具有抗炎和抗乳腺癌活性的生物活性成分在 Prunellae Spica 发育过程中的动态变化

Zhimin Zhang, Qian Su, Yan Lin, Bohou Xia, Yamei Li, Jingchen Xie, Ping Wu, Duanfang Liao, Limei Lin
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摘要

为探究刺五加采收期的科学内涵,采用高效液相色谱法对刺五加发育期的三萜类化合物和酚类化合物进行了定量分析,并对其抗炎和抗乳腺癌的特性进行了研究。此外,还采用灰色关联分析和皮尔逊关联分析筛选出抗炎和抗乳腺癌相关的有效成分,并通过网络药理学构建了 "成分-靶标-途径 "的多维网络。结果表明,刺五加的采收时间与其化学成分和药理活性密切相关。酚类物质,如丹参酸 A、咖啡酸和丹参皂苷主要在发育后期积累,而迷迭香酸则相反。齐墩果酸和熊果酸等三萜类化合物主要在发育早期积累,而白桦脂酸则在成熟期积累。刺五加在发育早期的抗乳腺癌活性强于发育后期,但发育后期的抗炎活性强于早期。与刺五加抗炎活性显著相关的是丹参皂苷,它可能通过作用于 CASP7、CASP8、CASP3、NOD2 和 CASP1 等靶点来调节 TNF 和 NOD 样受体信号通路。与抗乳腺癌活性显著相关的是齐墩果酸和熊果酸,它们可能通过 PTGS2、CYP19A1、ESR2、CYP17A1 和 MAPK3 等靶点调节卵巢类固醇生成和催乳素信号通路。这些结果表明,褐藻可以在成熟前采收用于抗乳腺癌,在成熟后采收用于抗炎。
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The Dynamics of Bioactive Ingredients With Anti-Inflammatory and Anti-Breast Cancer Activity During Prunellae Spica Development
To investigate the scientific connotation of harvest period for Prunella vulgaris L. ( P vulgaris, known as Prunellae Spica), the triterpenoids and phenols of Prunellae Spica in developmental stages were quantified by high performance liquid chromatography, and the anti-inflammatory and anti-breast cancer properties of which were investigated. Furthermore, Grey correlation and Pearson correlation analysis were used to screen the anti-inflammatory and anti-breast cancer–related effective ingredients, and a multidimensional network of “ingredient-target-pathway” through network pharmacology was constructed. The results showed that the harvest time of Prunellae Spica was closely related to its chemical composition and pharmacological activity. Phenols, such as salvianic acid A, caffeic acid, and salviaflaside, mainly accumulated in late development, while rosmarinic acid showed the opposite. Triterpenes, such as oleanolic acid and ursolic acid, mainly accumulated in early development, while betulinic acid accumulated during ripening. The anti-breast cancer activity of Prunellae Spica in early development was stronger than that in the later, but the anti-inflammatory activity in late development was stronger than that in the early stage. Significantly associated with anti-inflammatory activity in Prunellae Spica was salviaflaside, which may regulate TNF and NOD-like receptor signaling pathways by acting on targets such as CASP7, CASP8, CASP3, NOD2, and CASP1. Significantly associated with anti-breast cancer activity were oleanolic acid and ursolic acid, which may regulate Ovarian steroidogenesis and Prolactin signaling pathways on targets such as PTGS2, CYP19A1, ESR2, CYP17A1, and MAPK3. These results suggest that P vulgaris could be harvested before ripening for its anti-breast cancer use, and after ripening for its anti-inflammatory use.
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