- Coixol markedly reduces serum ALT, AST and triglycerides, and improves hepatic histopathology and lipid accumulation in ethanol-induced ALD mice.
- Mechanistically, Coixol upregulates SIRT6 and suppresses pyroptosis, apoptosis, necroptosis and NETosis, decreasing NLRP3, GSDMD, caspase-1, -3, -9 and P-MLKL.
- SIRT6 deficiency reduces Coixol's hepatoprotective effects in ethanol-activated primary hepatocytes, indicating SIRT6 dependency and therapeutic potential against ALD.
Nat Prod Res. 2026 Oct 29:1-5. doi: 10.1080/14786419.2026.2752030. Online ahead of print.
ABSTRACT
Coixol, a benzoxazolinone from Coix seeds, exhibits anti-inflammatory and hepatoprotective effects. This study investigated its protection against alcohol-associated liver disease (ALD) and mechanisms. Twenty-four male C57BL/6 mice were randomly allocated into four groups (n = 6): Control, EtOH, EtOH + Coixol (25 or 50 mg/kg, oral gavage). In vitro, primary mouse hepatocytes were treated with EtOH ± Coixol (25 or 50 μM). In vivo and in vitro, SIRT6 and programmed responses (pyroptosis, apoptosis, necroptosis) were involved in EtOH-induced injury. Coixol significantly reduced serum ALT (216.2 ± 40.21 to 98.6 ± 25.5 U/L), AST (210.1 ± 41.65 to 91.6 ± 18.19 U/L), and TG (4.3 ± 0.41 to 0.9 ± 0.25 mmol/L), ameliorated histopathology and lipid accumulation. Mechanistically, Coixol upregulated SIRT6, downregulated pyroptosis (NLRP3, GSDMD, caspase-1, IL-1β), apoptosis (caspase-3, -9, BCL-2/Bax), necroptosis (P-MLKL/MLKL), and inhibited NETosis. SIRT6 deficiency attenuated Coixol’s protection in EtOH-activated hepatocytes. Collectively, Coixol alleviates ALD via SIRT6-dependent regulation of programmed responses, supporting its therapeutic potential.
PMID:42952430 | DOI:10.1080/14786419.2026.2752030
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