Inhibitory activity of isoflavones of Pueraria flowers on nitric oxide production from lipopolysaccharide-activated primary rat microglia.

Abstract

Microglial activation plays an important role in alcohol-induced neuroinflammation. In search for natural medicines that may be of therapeutic potential for alcoholism, two new natural isoflavone glycosides, 6-hydroxybiochanin A-6,7-di-O-beta-d-glucopyranoside (1) and 6-hydroxygenistein-7-O-beta-d-glucopyranoside (2), were isolated from the ethanolic extract of the flowers of Pueraria thomsonii Benth., together with the seven known isoflavones, genistein (3), tectorigenin (4), irisolidone (5), genistin (7), tectoridin (8), tectorigenin-7-O-beta-d-xylosyl-(1 --> 6)-beta-d-glucopyranoside (9), and 6-hydroxygenistein-6,7-di-O-beta-d-glucopyranoside (11). Moreover, gehuain (6) and kakkalide (10) were obtained from the flowers of Pueraria lobata (Willd.) Ohwi. The structures of the new compounds were elucidated by UV, IR, HR-MS, and 1D and 2D NMR spectroscopic methods. Compounds 3-5 substantially inhibited the lipopolysaccharide-induced nitric oxide release from primary cultured rat cortical microglia (IC50: 1.3-9.3 microM). The inhibitory effects of compounds 6, 8, 9, and 11 (IC50: 38-62 microM) were significant but weaker than the above aglycones. However, compounds 1, 2, 7, and 10 showed little inhibitory activity. With regard to the structure-activity relationships of the isoflavonoids for the inhibition of microglial activation, the glycosylation at the C-7 hydroxyl group reduces the inhibitory activity. The methoxylation of 4'-hydroxyl group of 7-glycosylated isoflavonoids reduces the inhibitory activity, while the methoxyl group at the 6-position enhances the activity. The results suggest that isoflavonoids of Pueraria flowers may be of therapeutic potential in alcoholism related to microglial activation.

• Authors: Dan Yuan, Yuan-Yuan Xie, Xue Bai, Xia Wu, Jing-Yu Yang, Chun-Fu Wu
• Journal: Journal of Asian natural products research (J Asian Nat Prod Res) Vol. 11 Issue 6 Pg. 471-81 (Jun 2009) ISSN: 1477-2213 [Electronic] England
• PMID: 20183278 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 6-hydroxybiochanin A-6,7-di-O-beta-D-glucopyranoside
• 6-hydroxygenistein-7-O-beta-D-glucopyranoside
• Drugs, Chinese Herbal
• Glucosides
• Isoflavones
• Lipopolysaccharides
• genistin
• Nitric Oxide
• tectorigenin
• tectoridin

Topics

• Animals
• Drugs, Chinese Herbal (chemistry, isolation & purification, pharmacology)
• Flowers (chemistry)
• Glucosides (chemistry, isolation & purification, pharmacology)
• Isoflavones (chemistry, isolation & purification, pharmacology)
• Lipopolysaccharides (pharmacology)
• Microglia (drug effects)
• Molecular Structure
• Nitric Oxide (antagonists & inhibitors, biosynthesis)
• Nuclear Magnetic Resonance, Biomolecular
• Pueraria (chemistry)
• Rats
• Rats, Wistar
• Stereoisomerism
• Structure-Activity Relationship