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Constituents of Morus alba var. multicaulis leaf improve lipid metabolism by activating the AMPK signaling pathway in HepG2 cells

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Abstract

One new compound, 3Z-1-O-β-d-glucopyranosyl-3-hexene-1,5-diol (1), together with 26 known isolates (2–27) were obtained from the leaf of Morus alba var. multicaulis. Among the known compounds, 7, 11, 12, 14, 15, 18, 19, 23, and 24 were firstly obtained from the Morus genus; 2–5, 8, 10, 13, and 20 were firstly isolated from M. alba. var. multlcaulis. Meanwhile, the NMR data of 20 and 23 have been reported here for the first time. Moreover, compounds 1–11, 13, 21, and 23–27 showed inhibitory effects on triglyceride (TG) accumulation in HepG2 cells. In mechanism, compound 1 could activate the phosphorylation of AMP-activated protein kinase α (AMPKα) to accelerate the β-oxidation of fatty acids via promoting the phosphorylation of acetyl-CoA carboxylase 1 and up-regulating carnitine palmitoyl-transferase 1A. Besides, compound 1 exerted lipolysis effect by activating hormone-sensitive lipase. In brief, compound 1 might play a role by up-regulating phosphorylation of AMPKα, enhancing the fatty acid β-oxidation and lipolysis.

Graphical abstract

27 compounds were obtained from the leaf of Morus alba var. multicaulis. Among them, 18 showed inhibitory effects on TG accumulation in HepG2 cells. Moreover, the new compound, 3Z-1-O-β-d-glucopyranosyl-3-hexene-1,5-diol (1), was found to play a role by up-regulating phosphorylation of AMPKα, enhancing the fatty acids β-oxidation and lipolysis.

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Acknowledgements

This research was financially supported by Programs for National Natural Science Foundation of China (82074118), Important Drug Development Fund, Ministry of Science and Technology of China (2018ZX09735002).

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  1. Peijian Huang and Mimi Hao contributed equally to this work.

Authors and Affiliations

  1. Tianjin Key Laboratory of TCM Chemistry and Analysis, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, Tianjin, 301617, China

    Peijian Huang, Mimi Hao, Qian Gao, Jingya Ruan, Yi Zhang & Tao Wang

  2. Institute of TCM, Tianjin University of Traditional Chinese Medicine, 10 Poyanghu Road, West Area, Tuanbo New Town, Jinghai District, Tianjin, 301617, China

    Shengcai Yang, Mengyang Liu, Qian Chen, Yi Zhang & Tao Wang

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  1. Peijian Huang
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Huang, P., Hao, M., Gao, Q. et al. Constituents of Morus alba var. multicaulis leaf improve lipid metabolism by activating the AMPK signaling pathway in HepG2 cells. J Nat Med 76, 200–209 (2022). https://doi.org/10.1007/s11418-021-01581-3

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