Nobiletin Improves D-Galactose-Induced Aging Mice Skeletal Muscle Atrophy by Regulating Protein Homeostasis.

Sarcopenia, a decrease in skeletal muscle mass and function caused by aging, impairs mobility, raises the risk of fractures, diabetes, and other illnesses, and severely affects a senior's quality of life. Nobiletin (Nob), polymethoxyl flavonoid, has various biological effects, such as anti-diabetic, anti-atherogenic, anti-inflammatory, anti-oxidative, and anti-tumor properties. In this investigation, we hypothesized that Nob potentially regulates protein homeostasis to prevent and treat sarcopenia. To investigate whether Nob could block skeletal muscle atrophy and elucidate its underlying molecular mechanism, we used the D-galactose-induced (D-gal-induced) C57BL/6J mice for 10 weeks to establish a skeletal muscle atrophy model. The findings demonstrated that Nob increased body weight, hindlimb muscle mass, lean mass and improved the function of skeletal muscle in D-gal-induced aging mice. Nob improved myofiber sizes and increased skeletal muscle main proteins composition in D-gal-induced aging mice. Notably, Nob activated mTOR/Akt signaling to increase protein synthesis and inhibited FOXO3a-MAFbx/MuRF1 pathway and inflammatory cytokines, thereby reducing protein degradation in D-gal-induced aging mice. In conclusion, Nob attenuated D-gal-induced skeletal muscle atrophy. It is a promising candidate for preventing and treating age-associated atrophy of skeletal muscles.

[A comparison of different treatment conditions on the conformation changes of bovine lactoferrin].

In this study, the tertiary, secondary structures and disulfide bond changes of bovine lactoferrin (bLF) under 6 differents physico-chemical treatments were investigated by fluorescence, circular dichroism(CD) and UV-Vis absorption. A red shift from 333 to 354 nm in the fluorescence emission maximum (lambda(max)) was observed in the bLF treated by 6 mol x L(-1) GdnHCl, 8 mol x L(-1) Urea and 50 mmol x L(-1) DTT simultaneously, meanwhile a large number of exposed hydrophobic groups were detected. However, there was no marked shift in lambda(max) of bLF treated by heating (100 degrees C, 5 min), Ultrosonic(450 W, 5 s, 6 pulses) or beta-ME (1%), of which fluorescence intensity decreased significantly compared with the untreated bLF. The results indicated that the mechanism of changes in tertiary structure of the former three methods were different from the latter three. The detection by CD showed that the alpha- helix structure vanished completely in the bLF treated by GdnHCl. However, there was no remarkable change in the secondary structure of the bLF treated by the other five methods. In addition, UV-Vis absorption suggested that disulfide bond was seriously destructed in the bLF treated by DTT and Ultrosonict, but GdnHCl, beta-ME and heating induced a little damage merely. This study is instructive and meaningful to the further research on relationship between structure and activity of bLF.