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Brain-type glycogen phosphorylase inhibitors are potential new drugs for treating ischemic brain injury. In our previous study, we reported compound 1 as a novel brain-type glycogen phosphorylase inhibitor with cardioprotective properties. We also found that compound 1 has high blood–brain barrier permeability through the ADMET prediction website. In this study, we deeply analyzed the protective effect of compound 1 on hypoxic-ischemic brain injury, finding that compound 1 could alleviate the hypoxia/reoxygenation (H/R) injury of astrocytes by improving cell viability and reducing LDH leakage rate, intracellular glucose content, and post-ischemic ROS level. At the same time, compound 1 could reduce the level of ATP in brain cells after ischemia, improve cellular energy metabolism, downregulate the degree of extracellular acidification, and improve metabolic acidosis. It could also increase the level of mitochondrial aerobic energy metabolism during brain cell reperfusion, reduce anaerobic glycolysis, and inhibit apoptosis and the expression of apoptosis-related proteins. The above results indicated that compound 1 is involved in the regulation of glucose metabolism, can control cell apoptosis, and has protective and potential therapeutic effects on cerebral ischemia-reperfusion injury, which provides a new reference and possibility for the development of novel drugs for the treatment of ischemic brain injury. [ABSTRACT FROM AUTHOR]

Background: Diosgenin, obtained from Dioscorea nipponica Makino, possesses anti-inflammatory properties. Objective: The objective of this study is to explore the therapeutic effects of diosgenin against collagen-induced arthritis (CIA) in DBA/1J mice. Materials and Methods: The CIA model was established using chicken type II collagen-immunized DBA1/J mice (0.1 mL/mouse), with the same stimulus repeated on day 21. Next, the CIA mouse model was selected, and inguinal lymph nodes were excised to obtain a single-cell suspension. Using CCK-8, control group, model group, and high-/medium-/low-dose diosgenin group were set based on drug toxicity. Next, the ratio of T-helper 17 cells (Th17) to CD3+ T cells was analyzed using flow cytometer. The levels of interleukin 17 (IL)-17 and IL-6 were determined by the enzyme-linked immunosorbent assay. The expression of RORγt was determined using the reverse-transcription quantitative real-time polymerase chain reaction and Western blot analysis. Results: An in vitro inhibitory rate of ≥ 70% was set as the cutoff value to select the high (25 μmol/L), medium (12.5 μmol/L), and low (6.25 μmol/L) doses of diosgenin. The Th17 cell ratio in CD3+ T cells, the levels of IL-17 and IL-6, and mRNA and protein expression of RORγt showed significantly increased tendency in the model group compared with the control group (P < 0.01 and/or P < 0.05). Diosgenin significantly decreased the Th17 cell ratio in CD3+ T cells, IL-17 and IL-6 levels, and RORγt expression when compared with the model group (P < 0.01 and/or P < 0.05). Conclusion: Diosgenin exhibited an antiarthritic effect in CIA mice by downregulating the differentiation of Th17 cells. [ABSTRACT FROM AUTHOR]

Objective: To study the dynamic changes of Th1-type cytokines IFN-γ, IL-2, TNF-α in the serum of chicken type II collagen-induced arthritis (CIA) in mice., Methods: A total of 72 DBA1/J mice were randomly divided into control group (n=24) and model group (n=48), and each group was subgrouped into 4 groups (n=6 in control subgroup and n=12 in model subgroup) according to the time of taking the eyeball for blood and separating the serum under sterile condition (7, 14, 21 and 35 days after booster immunization). The dynamic changes of cytokines IFN-γ, IL2 and TNF-α in different periods were detected by flow cytometry., Results: The level of IFN-γ in the model group was significantly higher than that in the control group on the 7 day and 14 day after booster immunization (P<0.05), and it began to decline on the 21 day and there were no significant differences between the model group and the control group on the 21 day and 35 day (P>0.05). The levels of IL-2 and TNF-α in the model group on the 7 day after booster immunization significantly increased as compared with those of the control group (P<0.05), however, on the 14, 21 and 35 day there were no significant differences between the model group and the control group (P>0.05)., Conclusion: CD4⁺; Th1 cytokines participate in the pathogenesis of CIA and their alterations at different stages of the disease have a relation to the development of arthritis.