Bibliometric Analysis and Systemic Review of Cantharidin Research Worldwide.

BACKGROUND: Cantharidin (CTD), a natural toxic compound from blister beetle Mylabris, has been used for cancer treatment for millenary. CTD and its analogs have become mainstream adjuvant drugs with radiotherapy and chemotherapy in clinical applications. However, the detailed pharmacology mechanism of CTD was not fully elucidated. METHODS: Publications of CTD were collected from the Web of Science Core Collection database from 1991 to 2023 using CiteSpace, VOSviewer, and Scimago Graphica software. RESULTS: A total of 1,611 publications of CTD were mainly published in China and the United States. The University of Newcastle has published the most researches. Mcclusey, Adam, Sakoff, Jennette, and Zhang, Yalin had the most CTD publications with higher H. Notably, CTD researches were mainly published in Bioorganic & Medicinal Chemistry Letters and the Journal of Biological Chemistry. Cluster profile results revealed that protein phosphatase 2A (PP2A), human gallbladder carcinoma, Aidi injection, and cell apoptosis were the hotspots. Concentration on the pharmacology function of PP2A subunit regulation, hepatotoxicity, nephrotoxicity, and cardiotoxicity mechanism should be strengthened in the future. CONCLUSION: Bibliometric analysis combined with a systemic review of CTD research first revealed that PP2A and CTD analogs were the knowledge base of CTD, and PP2A subunit regulation and toxic mechanism could be the frontiers of CTD.

Integration of metabolomics and network pharmacology to reveal the protective mechanism underlying Wogonoside in acute myocardial ischemia rats.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional medicine, both Scutellaria baicalensis Georgi (SBG) and the traditional formulas composed of it have been used to treat a wide range of diseases, including cancer and cardiovascular. Wogonoside (Wog) is the biologically active flavonoid compound extracted from the root of SBG, with potential cardiovascular protective effects. However, the mechanisms underlying the protective effect of Wog on acute myocardial ischemia (AMI) have not yet been clearly elucidated. AIM OF THE STUDY: To explore the protective mechanism of Wog on AMI rats by comprehensively integrating traditional pharmacodynamics, metabolomics, and network pharmacology. METHODS: The rat was pretreatment with Wog at a dose of 20 mg/kg/d and 40 mg/kg/d once daily for 10 days and then ligated the left anterior descending coronary artery of rats to establish the AMI rat model. Electrocardiogram (ECG), cardiac enzyme levels, heart weight index (HWI), Triphenyltetrazolium chloride (TTC) staining, and histopathological analyses were adopted to evaluate the protective effect of Wog on AMI rats. Moreover, a serum metabolomic-based UHPLC-Q-Orbitrap MS approach was performed to find metabolic biomarkers and metabolic pathways, and network pharmacology analysis was applied to predict targets and pathways of Wog in treating AMI. Then, the network pharmacology and metabolomic results were integrated to elucidate the mechanism of Wog in treating AMI. Finally, RT- PCR was used to detect the mRNA expression levels of PTGS1, PTGS2, ALOX5, and ALOX15 to validate the result of integrated metabolomics and network analysis. RESULTS: Pharmacodynamic studies suggest that Wog could effectively prevent the ST-segment of electrocardiogram elevation, reduce the myocardial infarct size, heart weight index, and cardiac enzyme levels, and alleviate cardiac histological damage in AMI rats. Metabolomics analysis showed that the disturbances of metabolic profile in AMI rats were partly corrected by Wog and the cardio-protection effects on AMI rats involved 32 differential metabolic biomarkers and 4 metabolic pathways. In addition, the integrated analysis of network pharmacology and metabolomics showed that 7 metabolic biomarkers, 6 targets, and 6 crucial pathways were the main mechanism for the therapeutic application of Wog for AMI. Moreover, the results of RT-PCR showed that PTGS1, PTGS2, ALOX5, and ALOX15 mRNA expression levels were reduced after treatment with Wog. CONCLUSION: Wog exerts cardio-protection effects on AMI rats via the regulation of multiple metabolic biomarkers, multiple targets, and multiple pathways, our current study will provide strong scientific evidence supporting the therapeutic application of Wog for AMI.