网络药理学联合实验验证揭示仙莲解毒汤抗结直肠癌的机制
Network pharmacology alliance with experimental validation unveils the anti-colorectal cancer mechanism of Xianlian Jiedu decoction.
作者信息
Fan Xiaoxuan, Yan Qiuying, Xu Weicheng, Chen Hui, Xu Yanru, Lu Sicheng, Xu Changliang, Tan Jiani, Yu Chengtao, Lai Yueyang, Fan Minmin, Tao Lihuiping, Li Liu, Shen Weixing, Cheng Haibo, Sun Dongdong
机构信息
Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine in Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine in Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Key Laboratory of Acupuncture and Medicine Research of Minister of Education, Nanjing, 210023, China.
出版信息
J Ethnopharmacol. 2025 Feb 27;342:119361. doi: 10.1016/j.jep.2025.119361. Epub 2025 Jan 20.
ETHNOPHARMACOLOGICAL RELEVANCE
The Xianlian Jiedu Decoction (XLJDD), a traditional Chinese medicine (TCM) decoction, which is effective in clinical treatment of colorectal cancer (CRC). Nevertheless, the pharmacodynamic material basis and mechanism of its action have not been explored yet.
AIMS OF THE STUDY
To investigate the potential functional components and possible mechanism of XLJDD in anti-CRC.
MATERIALS AND METHODS
The UPLC-Q-TOF-MS method was applied to the qualification of absorbed phytochemical compounds in the plasma of rats administrated with XLJDD. Network pharmacology approach was used to create the compound-target network, GO and KEGG enrichment resolution was used to predict the potential biological mechanism of XLJDD anti-CRC. The binding of potential active ingredients to their targets was demonstrated using AutoDock Tools. And the anti-CRC efficacy of XLJDD was investigated through in vitro and in vivo experiments. Furthermore, the mechanism of XLJDD anti-CRC was validated by Western blot.
RESULTS
14 compounds from XLJDD were detected in the plasma of rats administrated with XLJDD. The results of network pharmacology analysis shown that PI3K/AKT and chemokine signaling pathways were strongly linked to XLJDD against CRC. The potential active compounds berberine, 7-methoxycoumarin and 13-methylberberubine may target PRKACA, PIK3CB, and EGFR to regulate PI3K/AKT signaling pathway, which plays a crucial role in cancer cell proliferation. In vitro experimental results revealed that XLJDD apparently inhibits the cell viability and proliferation of HCT116 cells. In vivo experimental results found that in contrast to the model group, the XLJDD treatment obviously cut down the size and weight of tumor. Further, Western blot results demonstrated that XLJDD significantly inhibited the CXCR2/PI3K/AKT signaling axis.
CONCLUSION
The therapeutic mechanism of XLJDD against CRC involves inhibiting CRC cells proliferation via modulating the CXCR2/PI3K/AKT signaling pathway.
民族药理学相关性
仙莲解毒汤（XLJDD）是一种中药汤剂，在临床治疗结直肠癌（CRC）方面具有疗效。然而，其药效物质基础及作用机制尚未得到探究。
研究目的
研究仙莲解毒汤抗结直肠癌的潜在功能成分及可能机制。
材料与方法
采用超高效液相色谱-四极杆飞行时间质谱（UPLC-Q-TOF-MS）法对给予仙莲解毒汤的大鼠血浆中吸收的植物化学化合物进行定性分析。运用网络药理学方法构建化合物-靶点网络，通过基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析预测仙莲解毒汤抗结直肠癌的潜在生物学机制。使用自动对接工具（AutoDock Tools）证明潜在活性成分与其靶点的结合。通过体外和体内实验研究仙莲解毒汤的抗结直肠癌疗效。此外，通过蛋白质免疫印迹法（Western blot）验证仙莲解毒汤抗结直肠癌的机制。
结果
在给予仙莲解毒汤的大鼠血浆中检测到14种来自仙莲解毒汤的化合物。网络药理学分析结果表明，磷脂酰肌醇-3-激酶/蛋白激酶B（PI3K/AKT）和趋化因子信号通路与仙莲解毒汤抗结直肠癌密切相关。潜在活性化合物小檗碱、7-甲氧基香豆素和13-甲基小檗红碱可能靶向蛋白激酶A催化亚基α（PRKACA）、磷脂酰肌醇-3-激酶催化亚基β（PIK3CB）和表皮生长因子受体（EGFR），以调节PI3K/AKT信号通路，该信号通路在癌细胞增殖中起关键作用。体外实验结果显示，仙莲解毒汤明显抑制人结肠癌细胞系HCT116细胞的活力和增殖。体内实验结果发现，与模型组相比，仙莲解毒汤治疗明显减小了肿瘤的大小和重量。此外蛋白质免疫印迹法结果表明，仙莲解毒汤显著抑制CXC趋化因子受体2（CXCR2）/PI3K/AKT信号轴。
结论
仙莲解毒汤抗结直肠癌的治疗机制包括通过调节CXCR2/PI3K/AKT信号通路抑制结直肠癌细胞增殖。
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