Protective Effect of Chlorogenic Acid and Its Analogues on Lead-Induced Developmental Neurotoxicity Through Modulating Oxidative Stress and Autophagy

Abstract

Lead (Pb) is among the deleterious heavy metal and has caused global health concerns due to its tendency to cause a detrimental effect on the development of the central nervous system (CNS). Despite being a serious health concern, treatment of Pb poisoning is not yet available, reflecting the pressing need for compounds that can relieve Pb-induced toxicity, especially neurotoxicity. In the quest of exploring protective strategies against Pb-induced developmental neurotoxicity, compounds from natural resources have gained increased attention. Chlorogenic acid (CGA) and its analogues neochlorogenic acid (NCGA) and cryptochlorogenic acid (CCGA) are the important phenolic compounds widely distributed in plants. Herein, utilizing zebrafish as a model organism, we modeled Pb-induced developmental neurotoxicity and investigated the protective effect of CGA, NCGA, and CCGA co-treatment. In zebrafish, Pb exposure (1,000 μg/L) for 5 days causes developmental malformation, loss of dopaminergic (DA) neurons, and brain vasculature, as well as disrupted neuron differentiation in the CNS. Additionally, Pb-treated zebrafish exhibited abnormal locomotion. Notably, co-treatment with CGA (100 µM), NCGA (100 µM), and CCGA (50 µM) alleviated these developmental malformation and neurotoxicity induced by Pb. Further underlying mechanism investigation revealed that these dietary phenolic acid compounds may ameliorate Pb-induced oxidative stress and autophagy in zebrafish, therefore protecting against Pb-induced developmental neurotoxicity. In general, our study indicates that CGA, NCGA, and CCGA could be promising agents for treating neurotoxicity induced by Pb, and CCGA shows the strongest detoxifying activity.

Chlorogenic acid improves growth performance and intestinal health through autophagy-mediated nuclear factor erythroid 2-related factor 2 pathway in oxidatively stressed broilers induced by dexamethasone

“…However, we noted that dietary supplementation of CGA induced autophagy in oxidatively stressed broilers, as evidenced by the increased LC3-II, Beclin1 and ATG7 mRNA expressions and LC3-II/LC3-I value and decreased mRNA expression of LC3-I and protein expression of p62, implying CGA inhibits oxidative stress through the activation of autophagy. Similar results were found in human neuroblastoma cells ( Gao et al, 2021 ) and zebrafish ( Ji et al, 2021 ). Moreover, with regards to apoptosis, our results showed that dietary supplementation of CGA decreased the mRNA expression of Caspase-9 in oxidatively stressed broilers, which was consistent with a previous study ( Liu et al, 2020 ) that found CGA inhibited the expressions of apoptosis-related proteins (caspase-3 and caspase-9) in the ischemia/reperfusion injury of rats.…”

A review of the protective effects of chlorogenic acid against different chemicals

“…for 8 weeks) decreased hepato‐renal damage induced by Pb (1.34 g/L in drinking water) in mice by restoration of Pb‐suppressed activities of GSH, SOD, CAT, and GPx and diminishing Pb‐induced MDA levels (Cheng, Li, et al, 2019). In addition, the neuroprotective activity of CGA (100 μM) against Pb (1000 μg/L) in zebrafish larvae was attributed to the suppression of oxidative stress (Ji et al, 2021).…”

A Tau Pathogenesis-Based Network Pharmacology Approach for Exploring the Protections of Chuanxiong Rhizoma in Alzheimer’s Disease

“…First, the results of this study need to be further validated, especially in AD transgenic animal models and related cell models. Second, we also found that RO5-violating CR phytochemicals (chlorogenic acid, cryptochlorogenic acid, and 3,5-O-dicaffeoylquinic acid) have some neuroprotective effects ( Kwon et al, 2010 ; Heitman and Ingram, 2017 ; Ji et al, 2021 ). This suggested that overemphasizing RO5 has the dangerous potential to overfilter compounds that may otherwise be good drug candidates and this inevitably results in reduced productivity for discovering new drugs.…”