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Paederus, belonging to the Coleoptera and Staphylinidae, can prevent cell mitosis and inhibit tumors. However, few studies exist on the mechanism of Paederus on inhibiting the growth of tumors. Consequently, the present study used network pharmacology, molecular docking and in vitro experiments explore the anti-Hepatocellular Carcinoma (HCC) mechanism of Paederus. Methods: Network pharmacology was used to predict the potential mechanisms through which Paederus acts against HCC. Therefore, the active compounds of Paederus were retrieved from the CNKI, Wanfang, PubMed and Web of Science databases. The targets for the active compounds were obtained from the Targetnet database, then the common targets and signaling pathways were obtained by Protein-protein interaction (PPI) network analysis, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. Thereafter, the compound-target and target-pathway networks were constructed. Finally, in vitro experiments using the SMMC-7721 HCC cells were used to further verify the predicted anti-HCC mechanism of Paederus. Results: The study screened 40 active compounds from Paederus, and 26 targets related to the anti-HCC mechanism of Paederus were predicted through network pharmacology. These targets were involved in the Nod-like receptor, MAPK, PI3K- Akt, TNF and AMPK signaling pathways. In addition, cell experiments showed that Paederus reduce the proliferation rate of SMMC-7721 HCC cells. Moreover, Paederus could down-regulated the expressions of the HSP90AA1, IRAK-4 and CTSB proteins in the Nod-like receptor signaling pathways in SMMC-7721 HCC cells. Conclusion: The study revealed the potential mechanism through which Paederus acts against HCC by combining network pharmacology, molecular docking, and experimental verification.

Cantharidin (CTD) is a principal bioactive component of traditional Chinese medicine Mylabris used in cancer treatment. However, CTD clinical application is limited due to nephrotoxicity, and the mechanism is unknown. The present study used widely-targeted metabolomics, network pharmacology, and cell experiments to investigate the nephrotoxicity mechanism after CTD exposure. In mice exposed to CTD, serum creatinine and urea nitrogen levels increased with renal injury. Then, 74 differential metabolites were detected, including 51 up-regulated and 23 down-regulated metabolites classified as amino acids, small peptides, fatty acyl, arachidonic acid metabolite, organic acid, and nucleotides. Sixteen metabolic pathways including tyrosine, sulfur, and pyrimidine metabolism were all disrupted in the kidney. Furthermore, network pharmacology revealed that 258 metabolic targets, and pathway enrichment indicated that CTD could activate oxidative phosphorylation and oxidative stress (OS). Subsequently, HK-2 cell experiments demonstrated that CTD could reduce superoxide dismutase while increasing malondialdehyde levels. In conclusion, after CTD exposure, biometabolic processes may be disrupted with renal injury in mice, resulting in oxidative phosphorylation and OS. [ABSTRACT FROM AUTHOR]

Cantharidin (CTD) is the major bioactive compound in Mylabris and has been shown to exhibit antitumor activity. However, its clinical application is relatively limited due to its potential toxic effects, especially nephrotoxicity. In this study, a UHPLC-QE/MS based metabolomics approach combined with network pharmacology was used to investigate the mechanism of CTD-induced nephrotoxicity in HK-2 cells. A total of 76 potential biomarkers and 28 disturbed metabolic pathways were identified in HK-2 cells exposed to CTD. And apoptotic protein expression levels of Caspase 3 and Bax/Bcl-2 ratio were increased in HK-2 cells exposed to CTD. In addition, combined with integrative network pharmacology analysis, the results demonstrated that CTD inhibits the glycerophospholipid and sphingolipid pathways, phosphatidylethanolamine, phosphatidylcholine, MAPK3, and PLD2. These may represent potential diagnostic markers and therapeutic targets, and may also lead to a strategy for reducing CTD-induced toxicity in the clinic. Image 1 • An integrative strategy was proposed for screening putative biomarkers based on metabolomics integrated with network pharmacology. • Potential association between biomarkers and targets was identified through the integrated strategy, for verifying the accuracy of biomarkers. • Cantharidin inhibits the glycerophospholipid, sphingolipid pathways, phosphatidylethanolamine, phosphatidylcholine, MAPK3, and PLD2 in HK-2 cells. [ABSTRACT FROM AUTHOR]

Cantharidin (CTD) is a widely used anticancer compound, but its clinical use is mainly limited due to hepatotoxicity. Ginsenoside Rb1 (GRb1) shows potential hepatoprotective effects. Nonetheless, the protective effect and underlying mechanism of GRb1 against CTD-induced hepatotoxicity in mice have not been investigated. This study aims to elucidate the effect and mechanism of GRb1 on CTD-induced hepatotoxicity using network pharmacology and in vivo experiments. Network pharmacology studies have shown that 263 targets were the main mechanisms by which GRb1 alleviates CTD-induced hepatotoxicity. KEGG enrichment analysis revealed that 75 hub genes were mainly enriched in TNF, IL-17 and apoptosis signalling pathways. Molecular docking analysis showed that GRb1 exhibited high affinity with Akt1, Tnf, Il6, Bcl2 and Caspase3. In addition, results from animal studies demonstrated that GRb1 could ameliorate CTD-induced hepatotoxicity by inhibiting protein expression of Caspase-3, Caspase-8, Bcl-2/Bax, GRP78, ATF6, ATF4, CHOP, IRE1α and PERK. This research revealed the mechanism of GRb1 against CTD-induced hepatotoxicity by inhibiting apoptosis and endoplasmic reticulum stress (ERS) and it may provide a scientific rationale for the potential use of GRb1 in the treatment of hepatotoxicity induced by CTD., (© 2024 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.)

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., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Dendrobium nobile Lindl. (DNL) is effective for the treatment of alcoholic liver disease (ALD), but the underly mechanism is still unclear., Objectives: This research aimed to investigate the effects and mechanism of the aqueous extract of Dendrobium nobile Lindl (AEDNL) in ALD rats based on a metabolomics approach., Materials and Methods: In this study, 18 Sprague-Dawley male rats were randomly divided into control, model, and AEDNL groups (n=six). Rats in the AEDNL group were given AEDNL (152 mg/kg) intragastric administration from the first day for 30 consecutive days. From day 15 to day 30, model and AEDNL groups were given 30% ethanol (10 ml/kg) after 4 h of daily administration. Then, serum and liver samples were collected for biochemical analysis, histopathological examination, and Ultra Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry (UPLC-Q-TOF/MS) determination for metabolomic analysis., Results: Compared with the model group, the liver/body weight index and serum levels of TC, LDL-C, and TBIL in the AEDNL group were significantly decreased. Hepatocyte cord arrangement, hepatocyte balloon, and fat vacuolization were significantly improved in the AEDNL group. Metabolism profiles were changed in the model and AEDNL groups. Seven and two common differential metabolites (Guanosine3',5'-cyclic monophosphate, and Glutaric acid) were found in serum and liver, respectively. In addition, the hepatoprotective effect of AEDNL on ALD was related to steroid hormone biosynthesis, riboflavin metabolism, and glycerophospholipid metabolism., Conclusion: The research could provide novel evidence of the protective effects of AEDNL on ALD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Nephrotoxicity of drugs contributes to acute kidney injury with high mortality and morbidity, which crucially limits the application and development of drugs. Although many publications on nephrotoxicity have been conducted globally, there needs to be a scientometric study to systematically analyze the intellectual landscape and frontiers research trends in the future. Methods: Publications on nephrotoxicity from 2011 to 2021 were collected to perform bibliometric visualization using VOSviewer, CiteSpace, and Scimago Graphica software based on the Web of Science Core Collection. Results: A total of 9,342 documents were analyzed, which were primarily published in the United States (1,861), China (1,724), and Egypt (701). For institutions, King Saud University (166) had the most publications; Food and Chemical Toxicology, PLOS One, and Antimicrobial Agents and Chemotherapy were productive journals, primarily concentrating on the mechanisms of nephrotoxicity and renoprotective in cisplatin and antibiotics, especially in oxidative stress. Burst detection suggested that cisplatin, piperacillin-tazobactam, vancomycin-induced nephrotoxicity, antioxidants, and new biomaterials are frontiers of research. Conclusion: This study first provides an updated perspective on nephrotoxicity and renoprotective strategies and mechanisms. This perspective may benefit researchers in choosing suitable journals and collaborators and assisting them in the deep understanding of the nephrotoxicity and renoprotective hotspots and frontiers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 He, Ao, Duan, Yan, Li, Liu, Zhang and Li.)