Comparative Subchronic Oral Toxicity of Gardeniae Fructus and Shuizhizi Water Extracts in Sprague-Dawley Rats Over 90 Days.

To compare the safety profiles of Gardeniae Fructus (Zhizi) and its counterfeit, Shuizhizi, Sprague-Dawley rats were orally administered aqueous extracts of Zhizi and Shuizhizi at 1.8 and 5.4 g/kg/day for 28 and 90 days, followed by a 28-day recovery period. Hematological indices, biochemical markers of liver and kidney function, organ coefficients, and histopathology were assessed at all three time points. Both substances induced dose-dependent abnormal hematological findings, disrupted liver/kidney function indices, altered organ coefficients, and caused histopathological damage. Shuizhizi induced significantly more severe toxicities than Zhizi. After the recovery period, the safety gap widened, with the Shuizhizi groups exhibiting delayed recovery: significantly reduced body weight in the high-dose Shuizhizi group (H-SZZ), significant alterations in most hematology and liver/kidney indices in both the low-dose Shuizhizi group (L-SZZ) and H-SZZ groups, and persistent marked liver pathology in the L-SZZ group. These findings indicate that Zhizi and Shuizhizi exhibit an identical spectrum of toxicity. However, the latter displayed significantly greater toxicity, with residual toxicity being particularly pronounced during the recovery phase. These results confirm that Shuizhizi is less safe for clinical application compared to Zhizi and should not be used as a substitute in clinical practice.