Abstract

Acute kidney injury (AKI) is characterized by rapid loss of renal function due to oxidative stress, inflammation, and apoptosis, with limited targeted therapies. Alpha-mangostin (AM), a natural compound from Garcinia mangostana, exhibits antioxidant and anti-inflammatory properties in preclinical studies, but its efficacy in AKI has not been reviewed. This systematic review and meta-analysis, registered on the Open Science Framework and adhering to PRISMA guidelines, analyzed in vivo and in vitro studies on AM’s effects in AKI models through searches of PubMed, Scopus, Embase, and Web of Science. Primary outcomes included serum creatinine and cell viability, while secondary outcomes encompassed oxidative stress markers (malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS)), inflammatory cytokines, apoptosis indicators, and histopathology. Data were extracted independently and assessed using the Toxicological Data Reliability Assessment Tool (ToxRTool). AM significantly reduced serum creatinine (mean difference (MD) = −0.67 mg/dL; 95% confidence interval (CI): −1.28 to −0.06; p = 0.03) and improved cell viability (MD = 28.26%; 95% CI: 17.25 to 39.26; p < 0.0001). It markedly decreased MDA and ROS, increased GSH, and enhanced antioxidant enzymes (glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD)). In vivo, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were lowered, and histopathology showed reduced tubular necrosis and structural damage. Subgroup analyses indicated dose- and model-dependent effects, with lower doses often yielding greater benefits. Sensitivity analyses confirmed robustness despite heterogeneity. Preclinical evidence supports AM’s nephroprotective potential and underscores the need for dose optimization, mechanistic validation, and clinical translation.