Dill extract attenuates liver fibrosis and steatohepatitis in obese rats via modulating TGF-β1 signaling and collagen accumulation

莳萝提取物通过调节TGF-β1信号通路和胶原蛋白积累,减轻肥胖大鼠的肝纤维化和脂肪性肝炎。

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Abstract

BACKGROUND AND PURPOSE: Dill (Anethum graveolens) is an herbal plant from the Apiaceae family often used as an effective remedy for several ailments. This study aimed to investigate the potential protective effect of dill against the development of non-alcoholic fatty liver disease in obese rats. EXPERIMENTAL APPROACH: For 12 weeks, rats were fed a high-fat diet (HFD) to induce obesity. In the treatment group, the extract of dill leaves (100 mg/kg) was administered by gavage. Then, blood and liver samples were harvested for further investigations. FINDINGS/RESULTS: Feeding HFD caused increased body mass index, abdominal circumference, adiposity index, weight gain, serum glucose, lipids, insulin, leptin, and insulin resistance. HFD-fed rats also showed increased hepatic triglycerides, fatty acid synthase, cytochrome P2E1, hydrogen peroxide, malondialdehyde, serum marker enzymes (AST, ALT, ALP, and GGT), and liver weight, with decreased antioxidants including superoxide dismutase, catalase, and glutathione. Besides, a significant elevation of hepatic interleukins 1β and 6,tumor necrosis factor-α, nuclear factor-kappa B, Kupfer cell markers (CD68 and CD163), fibronectin, andcollagen type 1, along with an increase of transforming growth factor-β1 expression, was observed. Histological changes presented by hepatocytes, including ballooning, inflammatory cell aggregation, and deposition of collagen fibers, have also been detected. Co-administration of dill with HFD succeeded in reducing weight gain, hepatic triglyceride accumulation, oxidative reactions, inflammation, fibrosis, and liver structural injury. CONCLUSION AND IMPLICATIONS: Dill extract could be approved as a promising therapeutic approach with multiple benefits for the management of obesity and associated steatohepatitis.

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