title: Reaction characteristics of andrographolide and its analogue AL-1 with GSH, as a simple chemical simulation of NF-κB inhibition.
abstract: 14-α-Lipoic acid-3,19-dihydroxyandrographolide (AL-1, 2) is an analogue of andrographolide (Andro, 1) coupled to α-lipoic acid (LA, 4). AL-1 was at least 10-fold more potent than the natural parent compound Andro in inhibiting nuclear factor (NF)-κB activation in RIN-m cells. In the present study, glutathione (GSH, 3) was used as a simple chemical model molecule of NF-κB with cysteine 62. The characteristics of the reaction between AL-1 or Andro and GSH were investigated to trace some possible elucidation for the inhibitive mechanism and stronger inhibition of AL-1 to NF-κB activation. The results showed that the main reaction products of AL-1 and Andro were identical, sulfhydryl adduct and amino adduct. AL-1 reacted much faster than Andro with GSH. The product yield of AL-1 was much higher than that of Andro. It was speculated that AL-1 might inhibit NF-κB by the same mechanism as Andro. And the faster reaction rate and higher yield may account for the stronger NF-κB inhibition of AL-1 when compared with Andro.
authors.affiliation: Department of Pharmaceutics, Jinan University College of Pharmacy, Guangzhou 510632, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yao
authors.forename: Sha
authors.initials: S
authors.lastname: Li
authors.forename: Pei
authors.initials: P
authors.lastname: Yu
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Tang
authors.forename: Jie
authors.initials: J
authors.lastname: Jiang
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Wang
mesh_terms: D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000737:chemistry; D004224:Diterpenes / Q000737:chemistry*; D004355:Drug Stability; D005978:Glutathione / Q000737:chemistry*; D008956:Models, Chemical; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010084:Oxidation-Reduction; D021241:Spectrometry, Mass, Electrospray Ionization; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: C571655:14-alpha-lipoic acid-3,19-dihydroxyandrographolide; D004224:Diterpenes; D016328:NF-kappa B; C030419:andrographolide; D008063:Thioctic Acid; D005978:Glutathione; D003545:Cysteine