1β–OH–arenobufagin induces mitochondrial apoptosis in hepatocellular carcinoma through the suppression of mTOR signaling pathway

Deng, Lijuan; Lei, Yuhe; Quan, Jingyu; Li, Baojing; Zhang, Dongmei; Tian, Hai‐Yan; Chen, Ye; Zhang, Enxin; Chen, Lei; Ye, Wen‐Cai; Ning, Weimin; Yu, Linzhong; Liu, Junshan

doi:10.1016/j.jep.2020.113443

Cited by 15 publications

(10 citation statements)

References 37 publications

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“…e practice of active compound screening from TCM is an important strategy for drug discovery [52]. Natural products exert their pharmacological activity through various novel mechanisms [53].…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics and Network Pharmacology-Based Approaches to Explore the Potential Mechanism of the Antidepressant Effect of Cyperi Rhizoma through Soothing the Liver

Lei

Zhang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Major depressive disorder (MDD) has become the second most common disease worldwide, making it a threat to human health. Cyperi Rhizoma (CR) is a traditional herbal medicine with antidepressant properties. Traditional Chinese medicine theory states that CR relieves MDD by dispersing stagnated liver qi to soothe the liver, but the material basis and underlying mechanism have not been elucidated. In this study, we identified the active compounds and potential anti-MDD targets of CR by network pharmacology-based approaches. Through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, we hypothesized that the anti-MDD effect of CR may be mediated by an altered response of the liver to lipopolysaccharide (LPS) and glucose metabolism. Through bioinformatics analysis, comparing normal and MDD liver tissue in rats with spontaneous diabetes, we identified differentially expressed genes (DEGs) and selected PAI-1 (SERPINE1) as a target of CR in combating MDD. Molecular docking and molecular dynamics analysis also verified the binding of the active compound quercetin to PAI-1. It can be concluded that quercetin is the active compound of CR that acts against MDD by targeting PAI-1 to enhance the liver response to LPS and glucose metabolism. This study not only reveals the material basis and underlying mechanism of CR against MDD through soothing the liver but also provides evidence for PAI-1 as a potential target and quercetin as a potential agent for MDD treatment.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics and Network Pharmacology-Based Approaches to Explore the Potential Mechanism of the Antidepressant Effect of Cyperi Rhizoma through Soothing the Liver

Lei

Zhang

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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“…Deng et al found that 1β-OH-ABG from bufadienolides could inhibit the increased proliferation of hepatoma cell lines Hep3B, HepG2, HuH7 and SK-HEP-1, but had less cytotoxic effect on normal hepatocyte LO2. The mechanism was that 1β-OH-ABG could obviously reduce the expression levels of p-AKT/AKT and p-mTOR (Ser2248 and Ser2481)/mTOR in a time-dependent manner [ 24 ].…”

Section: Pharmacological Activities Of Bufadienolidesmentioning

confidence: 99%

Novel Strategies for Solubility and Bioavailability Enhancement of Bufadienolides

Shao

et al. 2021

Molecules

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Toad venom contains a large number of bufadienolides, which have a variety of pharmacological activities, including antitumor, cardiovascular, anti-inflammatory, analgesic and immunomodulatory effects.. The strong antitumor effect of bufadienolides has attracted considerable attention in recent years, but the clinical application of bufadienolides is limited due to their low solubility and poor bioavailability. In order to overcome these shortcomings, many strategies have been explored, such as structural modification, solid dispersion, cyclodextrin inclusion, microemulsion and nanodrug delivery systems, etc. In this review, we have tried to summarize the pharmacological activities and structure–activity relationship of bufadienolides. Furthermore, the strategies for solubility and bioavailability enhancement of bufadienolides also are discussed. This review can provide a basis for further study on bufadienolides.

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“…Chansu injection is a prescription Chinese medicine, its main component is a derivative of indole base, and this product is a colorless to light yellow clear liquid, often used for clearing heat and detoxifying effect. It fights inflammation and infection and regulates immunity [ 20 , 21 ]. Chansu injection is now being widely administered to inhibit bacteria, fight viruses, suppress pain, reduce inflammation, inhibit the proliferation of tumor cells, increase the patient's albumin level after radiochemical therapy, and induce tumor cell apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Material Basis and Mechanism of Chansu Injection for COVID-19 Treatment Based on Network Pharmacology and Molecular Docking Technology

Peng

Han

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Purpose. The clinical efficacy of Chansu injection for COVID-19 treatment has been confirmed. Its mechanism of action remains unclear. We used network pharmacology and molecular docking technology to explore the potential material basis and mechanism of action of Chansu injection for COVID-19. Methods. The main components of Chansu injection were determined using HPLC. The PharmMapper, SwissTargetPrediction, SEA, and TCMID databases were used to screen for the active ingredients and therapeutic targets of Chansu injection, while the OMIM and GeneCards Suite databases were used to search for COVID-19-related targets. The STRING database was used for protein-protein interaction (PPI) network construction and topological analysis, while DAVID was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the core targets. The main active compounds of Chansu injection were docked with 3CL protease, ACE2, RdRp, and spike protein. Results. The three Chansu injection compounds were identified using HPLC. A total of 236 drug-related targets and 16,611 disease-related targets were identified, and 77 common targets were determined through mapping. The PPI mapping results revealed that 16 core targets were obtained through topological analysis and screening. Furthermore, GO and KEGG pathway enrichment analyses revealed that the PI3K and JAK-STAT signaling pathways are the major pathways. The molecular docking results suggest that the three Chansu injection components have high binding energies to the S protein. Conclusions. The potential mechanism of Chansu injection for COVID-19 involves multiple targets and pathways, thereby providing a scientific basis for its clinical application and further research.

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1β–OH–arenobufagin induces mitochondrial apoptosis in hepatocellular carcinoma through the suppression of mTOR signaling pathway

Cited by 15 publications

References 37 publications

Bioinformatics and Network Pharmacology-Based Approaches to Explore the Potential Mechanism of the Antidepressant Effect of Cyperi Rhizoma through Soothing the Liver

Bioinformatics and Network Pharmacology-Based Approaches to Explore the Potential Mechanism of the Antidepressant Effect of Cyperi Rhizoma through Soothing the Liver

Novel Strategies for Solubility and Bioavailability Enhancement of Bufadienolides

Material Basis and Mechanism of Chansu Injection for COVID-19 Treatment Based on Network Pharmacology and Molecular Docking Technology

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