β‐Sitosterol Protects against Myocardial Ischemia/Reperfusion Injury via Targeting PPARγ/NF‐κB Signalling

Lin, Fengxia; Xu, Luhua; Huang, Mei-zhu; Deng, Bin; Zhang, Weiwei; Zeng, Zhicong; Song, Yong Jung

doi:10.1155/2020/2679409

Cited by 31 publications

(24 citation statements)

References 24 publications

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“…Quercetin is an important flavonoid that has been normally viewed as a great antioxidant and anti-inflammatory molecule [ 35 – 37 ] and can prevent endothelial dysfunction and myocardial ischemia [ 38 ]. Beta-sitosterol exerted protective actions against myocardial injury [ 39 ] and is used in the treatment of hypercholesterolemia [ 40 ]. Kaempferol has antioxidant, anti-inflammatory effect [ 41 ] and protects against cardiac hypertrophy [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Research on Effect and Mechanism of Xuefu Zhuyu Decoction on CHD Based on Meta-Analysis and Network Pharmacology

Kui

Gao

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Xuefu Zhuyu Decoction (XFZY) is an ancient compound widely used in the treatment of coronary heart disease. However, its efficacy evaluation is not complete and its mechanism of action is not clear enough. In an attempt to address these problems, the efficacy was evaluated by meta-analysis and the mechanism was elucidated by the network pharmacology method. We systematically searched relevant studies in PubMed, Chinese National Knowledge Infrastructure Database (CNKI), Cochrane Library, Wanfang Data, and other databases from 2007 to 2019. The association between XFZY treatment and CHD was estimated by risk ratio (RR) and corresponding 95% confidence intervals (95% CIs). The compounds and the potential protein targets of XFZY were obtained from TCMSP, and active compounds were selected according to their oral bioavailability and drug similarity. The potential genes of coronary heart disease were obtained from TTD, OMIM, and GeneCards. The potential pathways related to genes were determined by GO and KEGG pathway enrichment analyses. The compound-target and compound-target-pathway networks were constructed. Molecular docking validates the component and the target. A total of 21 studies including 1844 patients were enrolled in the present meta-analysis, indicating that XFZY has a greater beneficial on total effect (fixed effect RR = 1.30; 95% Cl: 1.24–1.36; P = 0.82 ; I2 = 0.0%) and electrocardiogram efficacy (fixed effect RR = 1.40; 95% Cl: 1.26–1.56; P = 0.96 ; I2 = 0.0%) compared with the control group. A total of 1342 components in XFZY were obtained, among which, 241 were chosen as bioactive components. GO and KEGG analyses got top 10 significantly enriched terms and 10 enriched pathways. The C-T network included 192 compounds and 3085 targets, whereas the C-T-P network included 10 compounds, 109 targets, and 5 pathways. There was a good binding activity between the components and the targets. XFZY has the curative effect on coronary heart disease, and its mechanism is related to 10 compounds, 10 core targets, and 5 pathways.

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Section: Discussionmentioning

confidence: 99%

Research on Effect and Mechanism of Xuefu Zhuyu Decoction on CHD Based on Meta-Analysis and Network Pharmacology

Kui

Gao

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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“…Moreover, β -sitosterol could reduce the LPS-induced expression of PTGS2 and exert anti-inflammatory and analgesic effects [ 36 ]. Kaempferol, β -sitosterol, and sesamin can enhance insulin resistance, protect myocardial cells from injury, and prevent hyperlipidemia by increasing the expression of PPARG [ 37 , 38 ]. Sesamin also reduced the overexpression of PTGS2 by regulating the JNK and p38 MAP kinase pathways [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular Mechanism of Xixin-Ganjiang Herb Pair Treating Chronic Obstructive Pulmonary Disease-Integrated Network Pharmacology and Molecular Docking

Huang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Background. Chronic obstructive pulmonary disease (COPD) is characterized by high morbidity, disability, and mortality, which seriously threatens human life and health. Xixin and Ganjiang are classic herb pairs of Zhongjing Zhang, which are often used to treat COPD in China. However, the substance basis and mechanism of action of Xixin-Ganjiang herb pair (XGHP) in the treatment of COPD remain unclear. Methods. On the website of TCMSP and the DrugBank, effective compounds and targets of XGHP were found. COPD targets were obtained from GeneCards, DisGeNET, and GEO gene chips. Intersecting these databases resulted in a library of drug targets for COPD. Then, intersection targets were used for protein-protein interaction (PPI) and pathway enrichment analysis. Finally, the binding activity between compounds and core genes was evaluated by molecular docking to verify the expression level of PTGS2 and PPARG in rats. Results. Twelve effective compounds and 104 core genes were found in the intersection library, and kaempferol, sesamin, β-sitosterol, PTGS2, and PPARG were particularly prominent in the network analysis. A total of 113 pathways were obtained and enrichment of the TNF signaling pathway, IL-17 signaling pathway, and C-type lectin receptor signaling pathway was particularly obvious. Molecular docking indicated that kaempferol, sesamin, and β-sitosterol were closely related to PTGS2 and PPARG and were superior to aminophylline. Key compounds in XGHP could restrict the expression of PTGS2 in the lung tissues of COPD rats and promote the expression of PPARG. Conclusion. Inhibition of the expression of inflammatory factor PTGS2 and promotion of the expression of PPARG may be an effective target of XGHP in the treatment of COPD.

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“…Moreover, IRI leads to a high mortality rate in patients with MI, which is a serious clinical complication and affects the prognosis of these patients. Oxidative stress, cardiomyocyte apoptosis and cardiac dysfunction are all associated with IRI ( 18 , 19 ). It has been previously reported that intervention in cardiomyocyte apoptosis can restore IRI to a certain extent ( 19 ).…”

Section: Discussionmentioning

confidence: 99%

“…Oxidative stress, cardiomyocyte apoptosis and cardiac dysfunction are all associated with IRI ( 18 , 19 ). It has been previously reported that intervention in cardiomyocyte apoptosis can restore IRI to a certain extent ( 19 ). The present research also suggested that miR-24 can decrease cardiomyocyte apoptosis caused by IRI.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑24 protects against myocardial ischemia‑reperfusion injury via the NF‑κB/TNF‑α pathway

Fang

Lin

et al. 2021

Exp Ther Med

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Acute myocardial infarction (AMI) is a form of cardiomyopathy in which a blocked coronary artery leads to an irreversible loss of cardiomyocytes due to inadequate blood and oxygen supply to the distal myocardium tissues, eventually leading to heart failure. Recently, studies have revealed that microRNA (miRNA/miR)-24 has diagnostic value in the pathogenesis of AMI by affecting multiple cell processes such as cell proliferation, differentiation and apoptosis. However, the specific mechanism of miR-24 in ischemia-reperfusion injury (IRI) after AMI remains to be fully elucidated. The present study aimed to investigate the effects and mechanisms of miR-24 in IRI. In vitro , the current study detected cellular apoptosis and apoptotic-related protein expression levels in the cardiomyocyte H9C2 cell line (negative control group, model group and miRNA group) via flow cytometry and western blot analysis. In the in vivo study, rats were randomly divided into sham, model and miRNA groups. The infarct area was observed using nitro blue tetrazolium staining, pathological changes of the myocardium were detected via hematoxylin and eosin staining and TUNEL staining was used to detect cardiomyocyte apoptosis. The expression levels of related proteins were evaluated via immunohistochemistry and western blot analysis. The in vitro and in vivo results demonstrated that miR-24 significantly inhibited cardiomyocyte apoptosis compared with the model group. Concurrently, the expression levels of proteins associated with the NF-κB/TNF-α pathway (NF-κB, caspase-3, Bax, Bcl-2, TNF-α, vascular cell adhesion molecule 1, intercellular adhesion molecule 1 and monocyte chemoattractant protein-1) in the miRNA group were significantly different from the model group (P<0.001). Compared with the model group, miR-24 significantly improved pathological damage and infarct size of rat myocardium. Overall, the present results suggested that miR-24 improves myocardial injury in rats by inhibiting the NF-κB/TNF-α pathway.

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β‐Sitosterol Protects against Myocardial Ischemia/Reperfusion Injury via Targeting PPARγ/NF‐κB Signalling

Cited by 31 publications

References 24 publications

Research on Effect and Mechanism of Xuefu Zhuyu Decoction on CHD Based on Meta-Analysis and Network Pharmacology

Research on Effect and Mechanism of Xuefu Zhuyu Decoction on CHD Based on Meta-Analysis and Network Pharmacology

Molecular Mechanism of Xixin-Ganjiang Herb Pair Treating Chronic Obstructive Pulmonary Disease-Integrated Network Pharmacology and Molecular Docking

MicroRNA‑24 protects against myocardial ischemia‑reperfusion injury via the NF‑κB/TNF‑α pathway

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