Shuganning Injection Suppresses Apoptosis for Protecting Against Cantharidin-Induced Liver Injury by Network Pharmacology and Experiment Validation.

Cantharidin (CTD) is a compound of mylabris with antitumor activity, and CTD can potentially cause toxicity, especially hepatotoxicity. The classical Traditional Chinese Medicine prescription Shuganning injection (SGNI) exerts notable anti-inflammatory and hepatoprotective effects. However, the protective property and mechanism of SGNI against CTD-induced liver injury (CTD-DILI) have not yet been elucidated. To investigate the effective compounds, potential targets, and molecular mechanism of SGNI against CTD-DILI, network pharmacology combined with experiments were performed. This study found that SGNI could act with 62 core therapeutic targets, regulate multiple biological processes such as apoptosis, and oxidative stress, and influence apoptotic and p53 signaling pathways to treat CTD-DILI. Subsequently, HepaRG cell experiments demonstrated that SGNI pretreatment significantly increased the levels of GSH-Px and SOD, inhibiting the apoptosis induced by CTD. In vivo, according to H&E staining, SGNI can reduce the degeneration of hepatocytes and cytoplasmic vacuolation in mice exposed to CTD. Western blot analysis results indicated that SGNI pretreatment significantly suppressed the expressions of Caspase-3 and Bax while increasing the expression of Bcl-2. In conclusion, SGNI acted as a protective agent against CTD-DILI by inhibiting apoptosis.

Bibliometric and visual analysis of nephrotoxicity research worldwide.

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.

Exploring the protective mechanisms of total tannins from Geum japonicum var. chinense F.Bolle in mice with hematopoietic dysfunction via the JAK2/STAT3/5 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Geum japonicum var. chinense F.Bolle (Rnglish name Gei herba, GH), a traditional Miao medicine, promotes hematopoiesis. Emerging evidence shows that total tannins of GH (TGH) can treat ischemic diseases. AIM OF THE STUDY: To explore the protective mechanism of TGH in hematopoietic dysfunction (HD) mice. MATERIALS AND METHOD: Forty-eight female mice were randomly assigned to 6 groups: control, model, Zhenqi Fuzheng positive, and three doses TGH. Cyclophosphamide was injected in mice to establish an HD model. Spleen tissue was examined histomorphologically, peripheral hemograms and organ index were calculated, and serum hematopoietic factor levels were determined. The expression of proteins in the Janus kinase 2 (JAK2)/transcription 3/5 (STAT3/5) pathway, as well as upstream and downstream proteins, was examined using western blot to elucidate the underlying protective mechanisms of TGH. RESULTS: TGH could effectively alleviate spleen tissue damage in HD mice, improve peripheral hemogram and antagonize organ atrophy, and increase levels of Granulocyte-macrophage Colony Stimulating Factor (GM-CSF) and Erythropoietin (EPO) in HD mouse serum. Furthermore, after TGH treatment, the protein expression levels of P-JAK2, P-STAT3, P-STAT5, M-CSF, G-CSF, Bcl-2, and Bcl-xL were significantly higher than in the model group. At the same time, following TGH treatment, the protein expression levels of LC3 A/B, Beclin1, ATG5, and ATG7 were significantly lower than in the model group. CONCLUSIONS: TGH has been shown to protect HD mice through a mechanism linked to the activation of the JAK2/STAT3/5 pathway, as well as autophagy inhibition and apoptosis activation.

Endoplasmic reticulum stress contributes to autophagy and apoptosis in cantharidin-induced nephrotoxicity.

Mylabris, as a natural product of traditional Chinese medicine (TCM), exhibiting typical antitumor activity, and cantharidin (CTD) is the major bioactive component. However, drug-induced nephrotoxicity (DIN) extremely limited its clinical application. In this study, we proved that activation of the endoplasmic reticulum (ER) stress-dependent PERK/CHOP pathway exerts a toxic role in rats and HK-2 cells through inducing autophagy and apoptosis. Results showed that CTD could cause renal function damage, cytotoxicity, and apoptosis. The ER dilatation and autolysosomes were observed after CTD treatment. Furthermore, the distribution of LC3, ATF4, and CHOP proteins was observed in the nucleus and cytoplasm. In addition, the mRNA levels of ER stress-regulated genes (PERK, eIF2α, CHOP, and ATF4) were increased, and the expression levels of GRP78, ATF4, CHOP, LC3, Beclin-1, Atg3, Atg7, Caspase 3, and Bax/Bcl-2 proteins were increased both in vitro and in vivo. Consistently, this upregulation could be inhibited by an ER stress inhibitor 4-Phenylbutyric acid (4-PBA), indicating that ER stress is partly responsible for activation of autophagy and apoptosis in CTD-induced DIN. In conclusion, CTD could induce DIN by triggering ER stress, further activating autophagy and apoptosis both in vivo and in vitro.