Objective: To investigate the mechanisms underlying the renoprotective effects of celastrol, a bioactive compound extracted from the traditional Chinese medicinal plant Tripterygium wilfordii in diabetic kidney disease (DKD).
Methods: We established a DKD model using db/db mice and investigated the protective mechanisms of celastrol against DKD progression using integrated analysis of 16S rRNA sequencing and transcriptome analysis. We evaluated colon tissue damage using hematoxylin and eosin and immunofluorescence staining. In addition, 16S rRNA sequencing and transcriptomic analyses were performed to explore the potential mechanisms of celastrol. Immunofluorescence staining, Western blotting and real-time quantitative polymerase chain reaction analysis were performed to confirm the PPAR signaling pathway related proteins in kidney tissues.
Results: Celastrol alleviated colon injury and increased the expression of mucosal barrier markers, particularly occludin and zonula occludens-1. The 16S rRNA gene sequencing analysis demonstrated that treatment with celastrol altered the diversity and abundance of the gut microbiota. Spearman’s correlation analysis further revealed significant associations among gut microbial, renal injury markers, and serum lipid profiles. A subsequent renal transcriptome analysis revealed that celastrol significantly modulated the renal transcriptional landscape, primarily by regulating genes associated with the PPAR signaling pathway and lipid metabolism. Further investigations demonstrated that celastrol significantly downregulated adipose differentiation-related protein expression and attenuated DKD progression by activating the PPAR pathway.
Conclusions: This study demonstrates that celastrol alleviates both colonic and renal injuries by modulating the gut-kidney axis through PPAR-mediated lipid metabolism regulation, indicating its potential as a therapeutic approach for DKD management.
Objective: To evaluate the expression of IL-10 in mice immunized with a recombinant BCG expressing the MSP1C antigen (BCG- MSP1C), in the presence and absence of a TLR4 agonist CRX-527.
Methods: The BCG-MSP1C vaccine candidate was cultured and characterized using acid-fast staining and field-emission scanning electron microscopy. The mice were immunized with BCG-MSP1C in the presence or absence of CRX-527 intraperitoneally. The expression and production of IL-10 were measured via real-time PCR and ELISA in peritoneal macrophages, spleen, liver, and lymph nodes of immunized mice.
Results: IL-10 expression and production were significantly increased in peritoneal macrophages and lymph nodes in the presence of CRX-527. In contrast, spleen and liver samples showed a significant decrease in IL-10 levels with CRX-527.
Conclusions: BCG-MSP1C shows promise as a malaria vaccine candidate by inducing IL-10 expression in multiple immune compartments and displaying stable morphology. Tissue-specific modulation of IL-10 by CRX-527 results in increased expression in the lymph nodes and peritoneal macrophages, and decreased levels in the liver and spleen.
Objective: To assess the hepatoprotective effects of methanolic extract of Lagerstroemia indica leaves on carbon tetrachloride (CCl4)-induced liver damage in rats.
Methods: Fifty male Sprague Dawley rats were divided into five groups: the normal control, the CCl4 group, the CCl4 group treated with silymarin (200 mg/kg) or Lagerstroemia indica extract (200 and 400 mg/kg). Oxidative stress, inflammatory, and apoptotic markers, as well as liver enzymes were analyzed. Histopathological studies were performed to examine the effect of the plant extract on liver structure. In addition, quantitative RT-PCR analysis was carried out to determine Nrf2, Keapl, HMOX1, and NQO1 expression.
Results: Lagerstroemia indica extract significantly improved liver function by reducing aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and bilirubin levels. It also enhanced the activities of catalase, superoxide dismutase, and glutathione peroxidase, increased glutathione content, and reduced the levels of malondialdehyde, nuclear factor kappa-B, tumor necrosis factor-α, interleukin-1β, interleukin-6, cyclooxygenase-2, Bax, caspase-3 and caspase-9. In addition, the mRNA expression levels of Nrf2, Keapl, HMOX1, and NQO1 were markedly downregulated by treatment with Lagerstroemia indica extracts. Histopathological examination revealed the extract confered protection against CCl4-induced liver damage as evidenced by reduced sinusoidal dilatation, thinner fibrotic septa, decreased vacuolar degeneration, and improved hepatic cord organization.
Conclusions: Lagerstroemia indica extract possesses hepatoprotective activity by modulating the Nrf2-Keap1-HMOX1-NQO1 signaling pathway in a rat model of CCl4-induced liver damage.
Objective: To synthesize nanoformulated naringenin (NF-n) and evaluate its anti-angiogenic and anticancer activities.
Methods: NF-n was synthesized using the solvent evaporation method and characterized by dynamic light scattering, Fourier transform infrared spectroscopy, and scanning electron microscopy. Molecular docking studies were performed to assess NF-n’s binding affinity to vascular endothelial growth factor (VEGF). In vitro assays using HUVEC and MCF-7 cell lines were conducted to evaluate cytotoxicity and cell migration inhibition. The mRNA expression levels of angiogenesis- and inflammation-related markers (nestin, NRP-1, NRP-2, CD93, IL-1β, TNF-α, NF-κB, and Bcl-2) were quantified via RT-PCR. The anti-angiogenic effect of NF-n was further investigated using the chick chorioallantoic membrane assay.
Results: Molecular docking revealed effective binding of naringenin to VEGF. NF-n demonstrated significantly reduced particle size and improved physicochemical properties. In in vitro studies, NF-n reduced cell viability and inhibited migration in both HUVEC and MCF-7 cells. RT-PCR analysis showed that NF-n significantly downregulated pro-angiogenic and inflammatory markers. Furthermore, NF-n significantly decreased blood vessel density, total branching points, and vessel length in heparin-induced chick chorioallantoic membrane.
Conclusions: NF-n exhibits anti-angiogenic and anticancer properties, positioning it as a promising candidate for therapeutic application in cancer and other pathological conditions involving abnormal angiogenesis. Further preclinical studies are recommended to explore its translational potential.