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.

Based on the well-known toxicity of cyclophosphamide (CYP) on the immune system, this research investigated the modulating effects of the long-term dietary Chlorella vulgaris (CV) supplementation on the immunosuppression induced by CYP in mice, in order to provide a novel dietary design to mitigate the side effects of CYP therapy. Control, CYP-treated, CYP + CV (6%), CYP + CV (12%) and CYP + CV (24%) were used for 6 weeks, CV supplement in diet recovered the significantly reduced immunological function in CYP treated mice. As CV may have a modulating function through the inducible expression of cytokines, we assayed the expressions of interleukin-2 (IL-2), interleukin-12 (IL-12), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Our results suggested that CYP significantly reduced the lymphocytes proliferation and phagocytic activities of macrophages, and stimulated the production of IL-2, IL-12, TNF-α and IFN-γ and that this impairment has been successfully adjusted by CV supplementation. Treatment with the algae also enhanced the natural killer (NK) cells cytotoxicity, and ameliorate histological changes of the spleen in CYP-treated mice. Therefore, as we found in this study, a diet supplemented with whole CV has beneficial effects on CVP-induced immunosuppression, through its immunomodulatory potential.