Aqueous extract of Cissus quadrangularis L. alleviates heavy metal toxicity in Saccharomyces cerevisiae by limiting metal uptake and enhancing detoxification mechanisms.

Rapid industrialization has led to widespread environmental contamination by toxic metals. The aqueous extract of Moringa oleifera (AMO) has previously been shown to effectively inhibit intracellular metal accumulation. In this study, we screened 24 Thai herbal extracts for their detoxification efficacy against toxic metals and identified the aqueous extract of Cissus quadrangularis (ACQ) as the most effective in alleviating the toxicities of cadmium (Cd), cobalt (Co), and nickel (Ni) in Saccharomyces cerevisiae. Although ACQ exhibited approximately threefold lower antioxidant capacity, based on its DPPH and ABTS radical scavenging activities, compared to its ethanolic extract (ECQ), it effectively suppressed the generation of metal-induced reactive oxygen species to levels comparable to or even lower than those achieved with ECQ and the well-studied AMO. The effectiveness of ACQ in mitigating metal toxicity appears to be primarily mediated by its ability to inhibit metal uptake and accumulation by approximately 70-90 % compared to the untreated control. Furthermore, ACQ and AMO significantly restored antioxidant enzyme activities suppressed by toxic metals, likely through the upregulation of antioxidant genes including SOD1, SOD2, CTT1, and CTA1. Notably, ACQ demonstrated a greater ability than AMO to enhance the expression of genes involved in metal extrusion and sequestration, such as PCA1, YOR1, and YCF1. Additionally, comparative metabolomic profiling of ACQ revealed a predominance of organic acids and their derivatives as the major metabolite class, suggesting their high potential for metal detoxification through metal-chelating mechanisms. These findings highlight the potential of ACQ as a natural therapeutic agent for mitigating metal toxicity.