Photoprotective activities of Capsosiphon fulvescens in UVB-induced SKH-1 mice and human keratinocytes.

Capsosiphon fulvescens (CF) is a green alga widely consumed in East Asian countries, particularly in Korea. It has a rich composition of vitamins, minerals, dietary fibers, and bioactive compounds, which contribute to its multiple therapeutic properties. Its application ranges from acting as an antioxidant and anti-inflammatory agent to supporting the skin system. Despite these benefits of CF, the effects and mechanisms of action related to photoaging of the skin have not yet been elucidated. To investigate the photoprotective effects of CF against photoaging, both animal (SKH-1 mouse) and cell models (HaCaT cell line) were used in this study. As a result, administering the CF extract over a period of 10 weeks, which included times of Ultraviolet B (UVB) exposure, significantly reduced erythema and various UVB-induced skin changes, such as wrinkle formation, and the thickening of the epidermis and dermis, as well as alterations in the length and depth of wrinkles. Furthermore, our investigation into CF extract's antiwrinkle properties revealed its efficacy in enhancing skin hydration and collagen content, counteracting the collagen depletion and moisture loss induced by UVB radiation. Also, the fact that the levels of p-ERK, p-p38, and p-JNK proteins went down shows that the CF extract might have a controlling effect on the MAPK signaling pathways. Our findings suggest that CF holds significant potential for preventing photoaging, providing a foundation for the development of functional foods or botanical drugs targeting skin aging and related skin disorders. PRACTICAL APPLICATION: This research proved that Capsosiphon fulvescen, a green alga widely consumed in East Asian countries, provides photoprotective activities against UV-induced skin aging. Therefore, Capsosiphon fulvescen can be utilized as functional foods or botanical drugs targeting skin aging and related skin disorders.

Optimization of cultivar, germination time and extraction for radish sprout extract with high sulforaphene content.

BACKGROUND: Cruciferous vegetable sprout has been highlighted as a promising functional material rich in bioactive compounds called isothiocyanates (ITCs) and it can be grown in very short periods in controlled indoor farms. However, because ITCs content depends on multiple factors such as cultivar, germination time and myrosinase activity, those variables need to be controlled during germination or extraction to produce functional materials enriched in ITCs. Sulforaphene (SFEN), an ITC found primarily in radishes (Raphanus sativus L.), exerts beneficial effects on obesity. However, the optimal germination and extraction conditions for radish sprout (RSP) to increase SFEN content remain unascertained, and the extract's anti-obesity effect has yet to be evaluated. RESULTS: The present study found that the SFEN content was highest in purple radish sprout (PRSP) among the six cultivars investigated. Optimal SFEN content occurred after 2 days of PRSP germination (2 days PRSP). To maximize the dry matter yield, total ITCs and SFEN contents in RSP extract, we found the optimal conditions for extracting PRSP [27.5 °C, 60 min, 1:75.52 solute/solvent (w/v), no ascorbic acid] using response surface methodology. Consistent with high SFEN content, 2 days PRSP extract significantly outperformed 3 days or 4 days PRSP extract in inhibiting lipid accumulation in 3T3-L1 cells. Moreover, 2 days PRSP extract suppressed adipogenesis and lipogenesis-related protein expression. CONCLUSION: Regarding the cultivar, germination time and extraction conditions, optimally produced PRSP extract contains high SFEN content and exerts anti-obesity effects. Thus, we suggest PRSP extract as a potent functional material for obesity prevention. © 2024 Society of Chemical Industry.

Optimization of extraction condition for platycodin D from Platycodon grandiflorum root and verification of its biological activity.

Platycosides, major components of Platycodon grandiflorum (PG) extract, have been implicated in a wide range of biological effects. In particular, platycodin D (PD) is a well-known main bioactive compound of Platycosides. Despite the biological significance of PD, optimization of extract condition for PD from PG root has not been well investigated. Here, we established the optimum extraction condition as ethanol concentration of 0%, temperature of 50°C, and extraction time of 11 h to obtain PD-rich P. grandiflorum extract (PGE) by using response surface methodology (RSM) with Box-Behnken design (BBD). The 5.63 mg/g of PD was extracted from the PG root in optimum condition, and this result was close to the predicted PD content. To analyze the biological activity of PGE related to mucin production, we demonstrated the inhibitory effect of PGE on PMA-induced hyperexpression of MUC5AC as well as ERK activation, a signal mediator of MUC5AC expression. Moreover, we showed that PGE had expectorant activity in mice. These results indicated that PGE had sufficient functions as a potential mucoregulator and expectorant for treating diverse airway diseases. Additionally, we confirmed that PGE had antioxidant activity and inhibited LPS-induced proinflammatory cytokines, TNF-α, and IL-6. Taken together, PGE derived from novel optimizing conditions showed various biological effects, suggesting that PGE could be directly applied to the food industry as food material having therapeutic and preventive potential for human airway diseases.

Sulforaphane Mitigates High-Fat Diet-Induced Obesity by Enhancing Mitochondrial Biogenesis in Skeletal Muscle via the HDAC8-PGC1α Axis.

SCOPE: Histone deacetylases (HDACs) play a crucial role in the transcriptional regulation of various genes which can contribute to metabolic disorders. Although sulforaphane (SFN), a natural HDAC inhibitor, has been reported to alleviate obesity in humans and mice, the specific mechanisms and how HDACs contribute to SFN's anti-obesity effects remain unclear. METHODS AND RESULTS: Oral administration of SFN in mice fed high-fat diet increases peroxisome proliferator activating receptor γ coactivator (PGC1α)-induced mitochondrial biogenesis in skeletal muscle. Among HDACs, SFN specifically inhibits HDAC8 activity. SFN enhances mitochondrial DNA and adenosine triphosphate (ATP) production in C2C12 myotubes, similar to the action of PCI34051, a synthetic HDAC8-specific inhibitor. These effects are mediated by increased expression of PGC1α via upregulation of cAMP response element binding (CREB, Ser133 ) phosphorylation and p53 (Lys379 ) acetylation. These SFN-induced effects are not observed in cells with a genetic deletion of HDAC8, suggesting the existence of a regulatory loop between HDAC8 and PGC1α in SFN's action. CONCLUSION: SFN prevents obesity-related metabolic dysregulation by enhancing mitochondrial biogenesis and function via targeting the HDAC8-PGCα axis. These results suggest SFN as a beneficial anti-obesity agent providing new insight into the role of HDAC8 in the PGC1α-mediated mitochondrial biogenesis, which may be a novel and promising drug target for metabolic diseases.

Discovery and optimized extraction of the anti-osteoclastic agent epicatechin-7-O-ß-D-apiofuranoside from Ulmus macrocarpa Hance bark.

Ulmus macrocarpa Hance bark (UmHb) has been used as a traditional herbal medicine in East Asia for bone concern diseases for a long time. To find a suitable solvent, we, in this study, compared the efficacy of UmHb water extract and ethanol extract which can inhibit osteoclast differentiation. Compared with two ethanol extracts (70% and 100% respectively), hydrothermal extracts of UmHb more effectively inhibited receptor activators of nuclear factor κB ligand-induced osteoclast differentiation in murine bone marrow-derived macrophages. We identified for the first time that (2R,3R)-epicatechin-7-O-ß-D-apiofuranoside (E7A) is a specific active compound in UmHb hydrothermal extracts through using LC/MS, HPLC, and NMR techniques. In addition, we confirmed through TRAP assay, pit assay, and PCR assay that E7A is a key compound in inhibiting osteoclast differentiation. The optimized condition to obtain E7A-rich UmHb extract was 100 mL/g, 90 °C, pH 5, and 97 min. At this condition, the content of E7A was 26.05 ± 0.96 mg/g extract. Based on TRAP assay, pit assay, PCR, and western blot, the optimized extract of E7A-rich UmHb demonstrated a greater inhibition of osteoclast differentiation compared to unoptimized. These results suggest that E7A would be a good candidate for the prevention and treatment of osteoporosis-related diseases.

Micro-grinding-based production for sulforaphene-enriched radish seeds extract via facilitating glucosinolates-myrosinase reaction, and evaluation of its anti-adipogenic effects.

Sulforaphene (SFEN), an isothiocyanate (ITC) abundant in radish (Raphanus sativus) seeds (RS), has many health benefits, including anti-obesity effects. SFEN content is affected by multiple factors during processing, such as glucoraphenin (GLE) (the precursor of SFEN) availability, myrosinase (essential for conversion from GLE to SFEN) activity, and SFEN stability. We examined the physiochemical-properties and anti-adipogenic effects of SFEN-enriched RSE produced by two processes, roasting and micro-grinding. The roasting process lowered SFEN content and myrosinase activity over 50 °C. However, among micro-grinding conditions, smaller particle size (#2 grind, ≈11.31 µm) more effectively increased SFEN content in RS compared to larger particles (#1 grind, ≈ 179.50 µm) by accelerating available GLE and myrosinase release from RS. Grind #2 also effectively inhibited the adipogenesis of 3T3-L1 pre-adipocytes compared to #1. Thus, micro-grinding can be suggested for producing SFEN-enriched RSE with anti-adipogenic activity as a functional material for obesity prevention or treatment.

Enhancing stability and bioavailability of sulforaphene in radish seed extracts using nanoemulsion made with high oleic sunflower oil.

The effect of nanoemulsions on the stability and bioavailability of sulforaphene (SFEN) in radish seed extract (RSE) was investigated. Four types of oil were used as lipid ingredients of the nanoemulsions: soybean, high oleic acid sunflower, coconut, and hydrogenated palm oils. SFEN in RSE nanoemulsions showed greater stability to temperature, acid, and alkaline conditions than SFEN in RSE suspended in water (RSE-S). Particularly under alkaline conditions, the half-life of SFEN in the nanoemulsion with high oleic sunflower oil (RSE-HOSO) was 8 times longer than that of RSE-S. Furthermore, in the pharmacokinetics study, it was observed that AUC0-8 increased and oral clearance (CL/F) decreased significantly in rats orally administered RSE-HOSO compared with RSE-S (p < 0.05). This study indicates that the type of oil used in nanoemulsions affects the stability and bioavailability of SFEN in RSE. These results may provide a guideline for the development of functional foods containing RSE. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01304-2.

Ca2+-Permeable TRPV1 Receptor Mediates Neuroprotective Effects in a Mouse Model of Alzheimer's Disease via BDNF/CREB Signaling Pathway.

Transient receptor potential vanilloid 1 (TRPV1) protein is a Ca2+-permeable non-selective cation channel known for its pain modulation pathway. In a previous study, it was discovered that a triple-transgenic Alzheimer's disease (AD) mouse model (3xTg-AD+/+) has anti-AD effects. The expression of proteins in the brain-derived neurotrophic factor (BDNF)/cAMP response element binding protein (CREB) pathway in a 3xTg-AD/TRPV1 transgenic mice model was investigated to better understand the AD regulatory effect of TRPV1 deficiency. The results show that TRPV1 deficiency leads to CREB activation by increasing BDNF levels and promoting phosphorylation of tyrosine receptor kinase B (TrkB), extracellular signal-regulated kinase (ERK), protein kinase B (Akt), and CREB in the hippocampus. Additionally, TRPV1 deficiency-induced CREB activation increases the antiapoptotic factor B-cell lymphoma 2 (Bcl-2) gene, which consequently downregulates Bcl-2-associated X (Bax) expression and decreases cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP), which leads to the prevention of hippocampal apoptosis. In conclusion, TRPV1 deficiency exhibits neuroprotective effects by preventing apoptosis through the BDNF/CREB signal transduction pathway in the hippocampus of 3xTg-AD mice.

A machine learning-integrated stepwise method to discover novel anti-obesity phytochemicals that antagonize the glucocorticoid receptor.

As a type of stress hormone, glucocorticoids (GCs) affect numerous physiological pathways by binding to the glucocorticoid receptor (GR) and regulating the transcription of various genes. However, when GCs are dysregulated, the resulting hypercortisolism may contribute to various metabolic disorders, including obesity. Thus, attempts have been made to discover potent GR antagonists that can reverse excess-GC-related metabolic diseases. Phytochemicals are a collection of valuable bioactive compounds that are known for their wide variety of chemotypes. Recently, various computational methods have been developed to obtain active phytochemicals that can modulate desired target proteins. In this study, we developed a workflow comprising two consecutive quantitative structure-activity relationship-based machine learning models to discover novel GR-antagonizing phytochemicals. These two models collectively identified 65 phytochemicals that bind to and antagonize GR. Of these, nine commercially available phytochemicals were validated for GR-antagonist and anti-obesity activities. In particular, we confirmed that demethylzeylasteral, a phytochemical of the Tripterygium wilfordii Radix, exhibits potent anti-obesity activity in vitro through GR antagonism.

Glycine max Fermented by a Novel Probiotic, Bifidobacterium animalis subsp. lactis LDTM 8102, Increases Immuno-Modulatory Function.

Many probiotic species have been used as a fermentation starter for manufacturing functional food materials. We have isolated Bifidobacterium animalis subsp. lactis LDTM 8102 from the feces of infants as a novel strain for fermentation. While Glycine max has been known to display various bioactivities including anti-oxidant, anti-skin aging, and anti-cancer effects, the immune-modulatory effect of Glycine max has not been reported. In the current study, we have discovered that the extract of Glycine max fermented with B. animalis subsp. lactis LDTM 8102 (GFB 8102), could exert immuno-modulatory properties. GFB 8102 treatment increased the production of immune-stimulatory cytokines in RAW264.7 macrophages without any noticeable cytotoxicity. Analysis of the molecular mechanism revealed that GFB 8102 could upregulate MAPK2K and MAPK signaling pathways including ERK, p38, and JNK. GFB 8102 also increased the proliferation rate of splenocytes isolated from mice. In an animal study, administration of GFB 8102 partially recovered cyclophosphamide-mediated reduction in thymus and spleen weight. Moreover, splenocytes from the GFB 8102-treated group exhibited increased TNF-α, IL-6, and IL-1ß production. Based on these findings, GFB 8102 could be a promising functional food material for enhancing immune function.

Piceatannol, a metabolite of resveratrol, attenuates atopic dermatitis by targeting Janus kinase 1.

BACKGROUND: Piceatannol is a resveratrol metabolite commonly found in red wine, grapes. Several studies have investigated the immune-modulating effects of piceatannol on processes related to allergic reactions. However, the relationship between piceatannol and atopic dermatitis (AD) has not yet been reported. This study sought to investigate the effects of piceatannol in animal and cell line models. METHODS: AD-like symptoms and skin lesions were triggered by repeated topical treatment of Dermatophagoides farinae extract (DFE) on the skin of NC/Nga mice. The molecular mechanism of piceatannol was studied in the TNFα/IFNγ-induced HaCaT cell line. RESULTS: Piceatannol attenuated DFE-induced AD-like symptoms, as shown by skin thickness, dermatitis score, scratching time, and skin water loss. Histopathological analysis showed that piceatannol suppressed DFE-induced immune cell infiltration into the skin. These results occurred concomitantly with the downregulation of inflammatory markers, including serum and skin TARC and MDC. Piceatannol decreased phosphorylation of JAK-STAT protein in the TNFα/IFNγ-induced HaCaT cell line. A molecular docking study showed that piceatannol strongly interacts with JAK1, suggesting a possible mode of action. CONCLUSION: The study results showed that piceatannol, a metabolite of resveratrol, attenuates atopic dermatitis and provide important implication of development of piceatannol as functional ingredients or therapeutic agents.

Flavonoid Glycosides from Ulmus macrocarpa Inhibit Osteoclast Differentiation via the Downregulation of NFATc1.

The aim of this study was to isolate and identify chemical components with osteoclast differentiation inhibitory activity from Ulmus macrocarpa Hance bark. Spectroscopic analyses, including nuclear magnetic resonance (NMR) and electronic circular dichroism (ECD), resulted in the unequivocal elucidation of active compounds such as (2S)-naringenin-6-C-ß-d-glucopyranoside (1), (2R)-naringenin-6-C-ß-d-glucopyranoside (2), (2R,3S)-catechin-7-O-ß-d-xylopyranoside (3), (2R,3S)-catechin-7-O-ß-d-apiofuranoside (6), (2R,3R)-taxifolin-6-C-ß-d-glucopyranoside (7), and (2S,3S)-taxifolin-6-C-ß-d-glucopyranoside (8). Mechanistically, the compounds may exhibit osteoclast differentiation inhibitory activity via the downregulation of NFATc1, a master regulator involved in osteoclast formation. This is the first report of their inhibitory activities on the receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast differentiation in murine bone marrow-derived macrophages. These findings provide further scientific evidence for the rational application of the genus Ulmus for the amelioration or treatment of osteopenic diseases.

Ethanol Extract of Yak-Kong Fermented by Lactic Acid Bacteria from a Korean Infant Markedly Reduces Matrix Metallopreteinase-1 Expression Induced by Solar Ultraviolet Irradiation in Human Keratinocytes and a 3D Skin Model.

Yak-Kong is a type of black soybean that is colloquially referred to as the "medicinal bean" and it elicits several beneficial effects that are relevant to human health, including attenuating the formation of skin wrinkles. It has previously been shown that soybean extracts elicit additional bioactivity that is fermented by lactic acid bacteria. In this study of lactic acid bacteria strains that were isolated from the stools of breast-feeding infants (<100 days old), we selected Bifidobacterium animalis subsp. Lactis LDTM 8102 (LDTM 8102) as the lead strain for the fermentation of Yak-Kong. We investigated the effects of LDTM 8102-fermented Yak-Kong on solar-ultraviolet irradiation (sUV)-induced wrinkle formation. In HaCaT cells, the ethanol extract of LDTM 8102-fermented Yak-Kong (EFY) effectively reduced sUV-induced matrix metalloproteinase-1 (MMP-1) secretion. The effect of EFY was superior to that of unfermented (UFY)- and Lactis KCTC 5854 (another Bifidobacterium animalis species)-fermented Yak-Kong. Additionally, EFY reduced sUV-induced MMP-1 mRNA expression and promoter activity, as well as the transactivation of AP-1 and phosphorylation of ERK1/2 and JNK1/2. Furthermore, EFY alleviated sUV-induced MMP-1 secretion, the destruction of the epidermis, and degradation of collagen in a three-dimensional (3D) skin culture model. EFY had a higher total polyphenol content and anti-oxidative activity than UFY. Twelve metabolites were significantly (≥2-fold) increased in Yak-Kong extract after fermentation by LDTM 8102. Among them, the metabolites of major isoflavones, such as 6,7,4'-trihydroxyisoflavone (THIF), exerted the reducing effect of MMP-1, which indicated that the isoflavone metabolites contributed to the effect of EFY on MMP-1 expression as active compounds. These findings suggest that EFY is a potent natural material that can potentially prevent sUV-induced wrinkle formation.

Orobol, A Derivative of Genistein, Inhibits Heat-Killed Propionibacterium acnes-Induced Inflammation in HaCaT Keratinocytes.

Acne is a chronic skin disease that typically occurs in the teens and twenties, and its symptoms vary according to age, sex, diet, and lifestyle. The condition is characterized by hyperproliferation of keratinocytes in the epidermis, sebum overproduction, excessive growth of Propionibacterium acnes, and P. acnes-induced skin inflammation. Interleukin (IL)-1α and IL-6 are predominant in the inflammatory lesions of acne vulgaris. These cytokines induce an inflammatory reaction in the skin in the presence of pathogens or stresses. Moreover, IL-1α accelerates the production of keratin 16, which is typically expressed in wounded or aberrant skin, leading to abnormalities in architecture and hyperkeratinization. Orobol (3',4',5,7-tetrahydroxyisoflavone) is a metabolite of genistein that inhibited the P. acnes-induced increases in IL-6 and IL-1α levels in human keratinocytes (HaCaTs) more effectively compared with salicylic acid. In addition, orobol decreased the IL-1α and IL-6 mRNA levels and inhibited the phosphorylation of inhibitor of kappa-B kinase, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha, and mitogen-activated protein kinase induced by P. acnes. Finally, the expression of Ki67 was decreased by orobol. Thus, orobol ameliorated the inflammation and hyperkeratinization induced by heat-killed P. acnes and thus has potential for use in functional foods and cosmetics.

A short-term, hydroponic-culture of ginseng results in a significant increase in the anti-oxidative activity and bioactive components.

Panax ginseng CA Meyer has a variety of biological effects, including antioxidant and antidiabetic activities. Ginseng requires long-term cultivation, but this can be shortened using hydroponic systems to facilitate the commercial development of ginseng as a functional food. However, the characteristics of short-term-cultured (< 30 days) hydroponic ginseng (sHCG) are unclear. We investigated the characteristics of 21-day-cultured sHCG compared 5-year-old normally cultured ginseng. The free radical-scavenging activity and total ginsenoside and phenolic contents were significantly higher in sHCG than in normally cultured ginseng. Fifteen ginsenosides were detected in sHCG, and the concentrations of most were higher in shoots than roots. These findings suggest that 21-day-cultured sHCG, due to its enhanced antioxidant activity and higher concentrations of total phenolics and ginsenosides (including Rd and Re), has potential as a functional food.

Sulforaphene Suppresses Adipocyte Differentiation via Induction of Post-Translational Degradation of CCAAT/Enhancer Binding Protein Beta (C/EBPß).

Adipocyte differentiation (adipogenesis) is a crucial process that determines the total number and size of mature adipocytes that will develop. In this study, the anti-adipogenic effect of sulforaphene (SFEN), a dietary isothiocyanate (ITC) derived from radish, is investigated both in 3T3-L1 pre-adipocytes and in human adipose tissue-derived stem cells. The results revealed that SFEN significantly inhibit adipogenic cocktail-induced adipocyte differentiation and lipid accumulation at the early stage of adipogenesis. Additionally, the effects are more potent compared to those of other ITCs derived from various cruciferous vegetables. As a related molecular mechanism of action, SFEN promotes the post-translational degradation of CCAAT/enhancer-binding protein (C/EBP) ß by decreasing the stability of C/EBPß, which is responsible for decreasing the expression of master regulatory proteins such as peroxisome proliferator-activated receptor γ and C/EBPα. Collectively, these results suggest that the intake of SFEN-enriched natural materials could be helpful as a strategy for preventing obesity.

Ca2+-permeable TRPV1 pain receptor knockout rescues memory deficits and reduces amyloid-ß and tau in a mouse model of Alzheimer's disease.

The transient receptor potential vanilloid 1 (TRPV1) protein is a pain receptor that elicits a hot sensation when an organism eats the capsaicin of red chili peppers. This calcium (Ca2+)-permeable cation channel is mostly expressed in the peripheral nervous system sensory neurons but also in the central nervous system (e.g. hippocampus and cortex). Preclinical studies found that TRPV1 mediates behaviors associated with anxiety and depression. Loss of TRPV1 functionality increases expression of genes related to synaptic plasticity and neurogenesis. Thus, we hypothesized that TRPV1 deficiency may modulate Alzheimer's disease (AD). We generated a triple-transgenic AD mouse model (3xTg-AD+/+) with wild-type (TRPV1+/+), hetero (TRPV1+/-) and knockout (TRPV1-/-) TRPV1 to investigate the role of TRPV1 in AD pathogenesis. We analyzed the animals' memory function, hippocampal Ca2+ levels and amyloid-ß (Aß) and tau pathologies when they were 12 months old. We found that compared with 3xTg-AD-/-/TRPV1+/+ mice, 3xTg-AD+/+/TRPV1+/+ mice had memory impairment and increased levels of hippocampal Ca2+, Aß and total and phosphorylated tau. However, 3xTg-AD+/+/TRPV1-/- mice had better memory function and lower levels of hippocampal Ca2+, Aß, tau and p-tau, compared with 3xTg-AD+/+/TRPV1+/+ mice. Examination of 3xTg-AD-derived primary neuronal cultures revealed that the intracellular Ca2+ chelator BAPTA/AM and the TRPV1 antagonist capsazepine decreased the production of Aß, tau and p-tau. Taken together, these results suggested that TRPV1 deficiency had anti-AD effects and promoted resilience to memory loss. These findings suggest that drugs or food components that modulate TRPV1 could be exploited as therapeutics to prevent or treat AD.

Topical Application of 7,3',4'-Trihydroxyisoflavone Alleviates Atopic Dermatitis-Like Symptoms in NC/Nga Mice.

Atopic dermatitis is a skin disease characterized by chronic inflammatory lesions, and new therapies are needed to address its rising prevalence. Soy isoflavone has been highlighted as a potential new cosmeceutical material that may have applications in atopic dermatitis care. We have developed a technique to attach an additional -OH group to the ortho position of -OH in the phenol ring using a special enzyme. By adding the -OH group to daidzein, 7,3',4'-trihydroxyisoflavone can be generated for possible use as a cosmeceutical and functional food material. In this study, we sought to examine the anti-atopic effects of 7,3',4'-trihydroxyisoflavone, an analog of daidzein. Topical application of 7,3',4'-trihydroxyisoflavone reduced Dermatophagoides farina extract-induced atopic dermatitis symptoms in NC/Nga mice. Histological analysis demonstrated that 7,3',4'-trihydroxyisoflavone suppressed D. farina extract-induced infiltration of eosinophils and mast cells into skin lesions. We also found that 7,3',4'-trihydroxyisoflavone significantly reduces the D. farina extract-induced increases in serum IgE and macrophage-derived chemokine (CCL22) levels. We observed that 7,3',4'-trihydroxyisoflavone suppresses atopic markers including macrophage-derived chemokine (CCL22) and thymus and activation-regulated chemokine (CCL17) in HaCaT cells. 7,3',4'-Trihydroxyisoflavone also reduced TNF-α/IFN-γ-induced phosphorylation of ERK1/2 and JNK1/2. These results highlight several desirable properties of 7,3',4'-trihydroxyisoflavone, which support its use as a cosmeceutical ingredient for the treatment of atopic dermatitis.

Orobol, an Enzyme-Convertible Product of Genistein, exerts Anti-Obesity Effects by Targeting Casein Kinase 1 Epsilon.

Soy isoflavones, particularly genistein, have been shown to exhibit anti-obesity effects. When compared with the isoflavones genistin, daidzin, coumestrol, genistein, daidzein, 6-o-dihydroxyisoflavone, equol, 3'-o-dihydroxyisoflavone, and 8-o-dihydroxyisoflavone, a remarkably higher inhibitory effect on lipid accumulation was observed for orobol treatment during adipogenesis in 3T3-L1 cells. To identify the cellular target of orobol, its pharmacological effect on 395 human kinases was analyzed. Of the 395 kinases, orobol showed the lowest half maximal inhibitory concentration (IC50) for Casein Kinase 1 epsilon (CK1ε), and bound to this target in an ATP-competitive manner. A computer modeling study revealed that orobol may potentially dock with the ATP-binding site of CK1ε via several hydrogen bonds and van der Waals interactions. The phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1, a substrate of CK1ε, was inhibited by orobol in isobutylmethylxanthine, dexamethasone and insulin (MDI)-induced 3T3-L1 cells. It was also found that orobol attenuates high fat diet-induced weight gain and lipid accumulation without affecting food intake in C57BL/6J mice. These findings underline orobol's potential for development as a novel agent for the prevention and treatment of obesity.

Sulforaphane Upregulates the Heat Shock Protein Co-Chaperone CHIP and Clears Amyloid-ß and Tau in a Mouse Model of Alzheimer's Disease.

SCOPE: Sulforaphane is an herbal isothiocyanate enriched in cruciferous vegetables. Here, the authors investigate whether sulforaphane modulates the production of amyloid-ß (Aß) and tau, the two main pathological factors in Alzheimer's disease (AD). METHODS AND RESULTS: A triple transgenic mouse model of AD (3 × Tg-AD) is used to study the effect of sulforaphane. Oral gavage of sulforaphane reduces protein levels of monomeric and polymeric forms of Aß as well as tau and phosphorylated tau in 3 × Tg-AD mice. However, sulforaphane treatment do not affect mRNA expression of amyloid precursor protein or tau. As previous studies show that Aß and tau metabolism are influenced by a heat shock protein (HSP) co-chaperone, C-terminus of HSP70-interacting protein (CHIP), the authors examine whether sulforaphane can modulate CHIP. The authors find that sulforaphane treatment increase levels of CHIP and HSP70. Furthermore, observations of CHIP-deficient primary neurons derived from 3 × Tg-AD mice suggest that sulforaphane treatment increase CHIP level and clear the accumulation of Aß and tau. Finally, sulforaphane ameliorated memory deficits in 3 × Tg-AD mice as reveal by novel object/location recognition tests and contextual fear conditioning tests. CONCLUSION: These results demonstrate that sulforaphane treatment upregulates CHIP and has the potential to decrease the accumulation of Aß and tau in patients with AD.