Laboratory of Stem Cell Regulation with Chinese Medicine and Its Application, School of Pharmacy, Hunan University of Chinese Medicine, Changsha, China.
Science and Technology Innovation Center, Hunan University of Chinese Medicine, Changsha, China.
Pharm Biol. 2023 Dec;61(1):1108-1119. doi: 10.1080/13880209.2023.2234000.
Dihydromyricetin (DMY) is extracted from vine tea, a traditional Chinese herbal medicine with anti-cancer, liver protection, and cholesterol-lowering effects.
This study investigated the mechanism of DMY against hepatocellular carcinoma (HCC).
Potential DMY, HCC, and cholesterol targets were collected from relevant databases. PPI networks were created by STRING. Then, the hub genes of co-targets, screened using CytoHubba. GO and KEGG pathway enrichment, were performed by Metascape. Based on the above results, a series of experiments were conducted by using 40-160 μM DMY for 24 h, including transwell migration/invasion assay, western blotting, and Bodipy stain assay.
Network pharmacology identified 98 common targets and 10 hub genes of DMY, HCC, and cholesterol, and revealed that the anti-HCC effect of DMY may be related to the positive regulation of lipid rafts. Further experiments confirmed that DMY inhibits the proliferation, migration, and invasion of HCC cells and reduces their cholesterol levels . The IC is 894.4, 814.4, 467.8, 1,878.8, 151.8, and 156.9 μM for 97H, Hep3B, Sk-Hep1, SMMC-7721, HepG2, and Huh7 cells, respectively. In addition, DMY downregulates the expression of lipid raft markers (CAV1, FLOT1), as well as EGFR, PI3K, Akt, STAT3, and Erk.
The present study reveals that DMY suppresses EGFR and its downstream pathways by reducing cholesterol to disrupt lipid rafts, thereby inhibiting HCC, which provides a promising candidate drug with low toxicity for the treatment of HCC.
二氢杨梅素（DMY）是从藤茶中提取的一种中药，具有抗癌、护肝和降胆固醇作用。
本研究旨在探讨 DMY 抑制肝癌（HCC）的作用机制。
从相关数据库中收集潜在的 DMY、HCC 和胆固醇靶点。使用 STRING 构建 PPI 网络。然后，使用 CytoHubba 筛选共靶标中的枢纽基因。使用 Metascape 进行 GO 和 KEGG 通路富集分析。基于上述结果，用 40-160μM DMY 处理 24 小时进行一系列实验，包括 Transwell 迁移/侵袭实验、Western blot 和 Bodipy 染色实验。
网络药理学鉴定了 98 个 DMY、HCC 和胆固醇的共同靶点和 10 个枢纽基因，表明 DMY 的抗 HCC 作用可能与脂质筏的正调控有关。进一步的实验证实，DMY 抑制 HCC 细胞的增殖、迁移和侵袭，并降低其胆固醇水平。97H、Hep3B、Sk-Hep1、SMMC-7721、HepG2 和 Huh7 细胞的 IC 分别为 894.4、814.4、467.8、1878.8、151.8 和 156.9μM。此外，DMY 下调脂质筏标志物（CAV1、FLOT1）以及 EGFR、PI3K、Akt、STAT3 和 Erk 的表达。
本研究表明，DMY 通过降低胆固醇破坏脂质筏来抑制 EGFR 及其下游通路，从而抑制 HCC，为治疗 HCC 提供了一种有前景的低毒候选药物。
