Abstract：
Infection with Schistosoma japonicum (S. japonicum) is an important zoonotic parasitic disease that causes liver fibrosis in both human and domestic animals. The activation of hepatic stellate cells (HSCs) is a crucial phase in the development of liver fibrosis, and inhibiting their activation can alleviate this progression. Total flavonoids of litchi seed (TFL) is a naturally extracted drug, and modern pharmacological studies have shown its anti-fibrotic and liver-protective effects. However, the role of TFL in schistosomiasis liver fibrosis is still unclear. This study investigated the therapeutic effects of TFL on liver fibrosis in S. japonicum infected mice and explored its potential mechanisms. Animal study results showed that TFL significantly reduced the levels of Interleukin-1β (IL-1β), Tumor Necrosis Factor-α (TNF-α), Interleukin-4 (IL-4), and Interleukin-6 (IL-6) in the serum of S. japonicum infected mice. TFL reduced the spleen index of mice and markedly improved the pathological changes in liver tissues induced by S. japonicum infection, decreasing the expression of alpha-smooth muscle actin (α-SMA), Collagen I and Collagen III protein in liver tissues. In vitro studies indicated that TFL also inhibited the activation of HCSs induced by Transforming Growth Factor-β1 (TGF-β1) and reduced the levels of α-SMA. Gut microbes metagenomics study revealed that the composition, abundance, and functions of the mice gut microbiomes changed significantly after S. japonicum infection, and TLF treatment reversed these changes. Therefore, our study indicated that TFL alleviated granulomatous lesions and improved S. japonicum induced liver fibrosis in mice by inhibiting the activation of HSCs and by improving the gut microbiomes.
摘要：
日本血吸虫感染（S.japonicum）是一种重要的人畜共患寄生虫病，可导致人类和家畜的肝纤维化。肝星状细胞(HSCs)的激活是肝纤维化发展的关键阶段,抑制它们的激活可以缓解这种进展。荔枝籽总黄酮（TFL）是一种天然提取的药物，和现代药理学研究表明其抗纤维化和肝脏保护作用。然而,TFL在血吸虫病肝纤维化中的作用尚不清楚。本研究探讨了TFL对日本血吸虫感染小鼠肝纤维化的治疗作用及其可能的机制。动物实验结果表明,TFL能显著降低白细胞介素-1β(IL-1β)水平,肿瘤坏死因子-α(TNF-α),白细胞介素-4(IL-4),日本血吸虫感染小鼠血清中的白细胞介素-6(IL-6)。TFL降低小鼠脾脏指数，明显改善日本血吸虫感染引起的肝组织病理变化，降低α-平滑肌肌动蛋白（α-SMA）的表达，肝组织中的胶原蛋白I和胶原蛋白III。体外研究表明，TFL还可以抑制转化生长因子-β1（TGF-β1）诱导的HCSs的激活，并降低α-SMA的水平。肠道微生物宏基因组学研究表明,丰度,日本血吸虫感染后，小鼠肠道微生物组的功能发生了显著变化，和TLF治疗逆转了这些变化。因此,我们的研究表明，TFL通过抑制HSCs的活化和改善肠道微生物组，减轻肉芽肿性病变并改善日本血吸虫诱导的小鼠肝纤维化。
