Exploring the pharmacological mechanism of calculus bovis in cerebral ischaemic stroke using a network pharmacology approach

Du, Xin; Li, Changxiang; Zhang, Shuang; Sun, Chunyan; Zhang, Xiaole; Chen, Congai; Wang, Xueqian; Cheng, Fang; Wang, Qingguo

doi:10.1016/j.jep.2021.114507

Cited by 11 publications

(4 citation statements)

References 42 publications

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“…Indeed, Shen et al revealed the safety of oral administration of AGNHW for the treatment of ischemic stroke for 1 week, and AGNHW has been shown to have neuroprotective effects on ischemic reinjection of brain damage in rats [ 7 ]. Current literature evidence indicated that the mechanism of Calculus bovis in ischemic stroke may be related to the effective protection of neurovascular units in the brain by PI3K/Akt, HIF-1 α and VEGF pathways [ 8 ]. Moreover, realgar and cinnabar have synergistic effects with other herbal materials of AGNHW and are necessary components of AGNHW's neuroprotective effect on cerebral ischemia-reperfusion injury [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

In Silico Identification and Mechanism Exploration of Active Ingredients against Stroke from An-Gong-Niu-Huang-Wan (AGNHW) Formula

Song

et al. 2022

Oxidative Medicine and Cellular Longevity

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An-Gong-Niu-Huang-Wan (AGNHW) is a well-known formula for treating cerebrovascular diseases, with roles including clearing away heat, detoxification, and wake-up consciousness. In recent years, AGNHW has been commonly used for the treatment of ischemic stroke, but the mechanism by which AGNHW relieves stroke has not been clearly elucidated. In the current study, we developed a multiple systems pharmacology-based framework to identify the potential antistroke ingredients in AGNHW and explore the underlying mechanisms of action (MOA) of AGNHW against stroke from a holistic perspective. Specifically, we performed a network-based method to identify the potential antistroke ingredients in AGNHW by integrating the drug-target network and stroke-associated genes. Furthermore, the oxygen-glucose deprivation/reoxygenation (OGD/R) model was used to validate the anti-inflammatory effects of the key ingredients by determining the levels of inflammatory cytokines, including interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α. The antiapoptotic effects of the key ingredients were also confirmed in vitro. Integrated pathway analysis of AGNHW revealed that it might regulate three biological signaling pathways, including IL-17, TNF, and PI3K-AKT, to play a protective role in stroke. Moreover, 30 key antistroke ingredients in AGNHW were identified via network-based in silico prediction and were confirmed to have known neuroprotective effects. After drug-like property evaluation and pharmacological validation in vitro, scutellarein (SCU) and caprylic acid (CA) were selected for further antistroke investigation. Finally, systems pharmacology-based analysis of CA and SCU indicated that they might exert antistroke effects via the apoptotic signaling pathway and inflammatory response, which was further validated in an in vitro stroke model. Overall, the current study proposes an integrative systems pharmacology approach to identify antistroke ingredients and demonstrate the underlying pharmacological MOA of AGNHW in stroke, which provides an alternative strategy to investigate novel traditional Chinese medicine formulas for complex diseases.

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Section: Introductionmentioning

confidence: 99%

In Silico Identification and Mechanism Exploration of Active Ingredients against Stroke from An-Gong-Niu-Huang-Wan (AGNHW) Formula

Song

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…HIF-1 signaling pathway can regulate oxidative stress-induced apoptosis [38] , and the operation of hypoxia/reoxygenation increases HIF-1α expression in cell models [39] . HIF-1α is degraded by proteases under normoxia.…”

Section: Discussionmentioning

confidence: 99%

Exploring the protective effect and potential mechanism of acutumidine on myocardial ischemia based on “compound-target-pathway” network

Shao,

Yu,

Zheng

et al. 2024

Preprint

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Background Menispermi Rhizoma is a traditional Chinese medicine with significant anti-myocardial ischemia (MI) effects. Acutumidine is a major alkaloid component of Menispermi Rhizoma. However, the effect and mechanism of acutumidine on MI remain unknown. This research aims to explore the effect and potential mechanism of acutumidine in treating myocardial ischemia (MI). Methods The oxygen glucose deprivation (OGD) model of H9c2 cardiomyocytes was established to simulate MI in vitro. The protective effect of acutumidine against MI was evaluated by MTT assay, Hoechst/PI staining, lactate dehydrogenase (LDH), creatine kinase (CK) release, the levels of superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) and cell apoptosis rate. Based on network pharmacology, the potential the anti-MI mechanism of acutumidine is explored by constructing a "compound-target-pathway" network. GO and KEGG enrichment analysis were performed via metascape database. Finally, the key targets of acutumidine were validated by molecular docking. Results The experiment results showed that acutumidine could protect H9c2 cardiomyocytes against OGD injury by increasing the levels of SOD and GSH, and decreasing the release of LDH, CK and MDA significantly. The apoptosis rate of OGD H9c2 cells were reduced. All research results suggested that acutumidine could inhibit oxidative stress and cell apoptosis. Network pharmacology showed that the protective effect of acutumidine on MI was related to PI3K/AKT, HIF-1, and Ras signaling pathways. Molecular docking studies further showed that MAPK1, IGF1, EGFR, and KDR are the core targets of acutumidine in the treatment of MI. Conclusions Acutumidine was shown to have notable effects to inhibit oxidative stress and cell apoptosis in H9c2 cells through PI3K/AKT, HIF-1 and Ras signaling pathway. This study not only provides new insights into the anti-MI effect and mechanism of acutumidine, but also offers a promising candidate drug for the treatment of MI.

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“…ICCB significantly reduced the expression of Bax, Caspase‐9, Caspase‐3, and Cyt c protein, while increasing the expression of Bcl‐2, inhibiting neuronal apoptosis, and protecting mitochondrial function to reduce CIRI in rats (Lu et al, 2020). ICCB protects cerebral neurovascular units through HIF‐1/VEGF and PI3K/Akt signalling pathways (Du et al, 2022).…”

Section: Potential Mechanisms Of Tcm and Its Major Bioactive Constitu...mentioning

confidence: 99%

Traditional Chinese medicines treat ischemic stroke and their main bioactive constituents and mechanisms

Fan,

Liu,

Liu

et al. 2023

Phytotherapy Research

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Ischemic stroke (IS) remains one of the leading causes of death and disability in humans. Unfortunately, none of the treatments effectively provide functional benefits to patients with IS, although many do so by targeting different aspects of the ischemic cascade response. The advantages of traditional Chinese medicine (TCM) in preventing and treating IS are obvious in terms of early treatment and global coordination. The efficacy of TCM and its bioactive constituents has been scientifically proven over the past decades. Based on clinical trials, this article provides a review of commonly used TCM patent medicines and herbal decoctions indicated for IS. In addition, this paper also reviews the mechanisms of bioactive constituents in TCM for the treatment of IS in recent years, both domestically and internationally. A comprehensive review of preclinical and clinical studies will hopefully provide new ideas to address the threat of IS.

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Exploring the pharmacological mechanism of calculus bovis in cerebral ischaemic stroke using a network pharmacology approach

Cited by 11 publications

References 42 publications

In Silico Identification and Mechanism Exploration of Active Ingredients against Stroke from An-Gong-Niu-Huang-Wan (AGNHW) Formula

In Silico Identification and Mechanism Exploration of Active Ingredients against Stroke from An-Gong-Niu-Huang-Wan (AGNHW) Formula

Exploring the protective effect and potential mechanism of acutumidine on myocardial ischemia based on “compound-target-pathway” network

Traditional Chinese medicines treat ischemic stroke and their main bioactive constituents and mechanisms

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