Wei Chunshan, Wu Zhulin, Yang Xiaoya, Jiang Xiaoyan, Wang Lianan, He Jinsong, Tong Guangdong
Altern Ther Health Med. 2025 May;31(3):114-121.
In China, traditional Chinese medicine (TCM) is an important part of the comprehensive treatment of hepatocellular carcinoma (HCC), and Chinese herb formulas with the effect of "yiqi jianpi jiedu huayu" (replenishing qi, strengthening spleen, and removing toxicity and blood stasis) are the common and efficient treatments for HCC. However, the mechanism of these formulas in treating HCC remain unclear.
In this paper, our goal is to explore the potential mechanism of Phyllanthus urinaria L anti-neoplastic decoction (PAD), the representative formula of "yiqi jianpi jiedu huayu", in treating HCC.
The research team performed the network pharmacology and in vitro experiment (preparation of PAD aqueous extract, cell cultures and MTT assay, cell apoptosis assay, wound healing assay, transwell assays, western blot).
The study took place in the Department of Hepatology, the Fourth Clinical Medical College of Guangzhou University of Chinese Medicine (Shenzhen Traditional Chinese Medicine Hospital), China.
The active components and targets of PAD and HCC targets were screened by five Chinese herbs and two disease databases respectively. The network pharmacology was utilized to construct the relationship network between PAD and HCC, and the mechanism was predicted by pathway enrichment analysis. The experiment was performed to verify the intervention effect of PAD on HCC and phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway.
The relationship network between PAD and HCC suggested that PAD mainly regulated the potential therapeutic targets of HCC by key active components such as quercetin, luteolin, calycosin, wogonin, and pinocembrin. Pathway analysis demonstrated PAD could play an anti-HCC effect via multiple pathways (e.g., PI3K/Akt). Results of the experiment showed that PAD could effectively inhibit the proliferation and migration of HCC cells, and promote HCC cells apoptosis in a concentration-dependent behavior. Additionally, PAD could decrease the protein expression of phosphorylated PI3K/Akt.
PAD mainly exerts an anti-HCC effect through multiple active components represented by quercetin and multiple pathways represented by the PI3K/Akt pathway. This study provided an experimental basis for the clinical application of PAD.
在中国，传统中医药是肝细胞癌（HCC）综合治疗的重要组成部分，具有“益气健脾解毒化瘀”功效的中药方剂是治疗HCC常用且有效的方法。然而，这些方剂治疗HCC的机制尚不清楚。
本文旨在探讨“益气健脾解毒化瘀”代表方剂——叶下珠抗肿瘤汤（PAD）治疗HCC的潜在机制。
研究团队进行了网络药理学和体外实验（制备PAD水提取物、细胞培养及MTT法检测、细胞凋亡检测、划痕实验、Transwell实验、蛋白质免疫印迹法）。
研究在中国广州中医药大学第四临床医学院（深圳市中医院）肝病科开展。
分别通过五个中药和两个疾病数据库筛选PAD的活性成分和靶点以及HCC靶点。利用网络药理学构建PAD与HCC之间的关系网络，并通过通路富集分析预测其作用机制。进行实验验证PAD对HCC及磷酸肌醇3激酶/蛋白激酶B（PI3K/Akt）通路的干预作用。
PAD与HCC的关系网络表明，PAD主要通过槲皮素、木犀草素、毛蕊异黄酮、汉黄芩素和松属素等关键活性成分调节HCC的潜在治疗靶点。通路分析表明，PAD可通过多种途径（如PI3K/Akt）发挥抗HCC作用。实验结果显示，PAD可有效抑制HCC细胞的增殖和迁移，并呈浓度依赖性促进HCC细胞凋亡。此外，PAD可降低磷酸化PI3K/Akt的蛋白表达。
PAD主要通过以槲皮素为代表的多种活性成分和以PI3K/Akt通路为代表的多种途径发挥抗HCC作用。本研究为PAD的临床应用提供了实验依据。
