The diagnosis and treatment of chronic glomerulonephritis (CGN) during childhood pose distinct challenges. Acteoside (ACT) is the primary active ingredient extracted from the leaves of Rehmannia glutinosa by our research group, accounting for 2.15 %, which possess multiple biological activities, especially for nephropathy treatment. However, its mechanism intervention on CGN in children remains obscure. In this study, we established a model of purinomycin aminonucleoside (PAN)-induced CGN in childhood rats to assess the potential therapeutic effect and underlying mechanisms of ACT. Leveraging network pharmacology and multi-omics technology, we delved into the effects and mechanisms of ACT intervention on CGN. And these findings were further corroborated through qRT-PCR, western blot and targeted metabolomics. Our results demonstrated that ACT had significantly efficient in the treatment of CGN in childhood rats by improving the key indicators and pathological changes. Further, ACT could significantly regulate differences in endogenous small molecules and genes based on non-target metabolomics and transcriptomics. Meanwhile, target capture analysis found the crucial targets of ACT treatment in CGN. Integrated analysis of multi-omics study indicated that PI3K/Akt signaling pathway and its downstream amino acid metabolism were significantly enriched, hinting at the essential regulatory pathway for ACT in treating of CGN. Finally, through qRT-PCR, western blot and targeted metabolomics, it was verified that ACT could ameliorate CGN through Cxcr4-PI3K-Akt-eNOS signaling pathway, thereby regulating amino acid metabolism. The collective results were consistent with those of multi-omics analysis. Our study illuminated that ACT had notable curative effect on CGN rats, and preliminarily elucidated its mechanism of action. Our research will provide solid basis for the treatment of chronic glomerulonephritis in children with ACT and developing it into innovative traditional Chinese medicine.
For the surgical treatment of cardiovascular disease (CVD), there is a clear and unmet need in developing small-diameter (diameter < 6 mm) vascular grafts. In our previous work, sulfated silk fibroin (SF) was successfully fabricated as a potential candidate for preparing vascular grafts due to the great cytocompatibility and hemocompatibility. However, vascular graft with single layer is difficult to adapt to the complex internal environment. In this work, polycaprolactone (PCL) and sulfated SF were used to fabricate bilayer vascular graft (BLVG) to mimic the structure of natural blood vessels. To enhance the biological activity of BLVG, nicorandil (NIC), an FDA-approved drug with multi-bioactivity, was loaded in the BLVG to fabricate NIC-loaded BLVG. The morphology, chemical composition and mechanical properties of NIC-loaded BLVG were assessed. The results showed that the bilayer structure of NIC-loaded BLVG endowed the graft with a biphasic drug release behavior. The in vitro studies indicated that NIC-loaded BLVG could significantly increase the proliferation, migration and antioxidation capability of endothelial cells (ECs). Moreover, we found that the potential biological mechanism was the activation of PI3K/AKT/eNOS signaling pathway. Overall, the results effectively demonstrated that NIC-loaded BLVG had a promising in vitro performance as a functional small-diameter vascular graft.
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