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We collected stingless bee propolis Tetragonula biroi in order to find materials for medicine and cosmetics applications from tropical rainforest resources. Even though this bee has some biological functions including a cancer cell line, hair growth promotion, asthma remedy, α-glucosidase enzyme inhibition, and antiviral action, the investigation on anti-acne has not been reported yet. This study was to focus on propolis Tetragonula biroi extracts and leads us to isolate active compounds for antioxidant, anti-inflammatory, and anti-acne. We used methanol to obtain the extract from this propolis and assayed it with antioxidants, anti-inflammation, and anti-acne. The extract showed strong activity in antioxidants by DPPH radical scavenging activity (82.31% in 6.25 μg/ml). Via a column chromatography and Reveleris PREP purification system, we isolated 3'-O-methyldiplacone, nymphaeol A, and 5,7,3',4'-tetrahydroxy-6-geranyl flavonol. These compounds showed potential biological activity with IC

Our effort to find new material for anti cancer from natural resources leads us to focus on stingless bee products such as honey, bee pollen, and propolis. The products were from seven stingless bees named Homotrigona fimbriata, Heterotrigona itama, Heterotrigona bakeri, Tetragonula sarawakensis, Tetragonula testaceitarsis, Tetragonula fuscobalteata, Tetragonula laeviceps. The stingless bee products were evaluated for their cytotoxicity effect on MCF-7, HeLa and Caco-2 cancer cell lines. This is the first time to be reported that the honey, ethanol extracts of bee pollen and propolis of H. fimbriata displayed more potent cytotoxicity than other stingless bee products. By chromatography and biological activity-guided fractionation, ethanol extract of propolis from H. fimbriata was fractionated and isolated its active compound named mangiferonic acid. Mangiferonic acid showed a cytotoxicity effect with IC50 values 96.76 µM in MCF-7, >110.04 µM in HeLa, and > 110.04 µM in Caco-2, respectively. These results exhibited the potential of ethanol extracts from propolis of H. fimbriata to be further developed for drug and experiments to verify the function are essential.

Extracellular basic pH regulates cellular processes in wounds, and consequently influenced wound healing. Oxidative defence system modulation in the skin helps heal wounds, inhibits skin ageing and improves the skin condition. Moreover, the role of keratinocyte growth factor (KGF) and nuclear factor erythroid 2‐related factor 2 (Nrf2) in antioxidant systems has been reported in various skin models. However, the effects of extracellular basic pH on wound‐ or skin ageing‐related skin damage have not been examined. Thus, we investigated the antioxidant systems affected by extracellular basic pH in a 3D human skin equivalent system (3HSE). Extracellular basic pH decreased KGF expression and enhanced the oxidative defence system, and thus activated Nrf2 in the 3HSE. Additionally, extracellular basic pH and KGF treatment up‐regulated Nrf2 activation and its regulation of the oxidative defence system in the 3HSE. This indicates that Nrf2 up‐regulation is enhanced by reactive oxygen species production, rather than KGF, and by extracellular basic pH of the skin. The inhibition of skin damage through pH imbalance and KGF regulation suggests that the development of pH‐regulating or pH‐maintaining materials may provide effective therapeutic strategies for maintaining a healthy skin.

UV rays constitute an extremely important environmental factor known to operate adaptative mechanisms that maintain biological homeostasis in the skin, adrenal glands, and the brain. The skin is extremely vulnerable to UV rays. UV rays deform collagen, the main component of elastic fibers, decreasing its normal function, and ultimately reducing skin's elasticity. We confirmed that psychological stress occurring during the early stages of UVB-irradiation degraded collagen function by inhibiting production rather than the decomposition of collagen, thereby promoting skin aging. UV irradiation for 0-2 weeks increased the level of a stress factor, corticosterone (CORT). High-performance liquid chromatography and western blot analysis confirmed that the increase was caused by enhanced CYP11B1/2 levels during steroid synthesis in the adrenal gland. Precursor levels decreased significantly during the two weeks of UV irradiation. Skin collagen and collagen fibers reduced drastically during this time. Furthermore, the administration of osilodrostat, a USFDA-approved drug that selectively inhibits CYP11B1/2, preserved skin collagen. The mechanism underlying the reduction of CORT by osilodrostat confirmed that the amount of skin collagen could be preserved with treatment. In addition, upon suppression of the CORT receptor, the amount of collagen was controlled, and skin aging was suppressed by the hypothalamic-pituitary-adrenal axis. Therefore, this study confirmed an inverse relationship between adrenal CYP11B1/2 levels and collagen during the initial stages of UV irradiation of the skin. The findings of this study may be useful for developing new detection mechanisms for aging, following their further verification.

Hemp seeds and hempseed oil are marketed on- and off-line as health foods and cosmetics and have been reported to have high nutrient contents. However, because of the various side effects of cannabinoids, especially △9-tetrahydrocannabinol (THC), many countries regulate upper limits for THC in products, which creates the need for analytical techniques capable of measuring THC, cannabidiol (CBD), and cannabinol (CBN) levels in commercial hemp seeds and hempseed oil. In the present study, hemp seed and hempseed oil extracts obtained by methanol extraction, were analyzed by gas chromatography–mass spectrometry (GC/MS). Validation of the technique used was performed using calibration curves and by determining LODs, LOQs, specificities, selectivities, and intra- and inter-day precision and accuracies. In addition, matrix effects, process efficiencies, recoveries, and sample stabilities were investigated. In hemp seeds, as determined using the fully optimized method THC concentrations ranged from 0.06 to 5.91 μg/g, CBD concentrations from 0.32 to 25.55 μg/g, and CBN concentrations from 0.01 to 1.50 μg/g; CBN/THC ratios ranged from 0.1 to 1.60, and CBD/THC ratios from 0.11 to 62.56. Furthermore, the (THC + CBN)/CBD ratio of most hemp seed samples was less than one. In hempseed oil, THC concentrations ranged from 0.3 to 19.73 μg/mL, CBD concentrations from 6.66 to 63.40 μg/mL, CBN concentrations from 0.11 to 2.31 μg/mL, CBN/THC ratios from 0.12 to 0.42, and CBD/THC ratios from 3.21 to 22.50. Furthermore, (THC + CBN)/CBD ratios in all hempseed oil samples were less than one. The optimized methanol extraction-GC/MS technique was found to be satisfactory for determining THC, CBD, and CBN concentrations in hemp seeds and hempseed oil.

Allergic dermatitis (AD) clinically presents with skin erythematous plaques, eruption, and elevated serum IgE, and T helper cell type 2 and 1 (Th2 and Th1) cytokine levels. 6-Shogaol [1-(4-hydroxy-methoxyphenyl)-4-decen-one], a pungent compound isolated from ginger, has shown anti-inflammatory effects, but its inhibitory effects on AD are unknown. The aim of this study was to examine whether 6-shogaol inhibits AD-like skin lesions and their underlying mechanism in vivo and in vitro. An AD-like response was induced by tumor necrosis factor-α (TNF-α)+IFN-γ in human keratinocytes or by 2,4-dinitrochlorobenzene (DNCB) in mice. In vivo, 6-shogaol inhibited the development of DNCB-induced AD-like skin lesions and scratching behavior, and showed significant reduction in Th2/1-mediated inflammatory cytokines, IgE, TNF-α, IFN-γ, thymus and activation-regulated chemokine, IL-1, 4, 12, and 13, cyclooxygenase-2, and nitric oxide synthase levels. In vitro, 6-shogaol inhibited reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPKs) signaling, and increased the levels of total glutathione, heme oxygenase-1, and quinone 1 via nuclear factor erythroid 2 related factor 2 (Nrf2) activation. 6-Shogaol can alleviate AD-like skin lesions by inhibiting immune mediators via regulating the ROS/MAPKs/Nrf2 signaling pathway, and may be an effective alternative therapy for AD.

최근 남성성탈모증에 대한 관심이 증대되고 있으며, 이에 천연물 및 그의 활성성분을 활용한 새로운 약물 개발에 대한 연구가 증가하고 있다. 송지(Resina Pini, RP)는 Pinus sp. (Pinaceae)의 수지질로 전통의학적으로 감염, 우식증, 치주질환에 사용되어왔다. 본 연구진은 RP의 성분인 아비에트산(abietic acid, AA)이 남...

Skin damage is mainly caused by environmental factors such as ultraviolet light, heat, and smoking. It is known that reactive oxygen species production is commonly involved in the pathogenesis of skin damage induced by these factors, causing skin aging. Pyrus pyrifolia Nakai continues to be a popular and highly consumed fruit in many countries with known beneficial effects including antitumor, antioxidative, and anti-inflammatory effects. However, there is no evidence of a therapeutic effect of Pyrus pyrifolia extract (PPE) against skin aging via inhibition of mitochondria-mediated apoptosis. In this study, we investigated PPE protective effect against photoaging induced by UVB (50 mJ/cm 2 ) in HS68 human dermal fibroblasts. Lactate dehydrogenase assay showed that PPE significantly protected HS68 cells against UVB-induced damage in a dose-dependent manner. Other assays using DCF-DA demonstrated that PPE protected HS68 cells by regulating reactive oxygen species production. PPE also regulated

Atopic dermatitis (AD) is a chronic inflammatory skin disease with the hallmark characteristics of pruritus, psychological stress, and sleep disturbance, all possibly associated with an increased risk of attention-deficit/hyperactivity disorder (ADHD). However, the etiology of the possible association between AD and ADHD is still not well understood. 2,4-dinitrochlorobenzene or corticosterone was used to evaluate the atopic symptom and its psychologic stress in the atopic mice model. Melatonin, corticotropin-releasing hormone, corticotropin-releasing hormone receptor, urocortin, proopiomelanocortin, adrenocorticotropic hormone, corticosterone, cAMP, cAMP response element-binding protein, dopamine and noradrenaline were analyzed spectrophotometrically, and the expression of dopamine beta-hydroxylase and tyrosine hydroxylase were measured by Western blotting or immunohistochemistry. AD-related psychological stress caused an increase in the levels of dopamine beta-hydroxylase and tyrosine hydroxylase, degradation of melatonin, hyper-activity of the hypothalamic-pituitary-adrenal axis, and dysregulation of dopamine and noradrenaline levels (ADHD phenomena) in the locus coeruleus, prefrontal cortex, and striatum of the AD mouse brain. Notably, melatonin administration inhibited the development of ADHD phenomena and their-related response in the mouse model. This study demonstrated that AD-related psychological stress increased catecholamine dysfunction and accelerated the development of psychiatric comorbidities, such as ADHD.

The dried fruits of Evodia rutaecarpa Bentham have been used widely as a herbal medicine for the treatment of inflammatory disorders and abdominal pain. Benign prostatic hyperplasia (BPH) is a nonmalignant disease characterized by overgrowth of prostates. Despite the pharmacological efficacy of the fruits of E. rutaecarpa against various diseases, their effects against BPH have not been reported. Here, we investigated the inhibitory activity of a 70% ethanol extract of E. rutaecarpa (EEER) against BPH, and its underlying mechanisms regarding cell growth of BPH using BPH-1 cells. An in vitro 5α-reductase activity assay showed that EEER exhibited inhibitory activity against 5α-reductase. In BPH-1 cells, EEER treatment inhibited cell viability and reduced the expression of the proliferating cell nuclear antigen proliferating cell nuclear antigen (PCNA), cyclin D1, and phosphor-ERK1/2 proteins. Moreover, EEER also induced apoptosis, with chromatin condensation, apoptotic bodies, and internucleosomal DNA fragmentation. Regarding its underlying mechanisms, EEER exacerbated the activation of caspase-8 and caspase-3 in a concentration-dependent manner and eventually caused the cleavage of PARP. Taken together, these data demonstrated that EEER had a potent 5α-reductase inhibitory activity and that EEER treatment in BPH-1 cells inhibited cell viability via caspase-8- and caspase-3-dependent apoptosis. Therefore, EEER may be a potential phytotherapeutic agent for the treatment of BPH.

The dried fruits of

Objectives : The present study was conducted to examine whether Toosendan F ructus has an ameliorative effect on diabetes-induced alterations such as oxidative stress and in flammation in the pancreas of non-obese diabetic (NOD) mice, a model of human type I diabetes.Methods : Extracts of Toosendan Fructus (ETF) were administered to NOD mice at three doses (50 mg/kg, 100 mg/kg and 200 mg/kg). Mice at 18 weeks of age were measured glucose t olerance using intraperitoneal glucose tolerance test. After 28 weeks of ETF treatment, glucose, total cholesterol (TC), triglyceride (TG), and proinflammatory cytokines in serum, western blot analyses and a histopathologic al examination in pancreas tissue, and on the onset of diabetes were investigated.Results : The results showed that levels of glucose, glucose tolerance, TC, TG , interferon-γ, interleukin (IL)-1β, IL-6, and IL-12 in serum were down-regulated, while IL-4, IL- 10, SOD, and catalase significantly increased. In addition, ETF improved protein expression of proinflammatory mediaters (such as cyclooxygenase-2, and inducible nitric oxide synthase) and a proapoptotic protein (ca spase-3) in the pancreatic tissue. Also, in the groups treated with ETF (100 mg/kg or 200 mg/kg), insulitis and infiltration of granulocytes were alleviated. Conclusions : Based on these results, the anti-diabetic effect of ETF may b e due to its anti-inflammatory and antioxidant effect. Our findings support the therapeutic evidence for Toose ndan Fructus ameliorating the development of diabetic pancreatic damage via regulating inflammation and apop tosis. Our future studies will be focused on the search for active compounds in these extracts.Key words : Toosendanin fructose, Diabetes, inflammatory cytokine, pancrea tic beta cell

Atopic dermatitis (AD), also known as atopic eczema, is chronic pruritic skin disease. AD can increase psychological stress as well, increasing glucocorticoid release and exacerbating the associated symptoms. Chronic glucocorticoid elevation disturbs neuroendocrine signaling and can induce neuroinflammation, neurotoxicity, and cognitive impairment; however, it is unclear whether AD-related psychological stress elevates glucocorticoids enough to cause neuronal damage. Therefore, we assessed the effects of AD-induced stress in a mouse AD model. AD-related psychological stress increased astroglial and microglial activation, neuroinflammatory cytokine expression, and markers of neuronal loss. Notably, melatonin administration inhibited the development of skin lesions, scratching behavior, and serum IgE levels in the model mice, and additionally caused a significant reduction in corticotropin-releasing hormone responsiveness, and a significant reduction in neuronal damage. Finally, we produced similar results in a corticosterone-induced AD-like skin model. This is the first study to demonstrate that AD-related psychological stress increases neuroendocrine dysfunction, exacerbates neuroinflammation, and potentially accelerates other neurodegenerative disease states.

Some selected medicinal plants used by Bentian tribe from Indonesia were evaluated for potential antimicrobial and antioxidant properties. The leaves stem bark and root of the plants were extracted with n -hexane, ethyl acetate and ethanol to give respective extracts. Antimicrobial activity against Propionibacterium acnes and Candida albicans was determined by an agar well diffusion method. Antioxidant activity was assayed by the DPPH radical scavenging activity mechanism. The results showed that n -hexane, ethyl acetate and ethanol extracts of Cananga odorata , ethanolic extract of Chromolaena odorata , and ethanolic extracts of Hyptis capitata and Ampelocissus cinnamomeae displayed good activity against P. acnes at 25–400 μg/well of the extracts tested. The n -hexane and ethanol extracts of Chromolaena odorata and H. capitata , and the n -hexane, ethyl acetate and ethanol extracts of Cananga odorata displayed more activity against C. albicans than others at 25–400 μg/well of the extracts tested. The most antioxidant activities against DPPH were displayed by the ethanol extracts of Ficus variegata stem bark, Leucosyke quadrinerva root and Clausena excavata leaves exhibiting 91%, 91% and 86% inhibition, respectively. The present results showed potential of some medicinal plants used by Bentian tribe from Indonesia as natural anti-microbial and anti-oxidant and potentially anti-inflammatory agents.

Previously, we have shown that extracellular basic pH plays a significant role in both the direct and indirect regulation of cellular processes in a wound; this in turn affects the wound-healing process. Several studies have demonstrated the importance of apoptosis modulation in the wound-healing process, especially in removing inflammatory cells and in inhibiting scar formation. However, the effects of extracellular basic pH on wound healing-related skin damage are yet to be examined. Therefore, we investigated the induction of accelerated apoptosis by extracellular basic pH in skin. Apoptosis-related protein levels were measured using an array kit, target protein expression levels were detected by immunostaining, lactate dehydrogenase was analyzed spectrophotometrically, and Annexin V levels were measured by fluorescence staining. Basic pH (8.40) strongly upregulated extrinsic apoptosis proteins (Fas, high temperature requirement A, and p21) and slightly upregulated intrinsic apoptosis proteins (cytochrome c, B-cell lymphoma 2 [Bcl-2], Bcl-2-associated death promoter, and Bcl-2-like protein 4) in a 3D human skin equivalent system. Moreover, basic pH (8.40) induced heat shock protein (HSP) 60 and 70. In addition, basic pH-exposed Fas- and HSP60-knockdown cells showed significantly decreased levels of apoptosis. Taken together, these results indicate that extracellular basic pH increases early-stage apoptosis through Fas/FasL via modulation of HSP60 and HSP70.

Background: Oxidative radicals are major environmental causes of human skin damage. Oxidative defense factors, including nuclear factor erythroid-derived 2-related factor 2 (Nrf2), are centrally involved in repairing skin cells or protecting them from oxidative damage. Coriandrum sativum L. (coriander; CS) is a commonly consumed food and a traditional phytomedicine in Asia and Europe. In this study, we examined the protective effects of a standardized CS leaf extract against oxidative stress in human HaCaT keratinocytes. Methods and Results: CS significantly and dose-dependently protected cells against reduced cell viability caused by H2O2-induced damage, as assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Other assays demonstrated that CS protected HaCaT cells by increasing the levels of glutathione and activities of oxidative defense enzymes, such as superoxide dismutase and catalase. Moreover, it increased the expression of activated Nrf2, which plays a crucial role in protecting skin cells against oxidative stress. Conclusion: These results suggest that CS protects human keratinocytes from H2O2-induced oxidative stress through antioxidant effects.

This study was performed to investigate effects of Curculigo orchioides rhizome (curculiginis rhizome) on acute reflux esophigitis (RE) in rats that are induced by pylorus and forestomach ligation operation. Proinflammatory cytokine, as well as tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 were all assayed and the expression of TNF-α and COX2 analyzed by RT-PCR. The esophagic tissue damage of reflux esophagitis rat was increased compared to that of normal intact group. However, the esophagic damage percentage from the extract of curculiginis rhizoma (ECR) 600 mg/kg and ECR 300 mg/kg were significantly lower than that of the RE control group. Administration of α-tocopherol (30 mg/kg) and ECR (600 mg/kg, 300 mg/kg, and 150 mg/kg) had a significant effect on the gastric acid pH in rats with induced reflux esophagitis (p < 0.05). The treatment with ECR significantly reduced the production of cytokines TNF-α, IL-1β and IL-6 levels compared to the model group (p < 0.05). The expression of TNF-α and COX2 in the intact esophageal mucosa was low while those of the RE control group were significantly higher due to an inflammatory reaction in the esophagus. Compare to the model group, treatment with α-tocopherol or ECR significantly inhibited the expression levels of COX2 and TNF-α in a dose-dependent manner. These results suggest that anti-inflammatory and protective effects of ECR could attenuate the severity of reflux esophagitis and prevent esophageal mucosal damage.

In our effort to find antioxidant agent, we focused on Tahongai (Kleinhovia hospita) which have been used traditionally in Indonesia as medicinal herbal to cure liver disease. Based on the biologically guided fractionation using DPPH radical scavenging assay, eleutherol and kaempferol 3-O-β-d-glucoside was isolated from the leaves of K. hospita. Kaempferol 3-O-β-d-glucoside (1) and eleutherol (2) scavenged the radical with IC50 of 71.4 and 491.8 μM, respectively. In addition, both of the compounds did not exhibit cytotoxicity on HepG2 cells.

Extracts of Indonesian medicinal plants, Murraya koenigii, Syzygium polyanthum, and Zingiber purpurea were investigated for their biological activity. The presence of phytochemicals, cytotoxicity, and antimicrobial and antioxidant activities were investigated. Parts of M. koenigii, S. polyanthum, and Z. purpurea were extracted with ethanol. The extracts were evaluated for antimicrobial activity using the disc diffusion method, while antioxidant activity was determined with a 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay. Cytotoxicity was investigated using the brine shrimp lethality test, and phytochemical screening was performed using a standard method. M. koenigii leaf extract exhibited the most activity in the test microorganism activity index (AI), 0.38-1.25, when compared with standard drugs. S. polyanthum ripened fruit displayed significant antioxidant activity (90%) in comparison to ascorbic acid (95%). Z. purpurea rhizome extract possessed the highest cytotoxic effect with a LC50 of 52 μg/mL. Phytochemical analysis revealed that carbohydrate, tannin, alkaloid, steroid, triterpenoid, and flavonoid were present in the extracts of M. koenigii leaves and twigs, S. polyanthum leaves and ripened and unripe fruits, and Z. purpurea rhizome, while saponin was only present in the S. polyanthum ripened fruit extract. Our work revealed that the M. koenigii leaves, S. polyanthum ripened fruit, and Z. purpurea rhizome extracts have potential as sources of new antimicrobial, antioxidant, and cytotoxic compounds, respectively.

We researched the preventive and therapeutic activities of the extract of Ramulus Mori (ERM) to observe its effects on collagen-induced arthritis (CIA) in mice and to explore the mechanisms of ERM in the treatment of rheumatoid arthritis (RA). We examined the in vitro levels of tumor necrosis factor α (TNF-α) released in macrophages and of interferon (IFN)-γ and interleukin (IL)-4 released in splenocytes. For in vivo experiments, we randomly divided 24 mice into four groups, after type II collagen (CII) injections and at euthanization. The levels of plasma cytokines (TNF-α, IL-6, IL-17), rheumatoid factor (RF; IgG, IgM), and anti-CII antibody were measured using ELISA kits. The number of immunocytes (CD4+ T cells, CD3+/CD69+ T cells, B220+/CD45+ B cells, CD11b+/Gr-1+ cells) relative to RA was calculated using flow cytometry (FACS). The articular index (AI) was recorded once a week for 4 weeks. Sections of tissues from the knee joints were stained with hematoxylin and eosin (H&E) and Masson trichrome (MT) after the mice with CIA were euthanized. ERM reduced the levels of TNF-α in macrophages and IFN-γ in spleen cells, decreased AI scores, and improved inflammation of paw joints (PJ). ERM also suppressed the number of immunocytes in peripheral blood mononuclear cells (PBMCs) and PJ, and reduced the levels of cytokines (TNF-α, IL-6, and IL-17), RF, and anti-CII antibody in the sera. TNF-α and Th1 cells play very important roles in the formation and development of RA. ERM and methotrexate notably decreased the induction of RA in the CIA mice model by reducing the levels of inflammatory cytokines and RF in the sera and suppressing the number of immunocytes among PBMCs and PJ.

This study is an endeavor to evaluate the risk assessment of hazardous(aflatoxin ) in medicines from oriental medical prescription which are circulated much recently. For that, twelve globular and granule types, seven liquid types of herbal medicine were bought to compare and analyze the content of aflatoxin aflatoxin ), which are harmful to human body. Woo Hwang Cheong Sim Hwan of Aflatoxin concentration lower than the standard accepted by all the products have been detected, B company(tradition) is the concentration of , C company , A company(tradition) and B company did not detect. And the general pill of aflatoxin B1 concentration lower than the standard accepted by all the products have been detected, S-1 is the concentration of , S-2 of , S-3 of , S-4 of , S-6 of , S-5 did not detect. All the products eundan allowed in the concentration of aflatoxin levels were lower than detection, D company of , E company concentration was not detected. The liquid product of aflatoxin concentration was found liwer than the standard accepted by all the product, L-3 concentration of , K-4 was detected in the , L-1 and L-2 is not detected, L-5 concentration of , L-7 is detected as and, L-6 was not detected.

An active compound from the bulb of Eleutherine americana L. Merr. (Iridaceae) collected from East Kalimantan, Indonesia, was tested for its antidermatophyte and antimelanogenesis activity. Antifungal assay-directed fractionation of the n-hexane-soluble fraction of the methanolic extract of the bulb of E. americana led to the isolation of 1 as an active compound. The compound was identified as the naphthoquinone eleutherin by EI-MS and (1)H-, (13)C-, and two-dimensional NMR analyses. Antidermatophyte assay of 1 at concentrations of 10, 20, 40, 60, and 80 microg/disk and myconazole, a commercial antidermatophyte, at 10 microg/disk displayed 7, 8, 13, 16, 17, and 14 mm of inhibition zone against Trichophyton mentagrophytes, respectively. In a melanin formation inhibition assay, compound 1 displayed potent antimelanogenesis activity at 5 ppm with low toxicity compared with arbutin, a commercial skin-whitening agent. The results showed the high potential of 1, an active compound from E. americana, to be applied as an antidermatophyte and antimelanogenesis agent.

The 50% ethanol extracts from Resina Pini of Pinus sp. (Pinaceae) showed more potent inhibitory activity against testosterone 5α-reductase prepared from rat prostate than those from several medicinal plants used for the treatment of androgen-dependent diseases such as benign prostatic hyperplasia. The fraction responsible for this activity was purified, and the active constituent was isolated and identified as abietic acid, a diterpene resin acid, which exhibited potent testosterone 5α-reductase inhibitory activity. Methyl abietate was substantially inactive against testosterone 5α-reductase, whereas other diterpene resin acids, pimaric acid and neoabietic acid, were as active as abietic acid against testosterone 5α-reductase, indicating that the negatively charged anionic carboxyl group on the molecule is an important structural moiety for the inhibitory activity. These findings suggest that a nonsteroidal anionic diterpene compound of natural origin may have the potential to act as a transition state analogue inhibitor of testosterone 5α-reductase in the treatment of androgen-dependent diseases.

Carrots (Daucus carota L.) are consumed as an important dietary source of provitamin A including -carotene, -carotene and lutein. An HPLC method was applied to determine the content of the carotenoid composition in carrot cutivars cultivated in Korea. HPLC analyses were carried out with five carrot cultivars (Socheon-5-chon, Hongsim-5-chon, Myeongju-5-chon, Seonhongbom-5-chon and Betarich) sown at April, 2007 and six cultivars (Yeoreum-5-chon, Hanyeoreum-5-chon, Sinheukjeon-5-chon, Bibariheukjeon, Manina and Betarich) sown at August of the same year. In general, the former varieties are not used for the sowing at summer because of their bolting (growth of floral axis). The former and the latter carrots were harvested after 110 and 96 days from seeding, respectively, and the carotenoids were extracted with acetone after freeze-drying. The amount of -carotene () was similar to that of -carotene () for the carrot cultivars sown at spring, while the content () was about a half of -carotene content () for the latter cultivars. In addition, the average content of lutein () in the former cultivars was eight times higher than that in the latter cultivars (). Among the spring cultivation types, Socheon-5-chon and Myeongju-5-chon showed higher amount of -carotene and -carotene, while the higher amount was determined in Yeoreum-5-chon and Sinheukjeon-5-chon among the autumn cultivation types. Validation of the HPLC-DAD method showed good linearity ( > 0.997) of the three compounds analyzed in a wide concentration range (). The R.S.D. values for intra-day and inter-day precision were less than 19.2% and the mean recovery of each compound was 85.4~104.7%.

High-performance liquid chromatography (HPLC) was applied to determine the carotenoid composition of carrots during storage and cooking. Analyses were conducted immediately after harvest and 1, 2, 4, and 8 weeks after harvest. During the course of the storage, the carotenoid levels generally decreased, and this decrease was found to be greater during the first week for β-carotene (all-trans-β-carotene) and lutein, and during the second week for α-carotene. Additionally, the amount of the α- and β-carotenes in carrot leaves changed slightly within the first 2 weeks of harvest when stored at 4℃. Specifically, the level of lutein, the main component of carrot leaves, increased from 233.8±11.7 to 346.2±26.7 ㎍/g DW during the first 2 weeks. In addition, the change in carotenoid contents was observed during the home-processing of one Korean cultivar. Carrots fried in oil showed the highest amount of β-carotene (164.3±6.6 ㎍/g DW) and α-carotene (50.1±0.4 ㎍/g DW), while carrots that were prepared by sauteing, pressure-cooking in water and microwaving had the second highest levels. The greatest loss of in carotenoids occurred in response to boiling in water containing 1% NaCl, braising and baking. The content of lutein increased slightly after boiling in water containing 1% NaCl (9.3±0.4 ㎍/g DW), while a loss in lutein occurred after preparation using other home-processing methods. A cis-isomer of all-trans-β-carotene, 13-cis-β-carotene, was present in detectable amounts in all processed samples, but not in raw roots. Another isomer, 9-cis-β-carotene, was detected in carrots that were prepared by boiling, frying and pressure-cooking.

The human aldose reductase inhibitory effects of the methanol extracts of 17 medicinal and edible mushrooms were examined. Ganoderma lucidum showed the highest aldose reductase inhibitory activity compared with the other mushrooms. The effect of an ethanol extract of G. lucidum on the galactitol level in the eye lens was studied in a galactosemic rat model in vivo. This mushroom significantly decreased the galactitol accumulation.

Background/Aims: Wound healing is a complex regeneration process involving the degradation and reassembly of connective tissues and skin layers. Previous studies have shown that pH plays a significant role in both the direct and indirect regulation of cellular processes in the wound, which, in turn, affect the wound healing process. However, the effects of pH on the collagen breakdown component of wound healing have yet to be investigated. Therefore, we investigated the induction of accelerated collagen breakdown by pH imbalance in the skin. Methods: Na+/H+ exchanger and metalloproteinase (MMP)-1 were analyzed spectrophotometrically, and the expression of collagen type-I-alpha-1 (COL1A1) and mitogen-activated protein kinase (MAPK) was measured by Western blotting. Results: Accelerated collagen breakdown induced by extracellular basic pH via the overproduction of reactive oxygen species (ROS) and MAPK signaling was examined in skin fibroblasts and in a three-dimensional human skin equivalent system. Basic pH (>7.50) upregulated MMP-1 and downregulated COL1A1 levels via ROS generation and MAPK signaling pathways. Acidic pH (Conclusion: Our results indicate that skin pH is an important effector of collagen formation in wound healing. This finding will aid in the development of new pH-targeted therapeutic strategies.

A new pentacoordinated ferrous compound [TPAFeCl]+ (TPA = tris(2-pyridylmethyl)amine) was synthesized from the reaction between H3TPA(ClO4)3 and Fe(PnPr3)2Cl2 in MeCN. The unique trigonal bipyramidal [TPAFeCl]+ complex was characterized as a S = 2 high spin complex based on the crystallographic structure, magnetic susceptibility, 1H NMR spectrum and semi-empirical ZINDO/S calculations. Crystal of [TPAFeCl]2(FeCl4)(MeCN)2 was monoclinic with a = 12.019(2) A, b = 27.550(5) A, c = 14.138(2) A, β = 94.168(3)°, V = 4668.9(13) A3, space group C/c, and the unit cell contained a racemic mixture of Δ and Λ isomers with ferrous tetrachloride anion.

Cyclin-dependent kinase 2 (Cdk2) activity is thought to be involved in cell death-associated chromatin condensation and other manifestations of apoptotic death. Here we show that during TNFalpha-induced apoptosis, PKCdelta is activated in a caspase-3-dependent manner and phosphorylates p21(WAF1/CIP1), a specific cyclin-dependent kinase inhibitor, on (146)Ser. This residue is located near a cyclin-binding motif (Cy2) that plays an important role in the interaction between p21(WAF1/CIP1) and Cdk2, and its phosphorylation modulates the ability of p21(WAF1/CIP1) to associate with Cdk2. The phosphorylation of p21(WAF1/CIP1) is temporally related to the activation kinetics of Cdk2 activity during the apoptosis. We propose that during TNFalpha-induced apoptosis, PKCdelta-mediated phosphorylation of p21(WAF1/CIP1) at (146)Ser attenuates the Cdk2 binding of p21(WAF1/CIP1) and thereby upregulates Cdk2 activity.

Spontaneous ultra-weak photon emission and delayed luminescence were measured from the mouse liver injured by carbon tetrachloride (CCl4), a hepatotoxic chemical. After carbon tetrachloride in olive oil (4 ml/kg) was injected intraperitoneally into ICR mouse, spontaneous photon emission and delayed luminescence using metal halide lamp was measured from the excised liver. Twenty-four hours after injection, spontaneous photon emission from the livers was 69.3 ± 21.2 counts/min/cm2, which was two times higher than that from controls of 29.5 ± 5.9 counts/min/cm2. However, 72 hr after injection, spontaneous photon emission from the livers was lowered to 37.0 ± 14.9 counts/min/cm2. These observations were closely correlated with those of the activities of aspartate aminotransferase (AST/GOT) and alanine aminotransferase (ALT/GPT), which were released in the course of hepatocellular death. Delayed luminescence also showed clear distinction in its time course of relaxation between the carbon tetrachloride-treated and control groups. On the basis of these observations, we suggest that these photon emissions are involved in the process of death and/or proliferation of liver cells after acute exposure to carbon tetrachloride with sublethal doses. Further, these photon emissions might be originated from the process of lipid peroxidation and consequent radical scavenging by antioxidant enzymes in injured liver tissue. This model study might provide a basis for the analysis of hepatotoxicant induced liver injury and repair by means of measurements of the photon emissions.

The candidate proteins that are involved in the cyclin-dependent kinase 2 (cdk2) signaling pathway were analyzed by comparing different proteins between dominant negative cdk2 overexpressed and control HeLa cells using two-dimensional electrophoresis (2-DE) and mass spectrometry (MS). The 2-DE and MS indicated that stathmin and its monophosphorylated form were induced in etoposide-treated HeLa cells compared to untreated cells and this effect was inhibited by overexpression of dominant negative mutant form of cdk2. Further analysis showed that serine-25 (Ser-25), which comprises the conserved target motif for phosphorylation by mitogen-activated protein kinase (MAPK), was the major phosphorylation site of monophosphorylated form of stathmin. These findings indicate that etoposide-induced expression and phosphorylation at Ser-25 of stathmin might be mediated by activation of the MAPK signaling pathway, which is mediated by the cdk2 activation during the onset of the anticancer agent induced apoptotic events in the cancer cells.

Steroid 5α-reductase inhibition was studied using eleven polymethoxyflavones (PMFs). Homologous eleven PMFs showed wide range of steroid 5α-reductase inhibitory effects. Among the tested PMFs, 5-hydroxy-7,4′-dimethoxyflavone (5) was found to be the most potent inhibitor of steroid 5α-reductase with the IC50 of 20 μM. These results showed PMFs could be used as a nonsteroidal steroid 5α-reductase for the treatment of benign prostatic hyperplasia.

Forty-seven species of marine macroalgae from the coast of Korea havebeen screened for the presence of inhibitory compounds against humanimmunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) and HIV-1integrase (IN). One of 4 Chlorophyta, 8 of 17 Phaeophyta and 6 of 26 Rhodophytashowed inhibitory activity against HIV-1 reverse transcriptase. Five species(Ecklonia cava, Ishige okamurae,Sargassum confusum, Sargassumhemiphyllum, Sargassum ringgoldianum) belongingto Phaeophyta showed to inhibit the 3′-processing activity of HIV-1integrase. In cell-based assays, the methanol extracts ofBossiella sp. and Chondriacrassicaulis inhibited cytopathogenecity of HIV-1 at a concentrationbelow that cytotoxic for MT4 cells.

Testosterone 5α-reductase inhibitors represent important therapeutic drugs for use against androgen-dependent diseases such as benign prostatic hyperplasia, male pattern baldness, and acne. We have searched for inhibitors of rat prostate testosterone 5α-reductase in the cultured broths of many kinds of soil bacteria, and have found that cultured soybean-casein digest broths of certain bacterial strains have a potent inhibitory effect on the enzyme. We tested 10 selected isoflavonoids, including isoflavones and O-methylated isoflavones, for inhibitory effects on rat prostate testosterone 5α-reductase to determine the important structural elements for inhibition of the enzyme. Genistein, biochanin A, equol, and 3′,4′,7-trihydroxyisoflavone showed considerably higher inhibitory effects whereas daidzein, formononetin, glycitein, prunetin, ipriflavone, and 4′,7-dimethoxyisoflavone showed lower inhibitory effects. The IC 50 values of genistein, biochanin A, equol, 3′,4′,7-trihydroxyisoflavone, and riboflavin, a positive control, for rat prostate testosterone 5α-reductase were 710 μm, 140 μm, 370 μm, 690 μm, and 17 μm, respectively. Daidzein, genistein, biochanin A, formononetin, and equol are already known to be testosterone 5α-reductase inhibitors, but this is the first characterization of 3′,4′,7-trihydroxyisoflavone as an inhibitor of the enzyme.

The synthesis and evaluation of 5α-reductase inhibitory activity of some 4-azasteroid-20-ones and 20-oximes and 3β-hydroxy-, 3β-acetoxy-, or epoxy-substituted C21 steroidal 20-ones and 20-oximes having double bonds in the A and/or B ring are described. Inhibitory activity of synthesized compounds was assessed using 5α-reductase enzyme and [1,2,6,7-3H]testosterone as substrate. All synthesized compounds were less active than finasteride (IC50: 1.2 nM). Three 4-azasteroid-2-oximes (compounds 4, 6 and 8) showed good inhibitory activity (IC50: 26, 10 and 11 nM) and were more active than corresponding 4-azasteroid 20-ones (compounds 3, 5 and 7). 3β-Hydroxy-, 3β-acetoxy- and 1α,2α-, 5α,6α- or 6α,7α-epoxysteroid-20-one and -20-oxime derivatives having double bonds in the A and/or B ring showed no inhibition of 5α-reductase enzyme.