Brusatol

Brusatol (BRU), an extract from Brucea javanica, has been found to inhibit cancer progression. However, the downstream targets of Brusatol and its underlying mechanisms in lung cancer still not fully elucidate and warrant further investigation. Here, we identified that Brusatol significantly downregulated the mRNA and protein levels of phosphoserine aminotransferase 1 (PSAT1). Notably, overexpression of PAST1 could impair the antitumour effects of Brusatol on lung cancer cells in vitro and in vivo. Further mechanism studies revealed that FOXM1, an important transcription factor, was directly bound to the promoter of PSAT1, facilitating its transcription. Besides, FOXM1 upregulation antagonizes Brusatol's suppression of PSAT1 and sustains tumor cell viability. Collectively, our data suggested that the FOXM1/PSAT1 axis might play an important role in the antitumour effects of Brusatol and that Brusatol may hold promise as a novel therapeutic strategy for lung cancer.

Alzheimer's disease (AD) is a progressive neurodegenerative disease with no effective therapies. 4,4'-Dimethoxychalcone (DMC) is a natural chalcone extracted from Angelica keiskei (Miq.) Koidz and Angelica sinensis (Oliv.) Diels, which could promote autophagy and prolong lifespan. However, the neuroprotective effects and mechanisms of DMC on AD mice have not been reported. In this study, we proved that DMC treatment significantly mitigated cognitive impairment and depressive behavior, ameliorated blood-brain barrier permeability and amyloid β pathology, and inhibited p-Tau expression in 5 × FAD mice. Also, DMC suppressed glial cell activation, enhanced neurogenesis, and decreased oxidative stress in vivo and in vitro by activating the Kelch-like ECH-associated protein1 (Keap1)/nuclear factor-erythrocyte 2-associated factor 2 (Nrf2) signaling pathway. However, Brusatol, an inhibitor of the Keap1/Nrf2 signalling, partly attenuated the neuroprotective effects of DMC on lipopolysaccharide-induced HT22 cells injury and 5 × FAD mice. In conclusion, DMC exhibited neuroprotective effects on 5 × FAD mice via the activation of Keap1/Nrf2 signalling pathway. Thus, DMC may be a promising therapeutic drug for AD.