Antimelanoma Effects of Alchemilla vulgaris: A Comprehensive In Vitro and In Vivo Study

Diseases Pub Date : 2024-06-08 DOI:10.3390/diseases12060125
Sanja Jelača, Ivan Jovanović, Dijana Bovan, Sladjana Pavlović, N. Gajović, Duško Dunđerović, Z. Dajić-Stevanović, Aleksandar Acović, S. Mijatović, D. Maksimović‐Ivanić
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Abstract

Due to the rich ethnobotanical and growing evidence-based medicine records, the Alchemillae herba, i.e., the upper parts of the Lady’s mantle (Alchemilla vulgaris L.), was used for the assessment of antimelanoma activity. The ethanolic extract of A. vulgaris strongly suppressed the viability of B16F1, B16F10, 518A2, and Fem-X cell lines. In contrast to the in vitro study, where the B16F1 cells were more sensitive to the treatment than the more aggressive counterpart B16F10, the results obtained in vivo using the corresponding syngeneic murine model were quite the opposite. The higher sensitivity of B16F10 tumors in vivo may be attributed to a more complex response to the extract compared to one triggered in vitro. In addition, the strong immunosuppressive microenvironment in the B16F1 model is impaired by the treatment, as evidenced by enhanced antigen-presenting potential of dendritic cells, influx and activity of CD4+ T and CD8+ T lymphocytes, decreased presence of T regulatory lymphocytes, and attenuation of anti-inflammatory cytokine production. All these effects are supported by the absence of systemic toxicity. A. vulgaris extract treatment results in a sustained and enhanced ability to reduce melanoma growth, followed by the restoration of innate and adopted antitumor immunity without affecting the overall physiology of the host.
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紫苏的抗黑色素瘤作用:体外和体内综合研究
由于丰富的民族植物学和不断增加的循证医学记录,我们采用了Alchemillae herba,即斗篷草(Alchemilla vulgaris L.)的上半部分,来评估其抗黑色素瘤活性。A. vulgaris 的乙醇提取物强烈抑制了 B16F1、B16F10、518A2 和 Fem-X 细胞系的活力。在体外研究中,B16F1 细胞比攻击性更强的 B16F10 细胞对治疗更敏感,与此形成鲜明对比的是,使用相应的合成小鼠模型在体内获得的结果却截然相反。B16F10 肿瘤在体内具有更高的敏感性,这可能是因为与体外反应相比,体内对提取物的反应更为复杂。此外,B16F1 模型中的强免疫抑制微环境也受到了治疗的损害,这表现在树突状细胞的抗原递呈潜能增强、CD4+ T 和 CD8+ T 淋巴细胞的涌入和活性增强、T 调节淋巴细胞的存在减少以及抗炎细胞因子的产生减弱。所有这些作用都没有全身毒性。A.vulgaris萃取物能持续增强减少黑色素瘤生长的能力,继而恢复先天和后天抗肿瘤免疫力,而不会影响宿主的整体生理机能。
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