We report herein a study of aging using in vitro and in vivo models. Glial fibrillary acidic protein and ferritin expression levels increased, and the levels of glutamate transporter 1 and transferrin receptor 1 decreased in aging mouse spinal cord and its astrocytes. Mitochondrial transmembrane potential in astrocytes decreased after 60 d of culture. Given the relationship between aging and loss of antioxidant tolerance capacity, we examined the expression of heme oxygenase 1 (HO1) and NAD(P)H/quinone oxidoreductase 1 (NQO1) in the old mouse astrocytes and spinal cord. Indeed, both antioxidant enzymes decreased there. Total nuclear factor E2-related factor 2, which governs basal and inducible expression of HO1 and NQO1, decreased significantly. Significantly, epigallocatechin gallate restored the Nrf2 activity.

The research tries to establish Wistar rat's model of atherosclerosis for evaluating the antiatherosclerotic effect of hederagenin and exploring its antiatherosclerosis-related mechanisms. The statistical data have shown that hederagenin exhibits multiple pharmacological activities in the treatment of hyperlipidemia, antiplatelet aggregation, liver protection, and anti-inflammation, indicating that hederagenin may exert a protective effect on vascular walls by improving lipid metabolism disorders and lipid deposition. The results show that hederagenin can correct the imbalance of endothelial function by inhibiting the release of large amounts of iNOS and increasing eNOS contents and inhibits the IKKβ/NF-κB signaling pathway to reduce the release of IL-6, IFN-γ, TNF-α, and other inflammatory factors. The experimental results indicated that hederagenin can inhibit or ameliorate the pathological changes associated with AS, displaying an excellent preventive function against AS.

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KXP may have a similar effect as ramelteon. KXP improved depressive-like behavior by increasing the concentration of plasma MT and MT1 expression, thereby increasing three B(max) of MR to achieve the desired antidepressant effect.

Aim: To evaluate the efficacy and safety of DBPR108 (prusogliptin), a novel dipeptidyl peptidase-4 (DPP-4) inhibitor, as an add-on therapy in patients with type 2 diabetes (T2D) that is inadequately controlled with metformin. Materials and Methods:In this 24-week, multi-centre, randomized, double-blind, placebo-controlled, superiority, phase III study, adult T2D patients with HbA1c levels ranging from 7.0% to 9.5% on stable metformin were enrolled and randomized (2:1) into the DBPR108 + metformin and placebo + metformin groups. The primary endpoint was the change from baseline in HbA1c at week 24 of DBPR108 versus placebo as an add-on therapy to metformin.Results: At week 24, the least-square mean (standard error) change from baseline in HbA1c was significantly greater in the DBPR108 group (À0.70% [0.09%]) than in the placebo group (À0.07% [0.11%]) (P < .001), with a treatment difference of À0.63% (95% confidence interval: À0.87%, À0.39%) on the full analysis set. A higher proportion of patients achieved an HbA1c of 6.5% or less (19.7% vs. 8.5%) and an HbA1c of 7.0% or less (50.0% vs. 21.1%) at week 24 in the DBPR108 + metformin group. Furthermore, add-on DBPR108 produced greater reductions from baseline in fasting plasma glucose and 2-hour postprandial plasma glucose without causing weight gain. The overall frequency of adverse events was similar between the two groups.Conclusions: DBPR108 as add-on therapy to metformin offered a significant improvement in glycaemic control, was superior to metformin monotherapy (placebo) and was safe and well-tolerated in patients with T2D that is inadequately controlled with metformin.