Chlorogenic acid relieves lead-induced cognitive impairments and hepato-renal damage via regulating the dysbiosis of the gut microbiota in mice

Lead (Pb), a heavy metal which is widely recognized as an environmental toxicant, is transported from the earth's crust into the human body to a significant extent. To control and reduce the hazard of Pb burdens in the human body, chlorogenic acid (CGA) has been used to antagonize Pb-induced cognitive impairments, and hepatic and renal toxicity in the present study. Seven-week-old male Kunming mice were treated with PbCl2 (1.34 g L-1 in drinking water) and/or CGA (30 mg per kg mouse per day) by gavage administration for 8 weeks. In this study, we evaluated behavior tests, serum biochemical parameters, biomarkers of oxidative stress, and community structure of gut microbiota in mice to explore the potential mechanism of the protective effect. Based on our results, CGA appreciably prevented memory impairment, the release of serum biomarkers, and oxidative stress caused by Pb intake. CGA significantly inhibited Pb-induced increase of cytoplasmic NF-κB, Bax, cytochrome C, and caspase-9 protein expressions. Furthermore, Pb + CGA treatment had a remarkable reversion effect of the gut microbiota composition change induced by Pb, for example increasing the ratio of Helicobacter from 2.95% (Pb) to 11.24% (Pb + CGA) and decreasing the ratio of the Lachnospiraceae_NK4A136_ group from 7.09% (Pb) to 2.68% (Pb + CGA), which suggests that CGA is a superior natural product to eliminate Pb-induced nephrotoxicity and hepatotoxicity.