Influence of side chain structure changes on antioxidant potency of the [6]-gingerol related compounds.

[6]-Gingerol and [6]-shogaol are the major pungent components in ginger with a variety of biological activities including antioxidant activity. To explore their structure determinants for antioxidant activity, we synthesized eight compounds differentiated by their side chains which are characteristic of the C1-C2 double bond, the C4-C5 double bond or the 5-OH, and the six- or twelve-carbon unbranched alkyl chain. Our results show that their antioxidant activity depends significantly on the side chain structure, the reaction mediums and substrates. Noticeably, existence of the 5-OH decreases their formal hydrogen-transfer and electron-donating abilities, but increases their DNA damage- and lipid peroxidation-protecting abilities. Additionally, despite significantly reducing their DNA strand breakage-inhibiting activity, extension of the chain length from six to twelve carbons enhances their anti-haemolysis activity.

[Effect of melatonin on proliferation and apoptosis of fibroblasts in human hypertrophic scar].

OBJECTIVE: To study the effect of melatonin on proliferation and apoptosis of fibroblasts in human hypertrophic scar and its mechanism. METHODS: Fibroblasts from human hypertrophic scar were isolated and cultured with DMEM medium containing 10% FBS, and then they were divided into control (C, added with ethanol), low concentration (LC, added with 1 × 10(-5) mmol/L melatonin), middle concentration (MC, added with 1 × 10(-3) mmol/L melatonin), and high concentration (HC, added with 1 mmol/L melatonin) groups according to the random number table. After being cultured for 24 hours, cell morphologic change was observed under microscope; XTT-PMS assay was used to examine cell proliferative activity; cell cycle and apoptosis were assessed with flow cytometry after double staining of FITC and PI, and the levels of cyclin E, p53, and Fas mRNA were determined with fluorescence quantitative RT-PCR. Data were processed with analysis of variance and LSD test. RESULTS: (1) Fibroblasts in C group were spindle-shaped with growth in colonies. Along with the increase in melatonin concentration, fibroblasts in LC, MC, and HC groups gradually dispersed, deformed and atrophied, with shrunk cellular membrane, and decrease in ratio of nucleus and cytoplasm. (2) Proliferative activity of fibroblasts in LC, MC, and HC groups decreased along with an increase in melatonin concentration (1.49 ± 0.15, 1.24 ± 0.20, and 0.92 ± 0.09), which were lower that in C group (1.79 ± 0.10, F = 67.61, P < 0.05). Cell ratios of S and G2/M phases in LC, MC, and HC groups decreased along with an increase in melatonin concentration, which were all lower than those in C group [(10.6 ± 1.1)%, (6.1 ± 1.2)%, (3.2 ± 0.8)% vs.(16.9 ± 1.3)%, F = 286.10, P < 0.05; (13.5 ± 1.1)%, (9.8 ± 1.0)%, (6.0 ± 0.7)% vs. (16.7 ± 1.6)%, F = 162.69, P < 0.05]. Apoptotic rates in early and late stages of LC, MC, and HC groups increased along with an increase in melatonin concentration, all higher than those in C group (with F value respectively 424.05, 236.44, P values all below 0.05). The expressions of cyclin E mRNA in LC, MC, and HC groups decreased along with an increase in melatonin concentration, which were lower than that in C group (1.58 ± 0.21, 0.90 ± 0.20, and 0.24 ± 0.12 vs. 2.90 ± 0.30, F = 266.79, P < 0.05), while the expressions of p53 mRNA and Fas mRNA showed opposite tendency (with F value respectively 10.11, 12.03, P values all below 0.05). CONCLUSIONS: Melatonin can inhibit proliferation and induce apoptosis of fibroblasts in hypertrophic scar through regulating the gene expressions of cyclin E, p53, and Fas.

[Expression of secretions of hypothalamus-pituitary-adrenal axis in human hypertrophic scar].

OBJECTIVE: To explore the expression and significance of secretions of hypothalamus-pituitary-adrenal (HPA) axis in human hypertrophic scar. METHODS: Hypertrophic scar tissues obtained from 12 patients with deep-partial thickness burn or full-thickness burn and normal skin tissues from the same 7 patients with hypertrophic scar were harvested for determination of gene expression of corticotrophin-releasing hormone (CRH), CRH receptor 1 (CRH-R1), pro-opiomelanocortin (POMC), melanocortin receptor 2 (MC-2R), and glucocorticoid receptor α (GR-α) by real-time fluorescence quantitative PCR. After addition of corresponding antibodies, distribution differences of CRH, CRH-R1, adrenocorticotropic hormone (ATCH), MC-2R, and GR-α were observed with immunohistochemical staining. Data were processed with t test. RESULTS: The mRNA expression of CRH, CRH-R1, POMC, and GR-α in hypertrophic scar was respectively 3.1 ± 0.8, 0.05 ± 0.03, 0.020 ± 0.007, and 0.0030 ± 0.0010, which were significantly lower than those in normal skin (20.6 ± 4.7, 0.30 ± 0.12, 0.060 ± 0.020, and 0.0200 ± 0.0070, with t values from 2.10 to 4.75, P values all below 0.05). There was no statistical difference in MC-2R mRNA expression between hypertrophic scar and normal skin (t = 1.48, P = 0.15). Immunohistochemical observation showed CRH, CRH-R1, ACTH, MC-2R, and GR-α in hypertrophic scar were located in basal layer of epidermis, fibroblast of dermis, and tube wall of sweat gland. Expressions of these indexes could also be observed in sebaceous gland and hair follicle besides above-mentioned structures. CONCLUSIONS: Decreasing expression of active material of HPA axis may be related to formation of hypertrophic scar.