Background:

Liver fibrosis is a chronic pathological condition with a leading cause of liver-related mortality worldwide. In the present study, we have evaluated the antifibrotic effect of crocin, a carotenoid present in the stigma of Crocus sativus, and also explored its putative mechanism of action.

Methods:

Liver fibrosis was induced by intraperitoneal administration of 30% carbon tetrachloride (CCl₄). The crocin was administered orally at 20, 40 and 80 mg/kg body weight along with CCl₄ up to 8 weeks.

Results:

Chronic exposure to CCl₄ resulted in elevated levels of liver enzymes and reduced cytochrome P450 2E1 (CYP2E1) activity in the liver. The liver tissue showed cellular swelling, vacuolization, necrosis, infiltration of inflammatory cells and fibrotic changes. The crocin treatment significantly lowered the levels of liver enzymes in serum and improved the liver CYP2E1 mRNA levels. The pathological changes in the liver were also lowered by crocin treatment. The level of pro-inflammatory cytokines, nuclear factor-kappa B, interleukin-6 and tumor necrosis factor α and fibrogenic factor, transforming growth factor β, and α-smooth muscle actin were elevated by the CCl₄ in the liver tissue. However, crocin treatment at different doses significantly reduced the expression of these factors. The increased caspase 3/7 activity was also lowered by crocin. CCl₄ administration decreased the expression of peroxisome proliferator-activated receptor γ (PPAR-γ) in liver tissue. The improved PPAR-γ expression in the liver by crocin treatment indicates its role in the therapeutic effect of crocin.

Conclusions:

Crocin attenuated the various events in the progression of liver fibrosis via PPAR-γ mediated modulation of inflammatory and fibrogenic pathways.

中文翻译：

---

Crocin 通过 PPAR-γ 介导的大鼠炎症和纤维化调节减轻 CCl4 诱导的肝纤维化。

背景：

肝纤维化是一种慢性病理状况，是全球肝脏相关死亡的主要原因。在本研究中，我们评估了藏红花素（一种存在于番红花柱头中的类胡萝卜素）的抗纤维化作用，并探讨了其假定的作用机制。

方法：

通过腹膜内施用30%四氯化碳（CCl ₄）诱导肝纤维化。藏红花素以 20、40 和 80 mg/kg 体重与 CCl ₄一起口服给药长达 8 周。

结果：

长期暴露于 CCl ₄会导致肝酶水平升高并降低肝脏中的细胞色素 P450 2E1 (CYP2E1) 活性。肝组织呈细胞肿胀、空泡化、坏死、炎性细胞浸润和纤维化改变。藏红花素处理显着降低了血清中肝酶的水平，并提高了肝脏 CYP2E1 mRNA 水平。藏红花素治疗也降低了肝脏的病理变化。_{CCl 4}升高促炎细胞因子、核因子-κB、白细胞介素6和肿瘤坏死因子α和纤维化因子、转化生长因子β和α-平滑肌肌动蛋白的水平在肝组织中。然而，不同剂量的藏红花素处理显着降低了这些因子的表达。藏红花素也降低了增加的半胱天冬酶3/7活性。CCl ₄给药降低了肝组织中过氧化物酶体增殖物激活受体γ（PPAR-γ）的表达。藏红花素处理后肝脏中 PPAR-γ 表达的改善表明其在藏红花素治疗效果中的作用。

结论：

藏红花素通过 PPAR-γ 介导的炎症和纤维化途径的调节减弱了肝纤维化进展中的各种事件。