Rediocides A and G as potential antitoxins against cobra venom.
Rediocides A and G, the principle components of Trigonostemon reidioides (Kurz) Craib, which is known as Lotthanong in Thai, were investigated for a detoxification mechanism against Naja kaouthia venom by in silico, in vitro, and in vivo methods. Molecular dockings of alpha-cobratoxin with rediocides A and G were performed, and the binding energies were found to be -14.17 and -14.14 kcal/mol, respectively. Rediocides bind to alpha-cobratoxin at the same location as alpha-cobratoxin binds to the nicotinic acetylcholine receptor (nAChR), i.e., at the Asp27, Phe29, Arg33, Gly34, Lys35, and Val37 residues. alpha-Cobratoxin cannot bind to nAChR, because some of its binding sites are occupied with rediocides. From in vitro SDS-PAGE, it was found that rediocides can diminish the bands of alpha-cobratoxin. In the presence of acetylcholine-binding protein (AChBP), it was apparent that rediocides can bind both alpha-cobratoxin and AChBP. From an in vivo test, it was found that injection of rediocides at 0.5 mg/kg immediately after an alpha-cobratoxin dose of three times LD(50) cannot prolong the survival time of mice. However, rediocide can prolong the survival time, if it is injected 30 min before the injection of alpha-cobratoxin. The in vitro SDS-PAGE and the in vivo results support the in silico detoxification mechanism of rediocides against cobra venom at a molecular level.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayudhya Road, Bangkok 10400, Thailand.
Maleeruk
M
Utsintong
Atchara
A
Kaewnoi
Wichet
W
Leelamanit
Arthur J
AJ
Olson
Opa
O
Vajragupta
D000818:Animals; D000992:Antitoxins / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D003039:Cobra Neurotoxin Proteins / Q000737:chemistry / Q000378:metabolism*; D003198:Computer Simulation; D004224:Diterpenes / Q000737:chemistry* / Q000494:pharmacology; D006860:Hydrogen Bonding; D018942:Macrolides / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D011485:Protein Binding; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000378:metabolism
D000992:Antitoxins; D003039:Cobra Neurotoxin Proteins; D004224:Diterpenes; D018942:Macrolides; D011978:Receptors, Nicotinic; C483695:rediocide A; C507469:rediocide G; C025154:alpha-cobratoxin