验验证LGS的活性。
从中药系统药理学数据库与分析平台获取LGS的关键成分及相关靶点。从GeneCards和DisGeNET数据库中筛选ARDS相关靶点。使用Metascape数据库进行基因本体论和京都基因与基因组百科全书富集分析。采用分子对接分析确定核心化合物与关键治疗靶点的结合亲和力。最后，通过体外和体内实验确定LGS对关键信号通路和生物学过程的影响。
从数据库中总共获得了LGS相关靶点和496个ARDS相关靶点。网络药理学分析表明，LGS可基于以下信息治疗ARDS：LGS成分木犀草素、汉黄芩素和黄芩苷可能是潜在的候选药物。丝裂原活化蛋白激酶14（MAPK14）、重组V-Rel网状内皮增生症病毒癌基因同源物A（RELA）和肿瘤坏死因子α（TNF-α）可能是潜在的治疗靶点。活性氧代谢过程和凋亡信号通路是主要的生物学过程。p38MAPK/NF-κB信号通路可能是LGS对抗ARDS激活的关键信号通路。此外，分子对接表明木犀草素、汉黄芩素和黄芩苷与MAPK14、RELA和TNFα具有良好的结合亲和力。体外实验中，LGS抑制脂多糖诱导的人支气管上皮细胞（HBE）中p38和p65的表达及入核，抑制炎症反应和氧化应激反应，并抑制HBE细胞凋亡（P<0.05或P<0.01）。体内实验中，LGS改善结扎穿刺所致的肺损伤，减轻炎症反应，并抑制p38MAPK和p65的激活（P<0.05或P<0.01）。
LGS可通过抑制p38MAPK/NF-κB信号通路减少活性氧和炎性细胞因子的产生，从而减少细胞凋亡并减轻ARDS。
