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Background: Cucurbita pepo cv Dayangua (CPD) is an edible plant with diverse pharmacological properties. The current research on CPD has primarily focused on initial investigations of its chemical composition and pharmacological effects, and no comprehensive toxicity assessment has been conducted to date. Methods: In the present study, the toxicity of CPD was evaluated through both acute and sub-chronic oral toxicity tests in mice. 16S rDNA sequencing was used to analyze the composition of the gut microbiota of mice at different time points to observe the effect of CPD on these microbial communities. Results: In the acute toxicity test, CPD exhibited low toxicity, with a median lethal dose (LD50) > 2000 mg/kg. The sub-chronic toxicity test indicated that CPD administration at doses of 200, 400, and 600 mg/kg did not cause mortality or significant organ damage in mice. Furthermore, analysis of the gut microbiota after gavage administration of CPD at 400 and 600 mg/kg revealed an improved abundance of some beneficial gut bacteria. Conclusions: In summary, no acute or sub-chronic toxic effects were observed in mice following the oral administration of CPD. CPD did not affect the structure and diversity of the gut microbiota and may contribute to an increase in the number of beneficial gut bacteria. [ABSTRACT FROM AUTHOR]

Background: Polygonum multiflorum (PM), a widely used traditional Chinese medicine herb, is divided into two forms, namely raw polygonum multiflorum (RPM) and polygonum multiflorum praeparata (PMP), according to the processing procedure. Emerging data has revealed the differential hepatotoxicity of RPM and PMP, however, its potential mechanism is still unclear. Methods: In our study, we investigated the differential hepatotoxicity of RPM and PMP exerted in C57BL/6 mice. First, sera were collected for biochemical analysis and HE staining was applied to examine the morphological alternation of the liver. Then we treated L02 cells with 5 mg / mL of RPM or PMP. The CCK8 and EdU assays were utilized to observe the viability and proliferation of L02 cells. RNA sequencing was performed to explore the expression profile of L02 cells. Western blotting was performed to detect the expression level of ferroptosis-related protein. Flow cytometry was used to evaluate ROS accumulation. Results: In our study, a significant elevation in serum ALT, AST and TBIL levels was investigated in the RMP group, while no significant differences were observed in the PMP group, compared to that of the CON group. HE staining showed punctate necrosis, inflammatory cell infiltration and structural destruction can be observed in the RPM group, which can be significantly attenuated after processing. In addition, we also found RPM could decrease the viability and proliferation capacity of L02 cells, which can be reversed by ferroptosis inhibitor. RNA sequencing data revealed the adverse effect of PM exerted on the liver is closely associated with ferroptosis. Western blotting assay uncovered the protein level of GPX4, HO-1 and FTL was sharply decreased, while the ROS content was dramatically elevated in L02 cells treated with RPM, which can be partially restored after processing. Conclusions: The hepatotoxicity induced by RPM was significantly lower than the PMP, and its potential mechanism is associated with ferroptosis. [ABSTRACT FROM AUTHOR]

Doxorubicin (DOX) is a powerful anthracycline antineoplastic drug used to treat a wide spectrum of tumors. However, its clinical application is limited due to cardiotoxic side effects. Astragaloside IV (AS IV), one of the major compounds present in aqueous extracts of Astragalus membranaceus, possesses potent cardiovascular protective properties, but the underlying molecular mechanisms are unclear. Thus, the aim of this study was to investigate the effect of AS IV on DOX-induced cardiotoxicity (DIC). Our findings revealed that DOX induced pyroptosis through the caspase-1/gasdermin D (GSDMD) and caspase-3/gasdermin E (GSDME) pathways. AS IV treatment significantly improved the cardiac function and alleviated myocardial injury in DOX-exposed mice by regulating intestinal flora and inhibiting pyroptosis; markedly suppressed the levels of cleaved caspase-1, N-GSDMD, cleaved caspase-3, and N-GSDME; and reversed DOX-induced downregulation of silent information regulator 1 (SIRT1) and activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome in mice. The SIRT1 inhibitor EX527 significantly blocked the protective effects of AS IV. Collectively, our results suggest that AS IV protects against DIC by inhibiting pyroptosis through the SIRT1/NLRP3 pathway. [ABSTRACT FROM AUTHOR]

[Display omitted] • SiNiSan exerts therapeutic effects on adolescent depression caused by stress in early life and adolescence. • SiNiSan downregulates N-methyl-D-aspartic acid (NMDA) receptor expression and regulates serotonergic/GABAergic neuron activity in theDRN region of adolescent depression models. • SiNiSan regulates neuronal activity by downregulating NMDA receptors in DRN of adolescent depression models. [ABSTRACT FROM AUTHOR]