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Abstract: Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases with chronic, progressive, and irreversible characteristics, affecting nearly 50 million older adults worldwide. The pathogenesis of AD includes the formation of senile plaques, the abnormal aggregation of tau protein and the gradual degeneration and death of cerebral cortical cells. The main symptoms are memory loss, cognitive decline and behavioral disorders. Studies indicate that cannabidiol (CBD) possesses various pharmacological activities, including anti-inflammatory, anti-oxidation and neuroprotective activities. It has been suggested as a potential multi-target medicine for the treatment of AD. In this review, we aim to summarize the underlying mechanisms and protective effects of CBD on signaling pathways and central receptors involved in the pathogenesis of AD, including the endocannabinoid system (eCBs), the Transient receptor potential vanilloid type 1(TRPV1) receptor, and the Peroxisome proliferator-activated receptor (PPAR) receptor.

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.

Diabetes and cognitive dysfunction are highly prevalent disorders, while the underlying mechanism is still elusive. The effects of Gastrodin on central nervous system have been emphasized recently. In this study, we aim to explore the potential mechanism leading to cognitive dysfunction in diabetes and the therapeutic effect of Gastrodin. Diabetes was induced by a single injection of streptozotocin. RNA sequencing technique was used to identify the potential factors involved. Western blot and immunofluorescence were applied to detect the protein expression. Our results have shown that spatial learning was impaired and hippocampal pyramidal neurons were damaged in diabetic rats, which could be ameliorated by Gastrodin intervention. Transcriptional analysis identified differential expression genes, which were confirmed by qPCR and western blot. Furthermore, p21 activated kinase 2 (PAK2) was selected and its inhibitor could promote the survival of primary hippocampal neurons. It suggested that PAK2 pathway may be involved in cognitive dysfunction in diabetes and a therapeutic target for Gastrodin intervention.

Background Diastolic dysfunction is the most common change of diabetic cardiomyopathy (DCM), but there is no effective clinical treatment at present. Oxidative stress plays a crucial role in the pathophysiological process of diabetic diastolic dysfunction including hypertrophy, apoptosis and fibrosis. The novel Oral-edaravone (OED) alleviates oxidative stress by scavenging free radical and may be suitable for the treatment of chronic diseases such as DCM. Methods DCM was induced by high sugar and high fat diet with intraperitoneal injection of streptozotocin (STZ) in rats. OED (3mg/kg/day) was administration for 4 weeks. Cardiac structure and function were measured using transthoracic echocardiography. H9C2 cardiomyocytes with Nrf2 transfection or not were incubated in glucolipotoxicity and treated with OED for 48 hours to further explore the mechanism. Results In type 2 diabetic rats,oral administration of OED for 4 weeks decreased malondialdehyde (MDA) and increased superoxide dismutase (SOD). OED significantly improved E/A ratio and myocardium hypertrophy accompanied by decreased cross-sectional area of cardiomyocytes, proportion of apoptotic cells, collagen volume fractions and depositions of collagen I/III. In H9C2 cells, OED reduced reactive oxygen species (ROS), cell surface area and TUNEL-positive cells induced by glucolipotoxicity. OED remarkably up-regulated the expression of the Nrf2 signaling pathway both in vivo and in vitro, further promoted Nrf2 nuclear translocation and up-regulated nicotinamide adenine dinucleotide phosphate quinone oxidoreductase (NQO1) and heme oxygenase (HO-1). Moreover, Nrf2 gene silencing abolished the protective effect of OED in H9c2 cells. Conclusion Our findings demonstrated that OED treatment has the therapeutic potential to ameliorate diastolic dysfunction of DCM. The effect is mainly achieved by attenuating hyperglycemia and hyperlipidemia-induced cardiomyocytes hypertrophy, apoptosis and fibrosis via activating the Nrf2 signaling pathway.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Evidence suggests that people can benefit from consumption of diets rich in plant phenolics because they can attenuate AD symptoms. The phenolic glucoside gastrodin is the main bioactive compound of Rhizoma Gastrodiae and is widely used for treating various neurological disorders. In this study, we assess whether long term oral administration of gastrodin can improve cognitive impairment and AD-like pathology. Our results showed that chronic gastrodin administration inhibits aggregation and disaggregate oligomeric and fibrillar species of A beta 42, prevents A beta 42 induced neurotoxicity in cell SH-SY5Y, decreases the levels of A beta plaques and hyperphosphorylated tau, alleviates activation of glial cells and proinflammatory cytokines, attenuates oxidative stress in the APP/PS1 transgenic mice. The mechanisms underlying can be attributed to the inhibition levels of enzymes of A beta and prevention GSK3 beta activity. Our results suggest that gastrodin might be a potential agent for the treatment of AD. Refereed/Peer-reviewed

Chronic stress has been known as a main cause for human mood disorders. The understanding of the pathogenesis of the mood disorders are primarily based on the usage of animal models.Low reproducibility and complicacy of production are commonly known shortcomings in the current models with chronic stress. Here, we tested a simple stress paradigm, daily exposure of 6-min tail-suspension (TS), in modelling chronic stress-induced mood disorders in mice. We found that after 2-3-weeks of TS stress mice displayed a significant decrease in exploratory behavior, increases in anxiety-like and depression-like behaviors as well as significant decreases of NeuN and GFAP levels in the hippocampus. We also found that longer exposure of mice to TS stress (up to 4 weeks) resulted in significant adaptation of these responses and reversal of most of the behavioural and biochemical changes. This study suggests that chronicTS stress for 2-3 weeks could be used as a model of mood disorders usc Refereed/Peer-reviewed

The extracellular accumulation of amyloid beta protein (Aβ), reactive gliosis and cerebral amyloid angiopathy (CAA) play critical roles in the pathogenesis of Alzheimer’s disease (AD). Ginkgetin, a biflavone isolated from Ginkgo biloba leaves, was previously reported to exhibit strong neuroprotection against cytotoxic insults induced by oxidative stress and amyloid beta, but it remains unclear whether ginkgetin has therapeutic effect on Alzheimer’s disease (AD) in vivo. In the present study, we investigated 9 months treatment effects of ginkgetin diet in APP/PS1 mice. Our results show that ginkgetin can significantly reduce plasma Aβ levels 59% and Aβ plaque 51% in the brain of APP/PS1 transgenic mice (P

Refereed/Peer-reviewed Alzheimer's disease (AD) is a highly prevalent neurodegenerative disorder characterized by the pathological hallmarks of β-amyloid plaque deposits, tau pathology, inflammation, and cognitive decline. Hyperoside, a flavone glycoside isolated from Rhododendron brachycarpum G. Don (Ericaceae), has neuroprotective effects against Aβ 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 GSK3β 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.