Huang Leyi, Wang Yangyang, Yue Xinyi, Yu Fangfang, Wu Tong, Ge Yimeng, Wang Chunmiao, Tong Meihong
National Key Laboratory of Lead Druggability Research, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, 200437, Shanghai, China.
Heilongjiang Zhenbaodao Pharmaceutical CO., LTD., 158400, Hulin, Heilongjiang, China.
J Tradit Complement Med. 2024 Apr 12;15(3):250-263. doi: 10.1016/j.jtcme.2024.04.006. eCollection 2025 May.
Fufang Qinlan oral liquid (QLOL) is a traditional Chinese medicine formula used to treat fevers, sore throats and cough. This study was to evaluate QLOL's therapeutic effects on post infectious cough (PIC) and to investigate Q-markers and action mechanisms by integrating pharmacokinetics and network pharmacology.
PIC rats were measured for cough frequency, organ index, pathological section of lung and inflammatory factors to evaluate the effects of QLOL. Pharmacokinetic analyses were performed using HPLC-QQQ-MS/MS to explore the possible Q-markers of QLOL and the changes of them . Network pharmacology was used to obtain potential important targets and action mechanisms of treating PIC. The possible hub genes were evaluated using QPCR.
The symptoms of cough and lung injury were significantly alleviated and IL-6 and IL-1β were significantly decreased after treatment of QLOL. 6 compounds were considered as possible Q-makers and their pharmacokinetic parameters were analyzed. The compound-target network was constructed to identify 53 important targets. Among them, HSPA8, HSP90AA1, HSP90AB1, YWHAZ, EGFR, ESR1 and EP300 were selected as the core targets because of high degree value and direct connection with inflammation or microbial infection. All 6 compounds had potently binding activity to core targets in molecular docking. The QPCR results showed the up-regulation of core targets expression in QLOL group compared with PIC rats, which validated the effects of QLOL and the accuracy of Q-markers selection.
QLOL alleviated PIC symptoms through various targets and mechanisms. The potential Q-markers were baicalein, baicalin, oroxylin A-7--glucuronideloside, wogonoside, oroxylin A and forsythoside E.
the experimental approach.
复方芩兰口服液(QLOL)是一种用于治疗发热、咽痛及咳嗽的中药方剂。本研究旨在评价QLOL对感染后咳嗽(PIC)的治疗效果,并通过整合药代动力学和网络药理学来研究其Q-标志物及作用机制。
测定PIC大鼠的咳嗽频率、脏器指数、肺组织病理切片及炎症因子,以评价QLOL的作用效果。采用高效液相色谱-三重四极杆质谱联用仪(HPLC-QQQ-MS/MS)进行药代动力学分析,以探索QLOL可能的Q-标志物及其变化情况。运用网络药理学获取治疗PIC的潜在重要靶点及作用机制。采用实时荧光定量聚合酶链反应(QPCR)评估可能的关键基因。
QLOL治疗后,咳嗽症状及肺损伤明显减轻,白细胞介素-6(IL-6)和白细胞介素-1β(IL-1β)显著降低。确定了6种化合物作为可能的Q-标志物,并分析了它们的药代动力学参数。构建了化合物-靶点网络,鉴定出53个重要靶点。其中,热休克蛋白家族A成员8(HSPA8)、热休克蛋白90α家族成员1(HSP90AA1)、热休克蛋白90β家族成员1(HSP90AB1)、14-3-3ζ蛋白(YWHAZ)、表皮生长因子受体(EGFR)、雌激素受体1(ESR1)和E1A结合蛋白p300(EP(300))因度数较高且与炎症或微生物感染直接相关而被选为核心靶点。在分子对接中,所有6种化合物均对核心靶点具有较强的结合活性。QPCR结果显示,与PIC大鼠相比,QLOL组核心靶点表达上调,验证了QLOL的作用效果及Q-标志物选择的准确性。
QLOL通过多种靶点和机制减轻PIC症状。潜在的Q-标志物为黄芩素、黄芩苷、木犀草素-7-O-葡萄糖醛酸苷、汉黄芩苷、木犀草素和连翘酯苷E。
Evise分类法:实验方法。