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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.

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: 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.

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 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.

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.

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.

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 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.

Atopic dermatitis, a chronic relapsing and pruritic inflammation of the skin also thought to be involved in, or caused by immune system destruction is an upsetting health problem due to its continuously increasing incidence especially in developed countries. Mast cell infiltration in atopic dermatitis skin lesions and its IgE-mediated activation releases various cytokines and chemokines that have been implicated in the pathogenesis of atopic dermatitis. This study was aimed at investigating synergistic anti-inflammatory, anti-pruritic and anti-atopic dermatitis effects of Diospyros lotus leaf extract (DLE) and Muscat bailey A grapefruit stem extract (GFSE) in atopic dermatitis-like induced skin lesions in mice. Combinations of DLE and GFSE inhibited TNF-α and IL-6 production more than DLE or GFSE in PMA plus calcium ionophore A23187-activated HMC-1 cells. DLE and GFSE synergistically inhibited compound 48/80-induced dermal infiltration of mast cells and reduced scratching behavior than DLE or GFSE. Furthermore, DLE and GFSE synergistically showed a stronger ameliorative effect in skin lesions by reducing clinical scores; dermal infiltration of mast cells; ear and dorsal skin thickness; serum IgE and IL-4 production in atopic dermatitis-like mice. Collectively, these results suggest that DLE and GFSE synergistically exhibit anti-atopic dermatitis effects in atopic dermatitis-like skin lesions in mice.

The aim of this study was to compare the anti-oxidative and anti-inflammatory activities of gamma-irradiated persimmon leaf extract (GPLE) with those of non-irradiated persimmon leaf extract (PLE). Ethanolic extract of persimmon leaf was exposed to gamma irradiation at a dose of 10 kGy. After gamma irradiation, the color of the extract changed from dark brown to light brown. The anti-oxidative and anti-inflammatory activities of GPLE and PLE were assessed from: total polyphenol and total flavonoid contents; 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay; 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assay, and levels of pro-inflammatory mediators such as nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). The total polyphenol contents of GPLE and PLE were determined to be 224.44 ± 1.54 and 197.33 ± 5.81 mg gallic acid equivalents (GAE)/g, respectively, and the total flavonoid contents of GPLE and PLE were 206.27 ± 1.15 and 167.60 ± 2.00 mg quercetin equivalents (QUE)/g, respectively. The anti-oxidant activities of GPLE and PLE as measured by DPPH assays were 338.33 ± 30.19 μg/ml (IC50) and 388.68 ± 8.45 μg/ml (IC50), respectively, and those measured by ABTS assays were 510.49 ± 15.12 μg/ml (IC50) and 731.30 ± 10.63 μg/ml (IC50), respectively. IC50 is the inhibitor concentration that reduces the response by 50%. GPLE strongly inhibited the production of NO, PGE2 and IL-6 compared with PLE in lipopolysaccharide-stimulated RAW264.7 macrophages. Furthermore, GPLE significantly inhibited the production of TNF-α and IL-6 cytokines compared with PLE in phorbol 12-myristate 13-acetate (PMA) plus A23187-stimulated HMC-1 human mast cells. These results indicate that gamma irradiation of PLE can enhance its anti-oxidative and anti-inflammatory activities through elevation of the phenolic contents. Therefore, gamma-irradiated PLE has potential for use in the food and cosmetic industries.

The purpose of this study was to investigate the influence of irradiation on the anti-oxidative, anti-inflammatory and whitening effects of mulberry leaf extract. This was done by comparing the phenolic contents; 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging effects; 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonicacid) (ABTS) radical scavenging effects; in vitro tyrosinase inhibitory effects and the production of IL-6, TNF-α, PGE 2 , and NO in lipopolysaccharide-stimulated RAW264.7 macrophages and the production of IL-6 and TNF-α in phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated HMC-1 cells, respectively. The results showed that irradiated mulberry leaf extract possesses more anti-oxidant, anti-inflammatory, and tyrosinase inhibitory activities than their non-irradiated counterpart, probably due to increase in phenolic contents induced by gamma irradiation at dose of 10kGy. This research stresses on the importance of irradiation in functional foods.

This study investigated the ameliorative effects of acid hydrolyzed celery extract (HCE) and celery extract (CE) in an atopic dermatitis (AD) mice model. The results of the study showed that HCE, more than CE improved AD-like skin lesions caused by fluoro-2,4-dinitrobenzene and house dust mite antigen administration. Further analysis also showed the dominance of HCE than CE in preventing mast cell infiltration in the dermis; inhibiting the IL-31 expression in mice skin and reducing the immunoglobulin-E, IL-4, IL-5, TNF-α, IFN-γ, IL-31, and TSLP in serum of mice. Using in vitro studies in a murine macrophage cell line, we showed that apigetrin, luteolin, and apigenin present in both extracts could be accountable for the observed effects as these three compounds and not apiin prevented the nitric oxide production in the murine macrophage. Based on this study, we suggest that hydrolyzing celery extracts can improve the therapeutic efficacy of celery extracts for management of AD. PRACTICAL APPLICATIONS: Apigenin, apigetrin, and luteolin are known biologically active compounds present in celery. Acid hydrolysis could increase the biologically active compounds in natural products. The research investigated the effects of acid HCE in a mice model of atopic dermatitis. The data obtained from this study sheds light on the use of hydrolysis methods to improve the biological activities of plant extracts used in nutraceutical industries.

Neurodegenerative diseases are major threats to human health. Here, through fluorescence, colorimetric, immunoblotting, spectroscopy, and laser scanning confocal microscopic techniques, we investigated the neuroprotective properties of chlorogenic acid-rich Solanum melongena extracts (SM extract) in rotenone-induced PC-12 cell death. The results showed that rotenone caused apoptosis to PC-12 cells by elevating Bax/Bcl-2 ratio and increasing caspase-3 activity. Rotenone also increased ROS in cells while suppressing SOD and catalase activities. This resulted in the depletion of ATP in cells by blocking mitochondria complex I activity. Pretreatment of the cells with SM extract at concentrations of 100, 250, and 500 μg/ml before incubation for 24 hr with rotenone significantly prevented apoptosis, decreased ROS, and increased ATP production in the cells. SM extract upregulated SOD and catalase activities in the cells. These results unveil evidence that SM extract content neuroprotective properties that can be exploited to prevent and treat neurodegenerative diseases. PRACTICAL APPLICATIONS: Solanum melongena eggplant is a popular ingredient in many traditional recipes and is well known in Asia for its medicinal benefits. Despite numerous scientific reports of the potential health benefits of this plant, reports on its effects in neurodegenerative diseases is still lacking. This pilot study demonstrates that S. melongena eggplant can protect against neurotoxicity in neurodegenerative diseases. The results of this research serves as a base for further research on eggplant that will result in its usage on a larger scale as functional food materials.

Commiphora myrrha (Myrrh) is widely recognized for its anti-inflammatory and antimicrobial properties, which are utilized for the treatment of oral ulcers, gingivitis, sinusitis, glomerulonephritis, brucellosis and a variety of skin disorders. The current study aimed to assess whether myrrh modulates itch-associated interleukin (IL)-31 cytokine production and histamine release in stimulated human mast cells (HMC-1). To realize this, molecular biology techniques including real-time quantitiative PCR, western blotting and ELISA were employed. The results indicated that Myrrh successfully suppressed phorbol myristate acetate and calcium ionophore-stimulated mRNA expression, and reduced the production of IL-31 in HMC-1 cells. In addition, myrrh served as a suppressor of extracellular signal-regulated kinase and NF-κB activation, indicating its mechanism in the prevention of HMC-1 cell IL-31 production. Myrrh also prevented the release of histamine in HMC-1 cells. Whilst the present study awaits in vivo support, the pharmacological actions of myrrh provide new indications as to its potential applicability for itch treatment, which cannot be treated with histamine receptor blockers alone.

The present study demonstrated the anti-obesity effects of enzyme-treated celery extract (ECE) in mice on high-fat diet (HFD). In vitro studies showed that ECE has anti-adipogenic properties by inhibiting lipid accumulations in adipose cells. In vivo studies indicated that the administration of ECE markedly prevented HFD-induced body weight gain, food efficiency ratio, and epididymal fat and liver weights. ECE reduced lipid parameters, cardiac risk factor, and atherogenic index in obese mice. ECE prevented a diabetes state by improving adipokines levels, reducing glucose levels, and preventing insulin resistance. Moreover, ECE prevented HFD-induced liver damage by preventing hepatic steatosis and upregulation of liver antioxidant enzymes. The mechanism of ECE was partially investigated to involve the activation of 5' adenosine monophosphate-activated protein kinase and hence the downregulation of CCAAT/enhancer binding protein α and peroxisome proliferator-activated receptor γ by ECE. Our results suggest that ECE could be used as functional food materials for the prevention of obesity. PRACTICAL APPLICATIONS: Apium graveolens is a popular plant with nutritive and medicinal benefits. It contains bioactive compounds such as apiin, apigenin, and luteolin. However, these compounds are rendered insoluble due to their interaction with polysaccharides in the cell wall thus making them less bioavailable. Hydrolyzing them could increase the yield of bioactive compounds in celery. This pilot study demonstrates that pectinase-treated celery extract has anti-obesity effects. The results of this research demonstrate the use of enzymes in improving the biological activities of plant extracts and suggest the use of enzyme-assisted extraction techniques in the industrial production of health functional food from celery.

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.

IL-31 is a recently discovered cytokine that is produced not only in T-cells but also in mast cells. It is strongly implicated to play a key role in inflammatory diseases and in the pathogenesis of itch in atopic dermatitis. Apigenin, a flavonoid of plant origin has numerous biological applications. In this study, we showed that apigenin modulates IL-31 mRNA, protein expression, and release in stimulated human mast (HMC-1) by inhibiting the phosphorylation activation of MAPK and NF-&kappa, B. To determine whether apigenin has similar effects in vivo, using Compound 48/80, we developed an atopic dermatitis itch model in mice and found an increase in IL-31 expression in the skin. We also revealed that apigenin prevents the infiltration and degranulation of mast cells and suppressed mRNA and protein expression of IL-31 in the skin of mice. These results provide a new suggestion of the potential applicability of apigenin for treatment of various inflammatory diseases and itch mediated by IL-31.

This study was designed to investigate the antioxidant activities of the ethanol extracts (GBE) of grape branches (Campbell Early). The total polyphenol and flavonoid content of GBE was 201.42±4.16 and 11.85±0.44 mg GAE/g, respectively. The antioxidant activity of GBE was measured using the ABTS and DPPH assays, and the IC 50 values were 45.60±0.09 and 299.13±0.22, respectively. GBE inhibited the production of pro-inflammatory mediators (NO, iNOS, PGE₂, COX-2, IL-1β, and IL-6) in lipopolysaccharide-stimulated RAW 264.7 macrophages in a dose-dependent manner. Moreover, GBE treatment significantly suppressed the production of TNF-α and IL-6 cytokines in phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated HMC-1 human mast cells. Furthermore, the administration of GBE markedly inhibited the scratching behavior induced by the compound 48/80 in ICR mice. These results suggested that GBE has potential as a therapeutic agent against inflammation and itch-related skin diseases.

Diospyros lotus is traditionally used for the treatment of diabetes, diarrhea, tumor, and hypertension. The purpose of this study was to investigate the anti-inflammatory effect and underlying molecular mechanisms of myricetin in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Myricetin dose-dependently suppressed the production of pro-inflammatory mediators (NO, iNOS, PGE2, and COX-2) in LPS-stimulated RAW264.7 macrophages. Myricetin administration decreased the production of NO, iNOS, TNF-α, IL-6, and IL-12 in mice. Myricetin decreased NF-κB activation by suppressing the degradation of IκBα, nuclear translocation of p65 subunit of NF-κB, and NF-κB DNA binding activity in LPS-stimulated RAW264.7 macrophages. Moreover, myricetin attenuated the phosphorylation of STAT1 and the production of IFN-β in LPS-stimulated RAW264.7 macrophages. Furthermore, myricetin induced the expression of HO-1 through Nrf2 translocation. In conclusion, these results suggest that myricetin inhibits the production of pro-inflammatory mediators through the suppression of NF-κB and STAT1 activation and induction of Nrf2-mediated HO-1 expression in LPS-stimulated RAW264.7 macrophages. This study has elucidated the anti-inflammatory effects of myricetin in in vitro and in vivo.

The present study investigated the anti-atopic effects of mixed extracts from date plum, persimmon, and mulberry leaves (DPME) on atopic dermatitis (AD)-like skin lesions in hairless mice. The in vivo results demonstrated that DPME treatment significantly reduced the dermatitis clinical score and epidermal thickness in AD-like skin lesions. Histological analyses showed that DPME treatment strongly inhibited dermal infiltration of inflammatory cells and activity of mast cells in AD-like skin lesions. DPME treatment inhibited production of serum IgE and interluekin (IL)-4 in hairless mice with AD. Moreover, DPME treatment significantly suppressed production of tumor necrosis factor (TNF)-α and IL-6 cytokines in phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated HMC-1 human mast cells. In addition, DPME treatment reduced production of pro-inflammatory mediators (nitric oxide, prostaglandin E2, TNF-α, and IL-6) in lipopolysaccharide-stimulated RAW 264.7 macrophages. Therefore, the results of this study indicate that the anti-atopic and anti-inflammatory effects of DPME may be involved in the regulation of inflammatory responses, suggesting that DPME may be used as an anti-atopic dermatitis material and natural anti-inflammatory ingredient.

IL-31 and IL-33 are cytokines, which are expressed in many inflammatory and pathological disorders, thus suggesting an IL-31/IL-33 axis interaction in pathological diseases. Luteolin from natural products is known for its anti-inflammatory activities associated with the regulation of inflammatory signaling pathways. Here, we investigated the effects of luteolin in the regulation of IL-33-stimulated production and secretion of IL-31 in HMC-1.2 mast cells. Human mast cells (HMC-1.2) were treated with luteolin and stimulated with IL-33. Real-time PCR was used to measure IL-31 mRNA expression. Western blot and immunofluorescence assays were used to measure IL-31 expression. ELISA techniques were used to measure IL-31 secretion and NF-κB-DNA-binding activities. The results revealed that luteolin inhibited the expression of IL-31 in IL-33-stimulated HMC-1.2 cells at the mRNA and protein levels. Also, Luteolin inhibited the secretion of IL-31 into the cell culture media of the IL-33-stimulated HMC-1.2 cells. Further findings demonstrated that luteolin inhibited the activation of ERK, JNK, p38, and NF-κB p65 in the IL-33-stimulated HMC-1.2 cells. In addition, luteolin also prevented the nuclear translocation and binding of p65 to its DNA-binding site. Based on the results, luteolin may be considered as a potential therapeutic or functional food agent for the prevention and/or treatment of IL-31 and IL-33-related diseases.

Nonalcoholic fatty liver disease (NAFLD) corresponds to hepatic manifestations of inflammation and accumulations of fatty acids in the liver. Recently, IL-17 signaling pathways have been shown to contribute to the pathogenesis of NAFLD. Cirsium japonicum var. ussuriense is often used in treatment of human diseases such as hemorrhage, blood congestion and inflammation. Despite the known biological activities of C. japonicum var. ussuriense, its effect on NAFLD is still unknown. Here, we investigated the effects of C. japonicum var. ussuriense extract (CJE) and cirsimaritin, its main constituents, on high-fat diet (HFD) or oleic acid (OA)-induced IL-17 expressions associated with steatohepatitis. We found that the levels of IL-17 was reduced in OA-treated HepG2 cells and in mice fed with HFD and administered with CJE and cirsimaritin at the mRNA, protein, and serum expression levels. Further investigation showed that CJE and cirsimaritin suppressed MAPK and NF-κB, the key signaling pathway responsible for IL-17 expression in HFD-fed mice and OA-treated hepatocytes, thus suggesting that the action of CJE and cirsimaritin on signaling molecules might have been responsible for the suppression of IL-17. Here, we also demonstrated that administration of CJE and cirsimaritin reduced triglyceride, aspartate aminotransferase, alanine aminotransferase, and malondialdehyde levels in OA-treated HepG2 cells; and protected mice against HFD-induced triglyceride, aspartate aminotransferase, alanine aminotransferase, and malondialdehyde levels. The results collectively demonstrate that CJE and cirsimaritin may protect against IL-17 exacerbated HFD-induced steatohepatitis.

Muscat Bailey A grape stalk is an organic waste produced in marked amounts during the vinification of grapes. Previous studies have indicated that grape stalk is rich in bioactive phenolic compounds, and exhibits antioxidant and UV‑protective activities. However, its effects on obesity and obesity‑associated disorders have not yet been investigated. The effects of grape stalk extract on improving metabolic features were examined using a high‑fat diet (HFD)‑induced obesity mouse model. Oral administration of 200 mg/kg/day grape stalk extract over 16 weeks markedly prevented HFD‑induced obesity, hepatic steatosis, diabetic symptoms and the risk of developing cardiovascular disease. Furthermore, grape stalk extract prevented oxidative stress and inflammation caused by HFD in mice. The beneficial effect may be associated with CCAAT/enhancer‑binding protein α and peroxisome‑proliferator‑activated receptor γ down-regulation in liver tissue. Collectively, the results of the present study indicated that grape stalk extract may be a potent functional food ingredient for preventing obesity, hepatic steatosis and type 2 diabetes.

Diospyros (D.) lotus has been demonstrated to have antioxidant and anti‑inflammatory properties. The purpose of the present study was to evaluate the effect of D. lotus leaf water extract (DLE) on high‑fat diet (HFD)‑induced obesity in C57BL/6 mice. The present study first investigated the effect of DLE on the lipid accumulation and triglyceride (TG) contents in 3T3‑L1 cells, and the results revealed that treatment with DLE suppressed the lipid accumulation and TG level. Subsequently, the anti‑obesity effects of DLE were investigated in vivo. Oral administration of DLE reduced the body weight gain, food efficiency ratio, and liver and visceral fat weight in mice fed with a HFD. DLE administration in these mice also reduced TG, total cholesterol, low‑density lipoprotein cholesterol, glucose, insulin and leptin levels, as well as the atherogenic index. Furthermore, DLE administration decreased hepatic steatosis, as well as serum aspartate transaminase, alanine transaminase and alkaline phosphatase levels in mice fed with HFD. It was further observed that treatment of the HFD‑fed mice with DLE prevented lipid peroxidation, while it recovered glutathione depletion and the activities of superoxide dismutase, catalase and glutathione peroxidase. In conclusion, the current study suggests that the anti‑obesity effect of DLE may provide positive insights as a potential functional food ingredient for the prevention of obesity.