OBJECTIVES: To investigate the effects of quercetin on cuproptosis and L-type calcium currents in the myocardium of diabetic rats. METHODS: Forty SD rats were randomized into control group and diabetic model groups. The rat models of diabetes mellitus (DM) induced by high-fat and high-sugar diet combined with streptozotocin (STZ) injection were further divided into DM model group, quercetin treatment group, and empagliflozin treatment group (n=10). Blood glucose and body weight were measured every other week, and cardiac function of the rats was evaluated using echocardiography. HE staining, Sirius red staining, and wheat germ agglutinin (WGA) analysis were used to observe the changes in myocardial histomorphology, and serum copper levels and myocardial FDX1 expression were detected. In cultured rat cardiomyocyte H9c2 cells with high-glucose exposure, the effects of quercetin and elesclomol, alone or in combination, on intracellular CK-MB and LDH levels and FDX1 expression were assessed, and the changes in L-type calcium currents were analyzed using patch-clamp technique. RESULTS: The diabetic rats exhibited elevated blood glucose, reduced body weight, impaired left ventricular function, increased serum copper levels and myocardial FDX1 expression, decreased L-type calcium currents, and prolonged action potential duration. Quercetin and empagliflozin treatment significantly lowered blood glucose, improved body weight, and restored cardiac function of the diabetic rats, and compared with empagliflozin, quercetin more effectively reduced serum copper levels, downregulated FDX1 expression, and enhanced myocardial L-type calcium currents in diabetic rats. In H9c2 cells, high glucose exposure significantly increased myocardial expressions of FDX1, CK-MB and LDH, which were effectively lowered by quercetin treatment; Elesclomol further elevated FDX1, CK-MB and LDH levels in the exposed cells, and these changes were not significantly affected by the application of quercetin. CONCLUSIONS Quercetin ameliorates myocardial injury in diabetic rats possibly by suppressing myocardial cuproptosis signaling and restoring L-type calcium channel activity.
Animals ; Quercetin/pharmacology* ; Calcium Channels, L-Type/metabolism* ; Diabetes Mellitus, Experimental/metabolism* ; Rats, Sprague-Dawley ; Rats ; Myocytes, Cardiac/drug effects* ; Myocardium/pathology* ; Male

Objective:To explore the advantage of Fuzheng Huayu capsule in patients with hepatitis B cirrhosis based on neutrophil/lymphocyte ratio (NLR) risk stratification in reducing the incidence of hepatocellular carcinoma (HCC).Methods:916 cases diagnosed with hepatitis B cirrhosis and followed up for five years from January 2011 to January 2016 at Beijing Ditan Hospital Affiliated with Capital Medical University were included, and clinical data were collected. Patients were divided into a combination group and an antiviral group according to whether they were treated with anti-fibrosis for≥6 months. The antiviral group was treated with entecavir or tenofovir disoproxil, while the combination group was treated with Fuzheng Huayu capsules based on the antiviral therapy. The incidence of HCC was compared between the two groups of patients within five years. The advantaged groups treated with Fuzheng Huayu capsule were explored based on NLR risk stratification. The independent sample t-test and Mann-Whitney U test were used to compare measurement data between two groups. Categorical variable data were compared using either the χ2 test or Fisher's exact probability method. The incidence of HCC in the two groups of patients was analyzed through the Kalplan-Merier curve and compared using the log-rank method. Results:There were 299 (32.6%) and 617 (67.4%) cases in the combined group and the antiviral group, respectively. A total of 154 (16.8%) patients developed HCC during the follow-up period. The five-year cumulative incidence of HCC in the combination group was lower than that in the antiviral group (10.7% vs. 19.8%, χ2 = 11.848, P = 0.000 4). Patients with baseline NLR>3 had an increased risk of HCC. According to NLR risk stratification, there were 191 cases in the low-risk group (NLR<1.4), 462 cases in the medium-risk group (NLR1.4 ~ 3.0), and 263 cases in the high-risk group (NLR>3). Among medium to high-risk patients, the incidence of HCC was significantly reduced in the combination group (11.5% vs. 19.4%, χ2 = 4.519, P = 0.029; 13.2% vs. 26.2%, χ2 = 5.258, P = 0.019), while there was no statistically significant difference in the incidence of HCC among the low-risk group ( P = 0.38). Conclusion:Compared with antiviral treatment alone, Fuzheng Huayu capsules combined with antiviral treatment can better reduce the five-year HCC incidence rate in patients with hepatitis B cirrhosis. Medium-and high-risk patients with NLR stratification are the most advantageous population to be treated with Fuzheng Huayu capsules.

Alcohol abuse leads to alcoholic liver disease and no effective therapy is currently available. Wuzhi Tablet (WZ), a preparation of extract fromthat is a traditional hepato-protective herb, exerted a significant protective effect against acetaminophen-induced liver injury in our recent studies, but whether WZ can alleviate alcohol-induced toxicity remains unclear. This study aimed to investigate the contribution of WZ to alcohol-induced liver injury by using chronic-binge and acute models of alcohol feeding. The activities of ALT and AST in serum were assessed as well as the level of GSH and the activity of SOD in the liver. The expression of CYP2E1 and proteins in the NRF2-ARE signaling pathway including NRF2, GCLC, GCLM, HO-1 were measured, and the effect of WZ on NRF2 transcriptional activity was determined. We found that both models resulted in liver steatosis accompanied by increased transaminase activities, but that liver injury was significantly attenuated by WZ. WZ administration also inhibited CYP2E1 expression induced by alcohol, and elevated the level of GSH and the activity of SOD in the liver. Moreover, the NRF2-ARE signaling pathway was activated by WZ and the target genes were all upregulated. Furthermore, WZ significantly activated NRF2 transcriptional activity. Collectively, our study demonstrates that WZ protected against alcohol-induced liver injury by reducing oxidative stress and improving antioxidant defense, possibly by activating the NRF2-ARE pathway.