Anti-inflammatory activity of sulfur-containing compounds from garlic.
We identified four anti-inflammatory sulfur-containing compounds from garlic, and their chemical structures were identified as Z- and E-ajoene and oxidized sulfonyl derivatives of ajoene. The sulfur compounds inhibited the production of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) and the expression of the pro-inflammatory cytokines tumor necrosis factor-α, interleukin-1β, and interleukin-6 in lipopolysaccharide (LPS)-activated macrophages. Western blotting and reverse transcription-polymerase chain reaction analysis demonstrated that these sulfur compounds attenuated the LPS-induced expression of the inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins and mRNA. Moreover, these sulfur-containing compounds suppressed the nuclear factor-κB (NF-κB) transcriptional activity and the degradation of inhibitory-κBα in LPS-activated macrophages. Furthermore, we observed that they markedly inhibited the LPS-induced phosphorylations of p38 mitogen-activated protein kinases and extracellular signal-regulated kinases (ERK) at 20 μM. These data demonstrate that the sulfur compounds from garlic, (Z, E)-ajoene and their sulfonyl analogs, can suppress the LPS-induced production of NO/PGE(2) and the expression of iNOS/COX-2 genes by inhibiting the NF-κB activation and the phosphorylations of p38 and ERK. Taken together, these data show that Z- and E-ajoene and their sulfonyl analogs from garlic might have anti-inflammatory therapeutic potential.
Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women's University, Seoul, Korea.
Da Yeon
DY
Lee
Hua
H
Li
Hyo Jin
HJ
Lim
Hwa Jin
HJ
Lee
Raok
R
Jeon
Jae-Ha
JH
Ryu
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005737:Garlic / Q000737:chemistry*; D007249:Inflammation / Q000188:drug therapy; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D013457:Sulfur Compounds / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
D000893:Anti-Inflammatory Agents; D051546:Cyclooxygenase 2; D048049:Extracellular Signal-Regulated MAP Kinases; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D010936:Plant Extracts; D013457:Sulfur Compounds; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D000093242:Interleukin-6 Inhibitors; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse