Cycloastragenol

Psoriasis is a prevalent chronic skin disease. Cycloastragenol (CAG) has been shown to activate autophagy and alleviate epidermal keratinocyte hyperproliferation in psoriasis. This study aimed to clarify the mechanism of CAG‐mediated autophagy in psoriasis‐like models. We treated C57BL/6 mice with imiquimod cream and stimulated HaCaT cells with a cytokine mixture (C‐mix) to establish mouse and cell models. Psoriasis area and severity index scores were used to evaluate pathological changes. Autophagy flux was monitored using a monomeric red fluorescent protein–green fluorescent protein–microtubule‐associated protein 1 light chain 3 assay. The interaction between sirtuin 1 (SIRT1) and zinc finger containing Krüppel‐associated box and SCAN domain 3 (ZKSCAN3), as well as ZKSCAN3 acetylation, was examined using co‐immunoprecipitation. Our results found that CAG alleviated autophagy inhibition in the imiquimod‐induced psoriasis‐like mouse model and enhanced autophagy by upregulating SIRT1 expression. ZKSCAN3 inhibited autophagy in the C‐mix‐stimulated psoriasis‐like cellular model, while SIRT1 reduced the nuclear localization of ZKSCAN3 through deacetylation. ZKSCAN3 overexpression reversed SIRT1‐mediated autophagy enhancement, whereas CAG promoted autophagy by regulating the nuclear localization of ZKSCAN3. In conclusion, our findings demonstrate that CAG ameliorates autophagy inhibition by modulating the SIRT1/ZKSCAN3 axis in psoriasis.

In order to treat chronic atrophic gastritis (CAG) caused by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), the present study successfully fabricated a carboxymethyl chitosan (CMC)-silk fibroin (SF) hydrogel encapsulating cycloastragenol (Cyl) and sucralfate (SC) (Cyl-SC@SF/CMC). This represents a substantial improvement in drug delivery and therapeutic efficacy. The SEM analysis shows the porosity of fabricated Cyl-SC@SF/CMC revealed a network of pores inside the hydrogel. Thermogravimetric and rheological investigations confirmed that the hydrogel was the structure of SF and CFC forming intermolecular hydrogen bonds. A model was developed to stimulate the impact of MNNG on gastric epithelial cells. Furthermore, cell counting kit-8 (CCK-8) assay was employed to evaluate the viability and proliferation of MNNG induced CAG in GES-1 after exposed to fabricated Cyl-SC@SF/CMC hydrogels. The results displayed that Cyl-SC@SF/CMC is superior than SC@SF/CMC in promoting the growth of GES-1 cells while simultaneously reducing MNNG-triggered damage to GES-1 cells and mitochondrial dysfunction. Moreover, cell migration and invasion analysis revealed that Cyl-SC@SF/CMC significantly enhanced migration and suggesting its role in tissue repair and regeneration. Moreover, in CAG rats, Cyl and SC in the hydrogel exerted therapeutic effects by considerably reducing histological damage in gastric tissues as evidenced by histopathological examinations. Furthermore, the pharmacokinetics analysis showed that Cyl-SC@SF/CMC formulation exhibited a higher area under the curve (AUC_0-t) and longer mean residence time (MRT) in both blood and gastric tissues compared to SC@SF/CMC, suggesting enhanced therapeutic efficacy. Due to the importance of tumor-induced angiogenesis in the advancement of inflammation and malignance, this study also examines the levels of mRNA and protein expression of the HIF-1α and VEGF signaling pathways in vivo using Western blot qRT-PCR analysis.