Antioxidant, free radical-scavenging, and NF-kappaB-inhibitory activities of phytosteryl ferulates: structure-activity studies.
Some of the pharmacological properties of phytosteryl ferulates may be linked to their antioxidant potential. In this study, 2,2-diphenyl-1-picrylhydrazyl (DPPH), electron spin resonance (ESR), and thiobarbituric acid-reactive substances (TBARS) assays demonstrated that phytosteryl ferulates such as cycloartenyl ferulate (CAF), 24-methylenecycloartanyl ferulate (24-mCAF), and beta-sitosteryl ferulate (beta-SF) and ferulic acid (FA) each exerted strong free radical scavenging and antioxidation of lipid membrane, which were comparable to alpha-tocopherol. However, the sterol moiety alone, such as cycloartenol (CA), had neither activity. Since, the reactive oxygen species (ROS) production in the cell complex defense mechanism cannot be ruled out with the cell free system, we measured ROS production in NIH 3T3 fibroblast cells induced by H(2)O(2). CAF and ethyl ferulate (eFA) greatly decreased the ROS level in this system. CA also significantly inhibited the ROS level, suggesting that CA could inhibit ROS production in living cells. Besides these, CAF, 24-mCAF, beta-SF, as well as eFA and CA, all these chemicals significantly inhibited the NF-kappaB activity as analyzed by measuring translocation of NF-kappaB p65 in LPS-stimulated RAW 264.7 macrophages. These observations revealed that phytosteryl ferulates are responsible for the antioxidant and anti-inflammatory activity via ROS scavenging and inhibition of ROS production.
Islam
Md Shafiqul
MS
Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Japan.
Yoshida
Hiroshi
H
Matsuki
Naoaki
N
Ono
Kenichiro
K
Nagasaka
Reiko
R
Ushio
Hideki
H
Guo
Ying
Y
Hiramatsu
Toshiyuki
T
Hosoya
Takamitsu
T
Murata
Takahisa
T
Hori
Masatoshi
M
Ozaki
Hiroshi
H
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D003373:Coumaric Acids / Q000737:chemistry / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008567:Membranes, Artificial; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D041681:NIH 3T3 Cells; D010666:Phenylpropionates / Q000737:chemistry / Q000494:pharmacology*; D010840:Phytosterols / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D003373:Coumaric Acids; D016166:Free Radical Scavengers; D008567:Membranes, Artificial; D016328:NF-kappa B; D010666:Phenylpropionates; D010840:Phytosterols; D017382:Reactive Oxygen Species; C004999:ferulic acid; C013172:gamma-oryzanol