![]() ![]() NO has many biological functions involved in vasodilatation, neurotransmission, tissue homeostasis, wound repair, inflammation and cytotoxicity ( 12– 14). NO is a short-lived small molecule free radical produced from l-arginine ( 11) in a reaction catalyzed by NO synthase (NOS). These results give insight into the different mechanisms involved in the chemopreventive actions of rosemary. Additional studies have revealed that rosemary extracts, carnosic acid and carnosol strongly inhibited phase I enzyme, CYP 450 activities and induced the expression of the phase II enzyme, glutathione S-transferase (GST) ( 10). Rosmarinic acid was widely studied for its antimicrobial and complement inhibition properties ( 8, 9). Carnosol was stated to inhibit nitric oxide (NO) production in activated macrophages ( 7). Topical application of rosemary extract, carnosol or ursolic acid to mouse skin inhibited the covalent binding of benzopyrene to epidermal DNA, tumor initiation by 7,12-dimethylbenzanthracene (DMBA), TPA-induced tumor promotion, ornithine decarboxylase activity and inflammation ( 4, 6). Among the antioxidant compounds in rosemary leaves, ~90% of the antioxidant activity can be attributed to carnosol and carnosic acid. The antioxidant activity of an extract from rosemary leaves is comparable with known antioxidants, such as butylated hydroxyanisole and butylated hydroxytoluene, without the cytotoxic and carcinogenic risk of synthetic antioxidants ( 4, 5). Rosemary contains flavonoids, phenols, volatile oil and terpenoids ( 2, 3). Rosemary was stated to act as a mild analgesic and antimicrobial agent in traditional herbal use ( 2). Its herb and oil are commonly used as spice and flavoring agents in food processing for its desirable flavor and high antioxidant activity ( 1). Rosemary ( Rosmarinus officinalis Labiatae) originally grows in southern Europe. These results suggest that carnosol suppresses the NO production and iNOS gene expression by inhibiting NF-κB activation, and provide possible mechanisms for its anti-inflammatory and chemopreventive action.ĭPPH, α,α-diphenyl-β-picrylhydrazyl, G3PDH, glyceraldehyde-3-phosphate dehydrogenase, GST, glutathione S-transferase, IκB, inhibitor κB, IKK, IκB kinase iNOS, inducible nitric oxide synthase, LPS, lipopolysaccharide, MAPK, mitogen-activated protein kinase, NF-κB, nuclear factor-κB, NO, nitric oxide, PCR, polymerase chain reaction, PMSF, phenylmethylsulfonyl fluoride, RNS, reactive nitrogen species, RT, reverse transcription. Carnosol also inhibited LPS-induced p38 and p44/42 mitogen-activated protein kinase (MAPK) activation at a higher concentration (20 μM). These activities were referred to down-regulation of inhibitor κB (IκB) kinase (IKK) activity by carnosol (5 μM), thus inhibited LPS-induced phosphorylation as well as degradation of IκBα. Carnosol also showed inhibition of iNOS and NF-κB promoter activity in transient transfection assay. Carnosol treatment showed reduction of nuclear factor-κB (NF-κB) subunits translocation and NF-κB DNA binding activity in activated macrophages. Western blot, reverse transcription–polymerase chain reaction, and northern blot analyses demonstrated that carnosol decreased LPS-induced iNOS mRNA and protein expression. Treatment of mouse macrophage RAW 264.7 cell line with carnosol markly reduced lipopolysaccharide (LPS)-stimulated NO production in a concentration-related manner with an IC 50 of 9.4 μM but other tested compounds had slight effects. High concentrations of nitric oxide (NO) are produced by inducible NO synthase (iNOS) in inflammation and multiple stages of carcinogenesis. Carnosol showed potent antioxidative activity in α,α-diphenyl-β-picrylhydrazyl (DPPH) free radicals scavenge and DNA protection from Fenton reaction. In the present study, we compared the antioxidant activity of carnosol and other compounds extracted from rosemary. Carnosol functions as antioxidant and anticarcinogen. ![]() Carnosol is a naturally occurring phytopolyphenol found in rosemary.
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