ABSTRACT
In this study, the model of Propionibacterium acnes/lipopolysaccharide (P. acnes/LPS)-induced acute liver injury in mice was employed to investigate the protective effects of Fuzheng Yanggan Fomula (FYF) on acute liver injury. The effects of FYF on the contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and interleukin-1β (IL-1β) in the serum, and the levels of malondialdehyde (MDA), oxygen radical absorbance capacity (ORAC), and glutathione (GSH) were examined in the livers of mice treated with P. acnes/LPS; The protein expression levels of Nod-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), cysteinyl aspartate specific proteinase-1 (caspase-1), and IL-1β in liver tissues were detected by Western blot; Furthermore, hematoxylinendash-eosin (HE) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and immunohistochemical assay were used to observe pathological changes, apoptosis index, and inflammation infiltration of the liver tissue sections. All animal welfare and experimental procedures were followed by the Animal Ethics Committee of Jinan University. We conclude that FYF could alleviate P. acnes/LPS induced pathological damage and inflammatory infiltration in the liver of mice. Meanwhile, FYF decreases the contents of ALT, AST, IL-1β, and MDA, increases the contents of ORAC and GSH, and downregulates the expression of caspase-1 and IL-1β proteins. Collectively, these findings suggested that FYF could alleviate P. acnes/LPS induced acute liver injury in mice by inhibiting the activation of NLRP3 inflammasome, which provides a theoretical basis and a new drug target for the prevention and treatment of liver injury.
ABSTRACT
The model of drug-induced liver injury (DILI) induced by acetaminophen (APAP) in mice was established to investigate the anti-oxidation and anti-ferroptosis mechanisms of Fuzheng Yanggan Mixture on DILI. C57BL/6 mice were randomly divided into five groups: control group, model group, positive group, and low and high-dose Fuzheng Yanggan Mixture groups (0.12, 0.24 g·kg⁻¹). Mice were intragastrically administration with Fuzheng Yanggan Mixture (0.12, 0.24 g·kg⁻¹) once per day for 21 consecutive days, and at the same time, mice were weighted every day. The mice were injected intraperitoneally with 600 mg·kg⁻¹ of APAP to establish a mouse model of acute DILI after 16 h from the last administration of Fuzheng Yanggan Mixture. After 6 h from APAP challenge, the experimental animals were weighted and sacrificed to collect blood and liver tissue samples. And then, the effect of Fuzheng Yanggan Mixture on liver weight and the liver weight ratio of mice were examined; the content of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum and the level of malondialdehyde (MDA), glutathione (GSH) and nicotinamide adenine dinucleotide phosphate (NADPH) in the liver tissue were measured. Prostaglandinendoperoxide synthase 2(ptgs2) mRNA level in liver tissues was detected by Q-PCR, and protein expression levels of SLC7A11 and GPX4 in liver tissues were detected by Western blot. Moreover, HE staining, immunohistochemical assay and TUNEL staining were used to observe pathological changes of the liver tissue sections. It is found that Fuzheng Yanggan Mixture could relieve APAP-induced liver enlargement and inhibit hepatic weight ratio increase. Compared with model group, the mice in Fuzheng Yanggan Mixture groups showed decreases in the content of ALT, AST and MDA, and increases in the content of GSH and NADPH. What is more, Fuzheng Yanggan Mixture could down-regulate ptgs2 mRNA level and up-regulate SLC7A11 and GPX4 protein levels. All of the results lead to a conclusion that Fuzheng Yanggan Mixture plays a protective effect on DILI in mice, which may be associated with the inhibition of ferroptosis.