Isolation of a Natural Antioxidant, Dehydrozingerone from Zingiber officinale and Synthesis of lts Analogues for Recognition of Effective Antioxidant and Antityrosinase Agents원문보기
Kuo, Ping-Chung
(Department of Biotechnology, National Formosa University)
,
Damu, Amooru G.
(Department of Chemistry, National Cheng Kung University)
,
Cherng, Ching-Yuh
(Department of Applied Chemistry, National Chiayi University)
,
Jeng, Jye-Fu
(Department of Chemistry, National Cheng Kung University)
,
Teng, Che-Ming
(Pharmacological Institute, College of Medicine, National Taiwan University)
,
Lee, E-Jian
(Neurophysiology Laboratory, Neurosurgical Service, Departments of Surgery and Anesthesiology, and Institute of Biomedical Engineering, National Cheng Kung University Medical Center and Medical School)
,
Wu, Tian-Shung
(Department of Chemistry, National Cheng Kung University, National Research Institute of Chinese Medicine)
In the present study, the antioxidative and inhibitory activity of Zingiber officinale Rosc. Rhizomes-derived materials (on mushroom tyrosinase) were evaluated. The bioactive co mponents of Z. officinale rhizomes were characterized by spectroscopic analysis as zingerone and dehydrozingerone, which e...
In the present study, the antioxidative and inhibitory activity of Zingiber officinale Rosc. Rhizomes-derived materials (on mushroom tyrosinase) were evaluated. The bioactive co mponents of Z. officinale rhizomes were characterized by spectroscopic analysis as zingerone and dehydrozingerone, which exhibited potent antioxidant and tyrosinase inhibition activities. A series of substituted dehydrozingerones [(E)-4-phenyl-3-buten-2-ones] were prepared in admirable yields by the reaction of appropriate benzaldehydes with acetone and the products were evaluated in terms of variation in the dehydrozingerone structure. The synthetic analogues were examined for their antioxidant and antityrosinase activities to probe the most potent analogue. Compound 26 inhibited Fe$^{2+}$-induced lipid peroxidation in rat brain homogenate with an IC$_{50}$ = 6.3${\pm}$0.4 ${\mu}$M. In the 1,1-diphenyl- 2-picrylhydrazyl (DPPH) radical quencher assay, compounds 2, 7, 17, 26, 28, and 29 showed radical scavenging activity equal to or higher than those of the standard antioxidants, like ${\alpha}$-tocopherol and ascorbic acid. Compound 27 displayed superior inhibition of tyrosinase activity relative to other examined analogues. Compounds 2, 17, and 26 exhibited non-competitive inhibition against oxidation of 3,4- dihydroxyphenylalanine (L-DOPA). From the present study, it was observed that both number and position of hydroxyl groups on aromatic ring and a double bond between C-3 and C-4 played a critical role in exerting the antioxidant and antityrosinase activity.
In the present study, the antioxidative and inhibitory activity of Zingiber officinale Rosc. Rhizomes-derived materials (on mushroom tyrosinase) were evaluated. The bioactive co mponents of Z. officinale rhizomes were characterized by spectroscopic analysis as zingerone and dehydrozingerone, which exhibited potent antioxidant and tyrosinase inhibition activities. A series of substituted dehydrozingerones [(E)-4-phenyl-3-buten-2-ones] were prepared in admirable yields by the reaction of appropriate benzaldehydes with acetone and the products were evaluated in terms of variation in the dehydrozingerone structure. The synthetic analogues were examined for their antioxidant and antityrosinase activities to probe the most potent analogue. Compound 26 inhibited Fe$^{2+}$-induced lipid peroxidation in rat brain homogenate with an IC$_{50}$ = 6.3${\pm}$0.4 ${\mu}$M. In the 1,1-diphenyl- 2-picrylhydrazyl (DPPH) radical quencher assay, compounds 2, 7, 17, 26, 28, and 29 showed radical scavenging activity equal to or higher than those of the standard antioxidants, like ${\alpha}$-tocopherol and ascorbic acid. Compound 27 displayed superior inhibition of tyrosinase activity relative to other examined analogues. Compounds 2, 17, and 26 exhibited non-competitive inhibition against oxidation of 3,4- dihydroxyphenylalanine (L-DOPA). From the present study, it was observed that both number and position of hydroxyl groups on aromatic ring and a double bond between C-3 and C-4 played a critical role in exerting the antioxidant and antityrosinase activity.
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제안 방법
The sample was extracted with n-butanol (1 mL) and centrifuged at 10000xg for 10 min. The absorbance of the butanol phase was determined at 532 nm in a spectrophotometer (Hitachi, Model U-3200), and the amount of thiobarbituric acid reactive substance (TBARS) present was determined by linear regression analysis of a standard curve 너sing tetramethoxypropane as a standard.
Compound 27 exhibited profound inhibitory activity (IC50 = 27 μM) than kojic acid (ICso = 154 |iM). 자le activity of tyrosinase was analyzed in the presence of compounds 2, 7, 17, 26, 27, 28, and 29 without L-DOPA to determine the mode of inhibition. The curves obtained for 2, 17, and 26 resembled with those obtained for resveratrol (Bernard and Berthon, 2000).
이론/모형
The DPPH assay was based on reported methods (Ko et al., 1995; Mellors and Tappel, 1966). An ethanolic s이니tion of 100 μM of the chemically stable free radical 1, 1 -diphenyl-2-picryl-hydrazyl was incubated with antioxidant for 30 min.
The rat brain homogenate lipid peroxidation assay was based on reported methods (Ko et al., 1995). Wh이e rat brain homogenates were freshly prepared in Krebs buffer containing 15 mM Hepes (pH 7.
성능/효과
It was evident that compound 27 was a direct inhibitor of mushroom tyrosinase, since on pre-incubation with the enzyme in the absence of the substrate, it siginificantly decreased the enzyme activity. The results indicated that compound 27 was a characteristic competitive inhibitor, however, for compounds 2, 17, and 26, the four lines obtained from the uninhibited enzyme and from the three different concentrations of 250, 500, and 1000 μM, intersected on the horizontal axis. This result indicates that these compounds exhibited a noncompetitive inhibition for L-DOPA oxidation by mushroom tyrosinase.
The dihydroxyl s니bstit니tion at 2' and 3' of the phenyl ring was particularly important to the radical scavenging activity than at 2' and 5', and 3' and 4*. This study also revealed that a double bond at the C-3 and C-4 position would be essential for antioxidant activity. Experimental results indicated that compound 26 may be a promising antioxidant in light of fact that antioxidant therapy apparently offers protection against a wide range of free radical-induced diseases.
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