Exploration of the Protective Mechanism of Naringin in the Acetaminophen-Induced Hepatic Injury by Metabolomics

Abstract

Naringin is a dihydroflavone which was found in citrus fruits. Previous studies have indicated the antiapoptotic, antioxidative stress, and anti-inflammatory effects of naringin. It can improve many common diseases, including fibrosis or hepatotoxicity, cardiovascular disease, and diabetes. Acetaminophen (APAP) is a frequently used painkiller, and hepatotoxic side effects limit its use. The purpose of the current examination is to find the impact of naringin on APAP-induced hepatic injury. Firstly, we pretreated mice model groups with naringin. Then, the liver injury model was established by injecting intraperitoneally into mice with APAP. After the mice were euthanized, we obtained serum and liver tissue samples from the mice. Finally, these samples were analyzed using a metabolomics approach to find the underlying mechanism of the effects of naringin on APAPinduced liver injury and provide a new treatment strategy for APAP-induced liver injury. Our data indicate that naringin significantly improves APAP-induced liver injury in mice and reduces the expression levels of liver injury markers in a dosedependent manner. Furthermore, analysis of differential metabolites in mice with liver injury showed that naringin reduced APAP-induced hepatotoxicity due to reversing multiple metabolite expression levels and the rescue of energy, amino acid, and purine metabolism.

Regulatory mechanism and therapeutic potentials of naringin against inflammatory disorders

“…In most cases, Nrf2 activation plays a protective role in maintaining human health, and naringin can activate Nrf2 signaling to protect human health. Therefore, naringin plays a role in treating APAP-induced liver injury in mice, reducing the expression of liver injury markers in a dose-dependent manner, with potential mechanisms including antioxidant, rescue glucose metabolism, amino acid regulation, and purine metabolism [ 54 ].…”

Evaluating the anti-neuropathic effects of naringin-loaded chitosan nanocarriers in a murine model of constriction injury

“…17,47 Moreover, the effects observed with naringin-loaded NPs could be attributed to the combined characteristics of chitosan NPs and the continuous release of naringin, 48,49 along with the neuroprotective effects of naringin due to its antioxidant, anti-inflammatory, anti-apoptotic, and analgesic activities. 17,50,51…”

“…17,47 Moreover, the effects observed with naringin-loaded NPs could be attributed to the combined characteristics of chitosan NPs and the continuous release of naringin, 48,49 along with the neuroprotective effects of naringin due to its antioxidant, anti-inflammatory, anti-apoptotic, and analgesic activities. 17,50,51 In following, the anxiety-and depressive like behaviors were evaluated via OFT in the animals by using the three parameters. Regarding the parameter of the number of licking times (Figure 5), in the sham group, no difference was identified during the study period, and the number of licking times was remarkably low.…”

Naringenin prevents non‐alcoholic steatohepatitis by modulating the host metabolome and intestinal microbiome in MCD diet‐fed mice

“…Thus, misidentification is common in non‐targeted metabolomics, and targeted metabolomics that employ known standards are often required to further validate the chosen metabolite of interest. The protective effects of naringenin have been demonstrated to be associated with restoring metabolic profiles in various liver diseases, including CCl 4 ‐induced and acetaminophen‐induced liver injury (Ammar et al, 2022 ; Lin et al, 2022 ). The influence of naringenin on the metabolic profile of preclinical models of NASH has not been investigated until this present study.…”