Background: Epidemiological evidence suggests that consumption of phenolic compounds reduce the incidence of Alzheimer disease (AD). Results: Myricetin and rosmarinic acid reduced cellular and synaptic toxicities by inhibition of amyloid ␤-protein (A␤) oligomerization. Myricetin promoted NMR changes of A␤. Conclusion: Phenolic compounds are worthy therapeutic candidates for AD. Significance: Phenolic compounds blocked early assembly processes of A␤ through differently binding.

Brassinosteroids (BRs) are growth-promoting plant hormones that play a crucial role in biotic stress responses. Here, we found that BR treatment increased nitric oxide (NO) accumulation, and a significant reduction of virus accumulation in Arabidopsis thaliana. However, the plants pre-treated with NO scavenger [2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-1-oxyl-3-oxide (PTIO)] or nitrate reductase (NR) inhibitor (tungstate) hardly had any NO generation and appeared to have the highest viral replication and suffer more damages. Furthermore, the antioxidant system and photosystem parameters were up-regulated in brassinolide (BL)-treated plants but down regulated in PTIO- or tungstate-treated plants, suggesting NO may be involved in BRs-induced virus resistance in Arabidopsis. Further evidence showed that NIA1 pathway was responsible for BR-induced NO accumulation in Arabidopsis. These results indicated that NO participated in the BRs-induced systemic resistance in Arabidopsis. As BL treatment could not increase NO levels in nia1 plants in comparison to nia2 plants. And nia1 mutant exhibited decreased virus resistance relative to Col-0 or nia2 plants after BL treatment. Taken together, our study addressed that NIA1-mediated NO biosynthesis is involved in BRs-mediated virus resistance in A. thaliana.

Arabidopsis thaliana homeodomain-leucine zipper protein 1 (HAT1) belongs to the homeodomain-leucine zipper (HD-Zip) family class II that plays important roles in plant growth and development as a transcription factor. To elucidate further the role of HD-Zip II transcription factors in plant defense, the A. thaliana hat1, hat1hat3 and hat1hat2hat3 mutants and HAT1 overexpression plants (HAT1OX) were challenged with Cucumber mosaic virus (CMV). HAT1OX displayed more susceptibility, while loss-of-function mutants of HAT1 exhibited less susceptibility to CMV infection. HAT1 and its close homologs HAT2 and HAT3 function redundantly, as the triple mutant hat1hat2hat3 displayed increased virus resistance compared with the hat1 and hat1hat3 mutants. Furthermore, the induction of the antioxidant system (the activities and expression of enzymatic antioxidants) and the expression of defense-associated genes were down-regulated in HAT1OX but up-regulated in hat1hat2hat3 when compared with Col-0 after CMV infection. Further evidence showed that the involvement of HAT1 in the anti-CMV defense response might be dependent on salicylic acid (SA) but not jasmonic acid (JA). The SA level or expression of SA synthesis-related genes was decreased in HAT1OX but increased in hat1hat2hat3 compared with Col-0 after CMV infection, but there were little difference in JA level or JA synthesis-related gene expression among HAT1OX or defective plants. In addition, HAT1 expression is dependent on SA accumulation. Taken together, our study indicated that HAT1 negatively regulates plant defense responses to CMV.

Sinomenine hydrochloride (SH) is an ideal drug for the treatment of rheumatoid arthritis and osteoarthritis. However, high plasma concentration of systemically administered SH can release histamine, which can cause rash and gastrointestinal side effects. Topical delivery can increase SH concentration in the synovial fluid without high plasma level, thus minimizing systemic side effects. However, passive diffusion of SH was found to be inefficient because of the presence of the stratum corneum layer. Therefore, an effective method is required to compensate for the low efficiency of SH passive diffusion. In this study, transdermal experiments in vitro and clinical tests were utilized to explore the optimized parameters for electroporation of topical delivery for SH. Fluorescence experiment and hematoxylin and eosin staining analysis were performed to reveal the mechanism by which electroporation promoted permeation. In vitro, optimized electroporation parameters were 3 KHz, exponential waveform, and intensity 10. Using these parameters, transdermal permeation of SH was increased by 1.9–10.1 fold in mice skin and by 1.6–47.1 fold in miniature pig skin compared with passive diffusion. After the electroporation stimulation, the intercellular intervals and epidermal cracks in the skin increased. In clinical tests, SH concentration in synovial fluid was 20.84 ng/mL after treatment with electroporation. Therefore, electroporation with optimized parameters could significantly enhance transdermal permeation of SH. The mechanism by which electroporation promoted permeation was that the electronic pulses made the skin structure looser. To summarize, electroporation may be an effective complementary method for transdermal permeation of SH. The controlled release of electroporation may be a promising clinical method for transdermal drug administration.