Preclinical Toxicology and Anticholangiocarcinoma Activity of Oral Formulation of Standardized Extract of Zingiber Officinale.

Cholangiocarcinoma (CCA) remains a significant public health problem in Thailand. New effective and safe drugs are urgently needed. Roscoe (ZO) is a widely used medicinal plant for the treatment of several ailments, and the animal study suggests a potential anti-CCA activity. The present study aimed to develop the oral formulation of standardized extract of ZO and investigate toxicological profiles (acute, repeated dose, and chronic toxicity), including anti-CCA activity of the ZO formulation. The oral pharmaceutical formulation of the standardized ZO extract was successfully developed with an acceptable level of contamination and physicochemical and pharmaceutical properties. Acute, subacute, and chronic toxicity tests were conducted in healthy Sprague Dawley rats according to the OECD guidelines. The results showed no evidence of toxicity and death in the acute and subacute toxicity testing with the maximum tolerated dose (MTD) of 5000 and 2000 mg/kg body weight, respectively. Chronic toxicity revealed MTD and No-Observed-Adverse-Effect level (NOAEL) of 1000 mg/kg body weight. The anti-CCA activity was evaluated in CCA-xenografted mouse model. The formulated ZO powder was fed to animals daily for 30 days. Significant anti-CCA activity on tumor growth inhibition and prolongation of survival time were demonstrated at the high (2000 mg/kg body weight) and moderate (1000 mg/kg body weight) dose levels. Further investigation to elucidate molecular targets of action of ZO against CCA cells is encouraged.