Protective effect of betulin on cognitive decline in streptozotocin (STZ)-induced diabetic rats.

Betulin is extracted from birch tree bark and exerts diverse pharmacological activities. The present study was designed to investigate the protective effect of betulin (BE) on cognitive decline in streptozotocin (STZ)-induced diabetic rats. The diabetic model was built by streptozotocin (STZ) (30mg/kg, ip). After 4 weeks, the diabetic rats were treated with vehicle or BE (20mg/kg, 40mg/kg) for 4 weeks. The oral glucose tolerance (OGTT) and serum insulin were detected. Three days later, Morris water maze (MWM) test was used to evaluate memory function. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in hippocampus were examined. Inflammatory cytokines including interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) in serum and hippocampus were measured. The protein expressions of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and NF-κB pathways-related molecules in hippocampus were examined. As a results, BE could improve glucose intolerance and modify basal learning performance. Treatment with BE significantly restored SOD activity and decreased MDA content in hippocampus. BE also markedly reduced the contents of inflammatory cytokines in serum and hippocampus. Furthermore, administration of BE effectively upregulated the expressions of Nrf2, HO-1 and blocked the phosphorylations of IκB, NF-κB. In summary, BE might exhibit protective effect on cognitive decline in STZ-induced diabetic rats through HO-1/Nrf-2/NF-κB pathway.

Ma C ，Long H 《-》

The protective effect of formononetin on cognitive impairment in streptozotocin (STZ)-induced diabetic mice.

The present study was aimed to elucidate the pharmacological effect of Formononetin (FMN) treatment on STZ-induced diabetic cognitive dysfunction. The diabetic model was induced by an intraperitoneally injection of 180 mg/kg STZ. The animals were randomly divided into five groups: control group, streptozocin (STZ, 180 mg/kg) group, STZ + metformin (Met, 200 mg/kg) group, STZ + FMN (25 mg/kg) group, STZ + FMN (50 mg/kg) group. The mice were intragastrically administrated with metformin (Met, 200 mg/kg) or FMN (25, 50 mg/kg) once daily for 6 weeks. The blood glucose content and body weight were examined. Morris water maze test and Y maze test were used to evaluate the learning and memory abilities. The cognitive decline was reversed by regulating superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-a (TNF-α), interleukin(IL)-1β, IL-6 in serum and hippocampus. The protein expressions of high mobility group box-1 protein (HMGB1), toll like receptor 4 (TLR4), myeloid differentiating factor 88 (MyD88), inhibitor of NF-κB (IκBα), p-IκBα, nuclear factor kappa-B(NF-κB), p-NF-κB, NOD-like receptor 3(NLRP3), apoptosis-associated speck-like protein containing CARD(ASC) and caspase-1 were detected. Furthermore, the SH-SY5Y cells were exposed to high glucose stimulation, FMN (2.5, 5 and 10 μM) treatment, and glycyrrhizin, the selective inhibitor of HMGB1. After an incubation for 22 h, the SH-SY5Y cells were harvested for detection. As a result, FMN treatment effectively attenuated the body weight, learning and memory abilities, as well as the levels of blood glucose, SOD, MDA, TNF-α, IL-1β, IL-6. FMN administration also downregulated the protein expressions of HMGB1, TLR4, MyD88, p-IκB, p-NF-κB, NLRP3, ASC and caspase-1. The inhibition of HMGB1 by glycyrrhizin also confirmed the involvement of HMGB1/TLR4/NF-κB/NLRP3 pathway in high glucose-induced SH-SY5Y cells. In summary, the results suggested that FMN exhibited the protective effect on STZ-induced cognitive impairment possibly via the mediation of HMGB1/TLR4/NF-κB signaling and NLRP3 inflammasome.

Wang J ，Wang L ，Zhou J ，Qin A ，Chen Z ... -  《-》

The protective effect of betulinic acid (BA) diabetic nephropathy on streptozotocin (STZ)-induced diabetic rats.

Xie R ，Zhang H ，Wang XZ ，Yang XZ ，Wu SN ，Wang HG ，Shen P ，Ma TH ... -  《-》

Albiflorin alleviates cognitive dysfunction in STZ-induced rats.

Ma X ，Song M ，Yan Y ，Ren G ，Hou J ，Qin G ，Wang W ，Li Z ... -  《-》

Prophylactic Use of Troxerutin Can Delay the Development of Diabetic Cognitive Dysfunction and Improve the Expression of Nrf2 in the Hippocampus on STZ Diabetic Rats.

Zhang S ，Yuan L ，Zhang L ，Li C ，Li J ... -  《-》