Long-term oral administration of hyperoside ameliorates AD-related neuropathology and improves cognitive impairment in APP/PS1 transgenic mice.

Alzheimer's disease (AD) is a highly prevalent neurodegenerative disorder characterized by the pathological hallmarks of ß-amyloid plaque deposits, tau pathology, inflammation, and cognitive decline. Hyperoside, a flavone glycoside isolated from Rhododendron brachycarpum G. Don (Ericaceae), has neuroprotective effects against Aß both in vitro and in vivo. However, whether hyperoside could delay AD pathogenesis remains unclear. In the present study, we observed if chronic treatment with hyperoside can reverse pathological progressions of AD in the APP/PS1 transgenic mouse model. Meanwhile, we attempted to elucidate the molecular mechanisms involved in regulating its effects. After 9 months of treatment, we found that hyperoside can improve spatial learning and memory in APP/PS1 transgenic mice, reduce amyloid plaque deposition and tau phosphorylation, decrease the number of activated microglia and astrocytes, and attenuate neuroinflammation and oxidative stress in the brain of APP/PS1 mice. These beneficial effects may be mediated in part by influencing reduction of BACE1 and GSK3ß levels. Hyperoside confers neuroprotection against the pathology of AD in APP/PS1 mouse model and is emerging as a promising therapeutic candidate drug for AD.

Umbilical Cord Mesenchymal Stem Cells for Inflammatory Regulation After Excision and Grafting of Severe Burn Wounds in Rats.

Severe burns predispose to shock and necessitate escharectomy and skin grafting. Previous studies show that mesenchymal stem cells are effective for burn wound healing and immune regulation. In this study, we combined escharectomy and skin grafting after burn injury with stem cell application, so as to examine the immune regulation of stem cells and the effect on the transplanted skin graft. SD rats were randomly divided into normal group, sham group, normal + hUCMSCs group, and normal + SB203580 group. Normal saline, hUCMSCs, and SB203580 were injected into the tail vein of each group, and serum inflammatory factors were detected by ELISA. The expression of p38 MAPK/NF-κB pathway proteins in rat liver was detected by western blot. Skin activity was detected by Trypan blue staining and western blot. Skin graft inflammatory infiltration was detected by histological analysis. We found that hUCMSCs could regulate the phosphorylation levels of P38MAPK and NF-B P65 proteins in the liver to reduce the inflammatory response. These effects could continue to reduce the production of inflammatory factors HMGB-1, IL-6, and TNF-α, and increase the anti-inflammatory factor IL-10. The infiltration of inflammatory cells in skin graft was significantly reduced in the normal + hUCMSCs group, and the macrophages in the hUCMSCs group polarized to the anti-inflammatory M2 direction in 3 days. However, the changes of skin graft activity and necroptosis markers protein RIP3 were not observed. The present study demonstrates the immunomodulatory effects of hUCMSCs on the systemic and skin graft microenvironment after excision.