Mechanism and Protective Effect of Smilax glabra Roxb on the Treatment of Heart Failure via Network Pharmacology Analysis and Vitro Verification

Smilax glabra Roxb (SGR) has been widely applied alone or in combination with other Chinese herbs in heart failure (HF), but its mechanism and protective effect have not been investigated. We aimed to explore the mechanism and protective effect of SGR on the treatment of HF. Network pharmacology ana...

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Main Authors: Yingxin Long, Zunjiang Li, Chunxia Huang, Zhongyu Lu, Kuncheng Qiu, Meixing He, Zhijian Fang, Banghan Ding, Xiaohong Yuan, Wei Zhu
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-05-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2022.868680/full
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author Yingxin Long
Zunjiang Li
Chunxia Huang
Zhongyu Lu
Kuncheng Qiu
Meixing He
Zhijian Fang
Banghan Ding
Xiaohong Yuan
Wei Zhu
author_facet Yingxin Long
Zunjiang Li
Chunxia Huang
Zhongyu Lu
Kuncheng Qiu
Meixing He
Zhijian Fang
Banghan Ding
Xiaohong Yuan
Wei Zhu
author_sort Yingxin Long
collection DOAJ
description Smilax glabra Roxb (SGR) has been widely applied alone or in combination with other Chinese herbs in heart failure (HF), but its mechanism and protective effect have not been investigated. We aimed to explore the mechanism and protective effect of SGR on the treatment of HF. Network pharmacology analysis predicted that SGR was involved in the regulation of cell proliferation, oxidation–reduction process, apoptotic process, ERK1 and ERK2 cascade, MAPK cascade, etc. Its mechanism was mainly involved in the MAPK signaling pathway, calcium signaling pathway, cardiac muscle contraction, etc. Subsequently, SGR was proved to improve cellular viability, restore cellular morphology, suppress cellular and mitochondrial ROS production, improve H2O2-induced lysosome inhibition, attenuate mitochondrial dysfunction, and protect mitochondrial respiratory and energy metabolism in H9c2 cells. SGR activated the p38MAPK pathway by decreasing the mRNA expression of AKT, PP2A, NF-KB, PP2A, RAC1, and CDC42 and increasing the mRNA expression of Jun, IKK, and Sirt1. SGR also decreased the protein expression of ERK1, ERK2, JNK, Bax, and Caspase3 and increased the protein expression of p38MAPK and Bcl-2. In addition, Istidina at the highest degree was identified in SGR via the UHPLCLTQ-Orbitrap-MSn method, and it was suggested as anti-heart failure agents by targeting SRC with molecular docking analysis. In conclusion, SGR has a protective effect on HF through cellular and mitochondrial protection via multi-compounds and multi-targets, and its mechanism is involved in activating the p38 MAPK pathway. Istidina may be possible anti-HF agents by targeting SRC.
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spelling doaj.art-e1b625ba230249cab178f5924af0b2462022-12-22T00:57:04ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-05-011310.3389/fphar.2022.868680868680Mechanism and Protective Effect of Smilax glabra Roxb on the Treatment of Heart Failure via Network Pharmacology Analysis and Vitro VerificationYingxin Long0Zunjiang Li1Chunxia Huang2Zhongyu Lu3Kuncheng Qiu4Meixing He5Zhijian Fang6Banghan Ding7Xiaohong Yuan8Wei Zhu9The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaThe Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, ChinaDepartment of Emergency, Panyu Hospital of Traditional Chinese Medicine, Guangzhou, ChinaGuangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, ChinaGuangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, ChinaGuangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, ChinaSmilax glabra Roxb (SGR) has been widely applied alone or in combination with other Chinese herbs in heart failure (HF), but its mechanism and protective effect have not been investigated. We aimed to explore the mechanism and protective effect of SGR on the treatment of HF. Network pharmacology analysis predicted that SGR was involved in the regulation of cell proliferation, oxidation–reduction process, apoptotic process, ERK1 and ERK2 cascade, MAPK cascade, etc. Its mechanism was mainly involved in the MAPK signaling pathway, calcium signaling pathway, cardiac muscle contraction, etc. Subsequently, SGR was proved to improve cellular viability, restore cellular morphology, suppress cellular and mitochondrial ROS production, improve H2O2-induced lysosome inhibition, attenuate mitochondrial dysfunction, and protect mitochondrial respiratory and energy metabolism in H9c2 cells. SGR activated the p38MAPK pathway by decreasing the mRNA expression of AKT, PP2A, NF-KB, PP2A, RAC1, and CDC42 and increasing the mRNA expression of Jun, IKK, and Sirt1. SGR also decreased the protein expression of ERK1, ERK2, JNK, Bax, and Caspase3 and increased the protein expression of p38MAPK and Bcl-2. In addition, Istidina at the highest degree was identified in SGR via the UHPLCLTQ-Orbitrap-MSn method, and it was suggested as anti-heart failure agents by targeting SRC with molecular docking analysis. In conclusion, SGR has a protective effect on HF through cellular and mitochondrial protection via multi-compounds and multi-targets, and its mechanism is involved in activating the p38 MAPK pathway. Istidina may be possible anti-HF agents by targeting SRC.https://www.frontiersin.org/articles/10.3389/fphar.2022.868680/fullSmilax glabra Roxbheart failuremitochondrial dysfunctionnetwork pharmacology analysisUHPLC-LTQ-Orbitrap-MSn method
spellingShingle Yingxin Long
Zunjiang Li
Chunxia Huang
Zhongyu Lu
Kuncheng Qiu
Meixing He
Zhijian Fang
Banghan Ding
Xiaohong Yuan
Wei Zhu
Mechanism and Protective Effect of Smilax glabra Roxb on the Treatment of Heart Failure via Network Pharmacology Analysis and Vitro Verification
Frontiers in Pharmacology
Smilax glabra Roxb
heart failure
mitochondrial dysfunction
network pharmacology analysis
UHPLC-LTQ-Orbitrap-MSn method
title Mechanism and Protective Effect of Smilax glabra Roxb on the Treatment of Heart Failure via Network Pharmacology Analysis and Vitro Verification
title_full Mechanism and Protective Effect of Smilax glabra Roxb on the Treatment of Heart Failure via Network Pharmacology Analysis and Vitro Verification
title_fullStr Mechanism and Protective Effect of Smilax glabra Roxb on the Treatment of Heart Failure via Network Pharmacology Analysis and Vitro Verification
title_full_unstemmed Mechanism and Protective Effect of Smilax glabra Roxb on the Treatment of Heart Failure via Network Pharmacology Analysis and Vitro Verification
title_short Mechanism and Protective Effect of Smilax glabra Roxb on the Treatment of Heart Failure via Network Pharmacology Analysis and Vitro Verification
title_sort mechanism and protective effect of smilax glabra roxb on the treatment of heart failure via network pharmacology analysis and vitro verification
topic Smilax glabra Roxb
heart failure
mitochondrial dysfunction
network pharmacology analysis
UHPLC-LTQ-Orbitrap-MSn method
url https://www.frontiersin.org/articles/10.3389/fphar.2022.868680/full
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