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从桑白皮中分离得到的桑辛素 E 和 M 通过 PI3K-Akt-mTOR 信号通路诱导骨骼肌细胞增殖。

Moracin E and M isolated from Morus alba Linné induced the skeletal muscle cell proliferation via PI3K-Akt-mTOR signaling pathway.

机构信息

Yonsei Institute of Pharmaceutical Sciences, College of Pharmacy, Yonsei University, Incheon, 21983, South Korea.

Division of Practical Application, Honam National Institute of Biological Resources, Mokpo, 58762, South Korea.

出版信息

Sci Rep. 2023 Nov 23;13(1):20570. doi: 10.1038/s41598-023-47411-2.

DOI:10.1038/s41598-023-47411-2
PMID:37996535
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10667267/
Abstract

Twigs of Morus alba have been used in traditional medicine to treat muscle-related symptoms such as aches, numbness, and stiffness. Despite its clinical use in traditional medicine, its active compounds and mode of action have not yet been investigated. Therefore, we aimed to isolate the compounds from the twigs of M. alba and deduce active compounds, key gene targets, and mechanism of action against sarcopenia using network pharmacology analysis. Using various isolation techniques and spectroscopic methods, 43 phytochemicals, including 3 new flavonoids, were isolated and performed network pharmacology analysis. According to the computational-assistant analysis, 28 compounds, 9 genes, and the PI3K-Akt-mTOR signaling pathway were deduced as expected active compounds (EAC), key targets, and the main signaling pathway. To verify the predicted results, the cell proliferation activities of the EAC were evaluated. Especially, moracin E and M significantly increased by 130% (p < 0.001) and 57% (p < 0.05), respectively, which have more than 2- and 1.5-fold stronger effects compared to the control. Furthermore, both increased the expression level of proteins involved in the PI3K-Akt-mTOR signaling pathway and myogenic proteins, including myogenin and MyoD. This study demonstrated that moracin E and M exhibit cell proliferative effects on skeletal muscle cells through the PI3K-Akt-mTOR signaling pathway.

摘要

桑枝在传统医学中被用于治疗与肌肉相关的症状,如疼痛、麻木和僵硬。尽管它在传统医学中有临床应用,但它的活性化合物和作用机制尚未得到研究。因此,我们旨在从桑枝中分离化合物,并通过网络药理学分析推断出其对肌少症的活性化合物、关键基因靶点和作用机制。使用各种分离技术和光谱方法,从桑枝中分离得到 43 种植物化学物质,包括 3 种新的类黄酮,并进行了网络药理学分析。根据计算辅助分析,推断出 28 种化合物、9 个基因和 PI3K-Akt-mTOR 信号通路作为预期的活性化合物(EAC)、关键靶点和主要信号通路。为了验证预测结果,评估了 EAC 对细胞增殖活性的影响。特别是,moracin E 和 M 分别显著增加了 130%(p < 0.001)和 57%(p < 0.05),与对照组相比,其效果分别增强了 2 倍和 1.5 倍以上。此外,两者均增加了参与 PI3K-Akt-mTOR 信号通路和肌生成蛋白(包括肌生成素和 MyoD)的蛋白表达水平。本研究表明,moracin E 和 M 通过 PI3K-Akt-mTOR 信号通路对骨骼肌细胞表现出细胞增殖作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b897/10667267/7c81c0770774/41598_2023_47411_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b897/10667267/3433a8e075e8/41598_2023_47411_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b897/10667267/7c81c0770774/41598_2023_47411_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b897/10667267/3433a8e075e8/41598_2023_47411_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b897/10667267/a80bb8dc1c9a/41598_2023_47411_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b897/10667267/5838865a81d4/41598_2023_47411_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b897/10667267/60b3b603185c/41598_2023_47411_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b897/10667267/575e12e1d434/41598_2023_47411_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b897/10667267/7c57723214ed/41598_2023_47411_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b897/10667267/7c81c0770774/41598_2023_47411_Fig7_HTML.jpg

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