Studies On The Constituents Of Paeonia Suffruticosa Andr. And Their Inhibiting Effects On AGE Formation

The formation of AGEs plays an important role in the occurrence and development of many diseases induced by diabetes and aging, such as diabetic nephropathy, diabetic cataract, arteriosclerosis and Alzheimer's disease. Recently, developing more effective and less toxic AGEs formation inhibitors from traditional Chinese medicine has attracted the attention of researchers. In this study, 15 traditional Chinese medicines, which were considered to be able to invigorate blood circulation, have been screened for inhibiting effects on AGEs formation, in vitro, and Paeonia suffruticosa, which showed the best activity, has been selected for further study of its chemical constituents and AGEs formation inhibiting activity.Plants of the Paeonia genus are known to produce structurally unique "cage-like" pinane skeleton monoterpenes with a wide range of interesting physiological effects, including CNS, cardiovascular, liver protection, hypoglycemic and hypolipidemic effects.Extensive column chromatography led to the isolation 20 compounds, including seven new monoterpenes, named 4-O-Methyl-6'-benzoyl-4'"-hydroxyl-paeoniflorin (5), 4-O-Methyl-6'-benzoyl-4"-hydroxyl-paeoniflorin (6), 4"-Hydroxy-4"'- O-methyl -benzoylpaeonidanin (10), 4"'-Hydroxyl-benzoylpaeonidanin (11), 4"-Hydroxy-benzoylpaeonidanin (12), 4"-Hydroxy-4"'-O-hydroxy-benzoylpaeonidanin (13), 4-Thujone-7-hydroxyl-8-O-β-D-glucopyranoside (14). Other compounds were determined by spectral analysis, named 4-O-Methylpaeoniflorin (1), Paeonidanin (2), Paeonifiorigenone (3), Paeoniflorin (4), Benzoylpaeoniflorin (7), Benzoyloxy-paeoniflorin (8), Mudanpioside C (9), (+)-Catechin (15), Paeonol (16), Gallic acid (17), 2'-Methylorthheptyl-phthalate (18), 2,5-Dihydroxyl-4-methoxylacetophenone (19),β-Sitosterol (20). Compound 1 was isolated from plants for the first time, compound 15 was isolated from the genus paeonia for the first time and compound 2 and 3 were isolated from this plant for the first time.Six compounds have been tested for their AGEs inhibiting activities. Compound 15 and 17 exhibited strong activity, and showed clear dose-effect relationship at certain concentrations. According to the literatures, compounds 15 and 17 can scavenge the 1,1-diphenyl-2-picrylhydrazyl radical and superoxide anion radical generated by the xanthine-xanthine oxidase system. The inhibiting activities of compounds 15 and 17 on AGEs formation may correlate with the free radical scavenging mechanism. This result suggested that compounds with radical- scavenging activity might be a potential source for AGEs formation inhibitors.