Mechanism exploration of 6-Gingerol in the treatment of atherosclerosis based on network pharmacology, molecular docking and experimental validation

Hu, Youdong; Liu, Tingting; Zheng, Guangzhen; Zhou, Li; Ma, Keping; Xiong, Xiaolian; Cheng, Zheng; Li, Jin; Zhu, Yan; Bian, Wenhui; Zheng, Xiaojiao; Xiong, Qingping; Lin, Jiafeng

doi:10.1016/j.phymed.2023.154835

Cited by 3 publications

(2 citation statements)

References 54 publications

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“…The results showed that the PDB ID numbers of TNF, EGFR, CASP 3, AKT1 and CTNNB1 were 5UUI, 5Y9T, 5IBP, 1UNQ and 1JDH, respectively. The binding energy of most of these ingredients to the targets was less than −5 kcal/mol, indicating a good binding activity and strong stability between the key ingredients and targets 24 ( Table 1 ). In addition, Figure 14A–C exhibited an image of the optimal docking of ingredients and targets after visualization.…”

Section: Resultsmentioning

confidence: 99%

Integrated Approaches Revealed the Therapeutic Mechanisms of Zuojin Pill Against Gastric Mucosa Injury in a Rat Model with Chronic Atrophic Gastritis

Chen,

He,

Wang

et al. 2024

DDDT

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Background The Zuojin Pill (ZJP) is widely used for treating chronic atrophic gastritis (CAG) in clinical practice, effectively ameliorating symptoms such as vomiting, pain, and abdominal distension in patients. However, the underlying mechanisms of ZJP in treating CAG has not been fully elucidated. Purpose This study aimed to clarify the characteristic function of ZJP in the treatment of CAG and its potential mechanism. Methods The CAG model was established by alternant administrations of ammonia solution and sodium deoxycholate, as well as an irregular diet. Therapeutic effects of ZJP on body weight, serum biochemical indexes and general condition were analyzed. HE staining and AB-PAS staining were analyzed to characterize the mucosal injury and the thickness of gastric mucosa. Furthermore, network pharmacology and molecular docking were used to predict the regulatory mechanism and main active components of ZJP in CAG treatment. RT-PCR, immunohistochemistry, immunofluorescence and Western blotting were used to measure the expression levels of apoptosis-related proteins, gastric mucosal barrier-associated proteins and PI3K/Akt signaling pathway proteins. Results The results demonstrated that ZJP significantly improved the general state of CAG rats, alleviated weight loss and gastric histological damage and reduced the serum biochemical indicators. Network pharmacology and molecular docking found that ZJP in treating CAG by inhibiting inflammation, suppressing apoptosis, and protecting the gastric mucosal barrier via the PI3K/Akt signaling pathway. Further experiments confirmed that ZJP obviously modulated the expression of key proteins involved in gastric mucosal cell apoptosis, such as Bax, Bad, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, Cytochrome C, Bcl-2, and Bcl-xl. Moreover, ZJP significantly reversed the protein expression of Occludin, ZO-1, Claudin-4 and E-cadherin. Conclusion Our study revealed that ZJP treats CAG by inhibiting the PI3K/Akt signaling pathway. This research provided a scientific basis for the rational use of ZJP in clinical practice.

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Section: Resultsmentioning

confidence: 99%

Integrated Approaches Revealed the Therapeutic Mechanisms of Zuojin Pill Against Gastric Mucosa Injury in a Rat Model with Chronic Atrophic Gastritis

Chen,

He,

Wang

et al. 2024

DDDT

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“…Docking parameter settings: Referring to the original ligand binding site in the file, get the molecular docking coordinates and the size of the docking box, [ 39 , 40 ] set num_modes to 20, exhaustiveness to 10, and other parameters to their default settings.…”

Section: Methodsmentioning

confidence: 99%

Exploring the potential mechanism of Taohong Siwu decoction in the treatment of avascular necrosis of the femoral head based on network pharmacology and molecular docking

Chen,

Song,

Qiu

et al. 2023

Medicine

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Based on network pharmacology and molecular docking, this study seeks to investigate the mechanism of Taohong Siwu decoction (THSWD) in the treatment of avascular necrosis of the femoral head (AVNFH). The Traditional Chinese Medicine Systems Pharmacology database was used in this investigation to obtain the active ingredients and related targets for each pharmaceutical constituent in THSWD. To find disease-related targets, the terms “avascular necrosis of the femoral head,” “necrosis of the femoral head,” “steroid-induced necrosis of the femoral head,” “osteonecrosis,” and “avascular necrosis of the bone” were searched in the databases DisGeNET, GeneCards, Comparative Toxicogenomics Database, and MalaCards. Following the identification of the overlap targets of THSWD and AVNFH, enrichment analysis using gene ontology, Kyoto Encyclopedia of Genes and Genomes, Reactome, and WikiPathways was conducted. The “THSWD-drug-active compound-intersection gene-hub gene-AVNFH” network and protein-protein interaction network were built using Cytoscape 3.9.1 and string, and CytoHubba was used to screen hub genes. The binding activities of hub gene targets and key components were confirmed by molecular docking. 152 prospective therapeutic gene targets were found in the bioinformatics study of ONFH treated with THSWD, including 38 major gene targets and 10 hub gene targets. The enrichment analysis of 38 key therapeutic targets showed that the biological process of gene ontology analysis mainly involved cytokine-mediated signaling pathway, angiogenesis, cellular response to reactive oxygen species, death-inducing signaling complex. The Kyoto Encyclopedia of Genes and Genomes signaling pathway mainly involves TNF signaling pathway, IL-17 signaling pathway, and the Recactome pathway mainly involves Signaling by Interleukins, Apoptosis, and Intrinsic Pathway for Apoptosis. WikiPathways signaling pathway mainly involves TNF-related weak inducer of apoptosis signaling pathway, IL-18 signaling pathway. According to the findings of enrichment analysis, THSWD cured AVNFH by regulating angiogenesis, cellular hypoxia, inflammation, senescence, apoptosis, cytokines, and cellular proliferation through the aforementioned targets and signaling pathways. The primary component of THSWD exhibits a strong binding force with the key protein of AVNFH. This study sheds new light on the biological mechanism of THSWD in treating AVNFH by revealing the multi-component, multi-target, and multi-pathway features and molecular docking mechanism of THSWD.

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6-Gingerol alleviates placental injury in preeclampsia by inhibiting oxidative stress via BNIP3/LC3 signaling-mediated trophoblast mitophagy

Li,

Zhao,

Yang

et al. 2023

Front. Pharmacol.

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Background and aims: Preeclampsia (PE) is the leading cause of maternal and fetal morbidity and mortality worldwide. Apoptosis of trophoblast cells induced by oxidative stress is a principal reason of placental injury in PE. 6-Gingerol, an antioxidant from ginger, plays an important role in many disease models, but its effect on obstetric diseases has not been elucidated. In this study, we investigated the protective effect of 6-gingerol against placental injury.Methods:In vitro hypoxia/reoxygenation (H/R) model of HTR8/Svneo cells and preeclamptic mice model were established to simulate PE. The effects of 6-Gingerol on PE were evaluated by morphological detection, biochemical analysis, and Western blot.Results: We found that H/R treatment induced cell apoptosis, increased the production of reactive oxygen species, malondialdehyde and lactate dehydrogenase, and decreased superoxide dismutase in trophoblast. In addition, the polarization of mitochondrial membrane potential and the cellular calcium flux were also destroyed under H/R condition, which also activated BCL2-interacting protein 3 (BNIP3) and provoked excessive mitophagy. Importantly, 6-Gingerol reversed these corrosive effects. Furthermore, the placenta damage in PE-like mouse caused by the cell apoptosis, oxidative stress and mitophagy was mitigated by 6-Gingerol.Conclusion: These findings suggest that 6-Gingerol exerts a protective effect against placental injury in PE by reducing oxidative stress and inhibiting excessive mitophagy caused by mitochondrial dysfunction.

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Mechanism exploration of 6-Gingerol in the treatment of atherosclerosis based on network pharmacology, molecular docking and experimental validation

Cited by 3 publications

References 54 publications

Integrated Approaches Revealed the Therapeutic Mechanisms of Zuojin Pill Against Gastric Mucosa Injury in a Rat Model with Chronic Atrophic Gastritis

Integrated Approaches Revealed the Therapeutic Mechanisms of Zuojin Pill Against Gastric Mucosa Injury in a Rat Model with Chronic Atrophic Gastritis

Exploring the potential mechanism of Taohong Siwu decoction in the treatment of avascular necrosis of the femoral head based on network pharmacology and molecular docking

6-Gingerol alleviates placental injury in preeclampsia by inhibiting oxidative stress via BNIP3/LC3 signaling-mediated trophoblast mitophagy

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