Biochimica et biophysica acta. General subjects · 2026
SSD: Targeting inflammasome and oxidative stress as a therapeutic strategy in inflammatory diseases.
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Zhao Yukai, Fu Xinyu, Zuo Hongli, Wang Xiuqin, Li Sai, Wu Ting, Cheng Cheng, Xu Minghao, Xu Guanglin
Аннотация
OBJECTIVE AND DESIGN: This study systematically investigated the therapeutic efficacy of SSD, a stigmasterol derivative with H₂S-releasing properties, against NLRP3 inflammasome activation using both in vitro and in vivo models.
MATERIALS: Male FPS KM mice were utilized to establish acute liver injury and myocardial fibrosis models. THP-1 and J774A.1 cell lines served for in vitro analyses, while zebrafish models were employed to assess oxidative stress responses.
TREATMENT: SSD was administered through oral gavage at 25-100 mg/kg (acute liver injury) or 15-60 mg/kg/day (cardiac fibrosis models, daily for 7 days). In vitro experiments applied SSD at concentrations ranging from 2 to 8 μM.
METHODS: Key methodologies encompassed histopathological analysis (H&E/Masson staining), serum ALT/AST quantification, Western blot for IL-1β/caspase-1 profiling, molecular docking simulations, cellular thermal shift assays (CETSA), and ROS detection via DCFH-DA probes. Statistical analysis was performed using one-way ANOVA.
RESULTS: SSD treatment markedly attenuated acute hepatic injury and cardiac collagen deposition. Molecular docking simulations identified direct SSD-NLRP3 binding, a finding corroborated by CETSA. SSD dose-dependently suppressed NLRP3-associated protein expression and gene transcription across hepatic, cardiac, and macrophage models, while significantly mitigating oxidative stress in both cellular and organismal systems.
CONCLUSIONS: SSD dually inhibits NLRP3 via direct targeting and oxidative stress modulation, demonstrating therapeutic potential for NLRP3-driven inflammation.
MATERIALS: Male FPS KM mice were utilized to establish acute liver injury and myocardial fibrosis models. THP-1 and J774A.1 cell lines served for in vitro analyses, while zebrafish models were employed to assess oxidative stress responses.
TREATMENT: SSD was administered through oral gavage at 25-100 mg/kg (acute liver injury) or 15-60 mg/kg/day (cardiac fibrosis models, daily for 7 days). In vitro experiments applied SSD at concentrations ranging from 2 to 8 μM.
METHODS: Key methodologies encompassed histopathological analysis (H&E/Masson staining), serum ALT/AST quantification, Western blot for IL-1β/caspase-1 profiling, molecular docking simulations, cellular thermal shift assays (CETSA), and ROS detection via DCFH-DA probes. Statistical analysis was performed using one-way ANOVA.
RESULTS: SSD treatment markedly attenuated acute hepatic injury and cardiac collagen deposition. Molecular docking simulations identified direct SSD-NLRP3 binding, a finding corroborated by CETSA. SSD dose-dependently suppressed NLRP3-associated protein expression and gene transcription across hepatic, cardiac, and macrophage models, while significantly mitigating oxidative stress in both cellular and organismal systems.
CONCLUSIONS: SSD dually inhibits NLRP3 via direct targeting and oxidative stress modulation, demonstrating therapeutic potential for NLRP3-driven inflammation.