Network pharmacology analysis and experimental validation to explore the mechanism of Shenlian extract on myocardial ischemia

Li, Jingjing; Wang, Chun-Miao; Wang, Yajie; Yang, Qing; Cai, Wei; Li, Yujie; Song, Min Seok; Zang, Yuan-Long; Cui, Xihe; Qi, Li; Chen, Ying; Weng, Xiaogang; Zhu, Xiaoxin

doi:10.1016/j.jep.2022.114973

Cited by 11 publications

(8 citation statements)

References 38 publications

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“…Activation of the JAK2/STAT3 signaling pathway can increase the expression of SOCS3, which in turn negatively regulates the JAK2/STAT3 pathway by inactivating STAT3 18 . The JAK2/STAT3 pathway plays an important role in the apoptosis of various tumor and nontumor cells 19,20 . Therefore, we investigated the effect of atropine on the JAK2/STAT3 signaling pathway.…”

Section: Resultsmentioning

confidence: 99%

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High‐concentration atropine induces corneal epithelial cell apoptosis via miR‐30c‐1/SOCS3

Chen

Shu

2022

The Kaohsiung J of Med Scie

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Atropine is an anticholinergic drug widely used in the field of ophthalmology, but its abuse can cause cytotoxicity to the cornea, resulting in blurred vision. This study used cultured human corneal epithelial cells (HCECs) to investigate the mechanism of high‐concentration atropine‐induced cytotoxicity. HCECs were treated with different concentrations of atropine. The expression levels of microRNA (miR)‐30c‐1 and suppressor of cytokine signaling 3 (SOCS3) were manipulated in HCECs treated with 0.1% atropine. Cell counting kit‐8 assay and flow cytometry were used to assess the viability and apoptosis of HCECs. The relationship between miR‐30c‐1 and SOCS3 was obtained from an online database and validated using a dual‐luciferase reporter assay and RNA immunoprecipitation method. The effect of atropine on the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway was also investigated. High‐concentration atropine inhibited the viability of HCECs and promoted their apoptosis. Moreover, atropine reduced miR‐30c‐1 expression and increased SOCS3 expression in a dose‐dependent manner. It was found that miR‐30c‐1 targeted SOCS3. Overexpression of miR‐30c‐1‐reduced atropine‐induced HCEC cytotoxicity, whereas upregulation of SOCS3 reversed the effects of miR‐30c‐1 overexpression. High‐concentration atropine inhibited activation of the JAK2/STAT3 signaling pathway via miR‐30c‐1/SOCS3. High‐concentration atropine induces HCEC apoptosis by regulating the miR‐30c‐1/SOCS3 axis and JAK2/STAT3 signaling pathway.

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Section: Resultsmentioning

confidence: 99%

“…18 The JAK2/STAT3 pathway plays an important role in the apoptosis of various tumor and nontumor cells. 19,20 Therefore, we investigated the effect of atropine…”

Section: High-concentration Atropine Induces Hcec Cytotoxicity and In...mentioning

confidence: 99%

High‐concentration atropine induces corneal epithelial cell apoptosis via miR‐30c‐1/SOCS3

Chen

Shu

2022

The Kaohsiung J of Med Scie

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“…It was especially suited for the assessing the overall therapeutic effects of herbal medicine, which always contained various components [ 38 ]. Recently, network pharmacology has been increasingly applied to reveal the molecular mechanisms of herbal formula [ 39 – 42 ]. In this study, the public service tools were employed to find the potential protein targets of five main flavonoids in MSTF, which could be divided into three clusters, namely, inflammation, proliferation, and apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Mechanisms of Total Flavonoids from Mosla scabra against Influenza A Virus-Induced Pneumonia by Integrating Network Pharmacology and Experimental Verification

Cai

Zhang

2022

Evidence-Based Complementary and Alternative Medicine

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Influenza virus is one of the most common infectious pathogens that could cause high morbidity and mortality in humans. However, the occurrence of drug resistance and serious complications extremely complicated the clinic therapy. Mosla scabra is a natural medicinal plant used for treating various lung and gastrointestinal diseases, including viral infection, cough, chronic obstructive pulmonary disease, acute gastroenteritis, and diarrhoea. But the therapeutic effects of this herbal medicine had not been expounded clearly. In this study, a network pharmacology approach was employed to investigate the protective mechanism of total flavonoids from M. scabra (MSTF) against influenza A virus- (IAV-) induced acute lung damage and inflammation. The active compounds of MSTF were analyzed by LC-MS/MS and then evaluated according to their oral bioavailability and drug-likeness index. The potential targets of each active compound in MSTF were identified by using PharmMapper Server, whereas the potential genes involved in IAV infection were obtained from GeneGards. The results showed that luteoloside, apigenin, kaempherol, luteolin, mosloflavone I, and mosloflavone II were the main bioactive compounds found in MSTF. Primarily, 23 genes were identified as the targets of those five active compounds, which contributed to the inactivation of chemical carcinogenesis ROS, lipid and atherosclerosis, MAPK signaling pathway, pathways in cancer, PI3K-AKT signaling pathway, proteoglycans in cancer, and viral carcinogenesis. Finally, the animal experiments validated that MSTF improved IAV-induced acute lung inflammation via inhibiting MAPK, PI3K-AKT, and oxidant stress pathways. Therefore, our study demonstrated the potential inhibition of MSTF on viral pneumonia in mice and provided a strategy to characterize the molecular mechanism of traditional Chinese medicine by a combinative method using network pharmacology and experimental validation.

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“…SL has been shown in previous research to reduce inflammatory cytokines in the blood, regulate lipid metabolism, inhibit vascular endothelial damage, improve vascular endothelial function, and inhibit platelet aggregation, all of which help to prevent the formation of atherosclerotic plaques (Guo et al, 2016; Li et al, 2011; You et al, 2011). Our research has discovered that SL had a good therapeutic impact on myocardial ischemia and ischemia–reperfusion damage in recent years (Guo et al, 2020; Li et al, 2022). The underlying mechanism of SL on coronary artery NR generated by myocardial ischemia–reperfusion, on the other hand, is still unknown.…”

Section: Introductionmentioning

confidence: 99%

Shenlian extract decreases mitochondrial autophagy to regulate mitochondrial function in microvascular to alleviate coronary artery no‐reflow

Wang

et al. 2023

Phytotherapy Research

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Shenlian (SL) extract has been proven to be effective in the prevention and treatment of atherosclerosis and myocardial ischemia. However, the function and molecular mechanisms of SL on coronary artery no‐reflow have not been fully elucidated. This study was designed to investigate the contribution of SL extract in repressing excessive mitochondrial autophagy to protect the mitochondrial function and prevent coronary artery no‐reflow. The improvement of SL on coronary artery no‐reflow was observed in vivo experiments and the molecular mechanisms were further explored through vitro experiments. First, a coronary artery no‐reflow rat model was built by ligating the left anterior descending coronary artery for 2 hr of ischemia, followed by 24 hr of reperfusion. Thioflavin S (6%, 1 ml/kg) was injected into the inferior vena cava to mark the no‐reflow area. Transmission electron microscopy was performed to observe the cellular structure, mitochondrial structure, and mitochondrial autophagy of the endothelial cells. Immunofluorescence was used to observe the microvascular barrier function and microvascular inflammation. Cardiac microvascular endothelial cells (CMECs) were isolated from rats. The CMECs were deprived of oxygen–glucose deprivation (OGD) for 2 hr and reoxygenated for 4 hr to mimic the Myocardial ischemia‐reperfusion (MI/R) injury‐induced coronary artery no‐reflow in vitro. Mitochondrial membrane potential was assessed using JC‐1 dye. Intracellular adenosine triphosphate (ATP) levels were determined using an ATP assay kit. The cell total reactive oxygen species (ROS) levels and cell apoptosis rate were analyzed by flow cytometry. Colocalization of mitochondria and lysosomes indirectly indicated mitophagy. The representative ultrastructural morphologies of the autophagosomes and autolysosomes were also observed under transmission electron microscopy. The mitochondrial autophagy‐related proteins (LC3II/I, P62, PINK, and Parkin) were analyzed using Western blot analysis. In vivo, results showed that, compared with the model group, SL could reduce the no‐reflow area from 37.04 ± 9.67% to 18.31 ± 4.01% (1.08 g·kg−1 SL), 13.79 ± 4.77% (2.16 g·kg−1 SL), and 12.67 ± 2.47% (4.32 g·kg−1 SL). The extract also significantly increased the left ventricular ejection fraction (EF) and left ventricular fractional shortening (FS) (p < 0.05 or p < 0.01). The fluorescence intensities of VE‐cadherin, which is a junctional protein that preserves the microvascular barrier function, decreased to ~74.05% of the baseline levels in the no‐reflow rats and increased to 89.87%(1.08 g·kg−1SL), 82.23% (2.16 g·kg−1 SL), and 89.69% (4.32 g·kg−1 SL) of the baseline levels by SL treatment. SL administration repressed the neutrophil migration into the myocardium. The oxygen–glucose deprivation/reoxygenation (OGD/R) model was induced in vitro to mimic microvascular ischemia–reperfusion injury. The impaired mitochondrial function after OGD/R injury led to decreased ATP production, calcium overload, the excessive opening of the Mitochond...

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Network pharmacology analysis and experimental validation to explore the mechanism of Shenlian extract on myocardial ischemia

Cited by 11 publications

References 38 publications

High‐concentration atropine induces corneal epithelial cell apoptosis via miR‐30c‐1/SOCS3

High‐concentration atropine induces corneal epithelial cell apoptosis via miR‐30c‐1/SOCS3

Anti-Inflammatory Mechanisms of Total Flavonoids from Mosla scabra against Influenza A Virus-Induced Pneumonia by Integrating Network Pharmacology and Experimental Verification

Shenlian extract decreases mitochondrial autophagy to regulate mitochondrial function in microvascular to alleviate coronary artery no‐reflow

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