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Original Article | Open Access

Elucidation of the hepatoprotective effect and mechanism of Melastoma dodecandrum Lour. based on network pharmacology and experimental validation

Jinfeng Wanga, Linyuan Wangb, Zhihao Zhangc, Min Wud, Wenting Feib, Zhihui Yange, Jianjun Zhanga( )
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 102488, China
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, China
School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, China
Medical College, Yangzhou University, Yangzhou, 225001, China
Department of Emergency Medicine, University of Florida, Gainesville, 32611, USA

Peer review under responsibility of Beijing University of Chinese Medicine.

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Abstract

Objective

To systematically explore the effect and mechanism of melastomatis dodecandri herba (Melastoma dodecandrum Lour.) in the treatment of hepatitis based on network pharmacology.

Method

We evaluated the hepatoprotective effects of M. dodecandrum in concanavalin A (Con A)-induced hepatitis in mice by assessing survival rate, histological analysis, serum transaminases, and related cytokines. Then the mechanism of action was predicted by a network pharmacology-based strategy. Based on the results, we measured the hepatic expression of related genes at mRNA level and proteins related to the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) and nuclear factor-kappa B (NF-кB) pathways.

Results

Our study results clearly demonstrated that M. dodecandrum pretreatment significantly alleviated liver injury. This was demonstrated by an increase in survival rate, decreased severity of liver damage, and reduced serum transaminase levels compared with those in the Con A group. Moreover, M. dodecandrum significantly reduced the serum levels of tumor necrosis factor-α, interleukin-6, and interferon-γ and increased the liver levels of superoxide dismutase, which indicated that M. dodecandrum exhibits anti-inflammatory and antioxidant activities. On the basis of network pharmacology, 50 nodes were selected as major hubs based on their topological importance. Pathway enrichment analyses indicated that the putative targets of M. dodecandrum mostly participate in various pathways associated with the anti-inflammation response, which implies the underlying mechanism by which M. dodecandrum acts on hepatitis. Real-time fluorescent quantitative PCR analysis showed that M. dodecandrum downregulates the mRNA expression of interleukin-6, Toll-like receptor 7, interleukin-1 receptor-associated kinase-4, NF-кB and tumor necrosis factor-α in liver tissues. Western blotting showed that M. dodecandrum pretreatment protected against inflammation through activating the PI3K-Akt pathway by upregulating phosphorylated Akt (p-Akt) expression and suppressing NF-кB activation by inhibiting the phosphorylation of IKK, IκBα, and p65.

Conclusion

The present work demonstrated the hepatoprotective effects of M. dodecandrum by regulating the PI3K/Akt and NF-кB pathways in Con A-induced mice, which provide insights into the treatment of hepatitis using M. dodecandrum.

Keywords

InflammationMechanismHepatitisMelastoma dodecandrum Lour.Concanavalin ANetwork pharmacologyPhosphoinositide 3-kinase (PI3K)/protein kinase BNuclear factor-kappa B

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Journal of Traditional Chinese Medical Sciences
Volume 9 Issue 1,
January 2022
Pages 47-58
DOI: 10.1016/j.jtcms.2021.12.003
Cite this article:
Wang J, Wang L, Zhang Z, et al. Elucidation of the hepatoprotective effect and mechanism of Melastoma dodecandrum Lour. based on network pharmacology and experimental validation. Journal of Traditional Chinese Medical Sciences, 2022, 9(1): 47-58. https://doi.org/10.1016/j.jtcms.2021.12.003

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Received: 22 April 2021
Revised: 30 December 2021
Accepted: 30 December 2021
Published: 03 January 2022
© 2022 Beijing University of Chinese Medicine.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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