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DPHB, a diarylheptane from Alpinia officinarum Hance, ameliorates insulin resistance: A network pharmacology and in vitro study

(4E)-7-(4-Hydroxy-3-methoxyphenyl)-1-phenylhept-4-en-3-one (DPHB) derived from A. officinarum Hance has been reported to exert anti-inflammatory and anti-insulin resistance (IR) effects. We explored the molecular mechanism of DPHB ameliorating IR through network pharmacological prediction and in vit...

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Autores principales: Li, Xiangyi, Wen, Huan, Zhang, Yuxin, Liu, Aixia, Zhang, Xuguang, Fu, Minghai, Pan, Yipeng, Xu, Jian, Zhang, Junqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9475175/
https://www.ncbi.nlm.nih.gov/pubmed/36120365
http://dx.doi.org/10.3389/fphar.2022.956812
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author Li, Xiangyi
Wen, Huan
Zhang, Yuxin
Liu, Aixia
Zhang, Xuguang
Fu, Minghai
Pan, Yipeng
Xu, Jian
Zhang, Junqing
author_facet Li, Xiangyi
Wen, Huan
Zhang, Yuxin
Liu, Aixia
Zhang, Xuguang
Fu, Minghai
Pan, Yipeng
Xu, Jian
Zhang, Junqing
author_sort Li, Xiangyi
collection PubMed
description (4E)-7-(4-Hydroxy-3-methoxyphenyl)-1-phenylhept-4-en-3-one (DPHB) derived from A. officinarum Hance has been reported to exert anti-inflammatory and anti-insulin resistance (IR) effects. We explored the molecular mechanism of DPHB ameliorating IR through network pharmacological prediction and in vitro analysis. The PI3K/AKT and TNF signaling pathways are the core pathways for DPHB to exert anti-IR, and the key proteins of this pathway were confirmed by molecular docking. In the IR-3T3-L1 adipocyte model, DPHB significantly promoted glucose uptake and the glucose transporter type 4 (GLUT4) translocation. In addition, DPHB significantly improved lipid accumulation, triglyceride content, and the mRNA expression of key adipokines [such as peroxisome proliferator-activated receptors-gamma (PPARγ), CCAAT enhancer-binding protein alpha (C/EBPα), and sterol regulatory element-binding protein-1 (SREBP-1)]. DPHB inhibited the protein expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and phosphorylated nuclear factor-κB (NF-kB), as well as promoted the expression of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), phosphorylated PI3K, and phosphorylated AKT. More interestingly, validation of the PI3K inhibitor LY294002 revealed that these changes were dependent on the activation of PI3K. Our cumulative findings thereby validate the potential of DPHB to alleviate and treat IR and the related diseases by regulating the PI3K/AKT and TNF-α signaling pathways.
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spelling pubmed-94751752022-09-16 DPHB, a diarylheptane from Alpinia officinarum Hance, ameliorates insulin resistance: A network pharmacology and in vitro study Li, Xiangyi Wen, Huan Zhang, Yuxin Liu, Aixia Zhang, Xuguang Fu, Minghai Pan, Yipeng Xu, Jian Zhang, Junqing Front Pharmacol Pharmacology (4E)-7-(4-Hydroxy-3-methoxyphenyl)-1-phenylhept-4-en-3-one (DPHB) derived from A. officinarum Hance has been reported to exert anti-inflammatory and anti-insulin resistance (IR) effects. We explored the molecular mechanism of DPHB ameliorating IR through network pharmacological prediction and in vitro analysis. The PI3K/AKT and TNF signaling pathways are the core pathways for DPHB to exert anti-IR, and the key proteins of this pathway were confirmed by molecular docking. In the IR-3T3-L1 adipocyte model, DPHB significantly promoted glucose uptake and the glucose transporter type 4 (GLUT4) translocation. In addition, DPHB significantly improved lipid accumulation, triglyceride content, and the mRNA expression of key adipokines [such as peroxisome proliferator-activated receptors-gamma (PPARγ), CCAAT enhancer-binding protein alpha (C/EBPα), and sterol regulatory element-binding protein-1 (SREBP-1)]. DPHB inhibited the protein expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and phosphorylated nuclear factor-κB (NF-kB), as well as promoted the expression of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), phosphorylated PI3K, and phosphorylated AKT. More interestingly, validation of the PI3K inhibitor LY294002 revealed that these changes were dependent on the activation of PI3K. Our cumulative findings thereby validate the potential of DPHB to alleviate and treat IR and the related diseases by regulating the PI3K/AKT and TNF-α signaling pathways. Frontiers Media S.A. 2022-09-01 /pmc/articles/PMC9475175/ /pubmed/36120365 http://dx.doi.org/10.3389/fphar.2022.956812 Text en Copyright © 2022 Li, Wen, Zhang, Liu, Zhang, Fu, Pan, Xu and Zhang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Li, Xiangyi
Wen, Huan
Zhang, Yuxin
Liu, Aixia
Zhang, Xuguang
Fu, Minghai
Pan, Yipeng
Xu, Jian
Zhang, Junqing
DPHB, a diarylheptane from Alpinia officinarum Hance, ameliorates insulin resistance: A network pharmacology and in vitro study
title DPHB, a diarylheptane from Alpinia officinarum Hance, ameliorates insulin resistance: A network pharmacology and in vitro study
title_full DPHB, a diarylheptane from Alpinia officinarum Hance, ameliorates insulin resistance: A network pharmacology and in vitro study
title_fullStr DPHB, a diarylheptane from Alpinia officinarum Hance, ameliorates insulin resistance: A network pharmacology and in vitro study
title_full_unstemmed DPHB, a diarylheptane from Alpinia officinarum Hance, ameliorates insulin resistance: A network pharmacology and in vitro study
title_short DPHB, a diarylheptane from Alpinia officinarum Hance, ameliorates insulin resistance: A network pharmacology and in vitro study
title_sort dphb, a diarylheptane from alpinia officinarum hance, ameliorates insulin resistance: a network pharmacology and in vitro study
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9475175/
https://www.ncbi.nlm.nih.gov/pubmed/36120365
http://dx.doi.org/10.3389/fphar.2022.956812
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