Effect and Mechanism of Mulberry Leaf Alkaloid on Improving Hepatic Fibrosis in Mice

Objective: To investigate the regulatory effects of mulberry leaf alkaloid on the transforming growth factor-β1(TGF-β1)/Smads pathway and the expression of matrix metalloproteinase-13 (MMP-13) and inhibitor of metalloproteinase-1(TIMP-1), and to explore its action mechanism in alleviating hepatic fibrosis in mice.Methods: Hepatic fibrosis in mice was induced by intraperitoneal injection of 10% (V/V) CCl4 in olive oil at a dose of 5 mL/kg mb every other day combined with feeding a high-fat diet for 8 consecutive weeks.Thereafter, the mice in the control and model groups were given distilled water, those in the low-, medium- and high-dose treatment groups were intragastrically administered with 50, 100 and 200 mg/kg mb mulberry leaf alkaloid, and those in the positive drug group were gavaged with 100 mg/kg of silibinin for 45 days.The contents of hepatic α-smooth muscle actin (α-SMA), collagen I (Col I) and collagen III (Col III) in mice were determined by enzyme-linked immunosorbent assay (ELISA) kits, and the mRNA expression levels of TGF-β1, Smad3, Smad4, Smad7, MMP-13 and TIMP-1 were detected by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR).Results: Compared with the model group, the contents of α-SMA, collagen I and collagen III in the high-dose group decreased by 19.55%, 19.93% and 13.84% (P < 0.05), respectively.Similarly, the mRNA expression levels of TGF-β1, Smad3, Smad4 and TIMP-1 significantly decreased by 59.04%, 56.73%, 50.70% and 49.09% (P < 0.05), respectively.Moreover, Smad7 and MMP-13 mRNA expression levels increased by 48.29% and 25.72%(P < 0.05), respectively.Conclusion: Mulberry leaf alkaloids can improve hepatic fibrosis in mice, and its underlying mechanism may be related to the regulation of the TGF-β1/Smads signaling pathway related factors and TIMP-1 and MMP-13 mRNA expression. © 2021, China Food Publishing Company. All right reserved.