Pyrazine Derivatives and Spiro Alkaloids From Zingiberis Rhizoma Praeparatum and Their Protective Effects on Hydrogen Peroxide-induced Human Umbilical Vein Endothelial Cells.

One new pyrazine derivative, 4-[(8'-hydroxypyrazinyl)-2'-yl]-1,3,3-butanetriol (1), along with five known compounds (2-6) was isolated from Zingiberis Rhizoma Praeparatum (ZRP). Their structures were elucidated by one-dimensional (1D), two-dimensional nuclear magnetic resonance (2D-NMR), high-resolution electrospray ionization mass spectrometry spectroscopic data analysis, quantum chemical calculations of NMR Shifts (DP4+), and electronic circular dichroism calculation. Compounds 1, 2, and 5 demonstrated the protective effect on the hydrogen peroxide-damaged human umbilical vein endothelial cells within the safe concentration range. Based on the results, those isolates exert their antioxidant effects by regulating the intracellular antioxidant enzymes superoxide dismutase, glutathione peroxidase, L-lactic dehydrogenase activity, malonaldehyde content, and reactive oxygen species expression. Most noteworthy is the mentioned substances may secret vascular endothelial growth factors to promote the formation of blood tube generation. The results indicated that pyrazines and morpholines may be the candidate compositions of ZRP for the treatment of hemorrhagic disorders.