Guo Bindan, Dong Wenting, Huo Jinhai, Sun Guodong, Qin Zhiwei, Liu Xiaodong, Zhang Bihai, Wang Weiming
Institute of Chinese Materia Medica, Heilongjiang Academy of Chinese Medicine Sciences, Harbin, China.
Front Pharmacol. 2022 Apr 5;13:828175. doi: 10.3389/fphar.2022.828175. eCollection 2022.
Qifenggubiao granules (QFGBG) is a new Chinese medicine independently developed by Heilongjiang Academy of Traditional Chinese Medicine, which combines the essence of Yupingfeng powder and Shengmai yin (invention patent number: CN1325098C, approval number: Sinopharm Zhunzi B20020410), and has been included in the 2020 edition of Chinese Pharmacopoeia. It has remarkable pharmacodynamic results and conclusive clinical effects in the treatment of allergic rhinitis, chronic cough and other diseases. Previous pharmacological studies have shown that it has immunomodulatory effect, but its immunomodulatory mechanism is still unclear. In this study, cyclophosphamide (CTX) was used to establish the immune hypofunction model in mice, and the weight change, index of immune organs in spleen and thymus, pathological sections of immune organs and inflammatory factors were used to evaluate the model. Based on the metabolic biomarkers obtained by metabonomics technology, the potential targets of Qifeng Gubiao Granule immunomodulation were obtained by integrating the targets of blood components, metabolites and diseases through network pharmacology. Meanwhile, GO enrichment analysis and KEGG pathway analysis were carried out on the potential targets. QFGBG can increase body weight and organ index, and recover immune organ damage caused by CP. Metabonomics identified 13 metabolites with significant changes, among which the level of phospholipid (PC) metabolites decreased significantly in the model group. Sphingosine -1- phosphate, 1- palmitoyl phosphatidylcholine [LysoPC (16:0/0:0)] and other metabolites were significantly increased in the model group, and 98 targets of Qifeng's external immune regulation were obtained by intersecting 629 component targets, 202 metabolite targets and 1916 disease targets. KEGG pathway analysis obtained 233 related metabolic pathways, and the top 20 metabolic pathways mainly involved IL-17 signaling pathway, TNF signaling pathway, Sphingolipid signaling pathway, and so on. QFGBG may act on AKT1, IL6, MAPK3, PTGS2, CASP3, MAPK1, ESR1, PPARG, HSP90AA1, PPARA and other targets, acting through Sphingolipid signaling pathway and signaling pathway. Combined with pharmacodynamic evaluation, the immunomodulatory effect of QFGBG was confirmed, and the immunomodulatory mechanism of QFGBG with multiple targets and multiple pathways was preliminarily clarified.
芪风固表颗粒（QFGBG）是黑龙江中医药大学自主研发的一种中药新药，它融合了玉屏风散和生脉饮的精髓（发明专利号：CN1325098C，批准文号：国药准字B20020410），已被收录于《中国药典》2020年版。其在治疗过敏性鼻炎、慢性咳嗽等疾病方面具有显著的药效学成果和确切的临床疗效。以往的药理研究表明它具有免疫调节作用，但其免疫调节机制仍不明确。在本研究中，使用环磷酰胺（CTX）建立小鼠免疫功能低下模型，通过体重变化、脾脏和胸腺等免疫器官指数、免疫器官病理切片以及炎症因子来评估该模型。基于代谢组学技术获得的代谢生物标志物，通过网络药理学将血液成分、代谢产物和疾病的靶点整合，从而得到芪风固表颗粒免疫调节的潜在靶点。同时，对潜在靶点进行基因本体（GO）富集分析和京都基因与基因组百科全书（KEGG）通路分析。芪风固表颗粒可增加体重和器官指数，修复环磷酰胺所致的免疫器官损伤。代谢组学鉴定出13种有显著变化的代谢产物，其中模型组磷脂（PC）代谢产物水平显著降低。模型组中鞘氨醇-1-磷酸、1-棕榈酰磷脂酰胆碱[溶血磷脂酰胆碱（16:0/0:0）]等代谢产物显著升高，通过将629个成分靶点、202个代谢产物靶点和1916个疾病靶点进行交叉分析，得到芪风对外免疫调节的98个靶点。KEGG通路分析获得233条相关代谢通路，排名前20的代谢通路主要涉及白细胞介素-17信号通路、肿瘤坏死因子信号通路、鞘脂信号通路等。芪风固表颗粒可能作用于蛋白激酶B1（AKT1）、白细胞介素-6（IL6）、丝裂原活化蛋白激酶3（MAPK3）、前列腺素内过氧化物合酶2（PTGS2）、半胱天冬酶3（CASP3）、丝裂原活化蛋白激酶1（MAPK1）、雌激素受体1（ESR1）、过氧化物酶体增殖物激活受体γ（PPARG）、热休克蛋白90α家族成员1（HSP90AA1）、过氧化物酶体增殖物激活受体α（PPARA）等靶点，通过鞘脂信号通路等信号通路发挥作用。结合药效学评价，证实了芪风固表颗粒的免疫调节作用，并初步阐明了其多靶点、多通路的免疫调节机制。
