香连丸治疗胃癌的活性成分及作用机制：网络药理学分析及实验验证。
Bioactive compounds and mechanism of Xianglian pill in the treatment of gastric cancer: Network pharmacology analysis and experimental validation.
机构信息
Chengdu University of Traditional Chinese Medicine, Key Laboratory of Southwestern Chinese Medicine Resources, Key Laboratory of Standardization of Chinese Herbal Medicine of MOE, Chengdu, 610075, China.
School of Pharmacy, West China School of Pharmacy, Sichuan University, Chengdu, 610075, China.
出版信息
J Ethnopharmacol. 2023 Oct 5;314:116573. doi: 10.1016/j.jep.2023.116573. Epub 2023 May 2.
ETHNOPHARMACOLOGICAL RELEVANCE
Gastric cancer (GC) affects people's quality of life because of its high incidence rate and mortality. The Xianglian Pill (XLP) is a traditional Chinese medicine (TCM) prescription used to treat gastrointestinal (GI） diseases. Its anti-tumor effect has been found in recent years, but it's bioactive compounds and mechanism of action in treating GC are remain unknown.
AIM OF THE STUDY
This study reveals the bioactive compounds and mechanisms of XLP in the treatment of GC through network pharmacology analysis and experimental verification.
MATERIALS AND METHODS
The main compounds in XLP were searched and the active compounds with anti-GC activity were selected. Compounds targets and GC- related targets were predicted, and common targets were obtained. Subsequently, a protein-protein interaction (PPI) network of common targets is constructed, while GO and KEGG enrichment analyses were performed on common targets. Finally, the anti-GC effects of active compounds in XLP were verified in GC cell lines MGC-803 and HGC-27 by wound healing assay, cell cycle assay, cell apoptosis assay and western blotting (WB) assay.
RESULTS
A total of 33 active compounds of XLP were obtained. MTT assay showed that dehydrocostus lactone (DHL) and berberrubine (BRB) had lower IC value in GC cells HGC-27 and MGC-803, and has a less inhibitory effect on normal gastric epithelial cells. Further, 73 common targets were obtained after the total target of DHL and BRB intersected with GC. Among them, CASP3, AKT1, SRC, STAT3,and CASP9 were the most associated genes in the PPI network. GO and KEGG enrichment analyses indicated that apoptosis played a major role in the biological processes and signaling pathways involved. Moreover, the in vitro experiment revealed that DHL and BRB inhibited GC cell viability via inducing cell cycle arrest at G2/M phase, and promoting cell apoptosis by up-regulating the caspase3 expression and down-regulating the expression of Bcl2/Bax.
CONCLUSIONS
DHL and BRB are the two main anti-GC active compounds in XLP, and their mechanism is mainly to inhibit cell cycle and promote cell apoptosis.
民族药理学相关性
胃癌（GC）因其高发病率和死亡率而影响人们的生活质量。香连丸（XLP）是一种用于治疗胃肠道（GI）疾病的中药（TCM）处方。近年来发现其具有抗肿瘤作用，但治疗 GC 的生物活性化合物及其作用机制尚不清楚。
研究目的
本研究通过网络药理学分析和实验验证，揭示 XLP 治疗 GC 的生物活性化合物及作用机制。
材料与方法
搜索 XLP 中的主要化合物，筛选出具有抗 GC 活性的活性化合物。预测化合物靶点和 GC 相关靶点，获得共同靶点。然后构建共同靶点的蛋白质-蛋白质相互作用（PPI）网络，并对共同靶点进行 GO 和 KEGG 富集分析。最后，通过划痕愈合试验、细胞周期试验、细胞凋亡试验和 Western blot（WB）试验，在 GC 细胞系 MGC-803 和 HGC-27 中验证 XLP 中活性化合物的抗 GC 作用。
结果
共获得 XLP 中的 33 种活性化合物。MTT 试验表明，脱氢木香内酯（DHL）和小檗红碱（BRB）在 GC 细胞 HGC-27 和 MGC-803 中的 IC 值较低，对正常胃上皮细胞的抑制作用较小。进一步将 DHL 和 BRB 的总靶点与 GC 相交后，获得 73 个共同靶点。其中，PPI 网络中与 CASP3、AKT1、SRC、STAT3 和 CASP9 关联最密切。GO 和 KEGG 富集分析表明，细胞凋亡在涉及的生物过程和信号通路中起主要作用。此外，体外实验表明，DHL 和 BRB 通过诱导细胞周期停滞在 G2/M 期抑制 GC 细胞活力，并通过上调 caspase3 表达和下调 Bcl2/Bax 表达促进细胞凋亡。
结论
DHL 和 BRB 是 XLP 中两种主要的抗 GC 活性化合物，其作用机制主要是抑制细胞周期，促进细胞凋亡。
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