Integrating network analysis and experimental validation to reveal the mitophagy-associated mechanism of Yiqi Huoxue (YQHX) prescription in the treatment of myocardial ischemia/reperfusion injury

Chen, Mingtai; Zhong, Gongxun; Liu, Mengnan; He, Hongping; Zhou, Jie; Chen, Jianping; Zhang, Mingsheng; Liu, Qiang; Tong, Guangdong; Luan, Jienan; Zhou, Hua

doi:10.1016/j.phrs.2023.106682

Cited by 18 publications

(5 citation statements)

References 34 publications

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“…The utilization of therapeutic medications embodying the "Replenishing Qi and activating blood" effect ameliorates cardiovascular symptoms [34]. Numerous studies have embarked on exploring the mechanism of "Replenishing Qi and activating blood" in treating cardiovascular and cerebrovascular diseases [35][36][37]. However, these studies mainly focus on the overall study of prescriptions, and neither investigate specific small molecule drugs, nor the effect differences between small molecule drugs [38].…”

Section: Discussionmentioning

confidence: 99%

The combination of Tanshinone IIA and Astragaloside IV attenuates myocardial ischemia–reperfusion injury by inhibiting the STING pathway

Zhai,

Chen,

Wang

et al. 2024

Chin Med

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Background Astragaloside IV (As-IV) and Tanshinone IIA (Ta-IIA) are the main ingredients of traditional Chinese medicinal Astragalus membranaceus (Fisch.) Bunge and Salvia miltiorrhiza Bunge, respectively, both of which have been employed in the treatment of cardiovascular diseases. Nevertheless, the efficacy of the combination (Co) of Ta-IIA and As-IV for cardiovascular diseases remain unclear and warrant further investigation. This study aimed to investigate the efficacy and the underlying molecular mechanism of Co in treating myocardial ischemia–reperfusion injury (MIRI). Methods In order to assess the efficacy of Co, an in vivo MIRI mouse model was created by temporarily blocking the coronary arteries for 30 min and then releasing the blockage. Parameters such as blood myocardial enzymes, infarct size, and ventricular function were measured. Additionally, in vitro experiments were conducted using HL1 cells in both hypoxia-reoxygenation model and oxidative stress models. The apoptosis rate, expression levels of apoptosis-related proteins, oxidative stress indexes, and release of inflammatory factors were detected. Furthermore, molecular docking was applied to examine the binding properties of Ta-IIA and As-IV to STING, and western blotting was performed to analyze protein expression of the STING pathway. Additionally, the protective effect of Ta-IIA, As-IV and Co via inhibiting STING was further confirmed in models of knockdown STING by siRNA and adding STING agonist. Results Both in vitro and in vivo data demonstrated that, compared to Ta-IIA or As-IV alone, the Co exhibited superior efficacy in reducing the area of myocardial infarction, lowering myocardial enzyme levels, and promoting the recovery of myocardial contractility. Furthermore, the Co showed more potent anti-apoptosis, antioxidant, and anti-inflammation effects. Additionally, the Co enhanced the inhibitory effects of Ta-IIA and As-IV on STING phosphorylation and the activation of STING signaling pathway. However, the administration of a STING agonist attenuated the protective effects of the Co, Ta-IIA, and As-IV by compromising their anti-apoptotic, antioxidant, and anti-inflammatory effects in MIRI. Conclusion Compared to the individual administration of Ta-IIA or As-IV, the combined treatment demonstrated more potent ability in inhibiting apoptosis, oxidative stress, inflammation, and the STING signaling pathway in the context of MIRI, indicating a more powerful protective effect against MIRI. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

The combination of Tanshinone IIA and Astragaloside IV attenuates myocardial ischemia–reperfusion injury by inhibiting the STING pathway

Zhai,

Chen,

Wang

et al. 2024

Chin Med

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“…Network pharmacology, which is an advanced research tool rooted in the principles of biological network science, provides insights into intricate connections between diseases and drugs at a holistic level. The integration of network pharmacology with TCM represents a shift in TCM research from reductionism to a systemic approach …”

Section: Discussionmentioning

confidence: 99%

“…The integration of network pharmacology with TCM represents a shift in TCM research from reductionism to a systemic approach. 33 …”

Section: Discussionmentioning

confidence: 99%

Determining the Mechanism of Banxia Xiexin Decoction for Gastric Cancer Treatment through Network Analysis and Experimental Validation

Li,

Wang

et al. 2024

ACS Omega

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Gastric cancer (GC) is a widespread malignancy. Banxia Xiexin decoction (BXD) has been used for GC treatment, but the specific mechanisms underlying its therapeutic effects remain controversial. This study used a comprehensive approach to network pharmacology combined with experimental validation to elucidate the mechanism of BXD's anti-GC effects. Initially, we used the UHPLC-LTQ-Orbitrap-MS/MS technology to identify the main chemical constituents of BXD, as well as potential targets associated with these constituents. Then, we employed the Genecard and Online Mendelian Inheritance in Man (OMIM) to determine the targets specifically related to GC. We employed a combination of Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes pathway, and protein−protein interaction analysis to predict the crucial targets of BXD and uncover the pathways involved in its therapeutic effects against GC. The results were subsequently verified through cell experiments. The analysis revealed 174 common targets shared by BXD and GC. GO enrichment analysis highlighted biological processes, such as autophagy, protein kinase activity, and apoptosis. Moreover, the enrichment analysis revealed several significant pathways that serve as the primary mechanisms by which BXD exerts its effects. Notably, these pathways include PI3K-Akt, HIF-1, and Pathways in cancer. Subsequent in vitro experiments demonstrated that BXD effectively hindered GC cell proliferation, stimulated autophagy, and facilitated apoptosis by PI3K-Akt-mTOR signaling pathway regulation. These findings reveal the effectiveness of BXD against GC through diverse components, targets, and pathways, indicating that BXD holds potential therapeutic value in GC treatment. This study uncovers the intricate biological mechanisms that underlie BXD's efficacy in treating GC through the integration of network pharmacology analysis and rigorous in vitro experiments.

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“…However, when mitophagy is inhibited, the timely removal of impaired mitochondria is impeded, accumulating damaged mitochondria and subsequent mitochondrial dysfunction [ 27 ]. Evidence suggests that ischemia‒reperfusion-induced tissue damage is intricately linked to mitochondrial dysfunction, governed by a complex regulatory mechanism [ 17 , 56 , 57 ]. Nevertheless, it remains unclear whether NETs play a role in mitochondrial dysfunction by impeding mitophagy, causing microvascular endothelial damage during II/R.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil extracellular traps drive intestinal microvascular endothelial ferroptosis by impairing Fundc1-dependent mitophagy

Chu,

Wang,

Yang

et al. 2023

Redox Biology

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Integrating network analysis and experimental validation to reveal the mitophagy-associated mechanism of Yiqi Huoxue (YQHX) prescription in the treatment of myocardial ischemia/reperfusion injury

Cited by 18 publications

References 34 publications

The combination of Tanshinone IIA and Astragaloside IV attenuates myocardial ischemia–reperfusion injury by inhibiting the STING pathway

The combination of Tanshinone IIA and Astragaloside IV attenuates myocardial ischemia–reperfusion injury by inhibiting the STING pathway

Determining the Mechanism of Banxia Xiexin Decoction for Gastric Cancer Treatment through Network Analysis and Experimental Validation

Neutrophil extracellular traps drive intestinal microvascular endothelial ferroptosis by impairing Fundc1-dependent mitophagy

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