Protective Effects of Cashew Apple Bagasse and Its Hydroethanolic Extract Against Fatty Liver in Rats

Cashew apple bagasse (Anacardium occidentale L.) is an agro-industrial byproduct rich in fiber and phytochemicals, yet its effects on diet-induced fatty liver remain insufficiently characterized. This study evaluated the protective effects of cashew apple bagasse (CAB) and its hydroethanolic extract (HECAB) in rats fed a high-fat, high-carbohydrate (HFHC) diet. The proximate composition of CAB and the phenolic profile and antioxidant capacity of HECAB were characterized. Male Wistar rats were assigned to four groups and fed for 19 weeks with a standard diet, an HFHC diet, or an HFHC diet supplemented with CAB or HECAB. Anthropometric, biochemical, histological, immunohistochemical, and immunoblot analyses were performed. HECAB showed high phenolic content and marked radical-scavenging activity, and untargeted UPLC-QTOF-MS analysis yielded 12 putative secondary metabolite annotations (levels 3–4) based on accurate mass, isotope distributions, MS/MS fragmentation patterns, and predefined acceptance criteria. Relative to the standard diet group, the HFHC diet induced metabolic and hepatic alterations consistent with early-stage MASLD. Compared with HFHC, both CAB and HECAB reduced serum insulin and HOMA-IR, attenuated hepatic steatosis, increased SOD1 and CAT, and reduced NF-κB, IL-6, TNF-α, and IL-1β, whereas GPx1 remained unchanged. Both interventions also enhanced NRF2 and HO-1 compared to HFHC, with stronger nuclear positivity in the HECAB group, while CAB showed the clearest association with IL-10 restoration. These findings are consistent with modulation of antioxidant defense- and inflammatory-related pathways in early-stage MASLD and support further investigation of cashew apple bagasse as a valorized functional ingredient. However, because classical oxidative damage markers were not measured, these results should not be interpreted as direct evidence of reduced oxidative stress. In addition, the detected metabolites should be interpreted as putative annotations rather than definitive compound identifications.