OBJECTIVE To investigate whether total flavonoids from chamomile alleviate liver injury in db/db mice with type 2 diabetes mellitus(T2DM) through the NOD-like receptor protein 3(NLRP3)/nuclear factor kappa B(NF-κB) pathway.

METHODS  The contents of quercetin, luteolin, and apigenin in chamomile total flavonoids were simultaneously determined by HPLC. SPF grade db/db mice and control db/m mice were adaptively fed for 7 d, after which their fasting blood glucose (FBG) levels were measured. The db/db mice were randomly divided into 5 groups(n=6): model group, metformin group, and low-, medium-, and high-dose chamomile total flavonoids groups. Six db/m mice served as the control group. All mice were continuously administered by gavage for 7 weeks. General conditions were observed daily, body weight and FBG were recorded weekly. Serum levels of high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), triglycerides(TG), total cholesterol(TC), alanine amino-transferase(ALT), aspartate transferase(AST), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) were detected. The expression level of malondialdehyde(MDA), and the activities of superoxide dismutase(SOD) and glutathione peroxidase(GSH-Px) in mice liver tissues were measured. Western blotting and RT-qPCR were used to detect the protein and mRNA expression levels of NLRP3, NF-κB, c-Jun N-terminal kinase(JNK), and interleukin-1β(IL-1β) in the liver tissues of mice, respectively.

RESULTS  HPLC results showed that the average contents of quercetin, luteolin, and apigenin in the tested samples were 3.8218, 5.1119, 3.5353 mg·g⁻¹, respectively. Compared with the normal group, the model group exhibited significant increases in body weight, FBG, TG, TC, and LDL-C levels, while HDL-C levels were significantly decreased. In liver tissues, MDA expression was significantly increased, while the activities of SOD and GSH-Px were significantly decreased. Liver tissue showed consolidation, vacuolar degeneration of hepatocytes, accompanied by inflammatory cell infiltration, indicating severe liver injury. Serum IL-6 and TNF-α levels were increased, and the protein and mRNA expression levels of NLRP3, NF-κB, JNK, and IL-1β in liver tissues were significantly increased. After 7 weeks of drug intervention, compared with the model group, the body weight, FBG, TG, TC, LDL-C levels of mice in the metformin group and all chamomile total flavonoids dosage groups decreased, while HDL-C content increased. MDA expression in liver tissue was decreased, while SOD and GSH-Px enzyme activities were increased. Serum IL-6, TNF-α levels were decreased. The degree of liver lesions improved, and the protein and mRNA expression levels of NLRP3, NF-κB, JNK, IL-1β in liver tissue were decreased.

CONCLUSION Chamomile total flavonoids can improve the metabolism of glucose and lipid in db/db mice and improve the liver injury. The underlying mechanism may involve regulation of the NLRP3/NF-κB signaling pathway, reducing inflammatory response, and ameliorating oxidative stress, thereby delaying the progression of diabetic liver injury.