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Abstract：
The Yiqi Qubai (YQ) formula is a hospital preparation for treating vitiligo in China that has had reliable efficacy for decades. The formula consists of four herbs; however, the extraction process to produce the formula is obsolete and the active ingredients and mechanisms remain unknown. Therefore, in this paper, fingerprints were combined with the chemometrics method to screen high-quality herbs for the preparation of the YQ standard decoction (YQD). Then, the YQD preparation procedure was optimized using response surface methodology. A total of 44 chemical constituents, as well as 36 absorption components (in rat plasma) of YQD, were identified via UPLC-Q-TOF/MS. Based on the ingredients, the quality control system of YQD was optimized by establishing the SPE-UPLC-Q-TOF/MS identification method and the HPLC quantification method. Network pharmacological analysis and molecular docking showed that carasinaurone, calycosin-7-O-β-d-glucoside, methylnissolin-3-O-glucoside, genkwanin, akebia saponin D, formononetin, akebia saponin B, and apigenin may be the key active components for treating vitiligo; the core targets associated with them were AKT1, MAPK1, and mTOR, whereas the related pathways were the PI3K-Akt, MAPK, and FoxO signaling pathways. Cellular assays showed that YQD could promote melanogenesis and tyrosinase activity, as well as the transcription and expression of tyrosinase-associated proteins (i.e., TRP-1) in B16F10 cells. In addition, YQD also increased extracellular tyrosinase activity. Further efficacy validation showed that YQD significantly promotes melanin production in zebrafish. These may be the mechanisms by which YQD improves the symptoms of vitiligo. This is the first systematic study of the YQ formula that has optimized the standard decoction preparation method and investigated the active ingredients, quality control, efficacy, and mechanisms of YQD. The results of this study lay the foundations for the clinical application and further development of the YQ formula.
摘要：
益气祛白（YQ）方是中国治疗白癜风的医院制剂，几十年来一直具有可靠的疗效。该配方由四种草药组成；然而，生产配方的提取过程已经过时，活性成分和机制仍然未知。因此,在本文中，采用指纹图谱与化学计量学相结合的方法筛选出用于制备YQ标准汤剂(YQD)的优质药材。然后，采用响应面法对YQD制备工艺进行了优化。共有44种化学成分，以及YQD的36种吸收成分（在大鼠血浆中），通过UPLC-Q-TOF/MS鉴定根据成分，通过建立SPE-UPLC-Q-TOF/MS鉴别方法和HPLC定量方法,优化了YQD的质量控制体系。网络药理分析和分子对接表明，carasinaurone，calycosin-7-O-β-d-葡萄糖苷，甲基尼索溶胶-3-O-葡萄糖苷，Genkwanin,水草皂苷D,福蒙素,水草皂苷B,芹菜素可能是治疗白癜风的关键活性成分；与其相关的核心靶点是AKT1、MAPK1和mTOR，而相关通路是PI3K-Akt，MAPK,和FoxO信号通路。细胞实验表明，YQD可以促进黑素生成和酪氨酸酶活性，以及酪氨酸酶相关蛋白的转录和表达(即，TRP-1)在B16F10细胞中。此外,YQD还增加了细胞外酪氨酸酶活性。进一步的功效验证表明，YQD显着促进斑马鱼黑色素的产生。这些可能是YQD改善白癜风症状的机制。这是首次对YQ配方进行系统的研究,优化了标准汤剂的制备方法,考察了有效成分,质量控制,功效,和YQD的机制。本研究结果为YQ公式的临床应用和进一步开发奠定了基础。
