Graptopetalum paraguayense Extract Ameliorates Proteotoxicity in Aging and Age-Related Diseases in Model Systems.

Declines in physiological functions are the predominant risk factors for age-related diseases, such as cancers and neurodegenerative diseases. Therefore, delaying the aging process is believed to be beneficial in preventing the onset of age-related diseases. Previous studies have demonstrated that Graptopetalum paraguayense (GP) extract inhibits liver cancer cell growth and reduces the pathological phenotypes of Alzheimer's disease (AD) in patient IPS-derived neurons. Here, we show that GP extract suppresses ß-amyloid pathology in SH-SYS5Y-APP695 cells and APP/PS1 mice. Moreover, AMP-activated protein kinase (AMPK) activity is enhanced by GP extract in U87 cells and APP/PS1 mice. Intriguingly, GP extract enhances autophagy in SH-SYS5Y-APP695 cells, U87 cells, and the nematode Caenorhabditis elegans, suggesting a conserved molecular mechanism by which GP extract might regulate autophagy. In agreement with its role as an autophagy activator, GP extract markedly diminishes mobility decline in polyglutamine Q35 mutants and aged wild-type N2 animals in C. elegans. Furthermore, GP extract significantly extends lifespan in C. elegans.

Garcinoxanthones SV, new xanthone derivatives from the pericarps of Garcinia mangostana together with their cytotoxic and antioxidant activities.

Xanthones (9H-xanthene-9-ones) are considered to be very promising compounds due to a variety of interesting biological and pharmacological activities. In this study, column chromatography of the methanol extract of the Garcinia mangostana L. pericarps resulted in the isolation of four new xanthones (garcinoxanthones SV, 1-4) and five known analogs including garcinone E (5), 11-hydroxy-1-isomangostin (6) mangostenone E (7), 1,3,6,7-tetrahydroxyxanthone (8), and α-mangostin (9). The structures of the new compounds were elucidated by NMR, HRESIMS, and ECD spectra. Compound 8 (1,3,6,7-tetrahydroxyxanthone) was found from the G. mangostana pericarps for the first time. All the isolated compounds (1-8) were evaluated for their 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging capacity and cytotoxicity in vitro against three human cancer cell lines including SK-LU-1, MCF7, and HT-29 cell lines. Compounds 3, 5, and 8 exhibited significant DPPH scavenging capacity with IC50 values of 68.55, 63.05, and 28.45 µM, respectively, in comparison with ascorbic acid (IC50 = 48.03 µM). Compounds 5 and 8 showed moderate cytotoxic effects against the three human cancer cell lines with IC50 value ranges of 19.86-27.38 µM.

Controllable growth of Au nanostructures onto MoS2 nanosheets for dual-modal imaging and photothermal-radiation combined therapy.

Multifunctional theranostic nanoagents are attractive to realize comprehensive imaging and effective treatment of tumours. Herein, a novel strategy is developed to controllably guide the epitaxial growth of gold nanostructures onto MoS2 nanosheets. The as-prepared MoS2-Au nanostructures (MA) manifest an enhanced near-infrared (NIR) absorbance with strong photostability. After modification, the obtained MA-PEG shows strong X-ray attenuation and photothermal conversion ability, promising for CT and photoacoustic imaging with an enhanced intensity in tumours. Moreover, in vivo photothermal and radiation therapy with MA-PEG achieves synergistic tumour treatment efficiency through hyperthermia elevated oxygenation level and sensitized radiation therapy. This work illustrates the development of a unique MA nanostructure with enhanced NIR absorbance and strong photoelectric absorbance as a multifunctional theranostic agent with great potential for dual-modal imaging-guided photothermal-radiation therapy of cancer.