Oral chronic toxicity study of geniposide in rats

Ethnopharmacological relevance: Geniposide, the major active constituent of Fructus Gardeniae (FG), has been widely used to treat various diseases in China. Aim of the study: This chronic toxicity study was conducted to investigate the safety of geniposide. Materials and methods: Geniposide was administered to Sprague-Dawley (SD) rats of both sexes by oral gavage at dosages of 25, 50, or 100 mg/kg in a volume of 10 mL/kg once daily for 26 weeks. Endpoints included clinical observations, food consumption, body weights, blood biochemistry, haematology, and histomorphological observations. Results: The administration of geniposide did not influence animal mortality, the general conditions of the animals, body weights or food consumption. After 4 weeks of administration, significant toxicity was not observed. However, in the 13th week of the toxicity study, a few haematological parameters and some relative organ weights of male rats in the 50 and 100 mg/kg geniposide groups were significantly increased. The percentage of reticulocytes (Retic %) was significantly increased in male and female rats administered 100 mg/kg geniposide. In addition, two female rats in the 100 mg/kg geniposide group showed slight pathological changes in hepatic and renal tissues. Furthermore, in a chronic (26 weeks) toxicity study, differences were detected in alanine aminotransferase (ALT), aspartate aminotransferase (AST), sodium (Na+), potassium (K+), white blood cell (WBC), red blood cell (RBC), and haemoglobin (HGB) levels and the relative weights of the liver and spleen in male rats administered 100 mg/kg geniposide. In addition, differences were detected in Retic % and the relative weights of the liver, thymus, and kidneys in female rats administered 100 mg/kg geniposide. Urinalysis results from male and female rats in the 100 mg/kg geniposide group revealed noticeable changes. The histopathological structures of hepatic and renal tissues in the high-dose geniposide group exhibited serious abnormalities and pigment deposition. Conclusion: Geniposide affected serum biochemistry, urinalysis, and haematological parameters as well as relative organ weights. The treatment also caused noticeable pathological abnormalities in liver and kidney tissues. Therefore, administration of a high dose of geniposide (100 mg/kg) for 26 weeks could induced obvious liver and kidney damage.