Department of Infectious Disease, The Affiliated Hospital, Guizhou Medical University, Beijing Road 9, Guiyang, 550004, Guizhou, China.
Department of Blood Transfusion, The Affiliated Tumor Hospital, Guizhou Medical University, Beijing west Road1, Guiyang, 550000, Guizhou, China.
Eur J Pharmacol. 2020 Jun 5;876:172946. doi: 10.1016/j.ejphar.2020.172946. Epub 2020 Jan 26.
Liver fibrosis is involved in the progression of most chronic liver diseases. Even though we have made a huge progress in order to understand the pathogenesis of liver fibrosis, however, there is still a lack of productive treatments. Being a traditional Chinese medicine, Platycodin D (PD), an oleanane kind of triterpenoid saponin has been put to extensive use for treating different kinds of illnesses that include not just anti-nociceptive, but also antiviral, anti-inflammatory, and anti-cancer for thousands of years. Nonetheless, there has been no clarification made for its effects on the progression of liver fibrosis. In this manner, we carried out in vitro studies for the purpose of investigating the anti-fibrosis impact of PD. Activation of hepatic stellate cells was evaluated by means of the detection of the proliferation of HSCs and the expression of specific proteins. We discovered the fact that PD had the potential of activating HSCs. Thereafter, we detected the apoptosis and autophagy of the HSCs; as the results suggested, PD induced apoptosis and autophagy of the HSCs. It augmented the expression level of apoptotic proteins that included Bax, Cytochrome C (cyto-c), cleaved caspase3 and cleaved caspase9, in addition to the autophagy relevant proteins, for instance, LC3II, beclin1, Atg5 and Atg9. Further research was carried out for the investigation of the underlying molecular mechanism, and discovered that PD promoted the phosphorylation of JNK and c-Jun. Treating the JNK inhibitor P600125 inhibited the effect of PD, confirming the impact of PD on the regulation of JNK/c-Jun pathway. Thus, we speculated that PD alleviates liver fibrosis and activation of hepatic stellate via promoting phosphorylation of JNK and c-Jun and further altering the autophagy along with apoptosis of HSCs.
肝纤维化参与大多数慢性肝病的进展。尽管我们在理解肝纤维化发病机制方面取得了巨大进展，但仍缺乏有效的治疗方法。作为一种传统中药，桔梗皂苷 D（PD），一种齐墩果烷型三萜皂苷，几千年来一直被广泛用于治疗各种疾病，不仅具有抗伤害感受作用，而且具有抗病毒、抗炎和抗癌作用。然而，其对肝纤维化进展的影响尚未得到阐明。因此，我们进行了体外研究，旨在研究 PD 的抗纤维化作用。通过检测 HSCs 的增殖和特定蛋白的表达来评估肝星状细胞的激活。我们发现 PD 具有激活 HSCs 的潜力。然后，我们检测了 HSCs 的凋亡和自噬；结果表明，PD 诱导了 HSCs 的凋亡和自噬。它增加了凋亡蛋白的表达水平，包括 Bax、Cytochrome C（细胞色素 c）、cleaved caspase3 和 cleaved caspase9，以及自噬相关蛋白，如 LC3II、beclin1、Atg5 和 Atg9。进一步的研究旨在探讨潜在的分子机制，发现 PD 促进了 JNK 和 c-Jun 的磷酸化。用 JNK 抑制剂 P600125 处理抑制了 PD 的作用，证实了 PD 对 JNK/c-Jun 通路调节的影响。因此，我们推测 PD 通过促进 JNK 和 c-Jun 的磷酸化，进一步改变 HSCs 的自噬和凋亡，从而减轻肝纤维化和肝星状细胞的激活。
