Jiawei Taohe Chengqi decoction inhibition of the notch signal pathway affects macrophage reprogramming to inhibit HSCs activation for the treatment of hepatic fibrosis
Jiawei Taohe Chengqi decoction inhibition of the notch signal pathway affects macrophage reprogramming to inhibit HSCs activation for the treatment of hepatic fibrosis
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DOI：
10.1016/j.jep.2023.117486
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发表时间：
2023-12-07
影响因子：
5.4
通讯作者：
Zhang，Junjie
中科院分区：
文献类型：
--
作者：
Shao，Chang;Xu，Huihui;Zhang，Junjie
民族药理学相关性加味桃核承气汤（JTCD）是传统中医药（TCM）的改良方，称为桃核承气汤，在古代中医文献《伤寒论》中有描述。JTCD作为一种活血化瘀、调节阴阳的中药方剂，对慢性肝病和肝纤维化有较好的治疗作用。研究目的本研究旨在评价JTCD通过调节Notch信号通路对肝巨噬细胞的调节作用，并进一步研究导致HF.Materials and MethodsMolecular检测的巨噬细胞重编程的机制，使用人单核THP-1细胞和人源性肝星状细胞LX-2的体外培养物进行。CCl 4诱导的小鼠被用作体内模型，以模拟HF.ResultsOur结果表明，JTCD表现出双重作用，抑制肝星状细胞（HSC）的激活和调节极化的巨噬细胞对M2表型，同时减少M1表型。网络药理学分析和分子对接研究表明，Notch信号通路在JTCD抗心衰的治疗中具有重要作用。此外，通过建立共培养模型，我们验证了JTCD抑制巨噬细胞Notch信号通路，导致巨噬细胞重编程的改变，随后抑制HSC活化，并最终发挥抗HF作用。结论总之，我们的研究结果为JTCD治疗HF提供了坚实的证据，因为它抑制了巨噬细胞Notch信号通路，调节巨噬细胞重编程，并抑制HSC活化。
Ethnopharmacological relevanceJiawei Taohe Chengqi Tang (JTCD) is a modified formulation of Traditional Chinese Medicine (TCM) known as Taohe Chengqi Decoction, which has been described in the ancient TCM literature “Treatise on Febrile Diseases”. As a formula that can activate blood circulation and eliminate blood stasis and regulate Yin and Yang in traditional Chinese medicine applications, JTCD has been reported to be effective in the treatment of chronic liver disease and hepatic fibrosis (HF).Aim of studyThe current study aimed to evaluate the effectiveness of JTCD in modulating hepatic macrophages by regulating the Notch signal pathway, and to further investigate the mechanisms underlying macrophage reprogramming that leads to HF.Materials and methodsMolecular assays were performed using in vitro cultures of human mononuclear THP-1 cells and human-derived hepatic stellate cells LX-2. CCl4-induced mice were utilized as an in vivo model to simulate HF.ResultsOur results demonstrated that JTCD exhibited dual effects by inhibiting hepatic stellate cell (HSCs) activation and modulating the polarisation of macrophages towards the M2 phenotype while decreasing the M1 phenotype. Network pharmacological analyses and molecular docking studies revealed that the Notch signal pathway was significantly enriched and played a crucial role in the therapeutic response of JTCD against HF. Moreover, through the establishment of a co-culture model, we validated that JTCD inhibited the Notch signal pathway in macrophages, leading to alterations in macrophage reprogramming, subsequent inhibition of HSC activation, and ultimately exerting anti-HF effects.ConclusionIn conclusion, our findings provide solid evidence for JTCD in treating HF, as it suppresses the Notch signal pathway in macrophages, regulates macrophage reprogramming, and inhibits HSC activation.