Disease relevance of AIDS005842

• We have shown that carnosic acid, the major rosemary polyphenol, enhances the differentiating and antiproliferative effects of low concentrations of 1,25D(3) in human myeloid leukemia cell lines (HL60, U937) [1].
• Furthermore, carnosic acid protected red cells against oxidative hemolysis [2].
• Methanol extract containing 30% of carnosic acid, 16% of carnosol and 5% of rosmarinic acid was the most effective antimicrobial against Gram positive bacteria (minimal inhibition concentration, MIC, between 2 and 15 mug/ml), Gram negative bacteria (MIC between 2 and 60 mug/ml) and yeast (MIC of 4 mug/ml) [3].
• Inhibitory effect of carnosic acid on HIV-1 protease in cell-free assays [corrected] [4].
• Oxidation, reduction, and methylation of carnosic acid by Nocardia [5].

High impact information on AIDS005842

• METHODS: We evaluated monocytic differentiation markers (CD11b, CD14, and monocytic serine esterase), cell cycle parameters, and cell proliferation rates after treatment of cells with different agents with or without carnosic acid [6].
• Carnosic acid alone increased the expression of VDR and RXR-alpha, but the expression was greatly enhanced in the presence of 1alpha,25(OH)2D3 and ATRA [6].
• RESULTS: Monocytic differentiation induced by low (1 nM) concentrations of 1alpha,25(OH)2D3, ATRA, or TPA was enhanced by carnosic acid (10 microM), as shown by the increased expression of monocytic serine esterase (P<.001, P<.001, and P =.043, respectively) and of CD11b (P =.008, P =.046, and P =.041, respectively) [6].
• In combination with TPA, carnosic acid potentiated the expression of VDR and RAR-alpha [6].
• Carnosic acid in combination with 1alpha,25(OH)2D3 and ATRA resulted in decreased cell proliferation and blocked the cell cycle transition from G1 to S phase (P<.05) [6].

Biological context of AIDS005842

• We now examine the mechanisms associated with carnosic acid-induced enhancement of cell differentiation (in subline HL60-G) initiated by 1alpha,25(OH)2D3, ATRA, or 12-O-tetradecanoylphorbol-13-acetate (TPA) [6].
• CONCLUSION: Carnosic acid enhances a program of gene expression consistent with 1alpha,25(OH)2D3-, ATRA-, or TPA-induced monocytic differentiation of HL60-G cells [6].
• Subcellular localization studies show that carnosic acid protects chloroplasts from oxidative stress in vivo by following a highly regulated compartmentation of oxidation products [7].
• Furthermore, such combinations of carnosic acid and any of these differentiation inducers synergistically inhibited proliferation and cell cycle progression [8].
• Substances having inhibitory activity were purified and their chemical structure identified as the diterpenes carnosic acid and carnosol (IC50 values of 33 +/- 3 microM and 57 +/- 4 microM, respectively) [9].

Anatomical context of AIDS005842

• Carnosic acid also undergoes direct O-methylation within the chloroplasts, and its derived product, 12-O-methylcarnosic acid, accumulates in the plasma membrane [7].
• Photoprotective potential of lycopene, beta-carotene, vitamin E, vitamin C and carnosic acid in UVA-irradiated human skin fibroblasts [10].
• We previously showed that either carnosic acid, an antioxidant, or SB202190, a p38 MAPK inhibitor, increase the potency of 1,25D3 in the HL60 cell line [11].
• In this work, the bioactive compounds deriving from rosemary leaves (carnosol, CAR; carnosic acid, CA; rosmadial, RAL; genkwanin, GW; rosmarinic acid, RA) were isolated and their effects on the phase behaviour of model membranes were studied by several complementary biophysical techniques [12].
• Twenty hours of treatment with both carnosol and carnosic acid inhibited 3H-thymidine incorporation in a dose-dependent manner, with a 50% inhibitory concentration of 23 microM and significantly increased the doubling time of Caco-2 cells from 29.5 to 140 and 120 h, respectively [13].

Associations of AIDS005842 with other chemical compounds

• This observation is probably due to the transformation of carnosic acid into carnosol; the analysis of the corresponding ESR spectrum suggests the formation of a keto phenoxy radical exhibiting a great delocalization of the unpaired electron [14].
• The HPLC analysis of an aged solution of carnosic acid quinone revealed that several antioxidants are produced in the solution [15].
• The in vitro experiments in rat liver mitochondrial fraction display more effective antioxidant action of alpha-tocopherol in 1 microM concentration than 1 microM carnosic acid by an increase of the time between fast and slow chemiluminescence flashes (p < 0.01) [16].
• Through bioassay-guided separation using the inhibitory activity against pancreatic lipase activity, 4 abietan-type diterpenes (carnosic acid, carnosol, royleanonic acid, 7-methoxyrosmanol) and a triterpene (oleanolic acid) were isolated from the active fraction [17].
• 7. Carnosic acid and carnosol reduce cytochrome c but with a rate constant significantly lower than that of O2(-.) [18].

Gene context of AIDS005842

• Induction of G2/M phase cell cycle arrest by carnosol and carnosic acid is associated with alteration of cyclin A and cyclin B1 levels [13].
• Carnosol was found to exert its major cell cycle effect after prometaphase, and caused an increase in cyclin B1 protein levels whereas carnosic acid arrested cells prior to prometaphase, and caused a reduction in cyclin A levels [13].
• We have recently used the plant-derived polyphenolic antioxidant, carnosic acid (CA), to demonstrate an increase in the differentiating action of 1,25D(3) on human leukemia cells under these conditions (M. Danilenko et al., JNCI, 93: 1224-1233, 2001) [19].
• Radical intermediates and antioxidants: an ESR study of radicals formed on carnosic acid in the presence of oxidized lipids [14].
• Molar absorptivity (epsilon) of carnosic acid (CA) was determined from 200 to 300 nm, by the proposed method and those values were compared to tert-butyl-hydroxytoluene (BHT) ones for further comparative quantification [20].

Analytical, diagnostic and therapeutic context of AIDS005842

• Carnosol and carnosic acid were identified in the electrophoregrams of rosemary extracts through their migration times and UV spectra obtained by CZE analysis of pure compounds isolated from a rosemary extract by HPLC fractionation [21].
• Calculation of the molar absorptivity of polyphenols by using liquid chromatography with diode array detection: the case of carnosic acid [20].
• Carnosic acid, the polyphenolic diterpene derived from rosemary, is a strong dietary antioxidant that exhibits antimutagenic properties in bacteria and anticarcinogenic activity in various cell and animal models [8].
• 3. Carnosol and carnosic acid are good scavengers of peroxyl radicals (CCl3O2.) generated by pulse radiolysis, with calculated rate constants of 1-3 x 10(6) M-1 s-1 and 2.7 x 10(7) M-1 s-1 respectively [18].

References