关于 Aspilia pluriseta 抗前列腺癌的网络药理学、分子对接和体外研究。

IF 3.3 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE
Innocent Oluwaseun Okpako, Florence Atieno Ng'ong'a, Cleophas Mutinda Kyama, Sospeter Ngoci Njeru
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引用次数: 0

摘要

背景:目前治疗前列腺癌的方法都有危及生命的副作用,这促使人们寻找更有效、更安全的替代方法。Aspilia pluriseta Schweinf. ex Engl.曾在肺癌和肝癌细胞系中显示出抗癌活性。本研究调查了其治疗前列腺癌的潜力:方法:使用二氯甲烷/甲醇(1:1 v/v)制备 A. pluriseta 根的粗提取物,并将其分成正己烷、乙酸乙酯和水馏分。MTT 试验用于评估馏分的抗增殖活性。在人类前列腺癌 DU-145 细胞和非癌症 Vero E6 细胞上测试了 6.25-200 µg/ml 的活性馏分。对植物化学成分和气相色谱-质谱(GC-MS)进行了定性分析,以确定化合物。采用网络药理学预测已鉴定化合物的分子靶点和作用模式,随后通过分子对接和实时 PCR 进行验证:活性提取物包括粗二氯甲烷/甲醇、正己烷和乙酸乙酯馏分,它们抑制 DU-145 细胞增殖的 IC50 值分别为 16.94、20.06 和 24.14 µg/ml。选择性指数分别为 6.04(粗制)、3.62(己烷)和 6.68(乙酸乙酯)。鉴定出的植物化学物质包括酚类、萜类、黄酮类、单宁、甾醇和皂苷。GC-MS 分析发现了 79 种化合物,其中有 7 种符合理想的候选药物参数;它们的中心基因靶点包括 MAPK3、MAPK1、IL6、TP53、ESR1、PTGS2、MMP9、MDM2、AR 和 MAP2K1,表明 PI3K/Akt、MAPK 和 p53 信号通路的调节是潜在的作用模式。1-heneicosanol、羊毛甾醇、穿心莲内酯和维甲酸等核心化合物表现出很强的结合活性,特别是羊毛甾醇与 MAPK21(-9.7 kcal/mol)、ESR1(-8.9 kcal/mol)和 MAPK3(-8.8 kcal/mol)的结合活性。A.pluriseta能下调AR的表达,上调p53,同时还能下调CDK1和BCL-2,上调caspase-3:结论:A. pluriseta 提取物可抑制 DU-145 细胞的生长,且不会对细胞造成毒性,这表明它具有作为抗前列腺癌药物开发的巨大潜力。不过,建议进一步开展体外和体内实验。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Network pharmacology, molecular docking, and in vitro study on Aspilia pluriseta against prostate cancer.

Background: Current prostate cancer treatments are associated with life-threatening side effects, prompting the search for effective and safer alternatives. Aspilia pluriseta Schweinf. ex Engl. has previously shown anticancer activity in lung and liver cancer cell lines. This study investigated its potential for prostate cancer.

Methods: A crude extract of A. pluriseta root was prepared using dichloromethane/methanol (1:1 v/v) and partitioned into hexane, ethyl acetate, and water fractions. The MTT assay was used to assess the antiproliferative activity of the fractions. The active fractions were tested at 6.25-200 µg/ml on human prostate cancer DU-145 cells and non-cancerous Vero E6 cells. Qualitative phytochemical and gas chromatography-mass spectrometry (GC-MS) analyses were conducted to identify chemical compounds. Network pharmacology was employed to predict molecular targets and modes of action of the identified chemical compounds, with subsequent validation through molecular docking and real-time PCR.

Results: Active extracts included crude dichloromethane/methanol, hexane, and ethyl acetate fractions, inhibiting DU-145 cell proliferation with IC50 values of 16.94, 20.06, and 24.14 µg/ml, respectively. Selectivity indices were determined to be 6.04 (crude), 3.62 (hexane), and 6.68 (ethyl acetate). Identified phytochemicals comprised phenols, terpenoids, flavonoids, tannins, sterols, and saponins. GC-MS analysis revealed seventy-nine (79) compounds, with seven (7) meeting ideal drug candidate parameters; their hub gene targets included MAPK3, MAPK1, IL6, TP53, ESR1, PTGS2, MMP9, MDM2, AR, and MAP2K1, implicating regulation of PI3K/Akt, MAPK, and p53 signaling pathways as potential modes of action. Core compounds such as 1-heneicosanol, lanosterol, andrographolide, and retinoic acid exhibited strong binding activities, particularly lanosterol with MAPK21 (-9.7 kcal/mol), ESR1 (-8.9 kcal/mol), and MAPK3 (-8.8 kcal/mol). Treatment with A. pluriseta downregulated AR expression and upregulated p53, while also downregulating CDK1 and BCL-2 and upregulating caspase-3.

Conclusions: A. pluriseta extracts inhibited DU-145 cell growth without causing cellular toxicity, suggesting great potential for development as an anti-prostate cancer agent. However, further in vitro and in vivo experiments are recommended.

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来源期刊
BMC Complementary Medicine and Therapies
BMC Complementary Medicine and Therapies INTEGRATIVE & COMPLEMENTARY MEDICINE-
CiteScore
6.10
自引率
2.60%
发文量
300
审稿时长
19 weeks
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