微信公众号

官网二维码
中国癌症防治杂志

中国癌症防治杂志 ›› 2025, Vol. 17 ›› Issue (2): 156-163.doi: 10.3969/j.issn.1674-5671.2025.02.05

• 论著 • 上一篇    下一篇

环广豆根素和山豆根查尔酮的分离鉴定及其抗卵巢癌活性研究

  

  1. 广西医科大学生命科学研究院；区域性高发肿瘤早期防治研究教育部重点实验室（广西医科大学）；广西医科大学附属肿瘤医院实验研究部；广西药用植物园
  • 出版日期:2025-04-25 发布日期:2025-05-12
  • 通讯作者: 王琪 E-mail：wangqi@stu.gxmu.edu.cn; 宋志军 E-mail：songzj430@aliyun.com
  • 基金资助:
    国家自然科学基金项目(82260484；81860459)；广西科技计划项目(AB1850003；AA18242040)；广西医科大学区域高发肿瘤早期防治研究教育部重点实验室(GKE?ZZ202236；GKE?ZZ202016)

Isolation,identification and anti-ovarian cancer activity of sophoranochromene and sophoradin

  • Online:2025-04-25 Published:2025-05-12

PDF (PC)

612

赞

摘要： 目的 从传统中药山豆根中筛选和鉴定新的抗卵巢癌活性分子，探讨其对卵巢癌细胞凋亡和自噬的影响。方法 山豆根中黄酮类成分采用硅胶柱层析、减压旋蒸等技术进行系统分离， 检测分离馏分抑制卵巢癌细胞生长的活性。高效液相色谱⁃质谱(high performance liquid chromatography⁃mass spectrometry,HPLC⁃MS)进行抑癌活性单体的表征鉴定，核磁共振氢谱(nuclear magnetic resonance,1H NMR)和电喷雾电离(electrospray ionization,ESI)质谱进行结构确证。实时细胞分析(real⁃time cell analysis, RTCA)系统检测环广豆根素(Sophoranochromene)和山豆根查尔酮(Sophoradin)抑制6种卵巢癌细胞系（A2780、NIH:OVCAR3、SKOV3、Caov⁃3、Caov⁃4和ES⁃2）及正常卵巢上皮细胞IOSE80的效果。网络药理学和分子对接技术预测活性单体与卵巢癌细胞的互作靶点，流式细胞术检测细胞凋亡，采用Western blot分析细胞凋亡蛋白PARP、C⁃caspaes⁃3的剪切情况及自噬标志蛋白p62和LC3B的表达。结果 从山豆根抗卵巢癌有效馏分SdgfF中鉴定出抗卵巢癌的活性单体环广豆根素和山豆根查尔酮。RTCA系统证实这两种单体对6种卵巢癌细胞（A2780、NIH:OVCAR3、SKOV3、Caov⁃3、Caov⁃4和ES⁃2）的IC50值均低于IOSE80细胞(均P<0.0001)。流式细胞术结果显示这两种单体处理后A2780细胞凋亡率均明显上升(均P<0.05)。筛选获得10个环广豆根素⁃卵巢癌核心靶点，16个山豆根查尔酮⁃卵巢癌核心靶点。Western blot结果显示，环广豆根素处理后A2780细胞中凋亡相关蛋白C⁃PARP表达明显升高(P<0.05)，山豆根查尔酮处理后p62表达明显下降而LC3BⅠ/Ⅱ表达明显升高(P<0.05)。结论 环广豆根素和山豆根查尔酮通过诱导卵巢癌细胞凋亡和自噬，有望开发为新的卵巢癌治疗剂。

关键词:  , 卵巢癌；药用植物；山豆根；环广豆根素；山豆根查尔酮

Abstract: Objective To screen and identify  novel  anti⁃ovarian cancer active compounds from the traditional Chinese medicine sophora tonkinensis radix, and investigate their effects on apoptosis and autophagy of ovarian cancer cells. Methods Flavonoids components from sophora tonkinensis radix were systematically isolated by silica gel column chromatography and vacuum rotary evaporation techniques. The inhibitory activity of separated fractions on ovarian cancer cell growth was evaluated. High performance liquid chromatography⁃mass spectrometry (HPLC⁃MS) was employed to characterize and identify anti⁃cancer active monomers, while nuclear magnetic resonance (1H NMR) and electrospray ionization (ESI) mass spectrometry were used for structural confirmation. The inhibitory effects of the sophoranochromene and sophoradin on six ovarian cancer cell lines（A2780， NIH: OVCAR3, SKOV3, Caov⁃3, Caov⁃4, ES⁃2） and normal ovarian epithelial cells IOSE80 were assessed using real⁃time cell analysis (RTCA) system. Network pharmacology and molecular docking were employed to predict interaction targets between the active monomers and ovarian cancer cells. Apoptosis was measured via flow cytometry, and Western blotting was performed to analyze the cleavage of apoptosis⁃related proteins (PARP, C⁃caspase⁃3) and the expression of autophagy markers (p62, LC3B). Results Sophoranochromene and sophoradin were identified as anti⁃ovarian cancer active monomers from the effective fraction SdgfF of sophora tonkinensis radix. RTCA system confirmed that the IC50 values of both monomers on A2780, NIH: OVCAR3, SKOV3, Caov⁃3, Caov⁃4 and ES⁃2 cells were lower than those for IOSE80 cells (all P<0.0001). Flow cytometry revealed significantly increased apoptosis rates in A2780 cells treated with either compound (all P<0.05). Ten core targets for sophoranochromene⁃ovarian cancer and 16 core targets for sophoradin⁃ovarian cancer were identified. Western blotting demonstrated elevated C⁃PARP expression in A2780 cells treated with sophoranochromene (P<0.05), while sophoradin treatment significantly reduced p62 and increased LC3B⁃I/II expression (P<0.05). Conclusions Sophoranochromene and sophoradin exert anti⁃ovarian cancer effects by inducing apoptosis and autophagy in cancer cells, demonstrating potential as novel therapeutic agents for ovarian cancer.

Key words: Ovarian cancer, Medicinal plants, Sophora tonkinensis Radix, Sophoranochromene, Sophoradin

中图分类号: 

  • R737.31