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The objective of this study was to determine biological effects of Cirsium japonicum extract and its main component cirsimaritin on high‐fat diet (HFD)‐induced metabolic dysfunction‐associated fatty liver disease (MAFLD) in a mouse model. Mice were fed with a HFD to induce MAFLD and simultaneously administered with C. japonicum extract (CJE) or cirsimaritin. Various MAFLD biomarkers were evaluated using biological methods. Results demonstrated that triglyceride, aspartate aminotransferase, alanine aminotransferase, and malondialdehyde levels in the liver of mice were significantly reduced upon administration of CJE or cirsimaritin. Treatment with CJE or cirsimaritin also reduced the severity of liver injury in the experimental mouse model of MAFLD by inhibiting hepatic steatosis, oxidative stress, inflammation, and liver fibrosis. These results demonstrate that CJE and cirsimaritin as its main compound have a preventive action against the progression of hepatic steatosis to fibrosis and cirrhosis. Our study suggests that CJE and cirsimaritin might be promising agents for preventing and/or treating MAFLD., Cirsium japonicum and Cir improved HFD‐induced MAFLD through inhibition of hepatic steatosis, oxidative stress, and inflammation.

Purpose An increasing number of people are suffering from hair loss disorders. Niacinamide has long been used as an active ingredient for anti-hair loss preparations but the exact mechanism has not been clearly elucidated yet. The effects of niacinamide were investigated in cultured human dermal papilla cells (hDPCs). Methods To investigate the anti-hair loss effect of niacinamide and its molecular mechanisms, Western blot analysis, ELISA, quantitative RT-PCR and immunocytochemistry were performed. To study the protective effects of niacinamide against H2O2-induced oxidative stress, ROS generation and cytotoxicity were evaluated by DCF-DA assay and LDH release assay, respectively. Minoxidil was used as a positive control. Results Niacinamide decreased the protein expression level of DKK-1 which promotes regression of hair follicles by inducing catagen. The protein expression levels of cell senescence markers, p21 (CDKN1A) and p16 (CDKN2A) which are related to cell cycle arrest, were decreased. The expression of versican was increased by niacinamide treatment in cultured hDPCs. We have found that niacinamide decreased the H2O2-induced intracellular ROS production in cultured hDPCs. Moreover, niacinamide decreased the protein expression levels of H2O2-induced p21 and p16 and diminished the secretion of H2O2-induced DKK-1. Conclusion Our data demonstrate that niacinamide could enhance hair growth by preventing oxidative stress-induced cell senescence and premature catagen entry of hair follicles.

Astrocytes release biologically active substances that cause inflammation in neurodegenerative diseases. The present study investigated the effects of two flavonoids (apigenin and luteolin) on the production of IL-31 and IL-33 in lipopolysaccharide (LPS)-activated astrocytes. Cell viability was investigated using EZ-Cytox assay, mRNA expressions of IL-31 and IL-33 were analyzed by RT-PCR, protein expressions were analyzed by western blot, and cytokine secretion was analyzed by ELISA. Apigenin and luteolin prevented astrocyte activation and inhibited mRNA and protein expression and secretion of IL-31 and IL-33 in the LPS-treated astrocytes. Apigenin's suppression of ERK, NF-κB, and STAT3 activations was responsible for the inhibition of IL-31 and IL-33, while luteolin's suppression of JNK, p38, ERK, NF-κB, and STAT3 activations was responsible for the inhibition of IL-31 in the astrocytes. Also, luteolin's suppression of ERK, NF-κB, and STAT3 activations inhibited IL-33 production in the activated astrocytes. In addition, apigenin and luteolin also prevented the translocation of activated STAT3 and NF-κB to the nucleus of the activated astrocytes and subsequently affected their DNA binding activities. The results suggest that apigenin and luteolin may have potentials as neuroprotective agents for the treatment of diseases involving astrocyte activation and detrimental production of IL-31 and IL-33.

Objective Electroacupuncture (EA) is used in the treatment of various diseases through the use of electrical stimulation. Reports of adverse events (AEs) associated with acupuncture are relatively consistent, but the safety of EA has been less well reported. In this systematic review, we provide a summary of the types of AEs related to EA in clinical practice. Methods Twelve electronic databases, including those in English (PubMed, Ovid-EMBASE, CENTRAL), Korean (KMbase, KISS, NDSL, KISTI, OASIS), Chinese (CNKI, Wanfang, Weipu) and Japanese (J-STAGE), were systematically searched for single case studies and case series through April 2018. There were no language restrictions. We included clinical studies in which EA was used as a key intervention and in which AEs that may have been causally related to EA were reported. Results Thirty-seven studies, including 27 single case studies and 10 case series, were evaluated. The most frequently reported AEs were pallor (eight cases), skin pigmentation (eight cases), vertigo (seven cases), chest tightness (six cases), vomiting (six cases) and unconsciousness (five cases). Thirty-one cases (62%) achieved full recovery and three cases (6%) achieved partial recovery. There were also three cases of death (6%). Conclusion AEs related to EA included acupuncture-related AEs and serious AEs induced by electrical stimulation. Currently, specific stimulation conditions associated with EA-specific AEs are not identifiable due to inappropriate reporting. However, skin pigmentation, syncope or spasm, implantable cardioverter-defibrillator shock, cardiac emergencies, electrical burns, and potential internal organ injury are potential EA-specific AEs regarding which physicians should be cautious in clinical practice.

Objective: To evaluate the effect of different extracts of Diospyros lotus leaves in atopic dermatitis Methods: Diospyros lotus leaves were extracted in ethanol and treated with or without hydrochloric acid or α-rhamnosidase to obtain three different extracts-ethanol, acid-hydrolyzed, and enzyme-hydrolyzed leaf extracts of date plum. The myricitrin content in all samples was measured using HPLC analysis. In vitro antioxidant and anti-inflammatory activities of the extracts were determined by measuring DPPH radical scavenging activities and nitric oxide production in RAW264.7 cells, respectively. Seven- week-old male hairless mice were used to evaluate the anti-atopic dermatitis effects of three extracts in vivo. Splenocytes and mast cells were used to further determine the anti-atopic dermatitis effects of the major compound in the ethanol leaf extract. Results: Enzyme-hydrolyzed leaf extract showed significant in vitro antioxidant and anti-inflammatory activities, and attenuated atopic dermatitis-like skin symptoms and clinical signs more significantly than ethanol and acid-hydrolyzed leaf extracts in 1-fluoro-2,4- dinitrobenzene and house dust mite antigen-treated hairless mice. Enzyme-hydrolyzed leaf extract also suppressed the serum level of immunoglobulin E, interleukin (IL)-4, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, thymic stromal lymphopoietin, and thymus and activation-regulated chemokine in mice with atopic dermatitis. Furthermore, histological analysis revealed that enzyme- hydrolyzed leaf extract suppressed the increased epidermal thickness, dermal infiltration of inflammatory cells, and infiltration and degranulation of mast cells more markedly than the other two extracts in atopic dermatitis-like skin lesions. In addition, this extract effectively inhibited the production of IFN-γ, IL-4,and thymus and activation-regulated chemokine compared with the other two extracts in concanavalin A-stimulated splenocytes. Myricitrin, a major compound of enzyme-hydrolyzed leaf extract, suppressed atopic dermatitis biomarkers in stimulated mouse splenocytes and HMC-1 human mast cells. Conclusions: These results suggest that enzyme-hydrolyzed leaf extract might be a potential candidate to treat atopic dermatitis.

In the present study, we investigated the molecular mechanisms of adenosine for its hair growth promoting effect. Adenosine stimulated the Wnt/β-catenin pathway by modulating the activity of Gsk3β in cultured human dermal papilla cells. It also activated adenosine receptor signaling, increasing intracellular cAMP level, and subsequently stimulating the cAMP mediated cellular energy metabolism. The phosphorylation of CREB, mTOR, and GSK3β was increased. Furthermore, the expression of β-catenin target genes such as Axin2, Lef1, and growth factors (bFGF, FGF7, IGF-1) was also enhanced. The inhibitor study data conducted in Wnt reporter cells and in cultured human dermal papilla cells demonstrated that adenosine stimulates Wnt/β-catenin signaling through the activation of the adenosine receptor and Gsk3β plays a critical role in transmitting the signals from the adenosine receptor to β-catenin, possibly via the Gαs/cAMP/PKA/mTOR signaling cascade.

A normal inflammatory response is essential in protecting the body from foreign substances. However, excessive inflammation contributes to diseases such as oxidative stress, heart disease, and cancer. In this study, we evaluated the anti-inflammatory effects of RAPA (red ginseng marc

To explore the protective impact of the ginger root ethanol extract (GRE) against the oxidative stress induced by 6-hydroxydopamine (6-OHDA) and apoptotic and its mechanism. Parkinson's disease (PD) model was established using 6-OHDA in the cells of rat adrenal pheochromocytoma (PC12). The GRE pretreatment increased PC12 cell viability of injury induced by 6-OHDA. The GRE effectively suppressed 6-OHDA-induced death, apoptosis through decreased Bax and cleaved-caspase 3 expression, and up-regulated expression of B-cell lymphoma 2 (Bcl-2). GRE also inhibited 6-OHDA-inducel oxidative stress, decreased reactive oxygen species (ROS) and up-regulates the heme oxygenase (HO-1), antioxidant enzymes, catalase and, glutathione (GSH), superoxide dismutase (SOD), 8-oxoguanine glycosylase1 (OGG1) and NAD(P)H quinone oxidoreductase1 (NQO1). Besides, GRE up-regulating Protein kinase B (Akt), nuclear erythroid 2-related factor 2 (Nrf2), down-regulating nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) translocation, together with the mitogen-activated protein kinase (MAPK) phosphorylation. In conclusions, the GRE prevented apoptosis and oxidative stress in 6-OHDA-induced PC12 cells. The ginger ethanol extract could be treatment and prevention of PD.

In today's society, hair is not only used to protect the body and maintain body temperature, but to play an aesthetic role. Therefore, interest in natural products that can improve hair loss is increasing. In this study, the hair loss improvement effect of a mixture of Chrysanthemum zawadskii, peppermint and Glycyrrhiza glabra (FHH-CZ) was investigated in Human follicle dermal papilla cell (HFDPC) and C57BL/6 mice. ELISA, Western blot, RT-PCR and animal experiments were performed. The results showed that FHH-CZ suppressed the expression of 5α-reductase type 2 and androgen receptor in testosterone-treated HFDPC. In addition, pretreatment with FHH-CZ reduced the Bax/Bcl2 expression ratio through inhibition of Dkk-1 expression in testosterone-treated HFDPC. In animal experiments, FHH-CZ promoted hair growth and increased the number of hair roots in C57BL/6 mice. Therefore, the results of this study suggested that FHH-CZ could be used as a natural material with few side effects to improve hair loss.

To explore the protective activity of ginger (Zingiber officinale) root ethanol extract (GRE) on the neuroinflammation induced by lipopolysaccharide in microglial cells. Ginger has been investigated as a neuroprotective and anti-aging agent. Nevertheless, ginger extract attenuates neuroinflammation in microglia have not been discovered in depth. The results showed that GRE had high total phenolic and (55.63 ± 0.16 mg GAE/g) and total flavonoid content (4.33 ± 0.17 mg QUE/g), and antioxidant activity. GRE inhibited the release of cytokines and inflammatory mediators including COX-2, PGE2, Nitric oxide, interleukin-6, TNF-α, and iNOS. GRE ameliorated microglia-mediated neuronal insults via upregulating the expression of Bax and reducing the expression of Bcl-2. GRE suppressed NF-κB and AKT/STAT3, and the MAPK pathway in the neuroinflammatory response. In conclusions, GRE positively affected anti-neuroinflammatory and neuroprotective activity without serious side effects, which might be used as a functional food additive and/or therapeutic material for the management and prevention of neurodegenerative diseases.

The objective of the current study was to assess the antioxidant activity of different solvents containing Humulus japonicus extract (HJE) and their antioxidant effects on neurons. H. japonicus ethanol extracts (HEEs) together with H. japonicus water extracts (HWEs) were generated via extraction of H. japonicus leaves with 30%, 50%, and 80% ethanol solutions under a hot water temperature of 121 °C. HEEs showed higher levels of bioactive compounds, such as total flavonoids and polyphenols, with stronger antioxidant activities in contrast to HWEs. HEE (80%) showed the highest content of bioactive compounds and antioxidant activity. Next, we used a H2O2-induced rat model of pheochromocytoma PC12 cells to investigate the antioxidant activity and cellular signal regulation of 80% HEEs. The results showed that HJEs resisted oxidative stress via MAPK and/or AKT-NRF2 and NF-kappa B signaling pathways and upregulated antioxidant enzymes such as SOD, catalase, HO-1, and OGG1, thereby reducing intracellular ROS levels. Further, HJE promoted neuronal survival by upregulating sirtuin 1 expression. This study provides evidence supporting the potential benefits of HJE in preventing oxidative stress in PC12 cells, suggesting its application as a promising functional food additive or therapeutic agent for the prevention and the treatment of oxidative stress-related neurodegenerative diseases.

The aim of this study was to evaluate the inhibitory effect and mechanism of collagen degradation by Pectinase-assisted Halophyte Complex Extract (PHCE) in hairless mice. Collagen expression in vitro was measured using Enzyme-linked Immunosorbent Assay (ELISA) and Western blotting. After collecting mice skin in vivo, histological analysis was performed with Hematoxylin & Eosin (H & E) and trichrome stain. Molecular expression was measured by western blot analysis. In HaCaT cells, the collagen expression level was increased compared to the positive control group. Epidermal thickness inhibition and collagen expression levels were also increased in the skin of a hairless mouse model. Western blot analysis confirmed the increase in collagen and elastin by inhibiting phosphorylation of NF-κB and decreasing the expression of matrix metalloproteinases-1 (MMP-1) and matrix metalloproteinases-9 (MMP-9). The skin protective effect of PHCE is considered to be due to inhibition of MMPs expression through inhibition of NF-κB activation. Therefore, PHCE can be considered as a candidate material as a food material that can improve skin damage caused by UV rays.

Humulus japonicus (HJ) is administered to patients with pulmonary disease and skin disease owing to its anti-inflammatory and antioxidant effects. Lately, HJ has been shown to exert impacts on protection against neurodegenerative sickness. Nevertheless, its impacts on microglia have not been discovered in depth. As a result, anti-inflammatory impacts of HJ ethanol extract (HJE) and its active compound luteolin on lipopolysaccharide-stimulated SIM-A9 cells were investigated. The results showed that HJE luteolin inhibited generation of interleukin-1β, tumor necrosis factor-α, nitric oxide, interleukin-6, together with prostaglandin E2, iNOS, COX-2 along with HO-1 induction. Furthermore, HJE and luteolin reduced degrees of NF-κB pathway components within cytoplasm and nucleus, while reducing cytoplasmic MAPK levels and increasing Nrf2 levels in the cytoplasm and nucleus. In conclusion, our results demonstrate that HJE might exhibit neuroprotective effects and could be used as a novel drug for various neurological diseases.

The androgen receptor is a hormone activated transcription factor that regulates the development and maintenance of male characteristics and represents one of the most well-established drug targets, being implicated not only in prostate cancer but also in many non-cancerous human diseases including androgenetic alopecia, acne vulgaris, and hirsutism. In this study, the antiandrogenic effects of FMN were investigated in 22Rv1 and LNCaP prostate cancer cells. FMN inhibited dihydrotestosterone (DHT)-induced protein expression of androgen receptor in 22Rv1cells. In another prostate cancer LNCaP cells, FMN decreased the protein level of DHT-induced prostate specific antigen (PSA). In addition, FMN downregulated DHT-induced mRNA expression of androgen regulated genes in both cell lines, showing less prominent inhibition in 22Rv1cells where androgen receptor had been significantly decreased by FMN. FMN was found to bind androgen receptor, demonstrating that it acted as a competitive androgen receptor antagonist. FMN increased the phosphorylation of Akt in 22Rv1 cells and this increment was abrogated by PI3K inhibitor wortmannin, resulting in a rescued androgen receptor protein level which was decreased by FMN. Additionally, FMN was found to increase the mRNA and protein level of E3 ligase mouse double minute 2. Our data suggest that the androgen receptor signaling is regulated through PI3K-Akt-MDM2 pathway in 22Rv1 cells. Together, our results indicate that FMN facilitated the degradation of androgen receptor in 22Rv1 cells and inhibited the expression of androgen regulated genes by competing the binding of DHT to androgen receptor in LNCaP cells, demonstrating its therapeutic potential as an antiandrogen.

In this paper, we propose an improved optimal decoupling capacitor (decap) design method based on Q-learning algorithm for high-performance solid-state drive (SSD). The proposed method selects optimal decap combinations that satisfies target impedance with minimum decap number. Based on Q-learning algorithm combined with transmission line theory, optimal decap combinations of power distribution network (PDN) can be provided. The proposed method was verified with voltage ripple measurement and PDN impedance simulation using SSD for high-performance server application. Conventional decap optimization method are using complex and time-consuming analytical tool with power integrity (PI) domain expertise. However, the proposed method requires only the PDN and decap information along with a simple Q-learning model without PI knowledge, providing faster and accurate results than full search optimization method. For example, in 21 decaps combination problem, the proposed method’s computing time consumes only few minutes, 89.09 sec, which is significantly reduced result compared with the conventional full search simulation. Therefore, we expected the proposed method can be widely used to solve for decap optimization problem with complex PDN.

In this paper, we proposed a novel methodology to offer power distribution network (PDN) design guide for PCB power integrity (PI) design for high performance solid-state-drive (SSD). Compared with conventional target-impedance (Z) formulated by current profile of a chip power model (CPM), the proposed methodology utilizes a measurement based current spectrum and a hierarchical PDN-Z model. In order to solve the fundamental limitations of the narrow-banded CPM current model, we successfully measured the PCB-level current of memory packages consisting of the SSD device and converted the measured current values to the chip-level current values using Y-matrix of the hierarchical PDN-Z model consisting of a PCB, a test interposer, a package, and a chip. High-capacity SSD devices are too expensive to make PCBs for design of experiments to test device performance with current measurement. Therefore, we made a test interposer to measure cost-efficiently a current spectrum for each specific power-domain of a unit package such as a DRAM, a NAND, and a SSD controller that all consisting of a SSD device without disturbing SSD’s normal operations.

The present study was conducted with the aim to investigate the ameliorative effects of a new soybean product (cheonggukjang) fermented with Bacillus amyloliquefaciens SCGB1 (SFBA) in atopic dermatitis (AD) mouse model. Visual evaluation of AD induction in the mice indicated the remarkable control of SFBA in reducing the pathological severity of AD-like skin lesions reported as the SCORAD score of AD clinical symptoms. The results revealed that SFBA reduced dorsal skin and epidermal thickness to a similar extent with prednisolone. Further analysis revealed the dominance of SFBA in restraining mast cell infiltration in the dermis; immunoglobulin-E expression in serum; and TH2 IL-4 cytokine and itch-related IL-31 cytokine in the mice skin and serum. SFBA also suppressed scratching behaviours in mice induced by compound 48/80. Further histological findings also revealed the alleviation of collagen fiber deposition in dermal skin of the AD mice model. These actions of SFBA were examined to be mediated by its suppression of the phosphorylation activation of key signalling molecules such as NF-kappaB and MAPK responsible for the induction of cytokine production. Thus, SFBA can be considered as a promising functional food for managing clinical, histological and immunological spectra associated with AD.

V₂O5-P₂O5-TeO₂, a low-temperature vanadate-based glass sealant, was doped with metal oxides (MO = Ag₂O, BaO, or CuO), which generate Ag, Ba, and Cu ions, respectively, to strengthen the glass structure and improve its water resistance. These ions reduce the number of nonbridging oxygen atoms in the glass structure by forming V-O-M or P-O-M crosslinks in the V₂O5-P₂O5 glass system. Structural analysis using Fourier-transform infrared spectroscopy indicated that the numbers of P-O-P, V═O, and V-O-V bonds decreased with increasing metal oxide content. Thermal property analyses revealed that the glass transition temperatures increased by approximately 2-30 °C and that the coefficients of thermal expansion only varied within approximately ±10×10-7 K-1 among all the glass samples. The contact angles were measured to quantify the wetting properties of the doped glasses. The contact angle increased from 11 to 36° with increasing metal oxide content at 410 °C. As an indication of the water resistances of the doped glasses, the dissolution rates of the 9 mol% Ag₂O-doped and pure glasses were 0.078 and 0.523 g cm-2, respectively.

The aim of this study was to investigate the combined effects of Diospyros lotus leaves extracts (DLE) and Muscat Bailey A grape stalk extracts (MGSE) in obesity induced by high-fat diet (HFD) in mice. The mice were fed with HFD and orally administered daily with DLE, MGSE, a mixture of DLE and MGSE, and Garcinia cambogia extract over a period of 16 weeks. The results revealed that daily administration of DLE and MGSE mixtures markedly prevented HFD-induced weight gain, plasma lipid profile, hepatic steatosis, hepatic fibrosis, diabetic symptoms, and the risk of developing cardiovascular diseases. Also, DLE and MGSE mixtures administration greatly prevented oxidative stress and liver toxicity. The combined effects of DLE and MGSE mixtures were higher than effects of the single extracts and of G. cambogia, a plant known for its anti-obesity effects. In summary, these findings demonstrated that DLE and MGSE mixtures, exhibit anti-obesity activity in HFD-fed mice.

Apium graveolens (celery) of the family Apiaceae contains bioactive compounds including luteolin and apigenin. The purpose of this study was to increase the extraction yield of apigenin and luteolin in celery extract using green technology and to evaluate their biological activities. The results showed that CA and β-glucosidase-assisted celery extraction transformed apiin in the celery to apigenin with an increase in luteolin concentration. The CA and β-glucosidase-treated celery extract (CAGE) improved the anti-inflammatory properties of celery extract by inhibiting the expression and production of inflammatory cytokines (IL-6, IL-8, IL-31, and TNF-α) in IL-33-stimulated mast cells (HMC-1.2 cells). Their mechanism of action was tied to the inhibition of ERK, JNK, IKKα, IκBα, and NF-κB activation by CAGE in the stimulated cells. In conclusion, CA and enzyme treatment can be considered as a useful biotechnology tool for the improvement of bioactive compounds in celery and hence improve on their bioactivity. PRACTICAL APPLICATIONS: Apium graveolens commonly called celery is an edible agricultural product cultivated throughout the world and known as a "superfood." Celery contains bioactive compounds including apigenin and luteolin that contribute to their described biological activities. However, extracting celery using normal extraction procedures such as hot water and ethanol methods yields only a small amount of apigenin and luteolin. In the present study, we introduced an eco-friendly method using citric and β-glucosidase to obtain apigenin and luteolin-rich celery extract with improved anti-inflammatory activities. The present work will spark studies on the conversion of less biologically active compounds in functional food materials to more active compounds using CA and β-glucosidase, and the development of functional food with specifically enriched bioactive substances at the industrial levels.

The normal inflammatory reaction protects the body from harmful external factors, whereas abnormal chronic inflammation can cause various diseases, including cancer. The purpose of the present study was to investigate the anti‑inflammatory activity of a mixture of Chrysanthemum zawadskii, peppermint and Glycyrrhiza glabra (CPG) by analyzing the expression levels of inflammatory mediators, cytokines and transcription factors in lipopolysaccharide (LPS)‑stimulated Raw264.7 cells. A nitric oxide assay, ELISA, western blotting and immunofluorescence staining were performed to investigate the anti‑inflammatory activity of the CPG mixture. Pretreatment of Raw264.7 cells with CPG inhibited the increase of inflammatory mediators (inducible nitric oxide synthase, cyclooxygenase‑2 and IFN‑β) induced by LPS. Additionally, it inhibited the production of pro‑inflammatory cytokines (TNF‑α, IL‑6 and IL‑1β). CPG suppressed LPS‑induced phosphorylation of STAT1, AKT, Iκb and NF‑κB. Furthermore, CPG inhibited the translocation of NF‑κB into the nucleus. In summary, CPG could inhibit LPS‑induced inflammation, which occurs primarily through the AKT/Iκb/NF‑κB signaling pathway in RAW264.7 cells.

Adenosine is a cellular metabolite with diverse derivatives that possesses a wide range of physiological roles. We investigated the molecular mechanisms of adenosine and cordycepin for their promoting effects in wound-healing process. The mitochondrial energy metabolism and cell proliferation markers, cAMP responsive element binding protein 1 (CREB1) and Ki67, were enhanced by adenosine and cordycepin in cultured dermal fibroblasts. Adenosine and cordycepin stimulated adenosine receptor signaling via elevated cAMP. The phosphorylation of mitogen-activated protein kinase kinase (MEK) 1/2, mammalian target of rapamycin (mTOR) and glycogen synthase kinase 3 beta (Gsk3b) and Wnt target genes such as bone morphogenetic protein (BMP) 2/4 and lymphoid enhancer binding factor (Lef) 1 were activated. The enhanced gene expression by adenosine and cordycepin was abrogated by adenosine A2A and A2B receptor inhibitors, ZM241385 and PSH603, and protein kinase A (PKA) inhibitor H89, indicating the involvement of adenosine receptor A2A, A2B and PKA. As a result of Wnt/β-catenin pathway activation, the secretion of growth factors such as insulin-like growth factor (IGF)-1 and transforming growth factor beta (TGFβ) 3 was increased, previously reported to facilitate the wound healing process. In addition, in vitro fibroblast migration was also increased, demonstrating their possible roles in facilitating the wound healing process. In conclusion, our data strongly demonstrate that adenosine and cordycepin stimulate the Wnt/β-catenin signaling through the activation of adenosine receptor, possibly promoting the tissue remodeling process and suggest their therapeutic potential for treating skin wounds.

Limonium tetragonum, Triglochin maritimum, Artemisia scoparia and red ginseng have been used as folk remedies for treating a variety of diseases. In the current study, the protective effects of halophyte and red ginseng against ultraviolet (UV)-induced skin damage were investigated. Halophyte red ginseng complex extract (HRCE) was prepared and its effects on UV-B irradiated human keratinocytes and mouse skin were studied through ELISA, Western blotting immunofluorescence and histological staining. HRCE inhibited peroxide-induced damage in human keratinocytes. HRCE also inhibited UVB-induced collagen and elastin degradation in human keratinocytes and mouse skin. In addition, HRCE inhibited mast cell infiltration in the skin of mice irradiated with UVB light. This effect was likely due to HRCE inhibiting the activation of MAPK and NF-κB. By protecting the skin from UVB-induced skin damage, HRCE has the potential to be used in the treatment and prevention of UV-induced skin damage and photoaging.

Sophora flavescens, also known as Kushen, has traditionally been used as a herbal medicine. In the present study we evaluated the ameliorative effects of kushenol C (KC) from S. flavescens against tBHP (tert-Butyl hydroperoxide)-induced oxidative stress in hepatocellular carcinoma (HEPG2) cells and acetaminophen (APAP)-induced hepatotoxicity in mice. KC pretreatment protected the HEPG2 cells against oxidative stress by reducing cell death, apoptosis and reactive oxygen species (ROS) generation. KC pretreatment also upregulated pro-caspase 3 and GSH (glutathione) as well as expression of 8-Oxoguanine DNA Glycosylase (OGG1) in the HEPG2 cells. The mechanism of action was partly related by KC’s activation of Akt (Protein kinase B (PKB)) and Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) in the HepG2 cells. In in vivo investigations, coadministration of mice with KC and APAP significantly attenuated APAP-induced hepatotoxicity and liver damage, as the serum enzymatic activity of aspartate aminotransferase and alanine aminotransferase, as well as liver lipid peroxidation and cleaved caspase 3 expression, were reduced in APAP-treated mice. Coadministration with KC also up-regulated antioxidant enzyme expression and prevented the production of proinflammatory mediators in APAP-treated mice. Taken together, these results showed that KC treatment has potential as a therapeutic agent against liver injury through the suppression of oxidative stress.

Background Dermal papilla cells (DPCs) play a key role in hair growth among the various cell types in hair follicles. Especially, DPCs determine the fate of hair follicle such as anagen to telogen transition and play a pivotal role in androgenic alopecia (AGA). This study was performed to elucidate the hair growth promoting effects of Polygonum multiflorum extract (PM extract) in cultured human DPCs and its underlying mechanisms. Methods The effects of PM extract on cultured DPCs were investigated. Cell viability and mitochondrial activity were measured by CCK-8 and JC-1 analysis, respectively. Western blotting, dot blotting, ELISA analysis, immunocytochemistry and real-time PCR analysis were also performed to elucidate the changes in protein and mRNA levels induced by PM extract. 3D cultured DPC spheroids were constructed for mimicking the in vivo DPs. The hair growth stimulatory effect of PM extract was evaluated using human hair follicle organ culture model. Results PM extract increased the viability and mitochondrial activity in cultured human DPCs in a dose dependent manner. The expression of Bcl2, an anti-apoptotic protein expressed dominantly in anagen was significantly increased and that of BAD, a pro-apoptotic protein expressed in early catagen was decreased by PM extract in cultured DPCs and/or 3D DPC spheroid culture. PM extract also decreased the expression of catagen inducing protein, Dkk-1. Growth factors including IGFBP2, PDGF and VEGF were increased by PM extract, revealed by dot blot protein analysis. We also have found that PM extract could reverse the androgenic effects of dihydrotestosterone (DHT), the most potent androgen. Finally, PM extract prolonged the anagen of human hair follicles by inhibiting catagen entry in human hair follicle organ culture model. Conclusion Our data strongly suggest that PM extract could promote hair growth by elongating the anagen and/or delaying the catagen induction of hair follicles through activation of DPCs.

Kushenol C (KC) is a prenylated flavonoid isolated from the roots of Sophora flavescens aiton. Little is known about its anti-inflammatory and anti-oxidative stress activities. Here, we investigated the anti-inflammatory and anti-oxidative stress effects of KC in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, and tert-butyl hydroperoxide (tBHP)-induced oxidative stress in HaCaT cells. The results demonstrated that KC dose-dependently suppressed the production of inflammatory mediators, including NO, PGE2, IL-6, IL1&beta, MCP-1, and IFN-&beta, in LPS-stimulated RAW264.7 macrophages. The study demonstrated that the inhibition of STAT1, STAT6, and NF-&kappa, B activations by KC might have been responsible for the inhibition of NO, PGE2, IL-6, IL1&beta, in the LPS-stimulated RAW264.7 macrophages. KC also upregulated the expression of HO-1 and its activities in the LPS-stimulated RAW264.7 macrophages. The upregulation of Nrf2 transcription activities by KC in the LPS-stimulated RAW264.7 macrophages was demonstrated to be responsible for the upregulation of HO-1 expression and its activity in LPS-stimulated RAW264.7 macrophages. In HaCaT cells, KC prevented DNA damage and cell death by upregulating the endogenous antioxidant defense system involving glutathione, superoxide dismutase, and catalase, which prevented reactive oxygen species production from tert-butyl hydroperoxide (tBHP)-induced oxidative stress in HaCaT cells. The upregulated activation of Nrf2 and Akt in the PI3K-Akt signaling pathway by KC was demonstrated to be responsible for the anti-oxidative stress activity of KC in HaCaT cells. Collectively, the study suggests that KC can be further investigated as a potential anti-inflammatory candidate for the treatment of inflammatory diseases.

Microglia cells are resident cells of the central nervous system (CNS) charged with modulating inflammation in the CNS. Overstimulation of microglia cells continuously releases inflammatory mediators that contribute to neurodegenerative diseases. Apigenin and Luteolin are flavonoids with reported anti-inflammatory activities. However, their effects on IL-31 and IL-33 production in microglial cells are unknown. Here, we investigated the effects of apigenin and luteolin on the production of IL-31 and IL-33 by microglia cells. SIM-A9 microglial cells were pre-treated with apigenin or luteolin and stimulated with lipopolysaccharides to evaluate the production of IL-31 and IL-33. The study revealed that apigenin and luteolin inhibited the production of IL-31 and IL-33 at the gene and protein expressions and the secretion levels. Using potent inhibitors of MAPK, NF-&kappa, B, and STAT3 signaling pathways, we demonstrated that apigenin and luteolin&rsquo, s suppression of ERK and JNK contributed to the inhibition of IL-31 and IL-33 in the MAPK pathway. Luteolin&rsquo, s suppression of NF-&kappa, B and STAT3 also contributed to the inhibition of IL-31 and IL-33. Further analysis revealed that both compounds prevented nuclear translocation of activated NF-&kappa, B and STAT3, an act that subsequently prevented their DNA binding activities. Collectively, the study suggested that apigenin and luteolin&rsquo, s regulation of signaling pathways contributed to the inhibition of IL-31 and IL-33, thus suggesting its importance for the improvement of neurodegenerative diseases involving these two cytokines.

The anti-obesity effect of a combination of extracts made of Platycodon grandiflorum (PGE), Apium graveolens (AGE) and green tea (GTE) extracts was investigated in a high-fat diet-induced obese C57BL/6N mouse model. Body weight, epididymal adipose tissue weight, liver weight, adipocytes size and serum lipid profile, insulin, leptin and glucose levels were investigated. Additionally, hepatic steatosis, injury and oxidative burden were evaluated in the present study. The current study demonstrated that the PGE, AGE, and GTE (PAG) mixture were most effective in preventing obesity and its associated complications compared with the single extracts used alone. This was evidenced by the PAG's prevention of weight gain, reduction of adipocyte size, beneficial effects in serum lipid profile, levels of insulin, leptin and glucose, and the prevention of liver injury by reducing fat accumulation in the liver, decreased GOT and GPT enzymes and the upregulation of liver antioxidant enzymes. These results suggested that PAG may provide insights into functional food ingredients for use in the prevention of obesity.

Interleukin-31 (IL-31) is a recently discovered cytokine that is tightly linked to the pathogenesis of pruritus seen in atopic dermatitis. Flavonoids, like fisetin, are naturally occurring molecules with antioxidant, cytoprotective, and anti-inflammatory actions. Aim: the present study sought to investigate whether fisetin modulates IL-31 and histamine release in human mast cells (HMC-1). Main methods: HMC-1 cells were pretreated with fisetin at various doses and stimulated with phorbol-12-myristate 13-acetate and calcium ionophore A23187 (PI) for different time intervals. We evaluated IL-31 production and histamine release and signaling mechanism of the action of fisetin on IL-31 production. We also investigated the effects of fisetin on scratching behaviors in mice. Key findings: Fisetin decreased PI-stimulated mRNA expression and production of IL-31 in HMC-1 cells. Fisetin inhibited PI-induced phosphorylation of mitogen-activated protein kinases that further suppressed nuclear factor (NF-κB) activation and translocation to the nucleus through the inhibition of IκB-α phosphorylation. Fisetin also prevented mast cell release of histamine in HMC-1 cells. Mice in-vivo studies show that fisetin reduced scratching behaviors in mice. Significance: These pharmacological actions of fisetin provide new suggestions that fisetin can be of potential use for the treatment of pruritus that cannot be treated with histamine receptor blockers alone.

The effect of NiO nanopowder on the adhesion strength and formation of fish-scales in vitreous enamels has been investigated. The results of a ball drop test indicated that the adhesion strength was greatly increased by a mill addition of NiO nanopowder. The adhesion strength and bubbling microstructure of the enamel were studied using optical and scanning electron microscopy (SEM) in conjunction with energy dispersive spectroscopy (EDS) analysis. The results showed that, as a mill additive, NiO nanopowder changes the composition and structure at the enamel-steel interface and enables interdiffusion. In addition, as the amount of mill addition was increased, the size of the gas bubbles increased and the cracks of the enamel layer, generally referred to as fish-scaling, were reduced.

The aim of this study was to investigate the protective effect of Diospyros lotus leaf extract (DLE) on UVB-induced skin damage in mice. UVB irradiation of mice skin incurred significant damage to mice skin; increased thiobarbituric acid-reactive substance level; decreased superoxide dismutase; and glutathione levels in mice skin tissues. More so, UVB irradiation led to collagen degradation and infiltration of mast cell and neutrophils into mice skin leading to inflammation. However, topical application of DLE significantly reversed these conditions with the result comparable to l-ascorbic acid. Myricitrin, gallic acid, astragalin, myricetin-3-O-glactosside, and myricetin through high-performance liquid chromatography analysis were further determined to be the primary active compounds in DLE. In conclusion, our study showed that DLE has potentials as local therapeutic materials against skin damage by inhibiting oxidative stress and UVB-induced skin damage.

Humans have become exposed to another form of a trait which is ultraviolet B (UVB) radiation reaching the earth's surface. This has become a major source of oxidative stress that ultimately leads to inflammation, DNA damage, photoaging and pigmentation disorders etc. Although several studies have shown the photo-protective role of different grape parts like the fruits and seeds, little or no data demonstrating the in vivo photo-protective role of grape stem, which is the most discarded part of the grape are available. We evaluated the protective influence of grape stem extract against UVB-induced oxidative damage in C57BL mice characterized by epidermal hyperplasia, pigmentation, collagen degradation and inflammation. Grape stem extract was administered topically 1week before UVB irradiation (120mJ/cm2) and continued until the termination of the experiment. A group of non-irradiated mice and a group of irradiated mice topically administered with propylene were used as a negative and positive control. Epidermal thickness, pigmentation, erythema, mast cell and neutrophil infiltration, collagen degradation and COX-2, Nrf2, and HO-1 expressions were evaluated. Grape stem extract markedly recovered skin damage induced by the UVB radiation through the prevention of epidermal hyperplasia, pigmentation, erythema, mast cell and neutrophil infiltrations, collagen degradation and COX-2, Nrf2, and HO-1 expressions. Our study demonstrated for the first time in C57BL mice that grape stem extract reduces UVB-induced oxidative damage and hence can play a protective role in skin photo-damage.