Meta-analysis of 24 animal studies shows emodin reduces kidney injury markers in preclinical models.

BackgroundKidney injury is a growing global health problem with limited treatments. Emodin, an anthraquinone found in traditional Chinese medicinal herbs, shows both renoprotective and nephrotoxic effects in animal studies. This study aimed to systematically assess the effects of emodin on kidney injury in vivo and determine how dose, administration route, and treatment duration influence whether the overall outcome is beneficial or harmful.MethodsA pre-registered systematic review and random-effects meta-analysis was conducted, focusing exclusively on in vivo animal models and excluding in vitro and clinical data. Eight electronic databases were searched from inception to 1 October 2025. Two reviewers independently performed study selection, data extraction, and risk-of-bias assessment using the SYRCLE tool. The primary efficacy outcomes were serum blood urea nitrogen (BUN) and creatinine (Cr). Pre-specified subgroup analyses were undertaken according to disease model, dose, administration route, and intervention duration. Publication bias was evaluated using funnel plots and Egger’s regression test.ResultsFrom 2,915 records, 24 studies (408 animals: 396 rodents, 12 canines) met inclusion criteria (17 therapeutic, 7 toxicity). In kidney injury models, emodin significantly reduced BUN (n = 182; SMD = −2.39; 95% CI −3.54 to −1.25; P < 0.0001; I2 = 78.5%) and Cr (n = 284; SMD = −3.44; 95% CI −4.83 to −2.05; P < 0.0001; I2 = 86.3%). Subgroup results indicated robust effects at low–moderate doses (60 mg/kg) and with certain routes. For emodin-alone exposure studies, pooled BUN (n = 92; SMD = 2.11; 95% CI −1.51–5.72) and Cr (n = 112; SMD = 0.65; 95% CI −3.15–4.45) showed no overall significant elevation, but the kidney index decreased significantly (n = 100; SMD = −0.68; 95% CI −1.27 to −0.10; P = 0.022). High-dose exposure (>1,000 mg/kg), intraperitoneal administration and treatment >1 month were associated with toxicity signals.ConclusionEmodin exhibits dual effects on the kidney, with its net outcome determined primarily by dosage, administration route, and treatment duration. These findings underscore the need for precise dosing and exposure control in the further development of emodin as a renal therapeutic agent.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420261326554, identifier CRD420261326554.