Department of General Surgery, The Affiliated Bozhou Hospital of Anhui Medical University, Bozhou 236800, Anhui, China.
Department of Cancer Radiotherapy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China (Anhui Provincial Cancer Hospital), Hefei 230031, Anhui, China.
Aging (Albany NY). 2023 Aug 8;15(15):7831-7843. doi: 10.18632/aging.204948.
Hepatocellular carcinoma (HCC) is one of the most malignant tumors. The experiments on the application of Anhydroicaritin (AHI), the active ingredient of Bushen Huayu Decoction, in HCC treatment remain limited, particularly regarding its molecular mechanism.
The TCMSP platform was used for drug ingredient screening. The GeneCards database and DisGeNET database are used to collect liver cancer targets. PPI network construction of active component-target intersection target was completed with string database. The GO and KEGG pathway analyses were performed via bioinformatics analysis. The molecular docking was used to confirm AHI's target proteins. The experiments were performed to validate the effect of AHI on HCC cell and explore the molecular mechanism by western blotting analysis.
Through the intersection, 155 intersection targets are finally obtained. The top 15 active ingredients were quercetin, kaempferol, beta-sitosterol, luteolin, beta-carotene, Stigmasterol, naringenin, formononetin, baicalein, Anhydroicaritin, isorhamnetin, licochalcone, 7-O-methylisomucronulatol, aloe-emodin and 8-O-Methylreyusi. The molecular mocking analysis showed that the four active components (quercetin, kaempferol, luteolin and AHI) and targets had a good binding activity (affinity ≤ 5 kcal/mol). experiments reveled that AHI could suppress tumor proliferation, invasion and metastasis of HCC cells. Further analysis showed that AHI inhibited tumor growth by PI3K/AKT signal pathway in HCC.
The Bushen Huayu Decoction and its active ingredient AHI could fight HCC. The potential mechanism may be associated with inhibiting the activation of PI3K/AKT signal pathway, which may serve as a potential treatment for HCC therapy.
肝细胞癌（HCC）是最恶性的肿瘤之一。补肾化瘀汤的活性成分脱水淫羊藿素（AHI）在 HCC 治疗中的应用研究仍很有限，特别是其分子机制。
TCMSP 平台用于筛选药物成分。GeneCards 数据库和 DisGeNET 数据库用于收集肝癌靶点。使用 string 数据库构建活性成分-靶标交集靶点的 PPI 网络。通过生物信息学分析进行 GO 和 KEGG 通路分析。分子对接用于确认 AHI 的靶蛋白。通过 Western blot 分析进行实验，验证 AHI 对 HCC 细胞的作用，并探索分子机制。
通过交集，最终获得 155 个交集靶点。前 15 个活性成分分别为槲皮素、山柰酚、β-谷甾醇、木樨草素、β-胡萝卜素、豆甾醇、柚皮苷、芒柄花素、黄芩素、脱水淫羊藿素、异鼠李素、甘草查尔酮、7-O-甲基异槲皮苷、大黄素和 8-O-甲基瑞香素。分子模拟分析表明，四种活性成分（槲皮素、山柰酚、木樨草素和 AHI）和靶点具有良好的结合活性（亲和力≤5kcal/mol）。实验表明，AHI 可抑制 HCC 细胞的增殖、侵袭和转移。进一步分析表明，AHI 通过 PI3K/AKT 信号通路抑制 HCC 肿瘤生长。
补肾化瘀汤及其活性成分 AHI 可用于治疗 HCC。潜在机制可能与抑制 PI3K/AKT 信号通路的激活有关，可能为 HCC 治疗提供一种潜在的治疗方法。
