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• W4367177445 abstract "Abstract Liver fibrosis is caused by various liver diseases and eventually develops into liver cancer. Tomatidine (TD), an aglycone of α-tomatidine, is a major glycoalkaloid found in immature tomato fruits, leaves, and stems. In this study, we investigated that tomatidine may promote autophagy in hepatic stellate cells through the ERK/MAPK-mTOR-ULK1 signaling pathway to improve liver fibrosis and combined experimental validation and molecular docking to reveal the underlying mechanism. First, we found that tomatidine could inhibit the proliferation of hepatic stellate cells and the expression of fibrosis-related proteins α-smooth muscle actin (α-SMA) and collagen type I 1 gene (COL1A1) in LX2 cells. Tomatidine was found to promote the expression of autophagy-related proteins. Next, we performed a network pharmacology screen and found that among the targets of tomatidine and the common targets of tomatidine and liver fibrosis, no target related to autophagy was found in the current database. However, pharmacological studies of tomatidine have confirmed the existence of pro-autophagy pharmacological effects. Therefore, we used molecular docking to verify that tomatidine had good binding and affinity with autophagy-related targets. Further network pharmacological analysis showed that the MAPK signaling pathway may be involved in the biological process of tomatidine against hepatic stellate cells. We further verified the ERK/MAPK-mTOR-ULK1 pathway and found that tomatidine could promote autophagy in LX-2 cells by inhibiting the expression of P-ERK and P-mTOR and activating the expression of P-ULK1. Finally, molecular docking was performed to reveal the binding of tomatidine to the active sites of ERK, MAPK, mTOR, and ULK1." @default.
• W4367177445 created "2023-04-28" @default.
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• W4367177445 date "2023-04-27" @default.
• W4367177445 modified "2023-10-16" @default.
• W4367177445 title "Tomatidine improves liver fibrosis by promoting autophagy in hepatic stellate cells through the ERK/MAPK-mTOR-ULK1 pathway" @default.
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• W4367177445 doi "https://doi.org/10.21203/rs.3.rs-2761910/v1" @default.
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