Wu Zhenghua, Jia Mengqi, Zhao Wenjuan, Huang Xucong, Yang Xinyi, Chen Dongxin, Qiaolongbatu Xijier, Li Xiaojing, Wu Jiaqi, Qian Feng, Lou Yuefen, Fan Guorong
Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200080, PR China.
School of Pharmacy, Shanghai Jiao Tong University, Shanghai, 200240, PR China.
J Ethnopharmacol. 2022 May 10;289:115031. doi: 10.1016/j.jep.2022.115031. Epub 2022 Jan 26.
Schisandra chinensis decoction derived from the book of Waitai Miyao (Tao Wang, Tang dynasty) is often used in the treatment of idiopathic pulmonary fibrosis (IPF), which is included in the Grand Ceremony of Chinese formulae (Huairen Peng, 1994). Schisandrae Chinensis Fructus (Sch) is one of the most important herbs in this formula. According to the "Shennong's Herbal Classicherbal" of the Han Dynasty, Sch has sour taste, warm nature, which has the effect of tonifying qi and curing cough. In addition, according to the "Compendium of Materia Medica" of the Ming Dynasty, Sch is used to treat cough and asthma, which has the effect of moistening the lung and tonifying the kidney. However, the active ingredients of Sch absorption into the plasma and its pharmacological mechanism of treatment for IPF still remained unclear.
Our research aimed at identifying the absorbed active ingredients and metabolized of Sch in rat plasma and the mechanism of anti-IPF based on serum pharmacochemistry.
First, the rats were divided into control group and Sch group. Sch sample was orally administrated to the rats for seven days. The blood samples were drawn into an Eppendorf tube after the last dosing. The ultrahigh performance liquid chromatography coupled with quadrupole-time of flight mass spectrometry (UPLC-Q-TOF/MS) was applied to identify the absorption components and metabolites of Sch in rat plasma. Second, the network pharmacology combined with molecular docking analysis was further investigated to illuminate its potential mechanism of treatment for IPF by the biological targets regulating related pathways. Finally, the mechanism of action was verified by experimental in vitro and in vivo.
A total of 78 compounds, consist of 13 prototype lignans and 65 metabolites (including isomers) were identified. Network pharmacology study and molecular docking analysis indicated that schisandrol A (L1) play an anti-fibrosis role by regulating the TGF-β signaling pathway. Experimental in vitro and in vivo verified that the schisandrol A could inhibiting pulmonary fibrosis through TGF-β signaling pathway. The effect and mechanism of schisandrol A inhibiting pulmonary fibrosis were reported for the first time.
In this study, the absorption active ingredients of Sch in rat plasma were combined with the network pharmacology investigation and experimental in vitro and in vivo to elucidate its biological mechanism of treatment for IPF. The results provided a theoretical support for understanding the bioactive compounds and the pharmacological mechanism of Sch.
源自《外台秘要》（唐代王焘）的五味子汤常用于治疗特发性肺纤维化（IPF），该方被收录于《中国方剂大辞典》（彭怀仁，1994年）。五味子是该方中最重要的草药之一。据汉代《神农本草经》记载，五味子味酸、性温，具有补气止咳之功效。此外，据明代《本草纲目》记载，五味子用于治疗咳嗽气喘，具有润肺补肾之功效。然而，五味子吸收进入血浆的活性成分及其治疗IPF的药理机制仍不清楚。
本研究旨在基于血清药物化学鉴定五味子在大鼠血浆中的吸收活性成分及其代谢产物，并阐明其抗IPF的机制。
首先，将大鼠分为对照组和五味子组。五味子样品经口给予大鼠7天。末次给药后，将血样采集到Eppendorf管中。采用超高效液相色谱-四极杆-飞行时间质谱联用仪（UPLC-Q-TOF/MS）鉴定五味子在大鼠血浆中的吸收成分和代谢产物。其次，进一步采用网络药理学结合分子对接分析，通过调节相关通路的生物靶点阐明其治疗IPF的潜在机制。最后，通过体外和体内实验验证其作用机制。
共鉴定出78种化合物，包括13种原型木脂素和65种代谢产物（包括异构体）。网络药理学研究和分子对接分析表明，五味子醇甲（L1）通过调节TGF-β信号通路发挥抗纤维化作用。体外和体内实验验证了五味子醇甲可通过TGF-β信号通路抑制肺纤维化。首次报道了五味子醇甲抑制肺纤维化的作用及机制。
本研究将五味子在大鼠血浆中的吸收活性成分与网络药理学研究以及体外和体内实验相结合，阐明了其治疗IPF的生物学机制。研究结果为理解五味子的生物活性成分及其药理机制提供了理论支持。
