Guizhou Provincial College-based Key Lab for Tumor Prevention and Treatment with Distinctive Medicines, Zunyi Medical University, Zunyi, Guizhou, 563000, China; College of Basic Medicine, Zunyi Medical University, Zunyi, Guizhou, 563000, China; Institute of Life Sciences, Zunyi Medical University, Zunyi, Guizhou, 563000, China.
Topscience Company Limited, Shanghai, 200436, China.
Eur J Pharmacol. 2024 Oct 15;981:176917. doi: 10.1016/j.ejphar.2024.176917. Epub 2024 Aug 16.
Liver fibrosis is a pathological process that endangers human health, for which effective treatments remain elusive to date. Paeoniflorin (PAE), a pineane-type monoter penoid compound from the traditional Chinese medicine PaeoniaeRubra Radix, and metformin (MET), an oral biguanide hypoglycemic agent, both demonstrate anti-inflammatory and hepatoprotective effects. In current work, we first discovered that the combined treatment of PAE and MET synergistically inhibited the progression of liver fibrosis in two different animal models: therapeutic and preventive. This therapeutic effect is evidenced by a reduction in the expression levels of liver fibrosis markers and an improvement in histopathological characteristics. Mechanistic exploration further revealed that this combination therapy downregulated the expression of TGF-β1 and p-Smad2, while upregulating Smad7 expression in both models. Importantly, we also found that this combinatorial approach significantly reduced hepatotoxicity and nephrotoxicity in both models. Our findings suggest an effective combination therapy for liver fibrosis and provide the possibility of therapeutic improvement for patients with liver fibrosis.
肝纤维化是一种危害人类健康的病理过程，目前仍缺乏有效的治疗方法。芍药苷（PAE）是一种来源于传统中药白芍的派诺里型单萜类化合物，二甲双胍（MET）是一种口服双胍类降糖药，都具有抗炎和保肝作用。在目前的工作中，我们首次发现芍药苷和二甲双胍联合治疗在两种不同的动物模型中协同抑制肝纤维化的进展：治疗和预防。这种治疗效果表现为肝纤维化标志物的表达水平降低和组织病理学特征的改善。机制探索进一步表明，这种联合治疗下调了两种模型中 TGF-β1 和 p-Smad2 的表达，同时上调了 Smad7 的表达。重要的是，我们还发现这种组合疗法显著降低了两种模型中的肝毒性和肾毒性。我们的研究结果为肝纤维化提供了一种有效的联合治疗方法，并为肝纤维化患者的治疗改善提供了可能。
