Context: Lycium barbarum L. (Solanaceae) polysaccharides (LBPs) are important active constituents that have demonstrated kidney protection. Objective: This study investigated the effect of LBPs on hyperuricaemia and explored the underlying mechanism in mice. Materials and methods: Thirty-six C57BL/6 mice were randomly divided into the control group, hyperuricaemia group, allopurinol group (5 mg/kg) and three LBP groups (n ¼ 6). The LBP groups were treated orally with LBPs at 50, 100 and 200 mg/kg body weight for 7 days. We examined the levels of serum uric acid (S UA) and urinary uric acid (U UA), as well as xanthine oxidase (XOD) activities. mRNA and protein were quantified by quantitative real-time PCR and Western blotting, respectively. Results: LBPs treatment (100 and 200 mg/kg) significantly reduced the S UA levels to 4.83 and 4.48 mg/dL, and markedly elevated the U UA levels to 4.68 and 5.18 mg/dL (p < 0.05), respectively, while significantly increased the mRNA and protein expression levels of renal organic anti-transporter 1 (OAT1) and organic anti-transporter 3 (OAT3), and markedly decreased the levels of glucose transporter 9 (GLUT9) (p < 0.05). Additionally, the serum XOD activities were reduced to 31.5 and 31.1 mU/mL, and the liver XOD activities were reduced to 80.6 and 75.6 mU/mL after treatment with 100 and 200 mg/kg LBPs (p < 0.01), respectively. Discussion and conclusions: This study demonstrated the potential role of LBPs in reducing the uric acid level in hyperuricemic mice. A border study population should be evaluated. These results are valuable for the development of new anti-hyperuricaemia agents from LBPs.

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Doxorubicin (DOX) is an effective anticancer drug, but its therapeutic use is limited by its cardiotoxicity. The principal mechanisms of DOX-induced cardiotoxicity are oxidative stress and apoptosis in cardiomyocytes. Orosomucoid 1 (ORM1), an acute-phase protein, plays important roles in inflammation and ischemic stroke; however, the roles and mechanisms of ORM1 in DOX-induced cardiotoxicity remain unknown. Therefore, in the present study, we aimed to investigate the function of ORM1 in cardiomyocytes experiencing DOX-induced oxidative stress and apoptosis. A DOX-induced cardiotoxicity animal model was established in C57BL/6 mice by administering an intraperitoneal injection of DOX (20 mg/kg), and the control group was intraperitoneally injected with the same volume of sterilized saline. The effects were assessed after 7 d. Additionally, H9c2 cells were stimulated with DOX (10 μM) for 24 h. The results showed decreased ORM1 and increased oxidative stress and apoptosis after DOX stimulation in vivo and in vitro. ORM1 overexpression significantly reduced DOX-induced oxidative stress and apoptosis in H9c2 cells. ORM1 significantly increased the expression of nuclear factor-like 2 (Nrf2) and its downstream protein heme oxygenase 1 (HO-1) and reduced the expression of the lipid peroxidation end product 4-hydroxynonenal (4-HNE) and the level of cleaved caspase-3. In addition, Nrf2 silencing reversed the effects of ORM1 on DOX-induced oxidative stress and apoptosis in cardiomyocytes. In conclusion, ORM1 inhibited DOX-induced oxidative stress and apoptosis in cardiomyocytes by regulating the Nrf2/HO-1 pathway, which might provide a new treatment strategy for DOX-induced cardiotoxicity.

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Introduction: Diabetic cardiomyopathy is a chronic complication of diabetes in the absence of coronary artery disease, arterial hypertension and valvular disease. Autophagy plays an important role in the development of diabetic cardiomyopathy. Cellular repressor of E1A-stimulated genes 1 (CREG1) is an important myocardial protective factor. The aim of this study was to investigate the effects and mechanisms of CREG1 in diabetic cardiomyopathy. Methods: Male C57BL/6J mice, CREG1 transgenic mice, and CREG1 cardiac-specific knockout mice were used to establish a type 2 diabetic model. Small animal ultrasound, Masson’s staining, and western blotting were used to evaluate cardiac function, myocardial fibrosis and autophagy. Neonatal mouse cardiomyocytes (NMCMs) were isolated and cultured. NMCMs were infected with CREG1- overexpressing adenovirus or small interfering RNA, followed by stimulation with palmitic acid (PA), real-time PCR, western blotting and immunofluorescence staining were used. Results: CREG1 protein expression was decreased in the myocardium of diabetic cardiomyopathy. CREG1 deficiency in the heart aggravated cardiac dysfunction, cardiac hypertrophy, and fibrosis in mice with diabetic cardiomyopathy, accompanied by aggravated autophagy dysfunction. CREG1 overexpression improved cardiac function and ameliorated cardiac hypertrophy and fibrosis in diabetic cardiomyopathy, by improving autophagy. CREG1 protein expression was decreased in PA-stimulated NMCMs. CREG1 knockdown aggravated cardiomyocyte hypertrophy and inhibited autophagy, which were reversed by resveratrol treatment. Conversely, CREG1 overexpression inhibited cardiomyocyte hypertrophy and improved autophagy, which were reversed by chloroquine or bafilomycin A1 treatment. Overexpression of LAMP2 reversed the effect of CREG1 knockdown on the PA-induced inhibition of cardiomyocyte autophagy. CREG1 inhibited the LAMP2 protein degradation by inhibiting the expression of F-box protein 27 (FBXO27). Conclusions: CREG1-FBXO27-LAMP2 axis alleviated diabetic cardiomyopathy by promoting cardiomyocyte autophagy. Our findings might help clarify new roles of CREG1 in the development of diabetic cardiomyopathy.