Lepidium meyenii (Maca) polysaccharides mitigate liver toxicity of aflatoxin B1 through activation of NRF-2/GPX and AhR/STAT3 signaling pathways

Abstract

Aflatoxin B₁ (AFB₁) can induce serious liver toxicity in human. While completely avoiding AFB₁ exposure is difficult, dietary intake of natural products may be leveraged to mitigate its adverse health effects. The roots of Lepidium meyenii (Maca) is rich in beneficial polysaccharides. Here we first evaluated dietary safety of MPs and then investigated MPs mitigating effects on the liver toxicity of AFB₁. A 28-day sub-acute administration of Maca polysaccharides (MPs) demonstrated to be safe in mice at dose 0.2–1.2 g/kg.bw/day that significantly elevated mice stamina. Also, no toxicity was observed in human PC12 cells treated with MPs 25–100 μg/mL which successfully alleviated cobalt-caused cell apoptosis by ∼20%. In terms of anti-AFB₁ hepatoxicity function, MPs 0.4–1.6 g/kg.bw/day significantly alleviated liver tissue damage, lipid accumulation, ROS damage, NF-κB p65, secretion of cytokines such as IL-6 and TNF-α in AFB₁-treated mice. Flow cytometry found that MPs treatment recovered the elevation of F4/80 in the primary macrophages of AFB₁-treated mice. At molecular level, MPs treatment activated liver NRF-2/GPX/SOD anti-oxidant system. In human macrophage model, MPs restored the inflammatory AhR/STAT3 pathway and mRNA expressions of Tnf-a, Inos, Arg-1 disrupted by AFB₁. Our findings not only add to the current understanding on the toxicity mechanism of AFB₁, but also provide references to the development of dietary intervention strategy using MPs.