Evaluation of the mutagenic and genotoxic potential of Wujin: a traditional mineral medicine

Abstract

Ethnopharmacological relevance: Wujin, a mineral-derived Chinese medicine first recorded in the "Compendium of Materia Medica" (Bencao Gangmu), has been widely employed in the management of inflammatory conditions for millennia. Comprising numerous bioactive constituents, including humic acid and fulvic acid, it exhibits a range of pharmacological activities, such as anti-inflammatory effects, enhanced blood circulation, haemostasis, analgesia, and immunomodulation. While traditionally regarded as safe, its safety profile has not been systematically evaluated.

Aim of the study: This study aimed to assess the mutagenic and genotoxic potential of Wujin using the Ames Test, the Chromosomal Aberration Test, the Micronucleus Test, and quantification of toxicity-related components.

Materials and methods: In this study, five batches of Wujin from different origins were obtained. The contents of toxicity-related components, including fulvic acid and heavy metals and harmful elements (Pb, Lead; Cd, cadmium; As, arsenic; Hg, mercury; Cu, copper) in Wujin were determined using Dichromate Oxidation Titration (Potassium Dichromate Method) and Atomic Absorption Spectrophotometry respectively. The mutagenic and genotoxic potential of Wujin was assessed using the following assays: (1) the Ames Test, performed in Salmonella typhimurium strains: TA97a, TA98, TA100, TA102, and TA1535; (2) the Chromosomal Aberration Test, evaluated with Chinese Hamster Lung (CHL Cells); and (3) the Micronucleus Test, conducted in mouse bone marrow cells of NIH mice.

Results: The mean contents of fulvic acid, Pb, Cd, As, Hg, and Cu across five analysed batches of Wujin were 0.21 mg/g, 20.4 mg/kg, 0.48 mg/kg, 0.32 mg/kg, 0.052 mg/kg, and 37.8 mg/kg, respectively. The Ames Test showed that Wujin did not induce gene mutations in any Salmonella typhimurium strains, either in the presence or absence of S9 activation. Furthermore, negligible cytotoxicity and no significant chromosomal aberrations were observed in CHL cells with or without S9 activation. Oral administration of Wujin at doses up to 1500 mg/kg did not result in a significant increase in the number of micronucleated polychromatic erythrocytes or alter the polychromatic erythrocytes (PCEs) ratios.

Conclusion: Collectively, no evidence of mutagenic and genotoxic potential of Wujin was observed. These findings support the historical safety profile of Wujin and warrant further investigation into its therapeutic applications.

Keywords: Ames test; Chromosomal aberration test; Genotoxicity; Micronucleus test; Wujin.