Safflower yellow reduces DEN-induced hepatocellular carcinoma by enhancing liver immune infiltration through promotion of collagen degradation and modulation of gut microbiota
Safflower yellow reduces DEN-induced hepatocellular carcinoma by enhancing liver immune infiltration through promotion of collagen degradation and modulation of gut microbiota
复制标题
DOI：
10.1039/d1fo01321a
复制
发表时间：
2021-09-29
期刊：
影响因子：
6.1
通讯作者：
Shou, Qiyang
中科院分区：
文献类型：
--
作者：
Fu, Huiying;Liu, Xia;Shou, Qiyang
红花黄色素（SY）是从中药红花中提取的主要活性成分，是一种珍贵的天然食用色素，广泛用于治疗心脑血管疾病。然而，SY对肝细胞癌（HCC）的作用尚不清楚。在这项研究中，我们发现SY降低了二乙基亚硝胺（DEN）诱导的肝癌小鼠模型的损伤程度，并抑制了肝脏中炎症因子的释放。流式细胞术和免疫印迹显示，SY通过影响胶原纤维的表达，增加CD 8（+）T细胞和Gr-1（+）巨噬细胞的浸润，改善免疫微环境。进一步的细胞实验表明，SY通过TGF-β/Smad信号通路降解肝细胞中的胶原。SY还调节肠道微生物群，这可能有助于免疫微环境。总之，SY通过促进胶原降解和调节肠道微生物群来增强肝脏免疫浸润，从而对HCC的发展具有有效作用。这项研究为SY作为未来治疗肝癌的候选药物的机制提供了新的见解。
Safflower yellow (SY) is the main active ingredient isolated from the traditional Chinese medicine Carthamus tinctorius, which is a valuable natural edible pigment that is widely used to treat cerebrovascular and cardiovascular diseases. However, the effect of SY on hepatocellular carcinoma (HCC) remains unclear. In this study, we showed that SY decreased the degree of injury and inhibited the release of inflammatory factors in the liver of a diethylnitrosamine (DEN)-induced HCC mouse model. Flow cytometry and immunoblotting showed that SY increased the infiltration of CD8(+) T cells and Gr-1(+) macrophages to improve the immune microenvironment by affecting the expression of collagen fibers. Further cellular experiments showed that SY degraded the collagens in the liver cells through the TGF-beta/Smad signalling pathway. SY also regulated the gut microbiota which may contribute to the immune microenvironment. In conclusion, SY exhibited a potent effect on the development of HCC by enhancing liver immune infiltration by promoting collagen degradation and modulating the gut microbiota. This study provides novel insights into the mechanism of SY as a candidate for the treatment of HCC in the future.