Antioxidant and Antimelanogenic Activities of Compounds Isolated from the Aerial Parts of Achillea alpina L.

Achillea alpina is widely distributed in Korea and is often used as a folk medicine for stomach disorders. Although a previous study isolated antioxidant compounds (flavonoid O-glucoside, sesquiterpene) from this plant, no systematic study of its chemical constituents had been reported. The present study aimed to identify the phytochemicals present in a methanol extract of A. alpina, assess their potential antioxidant activities in vitro, and determine their effects on melanogenesis in B16F10 melanoma cells. Column chromatographic separation of aqueous fractions of A. alpina led to the isolation of 17 compounds. The chemical structures of these compounds were determined using spectroscopic data from electrospray ionization-mass spectrometry and nuclear magnetic resonance. To the best of our knowledge, the present study is the first to identify compounds 2-10 and 12-17 in A. alpina. Furthermore, compound 6 possessed powerful antioxidant activity, while compound 15 suppressed intracellular tyrosinase activity and thus reduced melanogenesis in B16F10 cells. Therefore, our research suggested that these naturally occurring compounds have the potential to reduce oxidative stress and promote skin whitening. Further investigations will be required to elucidate the mechanisms underlying the antioxidant and antityrosinase activities of these compounds.

A 90-Day Repeated Oral Dose Toxicity Study of Alismatis Rhizoma Aqueous Extract in Rats.

Alismatis rhizoma (AR), the dried rhizome of Alisma orientale (Sam.) Juzep, is a well-known, traditional medicine that is used for the various biological activities including as a diuretic, to lower cholesterol and as an anti-inflammatory agent. The present study was carried out to investigate the potential toxicity of the Alismatis rhizoma aqueous extract (ARAE) following 90-day repeated oral administration to Sprague-Dawley rats. ARAE was administered orally to male and female rats for 90 days at 0 (control), 500, 1,000 and 2,000 mg/kg/day (n = 10 for male and female rats for each dose). Additional recovery groups from the control group and high dose group were observed for a 28-day recovery period. Chromatograms of ARAE detected main compounds with four peaks. Treatment-related effects including an increase in the red blood cells, hemoglobin, hematocrit, albumin, total protein, and urine volume were observed in males of the 2,000 mg/kg/day group (p < 0.05). However, the diuretic effect of ARAE was considered, a major cause of hematological and serum biochemical changes. The oral no-observed-adverse-effect level (NOAEL) of the ARAE was > 2,000 mg/kg/day in both genders, and no target organs were identified.

Young leaves of reed (Phragmites communis) suppress melanogenesis and oxidative stress in B16F10 melanoma cells.

This study investigated the effects young leaves of reed (Phragmites communis) water extract (YLR) on melanogenesis and oxidative stress using B16F10 cells. YLR decreased the intracellular melanin content, protein expression and enzyme activity of tyrosinase in a dose-dependent manner. YLR significantly decreased the gene and protein expression of melanogeneis-related proteins, such as microphthalmia-associated transcription factor (MITF), and tyrosinase-related protein-1 and -2. In addition, YLR up-regulated the melanogenesis inhibitory proteins, extracellular signal-regulated kinase (ERK) and protein kinase B (AKT), while it dose-dependently down-regulated p38 and cAMP response element-binding protein (CREB). Moreover, YLR significantly reduced H2O2-induced reactive oxygen species levels in B16F10 cells and showed antioxidant activity based on DPPH and ABTS free radical scavenging activity and SOD-like activity. These results suggest that YLR have anti-melanogensis properties that function through regulation of the CREB/MITF/tyrosinase pathway in B16F10 cells and antioxidant activity. Overall, these findings indicate that YLR has the potential for use in treatment of skin disorders and skin-whitening.

Acute toxicity and cytotoxicity evaluation of Dendrobium moniliforme aqueous extract in vivo and in vitro.

Dendrobium moniliforme (L.) Sw., an herb of the Orchidaceae family, has long been used in traditional medicine to strengthen bones, nourish the stomach, and promote the production of bodily fluid. Recently, polysaccharides isolated from Dendrobium have been used in functional foods and nutraceutical products. A traditional method to process Dendrobium is to soak fresh stems in an ethanol solution, which is the most important factor to ensure high yields of aqueous-extractable polysaccharides. The present study was carried out to investigate the potential acute toxicity of D. moniliforme aqueous extract (DMAE), by a single oral dose in Sprague-Dawley rats. The test article was orally administered once by gavage to male and female rats at doses of 0, 2,500, and 5,000 mg/kg body weight (n=5 male and female rats for each dose). Throughout the study period, no treatment-related deaths were observed and no adverse effects were noted in clinical signs, body weight, food consumption, serum biochemistry, organ weight, or gross findings at any dose tested. The results show that a single oral administration of DMAE did not induce any toxic effects at a dose below 5,000 mg/kg in rats, and the minimal lethal dose was considered to be over 5,000 mg/kg body weight for both sexes. With respect to cytotoxicity, the cell viability of human embryonic kidney (HEK293) cells was less than 50% when the cells were treated with 10 mg/mL aqueous extract for 24 h.

Dietary umbelliferone attenuates alcohol-induced fatty liver via regulation of PPARα and SREBP-1c in rats.

This study investigated the effects of umbelliferone (UF) on alcoholic fatty liver and its underlying mechanism. Rats were fed a Lieber-DeCarli liquid diet with 36% of calories as alcohol with or without UF (0.05 g/L) for 8 weeks. Pair-fed rats received an isocaloric carbohydrate liquid diet. UF significantly reduced the severity of alcohol-induced body weight loss, hepatic lipid accumulation and droplet formation, and dyslipidemia. UF decreased plasma AST, ALT, and γGTP activity. UF significantly reduced hepatic cytochrome P450 2E1 activities and increased alcohol dehydrogenase and aldehyde dehydrogenase 2 activities compared to the alcohol control group, which resulted in a lower plasma acetaldehyde level in the rats that received UF. Chronic alcohol exposure inhibited hepatic AMPK activation compared to the pair-fed rats, which was reversed by UF supplementation. UF also significantly suppressed the lipogenic gene expression (SREBP-1c, SREBP-2, FAS, CIDEA, and PPARγ) and elevated the fatty acid oxidation gene expression (PPARα, Acsl1, CPT, Acox, and Acaa1a) compared to the alcohol control group, which could lead to inhibition of FAS activity and stimulation of CPT and fatty acid ß-oxidation activities in the liver of chronic alcohol-fed rats. These results indicated that UF attenuated alcoholic steatosis through down-regulation of SREBP-1c-mediated lipogenesis and up-regulation of PPARα-mediated fatty acid oxidation. Therefore, UF may provide a promising natural therapeutic strategy against alcoholic fatty liver.

Long-term supplementation of umbelliferone and 4-methylumbelliferone alleviates high-fat diet induced hypertriglyceridemia and hyperglycemia in mice.

This study was conducted to evaluate the effects of umbelliferone (UF) and 4-methylumbelliferone (mUF) on high-fat diet-induced hypertriglyceridemia and hyperglycemia in mice. The mice were assigned to normal control, high-fat control, and high-fat with UF or mUF groups. For UF or mUF groups, the high-fat diet was supplemented with UF or mUF at 0.02% (wt/wt) for 12weeks. Both UF and mUF significantly decreased plasma triglyceride, free fatty acid and glucose levels, adipocyte size, white adipose tissue weights, and hepatic phosphatidate phosphohydrolase activity and significantly increased plasma adiponectin levels and hepatic fatty acid ß-oxidation activity compared with the high-fat control group. UF and mUF improved glucose intolerance and hepatic steatosis in the high-fat fed mice. Long-term high-fat diet intake induced an increase in hepatic CYP2E1 activity and lipid peroxide and cytosolic hydrogen peroxide contents and suppressed superoxide dismutase and glutathione peroxidase activities, which were reversed by UF and mUF supplementation. These results indicate that UF and mUF similarly ameliorate hypertriglyceridemia and hyperglycemia partly by modulating hepatic lipid metabolism and the antioxidant defense system along with increasing adiponectin levels.