Psidium guajava Leaf Extract Attenuates High-Fat Diet–Induced Nonalcoholic Fatty Liver Disease in Wistar Rats

Abstract

Background and Aim: Nonalcoholic fatty liver disease represents the most prevalent chronic liver condition globally, despite the scarcity of approved drug treatments. Leaves of Psidium guajava L. (guava) are abundant in polyphenolic compounds known for their hepatoprotective, lipid-lowering, and insulin-sensitizing properties. This study aimed to assess the therapeutic potential of a standardized ethanolic P. guajava leaf extract against NAFLD induced by a high-fat diet combined with fructose in Wistar rats.

Materials and methods: Adult Wistar rats were fed a high-fat diet (60%) supplemented with 10% fructose in drinking water, or normal chow, for 16 weeks. From Week 9 to Week 16, high-fat-fed rats received daily oral doses of P. guajava leaf extract (PGE250; 250 mg/kg) or pioglitazone (PIO20; 20 mg/kg) as the reference insulin sensitizer. The extract was standardized by HPLC for ellagic acid, quercetin, and rutin. At Week 16, body weight, food intake, fasting glucose, insulin and HOMA-IR, plasma lipid profile, liver function markers, hepatic oxidative stress and antioxidant status, pro-inflammatory cytokines, and liver histopathology were assessed.

Results: High-fat and fructose feeding significantly increased body weight, fasting glucose, insulin, HOMA-IR, triglycerides, total cholesterol, LDL-C, ALT, AST, ALP, TNF-α, IL-1β, IL-6, MDA, absolute liver weight, and hepatosomatic index, while significantly reducing HDL-C, total protein, catalase, SOD, and GSH. Treatment with PGE250 significantly reversed all of these alterations (p < 0.001 to p < 0.0001), restored normal hepatic architecture — no abnormality detected on histopathology, versus vacuolar degeneration with inflammatory cell infiltration (grade < 2) in the disease control — and produced effects comparable to those of pioglitazone.

Conclusion: P. guajava leaf extract ameliorates high-fat diet and fructose-induced NAFLD in Wistar rats through coordinated insulin-sensitizing, hypolipidemic, antioxidant, and anti-inflammatory mechanisms, supporting its potential as a safe, plant-based therapeutic candidate for NAFLD.