Selenium (Se) is known to prevent from several cancers, while iron (Fe) is known to be associated with high risk of cancers. The role of Se on colon carcinogenesis was investigated in an animal model induced by azoxymethane (AOM) and dextran sodium sulfate (DSS) in low Fe mice. Six-week old ICR mice fed on a low Fe diet (4.5 ppm Fe; generally 10 times lower than normal Fe) with three different Se (0.02, 0.1 or 0.5 ppm) levels for 24weeks. The animals received weekly three (0~2nd weeks) i.p. injections of AOM (10 mg/kg B.W), followed by 2%DSS with drinking water for 1 week to induce the colon cancer. There were five experimental groups including vehicle,positive control (normal Fe level, AOM/DSS), Low Fe (LFe) + AOM/DSS+Low Se (LSe), LFe + AOM/DSS + medium Se (MSe) and LFe + AOM/DSS + high Se (HSe) groups. HSe group showed a 66.7% colonic tumor incidence, MSe group showed a 69.2% tumor incidence, and LSe group showed a 80.0% tumor incidence. The tumor incidence was negatively associated with Se levels of diets. Tumor multiplicity in Hse group was significantly low compared to the other groups (p < 0.05). With increasing Se levels of diets, the primary anti-proliferating cell nuclear antigen (PCNA)-positive cells were decreased and apoptotic bodies were increased in a dose-dependent manner. Sedependent glutathione peroxidase activity and its protein level were dependent on the levels of Se of diets. Malondialdehyde level in liver was lowest in Hse group among experimental groups. These findings indicate that dietary Se is chemopreventive for colon cancer by increasing antioxidant activity and decreasing cell proliferation in Fe-deficient mice.

This study was performed to investigate the antioxidant effects of 4 citrus fruits including Hallabong,Cheonhyehyang, Cheonggyeon, and Jinjihyang. In this study the citrus fruits were separated in three parts of peel, pulp segment membrane (PSM), and pulp and extracted with methanol, then concentrated using a rotary vacuum evaporator. Total polyphenol contents ranged 23.497~42.341 mg/g in peel, 13.285~21.872 mg/g in PSM and 6.333~11.627 mg/g in pulp of the citrus fruits. The total polyphenol contents were highest in the peel and PSM of Jinjihyang and in the pulp of Cheonhyehyang. 1,1-diphenyl-2picryl hydrazyl (DPPH) radical scavenging activities were highest in the peel and PSM of Jinjihyang and in the pulp of Cheonhyehyang. 2,2’-Azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging capacities were also highest in the peel and PSM of Jinjihyang and in the pulp of Cheonhyehyang. Reducing powers were highest in the peel of Cheonggyeon, in the PSM of Jinjihyang,and in the pulp of Cheonhyehyang. There were significant correlations in between total polyphenol contents and the radical scavenging activities, and reducing power each other. These results indicate that the 4 citrus fruits (Hallabong, Cheonhyehyang, Cheonggyeon, and Jinjihyang) evidently have antioxidant capacities and their peel parts have the highest antioxidant activities.

Selenium is an essential micronutrient which functions as an essential constituent of selenoproteins. The selenoproteins play an important role in the body’s defense from free radicals associated with chronic diseases such as cancer. The effect of selenium on colon carcinogenesis was investigated using an experimental animal model. Five-week old ICR mice were acclimated for one week, and fed on the Fe-overloaded diet (450 ppm) with different Se diets (0.02, 0.1 or 0.5 ppm) for 12 weeks. Animals were injected intraperitoneally with azoxymethane (AOM, 10 mg/㎏ B.W. weekly for 3 weeks), followed by 2% dextran sodium sulfate (DSS) in the drinking water for a week. There were three experimental groups including low Se group (Lse), medium (normal standard diet for mice) Se (MSe), and high Se (HSe). The numbers of aberrant crypt foci (ACF) and aberrant crypt (AC) were measured in the colonic mucosa. The iron and selenium concentrations in liver was measured using ICP-AES. Glutathione peroxidase (GPx) activity was determined in the liver and colon. TUNEL assay for cell apoptosis and proliferating cell nuclear antigen (PCNA) staining for cell proliferation were performed. Immunohistochemical staining of β-catenin was also performed in mucous tissue of colon. The dietary Se decreased the numbers of ACF/㎠ and AC/㎠ in a dose-dependent manner. HSe diet significantly decreased the numbers of AC/㎠, compared with LSe diet (p<0.05). The tumor incidence rate in low Se diet group was 5% higher than medium Se diet group and 20% higher than high Se diet group. The activities of GPx in the liver and colon were dependent on the content of dietary selenium. Apoptosis-positive cells were also increased by dietary Se in a dose-dependent manner. PCNA-positive staining was weak in high Se group. β-catenin stained area was increased in low Se group while it was decreased in high Se group. These findings indicate that dietary selenium exert a protecting effect on colon cancer by inhibiting the development of ACF/AC, increasing GPX and apoptosis, and decreasing cell proliferation and expression of β-catenin in mice.

Selenium (Se) obtained from dietary sources is an essential micronutrient for normal body function and it functions as an essential constituent of selenoproteins. We investigated the influence of Se on the formation of colonic aberrant crpyt foci (ACF) and tumor formation induced by azoxymethane (AOM) and dextran sodium sulfate (DSS) in male ICR mice. Five-week old ICR mice were acclimated for one week and fed on the low iron diet (LFe, 4.5 ppm) and different Se diet [Lse (0.02 ppm), Normal Se (0.1 ppm), HSe (0.5 ppm)] for 12 weeks. Animals received intraperitoneal injections of AOM (10㎎/㎏ B.W. in saline weekly for 3 weeks), followed by 2% DSS (molecular weight 36,000～50,000) in the drinking water for a week. There were five experimental groups, including a normal control group, AOM/DSS, LFe+AOM/DSS, LFe+AOM/DSS+LSe, LFe+AOM/DSS+HSe. After sacrifice of animals, the total numbers of AC and ACF were measured in the colonic mucosa. The number of mice bearing tumors was expressed as tumor incidence rate. The iron and selenium liver concentration was measured using ICP-AES. Glutathione peroxidase (GPx) activity was determined using a GPx assay kit in the liver and colon. TUNEL and proliferating cell nuclear antigen (PCNA) staining were performed to examine the cell apoptosis and cell proliferation. In addition, immunohistochemistry of β-catenin was also performed on the mucous membrane tissue of colon. In AOM/DSS-induced colon carcinogenesis animal model, LFe diet decreased the number of 2.95±2.5 ACF/cm2 to 1.85±1.1 ACF/cm2 but it increased the total number of 5.06±4.2 AC/cm2 to 6.19±4.8 AC/cm2 compared with normal iron diet. In the iron-deficient mice, selenium did not affect the either the number of ACF or AC. The tumor incidence rate was higher in LFe diet groups than in normal iron diet group and high selenium diet weakly reduced the tumor incidence. Low selenium diet decreased the activity of GPx in the liver and colon. Apoptotic positive cells were decreased in the low selenium diet group. In addition, on the β-catenin staining, positive cells were increased in the low selenium diet group while they were decreased in the high selenium diet group. These findings indicate that the dietary levels of selenium was not highly enough to exhibit a significant protection against colon carcinogenesis in the iron-deficient mice. However, our results also indicate that dietary selenium might exert a protecting effect against colon cancer by increasing GPx activity and apoptosis and by inhibiting cell proliferation and β-catenin over-expression.

Carnosine is a dipeptide (β-alanyl-L-histidine) found in mammalian brain, eye, olfactory bulb and skeletal muscle at high concentrations. Its biological functions include antioxidant and anti-glycation activities. The objectives of this study were to investigate anti-diabetic effects of carnosine as determined by blood glucose levels in glucose tolerance test (GTT) and insulin tolerance test (ITT), insulin level and serum biochemical and lipid levels in male C57BL/6J db/db mice. There were five experimental groups including normal (C57BL/6J), control (vehicle), and three groups of carnosine at doses of 6, 30, and 150 mg/kg b.w. Carnosine was orally administered to the diabetic mice everyday for 8 weeks. There was no significant difference in body weight changes in carnosine-treated groups compared to the control. The treatments of carnosine significantly decreased the blood glucose level in the diabetic mice compared with the control (p < 0.05) after 5 weeks. The treatments of carnosine also significantly decreased the blood glucose levels in GTT and ITT and glycosylated hemoglobin (HbA1c), compared with the control (p < 0.05). Carnosine at the dose of 6 mg/kg significantly decreased the serum insulin level compared to the control (p < 0.05). Carnosine significantly increased total proteins but significantly decreased lactate dehydrogenase and blood urea nitrogen compared with the control (p < 0.05). Carnosine also significantly decreased glucose, LDL, and triglyceride in the serum of diabetic mice compared to the control (p < 0.05). These results suggest that carnosine has a hypoglycermic effect resulting from reduction of glucose and lipid levels and that high carnosine-containing diets or drugs may give a benefit for controlling diabetes mellitus in humans.

Phytic acid (PA) (Inositol hexaphosphate, IP6) is a naturally occurring polyphosphorylated carbohydrate that is present in substantial amounts in almost all plants and mammalian cells. Recently PA has received much attention for its role in anticancer activity. In the present study, the preventive effects of PA on colon carcinogenesis were investigated. Six-week old Fisher 344 male rats were fed a AIN-93G purified diet and PA (0.5% or 2% PA in water) for 8 weeks. The animals received two (1st and 2nd week) injections of azoxymethane (AOM, 15 mg/kg b.w.) to induce colonic aberrant crypt foci (ACF). After sacrifice, the total numbers of aberrant crypts (AC) and ACF in colonic mucosa were examined after staining with methylene blue. Blood and serum were analyzed with a blood cell differential counter and an automatic serum analyzer. AOM induced the total numbers of 142.3 ± 22.3 ACF/colon and 336.6 ± 55.1 AC/colon. PA at the doses of 0.5 and 2% decreased the numbers of ACF and AC/colon in a dosedependent manner. The numbers of ACF/colon and AC/colon by PA at the dose of 0.5% were 124.4 ± 28.5 and 302.7 ± 67.3, respectively. PA at the dose of 2% significantly decreased the ACF and AC numbers to 109 ± 18.1 and 254.8 ± 50.6, respectively (p < 0.01). Especially, 2% PA significantly reduced the number of large ACF ( ≥ 4 AC/ ACF) from 26.8 ± 6.2 ACF/colon to 15 ± 6.7 ACF/colon (p < 0.01). Although some parameters in blood counts and serum chemistry were changed compared with the control, no specific toxicity was found. These findings suggest that phytic acid can be a chemopreventive agent for colon carcinogenesis resulting from inhibition of the development of ACF in the F344 rat.

The aim of this study was to examine the promoting effect of herbal extracts on hair regrowth in C3H/HeJ mice. The herbal extracts were obtained from the Damo-cosmetics Inc. There were four experimental groups including distilled water (D. W., negative control), 20% ethanol (EtOH, vehicle control), 3% minoxidil (MXD, positive control), and herbal extract (Ext). The herbal extract included the mixture of water and alcohol extract from Pleuropterus multflorus, Lonicera japonica Thunberg, Phellinus linteus, and Phaseolus radiatus. Test compounds were applied to the shaved dorsal skin of mice mouse for 3 weeks. The photograph of hair regrowth was taken at day 0, 4, 7, 10, 14, 17, and 21. The herbal extract group showed faster hair regrowth than negative control group or 20% EtOH groups after 10 and 14 days of treatments. The elongation of hair follicles in MXD and the herbal extract groups were observed. The activities of alkaline phosphatase (ALP) and γ-glutamyl transpeptidase were sfanificantly (γ-GT) increased in MXD and herbal extract groups compared with negative control group (p＜0.05). The expression of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) were also sfanificantly hfaher in MXD and herbal extract group than negative control group (p＜0.05), althouah there were no sfanificant differences amoularhe groups of 20% EtOH, MXD, and herbal extract. These results suagest that the herbal extract used in this study may have grpromoting effect on hair regrowth by increasing activities of ALP and γ-GT and expression of EGF and VEGF.

Anti-wrinkle effect of herbal extracts was investigated on the skin of in a model of animal irradiated by ultraviolet rey B (UVB). The female albino hairless mice (HR/ICR) were randomly allocated to the normal control group (NC-non irradiated-vechicle), positive control group (PC, UVB irradiated vehicle) and herbal extract (HE) group. The herbal extract included the mixture of water and alcohol extract from Pleuropterus multflorus, Lonicera japonica Thunbert, Phellinus linteus, and Phaseolus radiatus. The herbal extract was treated dorsally with 0.2 ml per mouse five times a week for 12 weeks. At fifth week of the treatment, the animals were exposed to UVB irradiation for subsequent eight weeks three times a week. The intensity of irradiation was gradually increased from 30 mJ/㎠ to 240 mJ/㎠ (1MED: 60 mJ/㎠). Dorsal skins were obtained and stained with H&E to examine histological changes and epidermal/dermal thckness. The collagen fiber was also observed in Masson-Trichrome staining. Hydroxyproline assay and western blot analysis were also carried out to detect the change of collagen amount and to investigate MMP-1 expression, respectively. The HE group showed a better appearance and weak wrinkling, compared to PC group, The treatment of herbal extract significantly increased the thickness of dermis and the amount of collagen fibers compared to PC group (p＜0.05). The treatment of HE significantly increased the hydroxyproline amount compared to PC group (p＜0.05). The chronic UVB irradiation to hairless mice skin increased expression of MMP-1 but the treatment of HE decreased the expression of MMP-1. These results indicate that the herbal extract used in this study have a preventive effect on the UVB-induced wrinkle in a hairless mice model, partly due to the reduction of MMP-1 expression and increment of collagen amount.