Gao Yu, Dai Haoran, Zhang Na, Jiang Hanxue, Zhang Zihan, Feng Zhendong, Dong Zhaocheng, Liu Wenbin, Liu Fei, Dong Xuan, Zhao Qihan, Zhou Xiaoshan, Du Jieli, Zhang Naiqian, Rui Hongliang, Liu Baoli
Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China.
School of Traditional Chinese Medicine, Capital Medical University, Beijing, China.
Front Pharmacol. 2022 Apr 21;13:820130. doi: 10.3389/fphar.2022.820130. eCollection 2022.
The increased incidence of membranous nephropathy (MN) has made it the most common pathological type of primary nephrotic syndrome in adults in China. According to the theory of Traditional Chinese Medicine (TCM), Mahuang Fuzi (Chinese ephedra and Radix Aconiti Lateralis Preparata) and Shenzhuo Decoction (MFSD) could be used to treat such diseases. We treated patients of MN with MFSD, and observed comparable efficacy to glucocorticoid and/or immunosuppressants. In this study, we observed the therapeutic effect of MFSD on the rat model of passive Heymann nephritis (PHN), a classical MN model. Our results showed that MFSD treatment significantly reduced urinary protein level and podocyte injury in PHN rats, and correspondingly improved renal pathology, with the improvement effect on MN comparable to that of Cyclosporine A (CsA) alone. To explore the potential therapeutical mechanism of MFSD, the main chemical components of MFSD were determined by High-performance liquid chromatography-mass spectrometry (HPLC-MS). There were about 30 active components of MFSD. Next, based on network pharmacology methods, we screened related targets of MSFD on MN, which provided a preliminary understanding of the MFSD bioactive compounds. The clustering analysis showed that its active site might be in the autophagy-related protein and Wnt/β-catenin pathway, which was related to podocyte injury. Finally, we observed an improvement in renal autophagy and a down-regulation of the Wnt/β-catenin pathway after MSFD treatment in a PHN rat model. According to this study, autophagy and Wnt/β-catenin pathway may be potential targets for MFSD in the treatment of MN.
膜性肾病（MN）发病率的增加使其成为中国成人原发性肾病综合征最常见的病理类型。根据中医理论，麻黄附子（麻黄和制附子）及参芪浊毒汤（MFSD）可用于治疗此类疾病。我们用MFSD治疗MN患者，并观察到其疗效与糖皮质激素和/或免疫抑制剂相当。在本研究中，我们观察了MFSD对被动型Heymann肾炎（PHN）大鼠模型（一种经典的MN模型）的治疗效果。我们的结果表明，MFSD治疗显著降低了PHN大鼠的尿蛋白水平和足细胞损伤，并相应改善了肾脏病理，对MN的改善效果与单独使用环孢素A（CsA）相当。为了探索MFSD的潜在治疗机制，采用高效液相色谱-质谱联用（HPLC-MS）法测定了MFSD的主要化学成分。MFSD约有30种活性成分。接下来，基于网络药理学方法，我们筛选了MFSD在MN上的相关靶点，这为初步了解MFSD的生物活性化合物提供了依据。聚类分析表明，其活性位点可能在自噬相关蛋白和Wnt/β-连环蛋白通路中，这与足细胞损伤有关。最后，我们观察到在PHN大鼠模型中，MFSD治疗后肾脏自噬得到改善，Wnt/β-连环蛋白通路下调。根据本研究，自噬和Wnt/β-连环蛋白通路可能是MFSD治疗MN的潜在靶点。
