Evaluation of the Systemic Serum Exposure and Acute Toxicity of the Aqueous Extract of Curcuma longa (Zingiberaceae) Rhizomes in Wistar Rats

Abstract

Introduction: Liver toxicity has become a public health concern as more people globally get exposed to xenobiotics with the potential to cause liver damage and consequent liver cirrhosis. The increase in liver toxicant abuse has necessitated the exploration of xenobiotic exposure levels when addressing therapeutic measures using alternative herbal remedies. The increasing use of herbal products as alternative therapy needs regulatory alignment through evidence-based support for the safety and efficacy of these natural products. To undertake preclinical discovery of new metabolites from medicinal products, the objective of this study was to investigate the systemic serum exposure and acute toxicity of the aqueous extract of Curcuma longa (Zingiberaceae) rhizomes on Wistar rat models. Methods: Phytochemical screening was carried out on the aqueous extract obtained by maceration of the dried plant rhizomes. Standard screening techniques for plant metabolites were used to screen blood serum after animal exposure with the extract. After a 500mg/Kg dose, systemic exposure was evaluated in blood samples collected at 30-minute intervals for one hour. For acute toxicity, a single 2000mg/Kg by body weight dose of the plant extract and the reference (Silymarin 50mg/Kg) were administered to rats, and they were observed for 14 days. Biochemical markers of toxicity such as ALAT, ASAT, GGT, Bilirubin were quantified, and histological studies of the liver were carried out. Results: No secondary metabolites were identified at 30 mins and 1hr in rat serum following a 500 mg/Kg oral dose. Administration of a 2000 mg/Kg oral dose to rats was well tolerated, and there were no deaths or significant target organ toxicity. The plant showed no lethality at the dose of 2000mg/kg body weight and decreased liver toxicity markers such as ASAT, ALAT, GGT, and Bilirubin. Histology revealed no significant damage to liver hepatocytes, no central vein occlusion, and no evidence of fibrosis. Conclusion: There were no systemically available secondary metabolites at a dose of 500 mg/Kg after the qualitative screening; more sensitive and specific methods are required to test these secondary metabolites in serum. This study confirmed the safety margin of Curcuma longa with no lethality following a single oral dose of 2000mg/Kg and after observation for 14 days. There was a low expression of biochemical markers of toxicity ALAT, ASAT, and no histological indication of liver damage.