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Illicium verum extract inhibits TNF-a and IFN-g-induced expression of chemokines and cytokines in human Kerationocytes

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Abstract

Illicium verum Hook. f. (star anise) has been used in traditional medicine for treatment of skin inflammation, rheumatism, asthma, and bronchitis. This study investigated the anti-inflammatory effects of Illicium verum extract (IVE) in the human keratinocyte HaCaT cell line. We investigated the effectiveness of IVE in tumor necrosis factor-α (TNF-α)/interferon-γ (IFN-γ)-induced human keratinocytes. To measure the effects of IVE on chemokine and pro-inflammatory cytokine expression in HaCaT cells, we used the following methods: cell viability assay, reverse transcription-polymerase chain reaction, enzyme-linked immunosorbent assay, western blotting, and luciferase reporter assay. IVE inhibited the expression of TNF-α/IFN-γ-induced mRNA and protein expression of thymus and activation-regulated chemokine (TARC/CCL17), macrophage-derived chemokine (MDC/CCL22), interleukin (IL)-6, and IL-1β. Furthermore, IVE decreased TNF-α/IFN-γ-induced mRNA expression of intercellular adhesion molecule-1 (ICAM-1). IVE inhibited nuclear factor (NF)-κB translocation into the nucleus, as well as phosphorylation and degradation of IκBα. IVE inhibited TNF-α/IFN-γ-induced NF-κB and signal transducer and activator of transcription (STAT)1 activation in a dose-dependent manner. In addition, IVE significantly inhibited activation of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK), and Akt. Furthermore, IVE contained 2.14% trans-anethole and possessed significant anti-inflammatory activities. IVE exerts anti-inflammatory effects by suppressing the expression of TNF-α/IFN-γ-induced chemokines, pro-inflammatory cytokines, and adhesion molecules via blockade of NF-κB, STAT1, MAPK, and Akt activation, suggesting that IVE may be a useful therapeutic candidate for inflammatory skin diseases, such as atopic dermatitis.

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... etanolowy ekstrakt z owoców/ trans-anetol [28] Działanie hamujące na translokację czynnika jądrowego (NF-κB) do jądra komórkowego, fosforylację i degradację IκBα trans-anetol wyizolowany z owoców [28] Obniżenie aktywności dehydrogenazy mleczanowej; regulacja ciśnienia krwi; obniżenie poziomu prozapalnych cytokin (IL-6, TNF-α) trans-anetol [31] Łagodzenie nadreaktywności dróg oddechowych; hamowanie produkcji immunoglobuliny E (IgE); zmniejszenie produkcji interleukiny 4 (IL-4) w supernatancie z hodowli splenocytów trans-anetol [32] Działanie hamujące na wytwarzanie IL-1β i TNF-α trans-anetol [33] Tom 78 · nr 4 · 2022 [24]. ...
... etanolowy ekstrakt z owoców/ trans-anetol [28] Działanie hamujące na translokację czynnika jądrowego (NF-κB) do jądra komórkowego, fosforylację i degradację IκBα trans-anetol wyizolowany z owoców [28] Obniżenie aktywności dehydrogenazy mleczanowej; regulacja ciśnienia krwi; obniżenie poziomu prozapalnych cytokin (IL-6, TNF-α) trans-anetol [31] Łagodzenie nadreaktywności dróg oddechowych; hamowanie produkcji immunoglobuliny E (IgE); zmniejszenie produkcji interleukiny 4 (IL-4) w supernatancie z hodowli splenocytów trans-anetol [32] Działanie hamujące na wytwarzanie IL-1β i TNF-α trans-anetol [33] Tom 78 · nr 4 · 2022 [24]. ...
... Sung i in. [28] przeprowadzili doświadczenie oceniające aktywność przeciwzapalną etanolowego ekstraktu z owoców I. verum na ludzkiej linii komórkowej keratynocytów HaCaT. Komorki HaCaT zostały inkubowane z TNF-α i IFN-γ w obecności lub braku I. verum. ...
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The growing requirements imposed on cosmetic products are associated with the need for continuous selection of natural raw materials to meet the changing trends on the cosmetics market. The appearance of newer and newer targeted actives reflects the dynamics in the skincare field. Certain trends, however, despite the passage of time, remain unchanged and will always constitute a solid basis in the canon of maintaining good skin condition. Regardless of the type of skin, its age or condition, it is extremely important for the cosmetic to provide adequate antioxidant, antimicrobial and anti-inflammatory protection. Few raw materials combine such a diverse biologically active activity, which is why star anise (Illicium verum) deserves special attention. It is the raw material relatively well known and used in Traditional Chinese Medicine (TMC) as a therapeutic agent. It also has an important position as a food and fragrance plant. In the European Pharmacopoeia 4.0 since 2002 and in the Polish Pharmacopoeia VIII (Farmakopea Polska VIII), since 2008 there are two monographs of raw materials obtained from I. verum: fruit - Anisi stellati fructus, and essential oil - Anisi stellati aetheroelum. Moreover, I. verum also appears in various forms as a source of raw materials for the production of cosmetics in the created by European Commission, CosIng database (Cosmetic Ingredients database). I. verum is a rich source of valuable biologically active compounds, such as: monoterpenoids, sesquiterpenoids, phenylpropanoids, and flavonoids, which determine the biological activity of these raw materials. In medicine, their expectorant and spasmolytic effects are mainly used. The documented by the latest scientific research; anti-inflammatory, antibacterial, antifungal and antioxidant of fruit extracts and / or essential oil, determine the use of this species in the production of cosmetics. Trans-anethole (E-anethole) is recognized to be the most important compound in the essential oil of I. verum, determining its activity. The valuable sensory features (aromatic, sweet taste) and biological properties (antibacterial, antifungal, antioxidant and anti-inflammatory) of this compound, are used in the food, cosmetic, perfume and pharmaceutical industries. Opinion-forming organizations such as: FEMA (Flavor and Extract Manufacturers Association) and FDA (Food Drug Administration) have granted both I. verum and trans-anethole the status of safe raw materials. This multifunctional biological effect makes anise an extremely interesting raw material in cosmetic formulations, however, its potential is still underestimated.
... Sung et al. [36] confirmed the anti-inflammatory activity of the ethanolic extract of I. verum fruits in a human keratinocyte cell line (HaCaT). Their study revealed that the extract suppressed the mRNA expression of pro-inflammatory cytokines IL-6 and IL-1β induced by TNF-α/IFN-γ. ...
... Ethanol extract of the I. verum fruit [36] Inhibitory activity against nuclear factor (NF-κB) translocation into the nucleus, phosphorylation and IκBα degradation ...
... Trans-anethole isolated from I. verum fruit [36] Decreased activity of lactate dehydrogenase, blood pressure regulation, the reduction of level of pro-inflammatory cytokines (IL-4, TNF-α) ...
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Illicium verum Hook f. (star anise) is considered an important species in Traditional Chinese Medicine and is also used in contemporary medicine in East Asian countries. It occurs in natural habitats in southeastern parts of China and Vietnam, and is cultivated in various regions in China. The raw materials - Anisi stellati fructus and Anisi stellati aetheroleum obtained from this species exhibit expectorant and spasmolytic activities. The European Pharmacopoeia (4th edition) indicates that these raw materials have been used in allopathy since 2002. The biological activities of the above-mentioned raw materials are determined by the presence of valuable secondary metabolites such as monoterpenoids, sesquiterpenoids, phenylpropanoids, and flavonoids. Recent pharmacological studies on fruit extracts and the essential oil of this species have confirmed their antibacterial, antifungal, anti-inflammatory, and antioxidant activities and thus their medicinal and cosmetic value. The aim of this review was to examine the progress of phytochemical and pharmacological studies that focused on possible cosmetic applications. In addition to fruit extracts and essential oil, the current consensus on the safety of trans-anethole, which is the main compound of essential oil used in cosmetology, is underlined here.
... IFN-γ and TNF-α activate the extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases (JNK), and p38 mitogen-activated protein kinase (MAPK) pathways in various cell types, including keratinocytes (Sung et al., 2012;Jeong et al., 2016). The MAPKs regulate the synthesis of proinflammatory molecules, such as chemokines, in AD through their intracellular signaling pathways, including signal transducer and activator of transcription 1 (STAT1) and nuclear factor kappa B (NF-κB) (Kwon et al., 2012;Park et al., 2015a;An et al., 2017). ...
... Upon stimulation with IFN-γ/TNF-α, STAT1 is activated, phosphorylated, and further translocated to the nucleus where it can activate the target genes by binding to promoters. Similarly, activation of NF-κB by the phosphorylation and degradation of inhibitor kappa B-alpha (IκB-α) causes translocation of NF-κB (p65 and p50) to the nucleus where it can activate the target genes by binding to promoters (Sung et al., 2012). Thus, inhibition of the MAPK/STAT1/NF-κB signaling pathway can alleviate the symptoms of AD and is considered an important strategy in the development of novel therapeutics for AD. ...
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S. patholobus suberectus Dunn, a traditional Chinese herbal medicine, has various pharmacological activities, such as anti-inflammatory properties. However, to the best of our knowledge, its therapeutic effect on atopic dermatitis (AD) has not been investigated. In this study, we explored the effect of S. suberectus Dunn water extract (SSWex) on AD in vivo and in vitro. In Dermatophagoides farina extract (DfE)–treated NC/Nga mice, the oral administration of SSWex alleviated AD-like symptoms, such as ear thickness, dermatitis score, epidermal thickness, immune cell infiltration, and levels of AD-related serum parameters (immunoglobulin E, histamine, and proinflammatory chemokines). In HaCaT cells, the production of proinflammatory chemokines induced by interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) was inhibited by SSWex pretreatment. SSWex treatment inhibited the phosphorylation of mitogen-activated protein kinase and activation and translocation of transcriptional factors, such as signal transducer and activator of transcription 1 and nuclear factor kappa B in IFN-γ/TNF-α–stimulated HaCaT cells. These results indicate that SSWex may be developed as an efficient therapeutic agent for AD.
... Los datos demuestran que no existen mayores discrepancias en la información publicada con respecto a los usos que la población jujeña de la ciudad capital práctica. Esto puede estar vinculado a numerosos factores, tales como la permanencia de saberes tradicionales y populares referidos a estas plantas de uso común desde hace siglos (Acosta, 2013, la difusión masiva realizada por los diferentes medios de comunicación (Acosta, 2013; Ladio y Albuquerque 2014) y la relación demanda/validación científica fitoquímica y farmacológica que es alta para estas especies (Cañigueral et al., 1998;Kloucek et al., 2005;Petenatti et al., 2011;Sarris et al., 2011;Yoon-Young et al., 2012;Yoon-Young y Kim, 2013;Asadi-Samani et al., 2014;Sebai et al., 2014;Sharifi et al., 2014). ...
... Las hojas y brácteas de T. cordata son calmantes de la tos y catarros, actuando como diaforético en estados febriles por resfriados, recomendable para un aumento de la sudoración. Los frutos de I. verum son estomáticos, expectorante (Cañigueral et al., 1998), mientras que los extractos de esta especie presentan actividad antiinflamatoria en enfermedades de la piel como psoriasis y dermatitis (Yoon-Young et al., 2012;Yoon-Young y Kim, 2013 (Cañigueral et al., 1998). El leño de P. excelsa es un tónico amargo estimulante del apetito y a veces puede provocar vómito en dosis muy alta (Cañigueral et al., 1998). ...
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Twelve medicinal species (Matricaria chamomilla, Senna alexandrina, Equisetum giganteum, Tilia cordata, Valeriana officinalis, Malva sylvestris, Illicium verum, Peumus boldus, Picrasma excelsa, Borago officinalis, Passiflora caerulea and Baccharis articulata), the most sold in the city of San Salvador de Jujuy, were evaluated according to general aspects of marketing, its botanical quality, its uses and role in urban medicine.. We have performed an urban inquiry in 31 sites of commercialization to obtain representative samples, then plants were analyzed by morphological and micrographic methods, and bibliographical research. The results have indicated that the presentation and labels of plants packages are marketed in inappropriate way in relation to national regulations. Half of the samples show signs of adulteration. Although these species are highly consumed by the people, few have been validated by ethno-pharmacological literature. We conclude that this situation could lead to discredit to phytoterapy.
... To test in vivo findings in vitro, we investigated the effects of OA on pro-inflammatory cytokine expression in tumor necrosis factor (TNF)-α/IFN-γ-stimulated HaCaT keratinocytes. HaCaT human keratinocytes are the most commonly used cell line in the AD model, which produces various AD-related pro-inflammatory mediators in response to a variety of stimuli [27]. OA had no signs of toxicity up to 100 µM in HaCaT keratinocytes (Supplementary Figure S1). ...
... Epidermal keratinocytes provide a functional skin barrier on the frontline of the defense system. In the skin of patients with AD, allergic sensitization, due to pathogen invasion, irritants, and allergens, occurs through a damaged skin barrier that leads to the stimulation of immune responses in keratinocytes, with increased skin inflammation [23][24][25][26][27][28][29][30][31][32]. The expression of various inflammatory cytokines and chemokines derived from keratinocytes plays important roles in the pathogenesis of AD [33,34]. ...
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Oleanolic acid (OA) is a pentacyclic triterpenoid, abundantly found in plants of the Oleaceae family, and is well known for its beneficial pharmacological activities. Previously, we reported the inhibitory effect of OA on mast cell-mediated allergic inflammation. In this study, we investigated the effects of OA on atopic dermatitis (AD)-like skin lesions and its underlying mechanism of action. We evaluated the inhibitory effect of OA on AD-like responses and the possible mechanisms using a 1-chloro-2,4-dinitrochlorobenzene (DNCB)-induced AD animal model and tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated HaCaT keratinocytes. We found that OA has anti-atopic effects, including histological alterations, on DNCB-induced AD-like lesions in mice. Moreover, it suppressed the expression of Th2 type cytokines and chemokines in the AD mouse model and TNF-α/IFN-γ-induced HaCaT keratinocytes by blocking the activation of serine-threonine kinase Akt, nuclear factor-κB, and the signal transducer and activator of transcription 1. The results demonstrate that OA inhibits AD-like symptoms and regulates the inflammatory mediators; therefore, it may be used as an effective and attractive therapeutic agent for allergic disorders, such as AD. Moreover, the findings of this study provide novel insights into the potential pharmacological targets of OA for treating AD.
... In previous studies, it has been reported that HaCaT cells differ in the degree of phosphorylation of MAPKs and NF-κB signaling pathways upon TNF-α stimulation for different time periods [5,25,26]. Hence, before confirming the signaling pathway involved in mediating the anti-inflammatory effects of DMC, we examined the time at which maximum expression of phosphorylated MAPKs and NF-κB signaling intermediates is seen, by treating HaCaT cells with TNF-α (50 ng/mL) for 5, 10, 15, 30, and 60 min. The expression of P-p38, P-JNK, and P-ERK in the MAPK signaling pathway was the highest at 10 min after TNF-α treatment (Figure 3a-d). ...
... In previous studies, it has been reported that HaCaT cells differ in the degree of phosphorylation of MAPKs and NF-κB signaling pathways upon TNF-α stimulation for different time periods [5,25,26]. Hence, before confirming the signaling pathway involved in mediating the antiinflammatory effects of DMC, we examined the time at which maximum expression of phosphorylated MAPKs and NF-κB signaling intermediates is seen, by treating HaCaT cells with TNF-α (50 ng/mL) for 5, 10, 15, 30, and 60 min. The expression of P-p38, P-JNK, and P-ERK in the MAPK signaling pathway was the highest at 10 min after TNF-α treatment (Figure 3a-d). ...
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7,8-dimethoxycoumarin (DMC, C11H10O4), a natural coumarin compound, is present in Citrus plants including Citrus decumana and grapefruit. It is known to have protective effects on the kidneys against Cisplatin and ischemia-reperfusion injury. However, the underlying mechanisms of its inhibitory effects on skin inflammation have not been investigated in vitro. Tumor necrosis factor (TNF)-α is known to be one of the main causative agents of skin inflammation. It induces pro-inflammatory cytokines and chemokines by activating nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling. In this study, we investigated the inhibitory effect of DMC on the expression of pro-inflammatory cytokines and chemokines in TNF-α-treated human keratinocyte HaCaT cells. Pretreatment with DMC inhibited TNF-α-treated cytokines (interleukin 6; IL-6) and chemokines (IL-8 and monocyte chemoattractant protein-1). In addition, DMC significantly inhibited TNF-α-treated NF-κB activation and phosphorylation of MAPKs, such as c-Jun N-terminal kinases (JNK) and extracellular-signal-regulated kinase (ERK). These results suggest that DMC may elicit an anti-inflammatory response by suppressing TNF-α-treated activation of NF-κB and MAPK pathways in keratinocytes. Hence, it might be a useful therapeutic drug against skin inflammatory diseases.
... Anethole has in vivo anti-inflammatory effects on animal models of nonimmune acute inflammation, including croton oil-induced ear edema and carrageenan-induced pleurisy [13]. We previously found that topical application of I. verum extract (IVE) improved dermatitis in house dust mite-induced NC/Nga mice by modulating the level of IgE and Th2 cytokines and chemokines [14]. AET has significant anti-inflammatory activities that are exerted by suppressing TNF-α/IFN-γinduced expression of proinflammatory cytokines and Th2 chemokines in human keratinocytes [15]. ...
... Allergic diseases, such as asthma and atopic dermatitis, are chronic inflammatory diseases mediated by Th2-driven inflammation in response to common environmental allergens and are increasing in prevalence [22]. Our previous studies reported that topical application of I. verum ethanolic extract in mite antigen-induced atopic dermatitis mice showed remarkable antiallergic properties exerted through inhibition of Th2 cell responses [14]. Therefore, we hypothesized that IVE may exhibit therapeutic effects on allergic asthma. ...
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Illicium verum is used in traditional medicine to treat inflammation. The study investigates the effects of IVE and its component, trans -anethole (AET), on airway inflammation in ovalbumin- (OVA-) induced asthmatic mice. Asthma was induced in BALB/c mice by systemic sensitization to OVA, followed by intratracheal, intraperitoneal, and aerosol allergen challenges. IVE and AET were orally administered for four weeks. We investigated the effects of treatment on airway hyperresponsiveness, IgE production, pulmonary eosinophilic infiltration, immune cell phenotypes, Th2 cytokine production in bronchoalveolar lavage, Th1/Th2 cytokine production in splenocytes, forkhead box protein 3 (Foxp3) expression, and lung histology. IVE and AET ameliorated OVA-driven airway hyperresponsiveness ( p<0.01 ), pulmonary eosinophilic infiltration ( p<0.05 ), mucus hypersecretion ( p<0.01 ), and IL-4, IL-5, IL-13, and CCR3 production ( p<0.05 ), as well as IgE levels ( p<0.01 ). IVE and AET increased Foxp3 expression in lungs ( p<0.05 ). IVE and AET reduced IL-4 and increased IFN- γ production in the supernatant of splenocyte cultures ( p<0.05 ). Histological studies showed that IVE and AET inhibited eosinophilia and lymphocyte infiltration in lungs ( p<0.01 ). These results indicate that IVE and AET exert antiasthmatic effects through upregulation of Foxp3 ⁺ regulatory T cells and inhibition of Th2 cytokines, suggesting that IVE may be a potential therapeutic agent for allergic lung inflammation.
... The findings reveal that dose-dependent reduction of intracellular ROS and increment of cell viability in stimulated HaCaT keratinocytes ensure the potency of BDB to diminish oxidative stress. Furthermore, TNF-α/IFN-γ-stimulated keratinocytes were reported in prior studies to induce the abnormal production of inflammatory cytokines and chemokines, resulting in skin inflammation [19,25,26]. The innate cytokines IL-25, -33, and TSLP, which are produced by epithelial and epidermal cells, play a significant role in the initiation of inflammatory reactions by stimulating the production of type-2 cytokines [27][28][29]. ...
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Polysiphonia morrowii is a well-known red alga that has promising pharmacological characteristics. The current study evaluates the protective effect of 3-bromo-4,5-dihydroxybenzaldehyde (BDB) isolated from P. morrowii on tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated inflammation and skin barrier deterioration in HaCaT keratinocytes. The anti-inflammatory effect of BDB in TNF-α/IFN-γ-stimulated HaCaT keratinocytes is evaluated by investigating nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, inflammatory cytokines, and chemokines. Further, the interaction between BDB and the skin barrier functions in stimulated HaCaT keratinocytes is investigated. The findings of the study reveal that BDB dose-dependently increases cell viability while decreasing intracellular reactive oxygen species (ROS) production. BDB downregulates the expression of inflammatory cytokines, interleukin (IL)-6, -8, -13, IFN-γ, TNF-α, and chemokines, Eotaxin, macrophage-derived chemokine (MDC), regulated on activation, normal T cells expressed and secreted (RANTES), and thymus and activation-regulated chemokine (TARC) by modulating the MAPK and NF-κB signaling pathways in TNF-α/IFN-γ-stimulated HaCaT keratinocytes. Furthermore, BDB increases the production of skin hydration proteins and tight junction proteins in stimulated HaCaT keratinocytes by preserving skin moisturization and tight junction stability. These findings imply that BDB exhibits a protective ability against inflammation and deterioration of skin barrier via suppressing the expression of inflammatory signaling in TNF-α/IFN-γ-stimulated HaCaT keratinocytes.
... The resulting free NF-κB is translocated to the nucleus where it can activate target genes by binding to regulatory elements in the target gene's promoter. Similarly, STAT-1 is phosphorylated and activated when stimulated with TNF-α/IFN-γ and translocated to the nucleus where it can activate target genes by binding to regulatory elements in the target gene's promoter [22]. As shown in Figure 3, EAH inhibited degradation of the nuclear factor-kappa B (NF-κB) inhibitory protein IκBα but did not inhibit phosphorylation of STAT-1. ...
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Artemisia apiacea Hance is a traditional herbal medicine used for treating eczema and jaundice in Eastern Asia including China, Korea, and Japan. However, the biological and pharmacological actions of Artemisia apiacea Hance in atopic dermatitis (AD) are not fully understood. An ethanolic extract of Artemisia apiacea Hance (EAH) was tested in vitro and in vivo to investigate its anti-inflammatory activity and anti-atopic dermatitis effects. The results showed that EAH dose-dependence inhibited production of regulated on activation, normal T-cell expressed and secreted (RANTES), interleukin (IL)-6, IL-8, and thymus and activation-regulated chemokine (TARC). EAH inhibited the activation of p38, extracellular signal-regulated kinases (ERK), and STAT-1 and suppressed the degradation of inhibited both nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha (IκB-α) in TNF-α/IFN-γ⁻stimulated HaCaT cells. EAH also suppressed the translocation of inflammation transcription factors such as NF-κB p65 in TNF-α/IFN-γ⁻stimulated HaCaT cells. In addition, EAH reduced 2,4-dinitrochlorobenzene (DNCB)-induced ear thickness and dorsal skin thickness in a dose-dependent manner. EAH appeared to regulate chemokine formation by inhibiting activation of and ERK as well as the NK-κB pathways. Furthermore, EAH significantly improved the skin p38 conditions in a DNCB-induced AD-like mouse model.
... Star anise (Illicium verum Hook. f.) is one of the most famous evergreen tree which has originally distributed in tropic and subtropic areas of Asia, especially China, and it is famous as in traditional Chinese medicine as well as traditional Asian medicine (Yokoyama et al., 2002;Yokoyama et al., 2003;Thuat and Ngoc, 2010;Sung et al., 2012;Zhongliang, 2012;Vermaak et al., 2013;Vecchio et al., 2016;Zhou et al., 2016Yoshikawa et al., 2018). Its fruit also commonly used spice. ...
... Abdallah et al. (2013) investigated the antiviral activity of anise oil against bovine herpes virus type 1-(BHV-1) in cell culture and they found that anise oil is non-toxic to MDBK cells up to 100 ug/ml, and also inhibited the growth and development of BHV-1. Sung et al. (2012) recommended star anise in the treatment of inflammatory diseases. Alhajj et al. (2015) indicated that Chinese star anise could be used as a natural additive to improve the immune responsiveness and performance of broiler chickens. ...
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Star anise (Illicium verum Hook. f.) is an important herb in traditional Chinese medicine as well as traditional Asian medicine. The fruit is aromatic and has a strong, pungent and mildly sweet taste. Star anise is one of the many species that contain bioactive compounds as well as a number of phenolic and flavonoid compounds, having antioxidant, preservative and antimicrobial properties. All relevant papers in the English language from researchers of different countries were collected. The keywords of Chinese star anise, anise, traditional Chinese medicine and modern pharmaceutical science were searched in Google Scholar, Scopus, Research Gate and PubMed. Its seeds are good source of minerals like calcium, iron, copper, potassium, manganese, zinc, and magnesium. The essential oil of Chinese star anise contains anethole which has shown several functional properties including antimicrobial, antioxidant, hypoglycemic, hypolipidemic and oestrogenic properties. Due to all positive characteristics, such as antidiabetic, hypolipidemic, antioxidant activities, anticancer and antimicrobial properties, both seeds and essential oils of anise is promising for safe use as super food supplements and raw constituents in the both pharmaceutical and food industries. Anise seed oil contains anethol, estragole, eugenol, pseudisoeugenol, methyl chavicol and anisaldehyde, coumarins, scopoleting, umbelliferon, estrols, terpene hydrocarbons, and polyacetylenes as the major compounds. The plant oil has both pharmacological and clinical effects. The pharmacological effects consist of antimicrobial, hepatopreotective, anticonvulsant, anti-inflammatory, antispasmodic, bronchodilator, estrogenic, expectorant and insecticidal effects, and clinical effects such as nausea, constipation, menopausal period, virus, diabetes, obesity and sedative action. Combined with a nutritious diet, other traditional Chinese and Asian medicine, Chinese star anise and ansie seed may improve various aspects of health. More clinical studies are necessary to uncover the numerous substances and their effects in ginseng that contribute to public health.
... 2) Previous studies demonstrated that pro-inflammatory cytokines were highly expressed in lesional skin of patients with skin diseases. 23) To determine the effects of PM 10 in human HaCaT keratinocytes, we evaluated the mRNA expression levels of pro-inflammatory cytokines in the presence or absence of PM 10 . HaCaT keratinocytes were treated with PM 10 concentrations ranging from 10 to 100 µg/mL for 4 h and the mRNA expression levels were measured by RT-quantitative (q) PCR. ...
Article
2′-Fucosyllactose (2FL) is the most abundant component of the oligosaccharide content in human milk. It has been reported that 2FL has the ability to protect against infectious disease caused by bacterial pathogens. In this study, we investigated the protective effects of 2FL on particulate matter (PM)10-induced pro-inflammatory cytokines in HaCaT keratinocytes. 2FL reduced PM10-induced excess expression of interleukin (IL)-6, IL-8, IL-1α and IL-1β in HaCaT keratinocytes. In addition, PM10 also increased hypoxia-inducible factor (HIF)-1α protein levels; however, 2FL inhibited the accumulation of HIF-1α protein and the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/Akt stimulated by PM10. Furthermore, 2FL improved PM10-induced the decrease in epidermal thickness and integrity of the cornified layer in the reconstructed human epidermal skin model (RHE). In our results, 2FL inhibited PM10-induced pro-inflammatory mediators by regulating the HIF-1α/PI3K/Akt pathway and protected the skin epidermis against PM10 irritation. Taken together, these results suggest that 2FL can be used as a primary ingredient in cosmeceutical products to alleviate skin irritation and inflammation caused by urban air pollution. Graphical Abstract Fullsize Image
... Illicium verum is used in both medicine and food and the ministry of health of people republic of china in March 2002 suggesting it as nontoxic to humans (Li et al., 2016). It is usually used in different therapeutic purposes, the fruit of Illicium verum is used to cure rheumatic pain, stomach aches, skin inflammation, insomnia and vomiting (Sung et al., 2012). The crude extract of Illicium verum and its compound show a broad variety of pharmacological activities like sedative anti-oxidant, insecticidal, anti-microbial, analgesic and anti-fungal activity (Wang et al., 2011). ...
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To assess the comparative effect of anti-anaemic drug (ferrous sulfate) with naturally occurring anti-anaemic compound (Illicium verum commonly called star anise) on liver in rat model. Model and both test groups were made anaemic. Ferrous sulfate was given to T1 group of rats as 30mg/kg body weight (b.w) and Illicium verum to T2 group of rats with dose of 80mg/kg b.w for six weeks. Illicium verum treated group (T2 rats) produced depression, decreased anxiety and enhanced short-term memory, whereas ferrous sulfate treated group (T1 rats) enhanced long term memory. The liver function test of T2 rats showed that the total bilirubin was in normal range, but direct bilirubin, SGPT, ALP and GGT were significantly decreased in T2 rats in comparison with T1 and also from model group of rats. It was concluded in this study that by comparing the effect of ferrous sulfate with naturally occurring Illicium verum on iron-defficiency anaemia, illicium verum produces same effects and can be used to treat iron-defficiency anaemia without affecting liver function.
... Reinforcing our dates, we recently found that anethole decreased the synthesis/release of TNF-a and IL-17 in inflammatory acute model [12,33]. In addition, Sung et al. [34] demonstrated that Illicium verum extract, whose main aromatic constituent is anethole ([90%), has important anti-inflammatory effects, reflected by a decrease in TNF-a levels via nuclear factor jB (NF-jB) blockade. NF-jB is the main transcription factor that is responsible for controlling genes that are related to inflammatory diseases [35,36]. ...
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Aim: This study evaluated whether anethole attenuates the inflammatory response and joint damage in a model of adjuvant-induced arthritis (AIA) in rats. Methods: The animals were treated with 62.5-, 125-, or 250-mg/kg anethole daily for 21 days after AIA and necropsied on days 14 and 21 to evaluate the number of serum and synovial leukocytes (total and differential), serum cytokines (IL-2, IL-6, IL-12, IL-17, and TNF-α), and nitric oxide concentrations. Morphologic changes in the cartilage and bone of the femorotibial articulation in both left paw and right paw were studied in hematoxylin/eosin and Sirius Red-hematoxylin sections. Results: Different doses of anethole suppressed paw swelling and the number of serum and synovial leukocytes. However, 250 mg/kg of anethole more effectively controlled local and systemic inflammation. Histological evaluation revealed significant prevention of cartilage damage and inflammatory infiltrate scores. Morphometric analysis showed pannus formation, the thickness of the articular cartilage, and bone resorption lower in the anethole-treated AIA group compared to untreated AIA group on both days 14 and 21. These significant anti-inflammatory effects in the anethole-treated AIA group were associated with downregulation of cytokines and nitric oxide levels. Conclusion: Therefore, anethole may be a useful intervention to treat inflammatory arthritis.
... These results indicated that icariin, not only inhibited the secretion of proinflammatory cytokines, but also induced keratinocytes to secrete anti-inflammatory cytokines. AKT and ERK have been reported to regulate cytokine production and release, and have been demonstrated to serve an important role in wound repair (28,29). Specific inhibitors for AKT and ERK blocked the downregulation of IL-6 and TNF-α and the upregulation of IL-10 induced by icariin treatment, suggesting that these kinases were involved in the process of icariin-induced cytokine expression alterations. ...
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Icariin is a traditional Chinese drug that has long been used to treat various diseases. In the present study, the effect of icariin was investigated on cutaneous wound healing. Using in vitro experiments, it was demonstrated that icariin significantly promoted the migration and proliferation of keratinocytes via the activation of AKT serine/threonine kinase 1 (AKT) and extracellular signal‑regulated kinase (ERK). Inhibition of AKT or ERK reversed the effects of icariin on the proliferation and migration of keratinocytes. In addition, icariin inhibited the production of interleukin (IL)‑6 and tumor necrosis factor (TNF)‑α and induced the production of IL‑10. Finally, animal experiments demonstrated that icariin treatment accelerated the wound closure rate. The present findings revealed that icariin may be a promising drug to promote the migration and proliferation of keratinocytes, and to accelerate the healing of skin wounds, through its role in the upregulation of AKT and ERK signaling.
... Previous studies showed that in psoriatic skin lesions, the expression levels of ERK, JNK, and p38 were increased in the MAPK pathway 16,32,33 . Therefore, we investigated the MAPK and NF-κB signaling pathways [34][35][36][37][38] . Our study demonstrated that VitabridC 12 could reduce the activities of p38, ERK, and MEK. ...
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Background VitabridC¹² is newly developed and composed of vitamin C and Vitabrid (lamellar, hydrated zinc oxide). Objective In this study, we aimed to investigate the effects of VitabridC¹² on psoriasis and atopic dermatitis. Methods Mice with imiquimod-induced psoriasis or Dermatophagoides farinae-induced atopic dermatitis were applied with VitabridC¹². The effects of VitabridC¹² were evaluated by clinical features, histology, and immunologic features by examining cytokines and chemokines. Results In psoriasis model, VitabridC¹² decreased epidermal thickness and reduced inflammatory cell infiltration. In atopic dermatitis model, VitabridC¹² decreased dermal infiltration of inflammatory cells, epidermal hyperplasia, and hyperkeratosis. VitabridC¹² reduced the expression levels of proinflammatory mediators such as interleukin (IL)-1β, IL-6, IL-8, IL-17A, IL-22, tumor necrosis factor-α, CXCL1, CCL17, and CCL20 as well as COX-2 in imiquimod-induced psoriatic skin lesions. Likewise, VitabridC¹² reduced the expression levels of IL-4, IL-5, IL-13, thymic stromal lymphopoietin, and CCL4 in D. farinae-induced skin lesions, and decreased the serum immunoglobulin E level in the atopic dermatitis mouse model. Particularly, the VitabridC¹²-treated mice showed downregulated expressions of mitogen-activated protein kinase (MAPK), including extracellular signal-regulated kinase (ERK), p38, and MAPK/ERK kinase, as well as inhibited phosphorylation of nuclear factor-κB p65. Conclusion Taken together, these findings indicate that VitabridC¹² exhibits anti-inflammatory activities and is a promising candidate as a treatment option for psoriasis or atopic dermatitis.
... Abdallah et al. (2013) investigated the antiviral activity of anise oil against bovine herpes virus type 1-(BHV-1) in cell culture and they found that anise oil is non-toxic to MDBK cells upto 100 ug/ml, and also inhibited the growth and development of BHV-1. Sung et al. (2012) recommended star anise in the treatment of inflammatory diseases. Alhajj et al. (2015) indicated that Chinese star anise could be used as a natural additive to improve the immune responsiveness and performance of broiler chickens. ...
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Botanical insecticides keep attracting more attention from environmental and small farmers worldwide as they are considered as a suitable alternative to synthetic insecticides. The outstanding properties of pyrethrum include rapid action, low mammalian toxicity, broad spectrum of activity, lack of insect immunity, lack of persistence and of course effective insect repellent. Pyrethrum is a natural insecticide which has many properties, but the most important are rapid action, very low toxicity for mammalian, lack of insect immunity, broad of activity, lack of persistence and quick degradation by UV-sunlight and very effective insect repellent. Using natural pesticide may lead to organic farming, and advantage of organic farming is more beneficial to biodiversity and the environment, which reduces dietary exposure to pesticides. Chinese star anise has anti-bacterial and anti-fungal characters. It is useful in treatment of diseases like asthma, bronchitis and dry cough. One of its most compounds is Shikimic acid which is used as a drug in curing influenza and flu virus. It also consists of Linalool which is good for overall health because of its anti-oxidants characters. Its seeds are good source of minerals like calcium, iron, copper, potassium, manganese, zinc, and magnesium. The seeds are a great source of essential B-complex vitamins such as pyridoxine, niacin, riboflavin and thiamin. Chinese star anise is also a good source of anti-oxidant vitamins such as vitamin-C and vitamin-A. The essential oil of Star anise contains anethole which has shown several functional properties including antimicrobial, antioxidant, hypoglycemic, hypolipidemic and oestrogenic properties. Star anise primarily contains anethole and fatty oil. Its essential oil has a sweetish, burning flavor and a highly aromatic odor. Organic farmers may use these two ancient Chinese herbs which can lead to industrial sustainability.
... Previous studies reported that TNF-α/IFN-γ stimulation activates signaling molecules, including STAT-1, extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38 mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB in HaCaT cells (26)(27)(28)(29)(30). Thus, the present study evaluated whether ISTP affects the STAT signaling pathway in TNF-α/IFN-γ-stimulated HaCaT cells using western blot analysis. ...
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The present study aimed to investigate the anti‑inflammatory effect and mechanism of action of isosecotanapartholide (ISTP), isolated from Artemisia princeps Pampanini extract (APE). The effects of ISTP and APE on the proliferation of human keratinocytes following stimulation by tumor necrosis factor‑α/interferon‑γ were assessed. ISTP and APE downregulated the expression levels of signal transducer and activator of transcription‑1 (STAT‑1), and reduced interleukin‑33 (IL‑33) production. ISTP and APE inhibited the mRNA expression levels of thymus and activation‑regulated chemokine (TARC/CCL17) in a dose‑dependent manner. Western blot analysis demonstrated that ISTP and APE dose‑dependently inhibited protein expression levels of intercellular adhesion molecule‑1 and phosphorylation of STAT‑1. The results of the present study indicate that ISTP may inhibit TARC/CCL17 production in human epidermal keratinocytes via the STAT‑1 signaling pathway and may be associated with the inhibition of IL‑33 production. The current study indicated that ISTP is an active component in APE and may be a potential therapeutic agent for the treatment of inflammatory skin disorders.
... Previous studies show that the keratinocytes of AD sufferers produce cytokines and chemokines that promote development of inflammatory skin diseases; the secretion of pro-inflammatory cytokines is triggered by activation of the MAPK signalling pathway. [41] Indeed, the intracellular MAPK signalling pathway is activated in keratinocytes stimulated by TNFa and IFN-c. [42] Pro-inflammatory cytokines, including IL-1 and IL-6, then induce keratinocyte migration and proliferation. ...
Article
Objectives: Here, we hypothesized that Hovenia dulcis branch extract (HDB) and its active constituents ameliorates 2,4-dinitrochlorobenzene-induced atopic dermatitis (AD)-like skin lesions by modulating the T helper Th1/Th2 balance in NC/Nga mice and TNF-α- and IFN-γ-induced production of thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) in HaCaT cells. Methods: HaCaT cells were stimulated by TNF-α/IFN-γ in the presence of HDB and its constituents. TARC and MDC were measured by ELISA and RT-PCR. For the in-vivo study, oral feeding of HDB was performed for 5 weeks with 2,4-dinitrochlorobenzene (DNCB) treatment every other day. The efficacy of HDB on parameters of DNCB-induced AD was evaluated morphologically, physiologically and immunologically. Key findings: In-vitro studies showed that HDB and its constituents suppressed TNF-α/IFN-γ-induced production of TARC and MDC in HaCaT cells by inhibiting MAPK signalling. In-vivo studies showed that HDB regulated immunoglobulin (Ig) E and immunoglobulin G2a (IgG2a) levels in serum and the expression of mRNA for Th1- and Th2-related mediators in skin lesions. Histopathological analyses revealed reduced epidermal thickness and reduced infiltration of skin lesions by inflammatory cells. Conclusion: These results suggest that HDB inhibits AD-like skin diseases by regulating Th1 and Th2 responses in NC/Nga mice and in HaCaT cells.
... MAPKs and STAT/Jak signaling pathways have been shown to be involved in the regulation of chemokine production in HaCaT cells. These cascades play an important role in immune responses and regulate the inflammatory signaling pathway [9,12]. ...
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Background Sanguisorbae Radix (SR) is a well-known herbal medicine used to treat inflammatory disease and skin burns in Asia. In addition, it is used to treat many types of allergic skin diseases, including urticaria, eczema, and allergic dermatitis. SR has been reported to exhibit anti-wrinkle, anti-oxidant, and anti-contact dermatitis bioactivities. Methods In this study, we investigated the mechanism underlying the anti-inflammatory effects of SR water extract (WSR) using human keratinocyte (HaCaT) cells and BALB/c mouse bone marrow-derived mast cells (BMMCs). Viability assays were used to evaluate non-cytotoxic concentrations of WSR in both BMMCs and HaCaT cells. To investigate the effect of WSR treatment on the degranulation of IgE/Ag-activated BMMCs, we measured the release of β-hexosaminidase (β-HEX). We determined the production of pro-inflammatory chemokines including thymus and activation regulated chemokine (TARC; CCL17), regulated on activation, normal T-cell expressed and secreted (RANTES; CCL5), macrophage-derived chemokine (MDC; CCL22), and interleukin 8 (IL-8; CXCL8) in stimulated human keratinocytes. The ability of WSR to reduce the expression of pro-inflammatory marker proteins was evaluated by Western blotting in HaCaT cells stimulated with tumor necrosis factor (TNF)-α/interferon (IFN)-γ. ResultWSR inhibited IgE/Ag-activated mast cell degranulation in BMMCs. Treatment with various concentrations of WSR decreased β-HEX release in a dose-dependent manner with an IC50 of 27.5 μg/mL. In keratinocytes, WSR suppressed TNF-α/IFN-γ-induced chemokine production and pro-inflammatory molecules via a blockade STAT-1, Jak-2, p38, and JNK activation. Conclusions This results demonstrate that WSR inhibits degranulation of IgE/Ag-activated mast cells and inhibits the production of pro-inflammatory chemokines by suppressing the phosphorylation of p38 and JNK in HaCaT cells.
... Star anise (Illicium verum Hook. f.) is one of the most famous evergreen tree which has originally distributed in tropic and subtropic areas of Asia, especially China, and it is famous as in traditional Chinese medicine as well as traditional Asian medicine (Yokoyama et al., 2002;Yokoyama et al., 2003;Thuat and Ngoc, 2010;Sung et al., 2012;Zhongliang, 2012;Vermaak et al., 2013;Vecchio et al., 2016;Zhou et al., 2016Yoshikawa et al., 2018). Its fruit also commonly used spice. ...
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Traditional Chinese Medicine (TCM) has been used for thousands of years by different generations in China and other Asian countries as foods to promote good health and as drugs to treat disease. Goji berry (Lycium barbarum), as a Chinese traditional herb and food supplement, contains many nutrients and phytochemicals, such as polysaccharides, scopoletin, the glucosylated precursor, amino acids, flaconoids, carotenoids, vitamins and minerals. It has positive effects on anitcancer, antioxidant activities, retinal function preservation, anti-diabetes, immune function and anti-fatigue. Widely used in traditional Chinese medicine, Goji berries can be sold as a dietary supplement or classified as nutraceutical food due to their long and safe traditional use. Modern Goji pharmacological actions are improving function, enhances the body ,s ability to adapt to a variety of noxious stimuli; it significantly inhibits the generation and spread of cancer cells and can improve eyesight and increase reserves of muscle glycogen and liver glycogen which may increase human energy and has anti-fatigue effect. Goji berries may improve brain function and enhances learning and memory. It may boost the body ,s adaptive defences, and significantly reduce the levels of serum cholesterol and triglyceride, it may help weight loss and obesity and treats chronic hepatitis and cirrhosis. Today they are considered functional food with many beneficial effects, which is why they have become more popular recently, especially in Europe, North America and Australia, as they are considered as superfood with highly nutritive and antioxidant properties. Geographical origin of Goji berries are one of the most important quality parameters in TCM since the differences in climate, soil, and cultivation methods cause differences in the chemical composition of the plants. Goji berry has huge health benefits that attract good international markets. Goji berry which is as knows as the super fruit and super food in TCM for the claimed health benefits and it should be part of daily diet. Ginger (Zingiber officinale) has been used as a spice and a medicine for over 200 years in Traditional Chinese Medicine. Ginger is an important plant with several medicinal, and nutritional values used in Asian and Chinese Tradition medicine. Ginger and its general compounds such as Fe, Mg, Ca, vitamin C, flavonoids, phenolic compounds (gingerdiol, gingerol, gingerdione and shogaols), sesquiterpenes, paradols has long been used as an herbal medicine to treat various symptoms including vomiting, pain, cold symptoms and it has been shown to have anti-inflammatory, anti-apoptotic, anti-tumor activities, anti-pyretic, anti-platelet, anti-tumourigenic, anti-hyperglycaemic, antioxidant anti-diabetic, anti-clotting and analgesic properties, cardiotonic, cytotoxic. It has been widely used for arthritis, cramps, sprains, sore throats, rheumatism, muscular aches, pains, vomiting, constipation, indigestion, hypertension, dementia, fever and infectious diseases. Ginger leaves have also been used for food flavouring and Asian Traditional Medicine especially in China. Ginger oil also used as food flavouring agent in soft drink, as spices in bakery products, in confectionary items, pickles, sauces and as a preservatives. Ginger is available in three forms, namely fresh root ginger, preserved ginger and dried ginger. The pharmacological activities of ginger were mainly attributed to its active phytocompounds 6-gingerol, 6-shogaol, zingerone beside other phenolics and flavonoids. Gingerol and shogaol in particular, is known to have anti-oxidant and anti-inflammatory properties. In both Traditional Chinese Medicine, and modern China, Ginger is used in about half of all herbal prescriptions. Traditional medicinal plants are often cheaper, locally available and easily consumable raw and as simple medicinal preparations. Ginseng is the most famous of the Chinese herbs throughout the world, and has been one of the most valued herb in China. Traditional Chinese Medicine as an important component of complementary and alternative medicine, evolved over thousands of years with its own unique system of theories, diagnostics and therapies in Asian countries, especially China. In most parts of the world, especially western countries, Ginseng has been increasingly used in the last decades and has become well known for its significant role in preventing and treating so many diseases. Ginseng species are Panax ginseng C. A. Meyer (Korean ginseng), Panax japonicas C. A. Meyer (Japanese ginseng), Panax major Tings, Paanx notoginseng (Burkill) F. H. Chen (Sanchi ginseng), Panax omeiensis J. Wen, Panax pseudoginseng Wallich, Paanx quinquefolius L. (American ginseng), Panax sinesis J. Wen, Panax trifolius L (Dwarf ginseng), Panax wangianus Sun, Panax zingiberensis C. Y. Wu & K. M. Feng, Panax vietnamensis Ha et Grushv. (Vietnamese ginseng) and etc. But the most important species are Panax ginseng (Chinese ginseng), and Panax quinquefolius (American ginseng). Panax ginseng has consisted of a number of active constituents, such as saponins or ginsenosides, carbohydrates, nitrogenous substances, phytosteril, essential oils, organic acids, amino acids, peptidoglycans, carbohydrate, nitrogen-containing compounds, fatty acids, vitamins, minerals and other phenolic compounds. Ginsenosides are classified into two main groups known as protopanaxadiol (PPD), and protopanaxatriol (PPT). Pharmacological activities of ginseng extracts are effects on the central nervous system; antipsychotic action; tranquilizing effects; protection from stress ulcers; increase of gastrointestinal motility; anti-fatigue action; endocrinological effects; enhancement of sexual behaviour; acceleration of metabolism; or synthesis of carbohydrates, lipids, RNA, and proteins. In Traditional Chinese Medicine, ginseng help to maintain a healthy immune system. Ginseng contains an abundance of diversified chemical elements hardly found in other medicinal herbs. More clinical studies are necessary to uncover the numerous substances and their effects in ginseng that contribute to public health. Astragalus is a common Traditional Chinese Medicinal plant which is a widely used herbal product in China, other Asian countries and some western countries. Astragalus has been used for almost 2000 years in China to boost the body ,s general vitality and strengthening resistance to exogenous pathogens. Saponins, polysaccharides, amino acids, flavonoids, organic acid, glycosides, alkaloid, and trace elements, are the major class of chemical compounds occurring in species of Astragalus genus, the largest one in the family of Leguminosae. In Traditional Chinese Medicine, Astragalus considers to used in the treatment of diabetes, mellitus, nephritis, leukemia, uterine cancer, besides its tonic agent and diuretic effects. Astragalus polysaccharide, the active component extracted from Astragali Radix which is the root of Astragalus membranaceus Bunge. Some uses of Astragalus are in kidney and urinary problems, Digestion, liver problems, female reproductive system problems, muscular, skin problems, cardiovascular and blood, immune and lymphatic system, nervous system, respiratory system, and for some specific disease. It helps protect the body against various types of stress such as physical and emotional stress. Astragalus root including anti-aging properties, and also helping to prevent bone loss. In TCM, huang qi is never administered as a mono drug, but forms part of mixtures depending on the indications. Astragali Radix, the root of Astragalus membranaceus Bunge, has been reported to exert hepatoprotective effects, antioxidative effects, antiviral activity, anti-oxidative effects, anti-hypertensive effects, and immunostimulant properties; it has also been reported to strengthen superficial resistance, drainage action and new tissue growth. Although, TCM in China is partly integrating with western medicine science, researchers should learn more from TCM and carry out more studies.
... Experiments were carried out with RAW 264.7 at 80% confluence or HaCaT cells at 90% confluence. Inflammatory responses in RAW 264.7 were induced by LPS and HaCaT cells by IFN-γ/TNF-α (Akram et al., 2015;Sung et al., 2012). ...
Article
Impaired immune responses in skin play a pivotal role in the development and progression of chemical-associated inflammatory skin disorders. In this study, we synthesized new flavonoid derivatives from macakurzin C, and identified in vitro and in vivo efficacy of a potent anti-inflammatory flavonoid, Compound 14 (CPD 14), with its underlying mechanisms. In lipopolysaccharide (LPS)-stimulated murine macrophages and IFN-γ/TNF-α-stimulated human keratinocytes, CPD 14 significantly inhibited the release of inflammatory mediators including nitric oxide (NO), prostaglandins, and cytokines (IC50 for NO inhibition in macrophages: 4.61μM). Attenuated NF-κB signaling and activated Nrf2/HO-1 pathway were responsible for the anti-inflammatory effects of CPD 14. The in vivo relevance was examined in phorbol 12-myristate 13-acetate (TPA)-induced acute skin inflammation and oxazolone-induced atopic dermatitis models. Topically applied CPD 14 significantly protected both irritation- and sensitization-associated skin inflammation by suppressing the expression of inflammatory mediators. In summary, we demonstrated that a newly synthesized flavonoid, CPD 14, has potent inhibitory effects on skin inflammation, suggesting it is a potential therapeutic candidate to treat skin disorders associated with excessive inflammation.
... showed an inhibition potential to the inflammation caused the C. acnes (Table 2). Here, B. davidii aqueous extract showed a stronger inhibition toward the inflammatory process caused by C. acnes than I. verum which was reported in the previous studies [15], A. japonica A. Gray, and P. fibrosa (Table 2). ...
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Acne is an inflammatory skin disorder; although some anti-inflammatory medicines for treating acne are available in a market, they have considerable side effects; therefore, new treatment options are needed. In the present study, among the 16 aqueous extracts of plants collected from Jeju Island in Korea which are used to test anti-inflammatory activity, B. davidii showed the strong decline of the proinflammatory cytokine expression against the inflammatory process caused by C. acnes in Human HaCaT keratinocyte cells. B. davidii downregulated the expression of 57% of COX-2, 41% of iNOS, and proinflammatory cytokines 29% of TNF-α, 32% of IL-1β, 21% of IL-6, and 35% of IL-8. Furthermore, B. davidii inhibited NF-κB and MAPK signaling cascades in keratinocytes that activated by toll-like receptor 2 (TLR-2) in response to C. acnes. Given those results, B. davidii is a potential agent to reduce the proinflammatory cytokine expression against C. acnes-induced inflammation and might provide an alternative to the current medications.
... The oil of star anise is valuable in providing relief from rheumatism and lower back pain (Soher et al., 2016). The star anise fruit has been used in traditional medicine for treatment of stomach aches, vomiting, rheumatic pain, insomnia, skin inflammation (Mosaffa-Jahromi et al., 2017), flatulence, facial paralysis, asthma, and bronchitis (Sung et al., 2012). The compositions of essential oil from star anise were considered by using water distillation method and water distillation combined headspace solvent micro-extraction method (Gholivand et al., 2009). ...
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This study focused on the extraction of the essential oil and extract from star anise (Illicium verum Hook.f.) and the evaluation of the physicochemical properties and bioactivities of these products. This study was conducted by one-factor-at-a-time method on the factors affecting on the extraction yield of essential oil and the antioxidant activity of the extract. The optimized conditions for the separating process of the essential oil were raw material size (8 mm), solid/solvent ratio (1/8 w/v), extracting temperature (130 °C) and material non-compression within 180 min. The optimized conditions for the extraction process were two-times extractions at extracting temperature (50 °C), ethanol 60 % and solid/solvent ratio (1/6 w/v) during 75 min. Total phenolic content and antioxidant activity (IC50) of star anise extract were 120.69 ± 0.97 mg GAE/g dried and 36.8 ± 0.4 µg/mL. Star anise essential oil (with 94.7 % of anethole) showed lower antioxidant activity than the extracts. The anti-inflammatory activity of the essential oil and extracts was studied by their ability to inhibit protein denaturation. IC20 value of star anise essential oil, extract were 935.5 ± 1.2 µg/mL and 122.4 ± 0.8 µg/mL.
... It has been recognized as safe by the Food and Drug Administration (FDA), and mainly applied in food, cosmetic, perfume, and medical industries (Aprotosoaie et al., 2016). Numerous studies shed light on the anti-inflammatory activity of TA in intestinal inflammation, pulmonary inflammation, hepatic inflammation, and so forth (Yea et al., 2006;Sung et al., 2012;Ritter et al., 2013;Wisniewski-Rebecca et al., 2015). Moreover, TA is reported to inhibit the activation of nuclear factor kappa B (NF-kB) signaling pathway in LPS-stimulated inflammatory response (Kang et al., 2013). ...
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The aim of this study was to investigate the protective effect of trans-anethole (TA) on lipopolysaccharide-induced acute liver inflammation model of chickens by determining the levels of inflammatory mediators in serum and liver, relative mRNA expression and protein expression of inflammation-related genes in NF-κB signaling pathway. A total of 160 one-day-old male chickens (Arbor Acres) were assigned into four treatments with eight replicates of five birds each. On d 20, the control group was intraperitoneally injected with sterile saline and the other groups were injected with lipopolysaccharide (LPS) (5 mg/kg body weight). There were no significant differences in average daily gain (ADG), average daily feed intake (ADFI) and feed conversion ratio (FCR) among groups. However, compared with the control group, the LPS group significantly increased (P < 0.01) the serum levels of interleukin-6 (IL-6), interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and decreased (P < 0.01) the interleukin-10 (IL-10) level. TA attenuated (P < 0.01) these increases in IL-1β, TNF-α, ALT and AST levels and improved (P < 0.01) the IL-10 level. In liver, the groups fed with TA had lower (P < 0.01) concentrations of IL-6 and TNF-α as well as higher (P < 0.05) concentration of IL-10. Furthermore, TA down-regulated (P < 0.05) the mRNA expression levels of nuclear factor kappa B p65 (NF-κB p65) and TNF-α, also up-regulated (P < 0.05) IL-10 and inhibitor of NF-κB alpha (IκBα) upon LPS challenge. In protein level, supplementation of 600 mg/kg of TA down-regulated (P < 0.05) and up-regulated (P < 0.05) the protein expression of NF-κB p65 and IκBα, respectively. The present findings suggest that TA could alleviate the acute liver inflammation induced by LPS via blocking the activation of NF-κB and the 600 mg/kg of TA plays more fruitful role in protecting broilers against LPS stimulus.
... MAPKs and STAT/JAK signaling pathways have been shown to participate in controlling the development of chemokines in HaCaT cells. These cascades play an important role in immune response, and control the signaling pathway to inflammation [30]. In the present study, Ac2-26 suppresses chemokines secretion and mRNA expression levels in TNF-α/IFN-γ-stimulated HaCaT cells. ...
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Inflammation of the skin is the most common dermatological problem in human. The anti-inflammatory mediated responses of the skin cells provide a mechanism for combating these conditions. Annexin A1 (AnxA1) is one of the proteins that has been shown to have a potent anti-inflammatory effect. However, the effects and mechanisms of AnxA1 in skin keratinocyte and fibroblast have not been reported yet. In the current study, we hypothesized that Ac2-26, AnxA1 mimetic peptide, ameliorates inflammation and wrinkle formation in human skin cells. Therefore, we aimed to identify whether Ac2-26 has anti-inflammatory and anti-wrinkle effects in human keratinocyte (HaCaT) and fibroblast (Detroit 551) cells, respectively. Human HaCaT cells were stimulated by TNF-α/IFN-γ with or without Ac2-26, to identify the anti-inflammatory effect. Human Detroit 551 cells were treated with Ac2-26 to verify the anti-wrinkle effect. Initially, cell cytotoxicity was carried out in each cell line treated using Ac2-26 by MTT assay. Human MDA, IL-8, and procollagen secretion were detected by ELISA assay. The inflammatory chemokines were measured by qRT-PCR analysis. To demonstrate the mechanism, MAPK, NF-κB, JAK/STAT, and MMPs were analyzed by Western blotting. As a result, we identified that Ac2-26 significantly decreased the expression of TNF-α/IFN-γ-stimulated pro-inflammatory chemokines, including IL-1β, IL-6, IL-8, MDC, TARC, and TNF-α, by inhibiting the activation of MAPK, NF-κB, and JAK/STAT pathway in TNF-α/IFN-γ-stimulated HaCaT human keratinocytes. In addition, we also identified that Ac2-26 significantly induced collagen synthesis by generating pro-collagen, and suppressed collagen degradation by inhibiting the collagenase MMP-1 and MMP-8 expression. Collectively, these results suggest that Ac2-26 shows anti-inflammatory and anti-wrinkling effect. These effects may lead to the development of preventive and therapeutic application for inflammation-related skin disease and wrinkle formation.
... These powerful reports confirmed the underlying therapeutic effects of TA against NE infection by inhibition of NF-κB signaling pathway. In addition, activated NF-κB promoted the transcription of several genes encoding proinflammatory mediators including TNF-α, iNOS, and IL-6 (Sung et al., 2012;Wang et al., 2012). In the present study, we found that the concentrations of serum TNF-α and IFN-γ and intestinal IL-1β, IL-8, TNF-α, and IFN-γ were elevated, but jejunal levels of IL-10 and sIgA were decreased after subclinical NE infection. ...
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This study investigated the alleviative potential of trans-anethole (TA) on the impaired intestinal barrier and intestinal inflammation and its regulatory effects on gut microbiota in broilers with subclinical necro-hemorrhagic enteritis (NE) challenge. Subclinical NE challenge led to a severe decline in the 21-day body weight (BW) and average daily gain (ADG), but an increase in feed conversion ratio (FCR) and intestinal lesion score of birds compared with controls (P < 0.05). Compared with the subclinical NE group, the TA administration group exhibited lower (P < 0.05) intestinal lesion score and crypt depth (CD), serum diamine oxidase activity, and D-lactate concentration, but higher (P < 0.05) intestinal tight junction protein expressions, villus height (VH), VH/CD, and numbers of proliferating cell nuclear antigen (PCNA)-positive cells. The administration of TA also inhibited (P < 0.05) the expression of intestinal pro-inflammatory cytokines including interleukin (IL)-1β, IL-8, interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) but increased (P < 0.05) jejunal IL-10 and secretory immunoglobulin A (sIgA) concentration. TA inclusion also led to a remarkable reduction of intestinal NF-kappa-B inhibitor alpha (IκBα) degradation and nuclear factor kappa beta (NF-κB) translocation. Moreover, TA modulated the cecal microbiota abundance and diversity of NE birds, as confirmed by reducing the phylum Firmicutes and genera Ruminococcaceae_UCG-014, Eubacterium_coprostanoligenes_group, and Ruminococcaceae_NK4A214_group when supplemented at 600 mg/kg and reducing genera Butyricicoccus, Oscillibacter, and Flavonifractor when supplemented at 400 mg/kg (P < 0.05). Supplementation of TA in broiler diets could alleviate subclinical NE infection by restoring intestinal barrier integrity, inhibiting NF-κB signaling pathway, and modulating gut microbiota. A 600-mg/kg dose of TA is the optimum concentration for ameliorating subclinical NE in broilers.
... Stimulation with both TNF-α and IFN-γ in keratinocytes led to an increased expression of various proinflammatory cytokines and chemokines. These cytokines contributed to the infiltration of inflammatory cells to dermal skin [20]. NHGR did not affect cell viability in HaCaT cells (Figure 7a). ...
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Atopic dermatitis is a persistent inflammatory skin disorder. Siraitia grosvenorii fruits (monk fruit or nahangwa in Korean, NHG) are used as a natural sweetener and as a traditional medicine for the treatment of asthma and bronchitis. We evaluated the activity of S. grosvenorii residual extract (NHGR) on allergic inflammation of atopic dermatitis in a Dermatophagoides farinae mite antigen extract (DfE)-treated NC/Nga murine model and in vitro. Oral administration of NHGR significantly reduced epidermal hyperplasia and inflammatory cell infiltration in the skin lesions of DfE-induced atopic dermatitis, as well as the dermatitis severity score. NHGR reduced serum immunoglobulin E levels. Splenic concentrations of IFN-γ, interleukin (IL)-4, IL-5, and IL-13 were reduced by NHGR administration. Immunohistofluorescence staining showed that NHGR administration increased the protein levels of claudin-1, SIRT1, and filaggrin in atopic dermatitis skin lesions. In addition, NHGR inhibited the phosphorylation of mitogen-activated protein kinases and decreased filaggrin and chemokine protein expression in TNF-α/IFN-γ-induced human keratinocytes. Moreover, NHGR also inhibited histamine in mast cells. The quantitative analysis of NHGR revealed the presence of grosvenorine, kaempferitrin, and mogrosides. These results demonstrate that NHGR may be an efficient therapeutic agent for the treatment of atopic dermatitis.
... It is well known that the activation of the degradation of IκB-α, STAT-1, and MAPK in keratinocytes are associated with AD, and keratinocytes stimulated with TNF-α/IFN-γ are widely used for verification of the in vitro efficacy of anti-atopic dermatitis [19,20]. In the current study, EAA suppressed the phosphorylation of STAT-1, ERK and the degradation of IκB-α in TNF-α/IFN-γ-stimulated keratinocytes. ...
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Artemisia anomala S. Moore is a perennial herbaceous plant classified as Asteraceae of the genus Artemisia. Many species of Artemisia have been used as medicinal materials. Artemisia anomala S. Moore has been widely used in China to treat inflammatory diseases. However, the mechanism of its action on the keratinocyte inflammatory response is poorly understood. Here, we investigated the anti-inflammatory reaction of Artemisia anomala S. Moore ethanol extract (EAA) using human keratinocyte (HaCaT) cells, which involved investigating the nuclear factor kappa B (NF-κB), signal transducer, and activator of transcription-1 (STAT-1), as well as mitogen-activated protein kinase (MAPK) signaling pathways and atopic dermatitis-like skin lesions in mice. We elucidated the anti-inflammatory effects of EAA on tumor necrosis factor-α/interferon-γ (TNF-α/IFN-γ)-treated human keratinocyte cells and 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD)-like mice. The levels of chemokines and cytokines (IL-8, IL-6, TARC, and RANTES) were determined by an enzyme-linked immunosorbent assay. The NF-κB, STAT-1, and MAPK signaling pathways in HaCaT cells were analyzed by western blotting. Thickening of the mice dorsal and ear skin was measured and inflammatory cell infiltration was observed by hematoxylin and eosin staining. Results showed that EAA suppressed IL-8, IL-6, TARC, and RANTES production. EAA inhibited nuclear translocation of NFκB and STAT-1, as well as reduced the levels of phosphorylated ERK MAPKs. EAA improved AD-like skin lesions in DNCB-treated mice. These findings suggest that EAA possesses stronger anti-inflammatory properties and can be useful as a functional food or candidate agent for AD.
... The inflammatory factors TNF-α and IFNγ in the skin of a patient with atopic dermatitis can activate the patient's keratinocytes to produce an overexpression of inflammatory factors [18]. These cytokines contribute to the infiltration of inflammatory cells into dermal skin [19]. Therefore, we examined the role of neferine in TNF-α/IFN-γ-treated HaCaT cells to investigate whether neferine is a promising agent for the treatment of atopic dermatitis. ...
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Atopic dermatitis (AD) is a chronic and persistent inflammatory skin disease characterized by eczematous lesions and itching, and it has become a serious health problem. However, the common clinical treatments provide limited relief and are accompanied by adverse effects. Therefore, there is a need to develop novel and effective therapies to treat AD. Neferine is a small molecule compound isolated from the green embryo of the mature seeds of lotus (Nelumbo nucifera). It has a bisbenzylisoquinoline alkaloid structure. Relevant studies have shown that neferine has many pharmacological and biological activities, including anti-inflammatory, anti-thrombotic, and anti-diabetic activities. However, there are very few studies on neferine in the skin, especially the related effects on inflammatory skin diseases. In this study, we proved that it has the potential to be used in the treatment of atopic dermatitis. Through in vitro studies, we found that neferine inhibited the expression of cytokines and chemokines in TNF-α/IFN-γ-stimulated human keratinocyte (HaCaT) cells, and it reduced the phosphorylation of MAPK and the NF-κB signaling pathway. Through in vivo experiments, we used 2,4-dinitrochlorobenzene (DNCB) to induce atopic dermatitis-like skin inflammation in a mouse model. Our results show that neferine significantly decreased the skin barrier damage, scratching responses, and epidermal hyperplasia induced by DNCB. It significantly decreased transepidermal water loss (TEWL), erythema, blood flow, and ear thickness and increased surface skin hydration. Moreover, it also inhibited the expression of cytokines and the activation of signaling pathways. These results indicate that neferine has good potential as an alternative medicine for the treatment of atopic dermatitis or other skin-related inflammatory diseases.
... I. verum extracts exert antiinflammatory effects by suppression of expression of proinflammatory cytokines, TNF-a/IFNg-induced chemokines and adhesion molecules. It also causes obstruction of STAT1, NF-kB, MAPK and Akt activation, proving its usefulness as emerging beneficial drugs for inflammatory conditions (Sung et al., 2012). ...
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... Stimulation of keratinocytes with TNF-α + IFN-γ upregulates various MAPK signaling pathways [57,58]. To evaluate the anti-inflammatory effects of the six compounds from C. tricuspidata on the MAPK pathway, Western blotting analysis was used to determine the phosphorylation levels of JNK1/2, ERK1/2, and p38 in TNF-α + IFN-γ-treated HaCaT cells. ...
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The root bark of Cudrania tricuspidata has been reported to have anti-sclerotic, anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, and cytotoxic activities. In the present study, the effect of 16 compounds from C. tricuspidata on tumor necrosis factor-α+interferon-γ-treated HaCaT cells were investigated. Among these 16 compounds, 11 decreased IL-6 production and 15 decreased IL-8 production. The six most effective compounds, namely, steppogenin (2), cudraflavone C (6), macluraxanthone B (12), 1,6,7-trihydroxy-2-(1,1-dimethyl-2-propenyl)-3- methoxyxanthone (13), cudraflavanone B (4), and cudratricusxanthone L (14), were selected for further experiments. These six compounds decreased the expression levels of chemokines, such as regulated on activation, normal T cell expressed and secreted (RANTES) and thymus and activation-regulated chemokine (TARC), and downregulated the protein expression levels of intercellular adhesion molecule-1. Compounds 2, 6, 12, 4, and 14 inhibited nuclear factor-kappa B p65 translocation to the nucleus; however, compound 13 showed no significant effects. In addition, extracellular signal regulatory kinase-1/2 phosphorylation was only inhibited by compound 14, whereas p38 phosphorylation was inhibited by compounds 13 and 4. Taken together, the compounds from C. tricuspidata showed potential to be further developed as therapeutic agents to suppress inflammation in skin cells.
... In keratinocytes, IFN-γ/TNF-α activates several intracellular signaling pathways, including those of mitogen-activated protein kinases (MAPKs) [32]. The MAPK cascade plays an important role in immune responses, regulates multiple cellular processes, including gene expression, cell death, and cell proliferation and is involved in the production of inflammatory chemokines [33,34]. ...
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Pyropia yezoensis, a red alga, is popular and harvested a lot in East Asia and is famous for its medicinal properties attributable to its bioactive compounds including amino acids (porphyra-334 and shinorine, etc.), polysaccharides, phytosterols, and pigments, but its anti-inflammatory effect and mechanism of anti-atopic dermatitis (AD) have not been elucidated. In this study, we investigate the anti-AD effect of P. yezoensis extract (PYE) on mRNA and protein levels of the pro-inflammatory chemokines, thymus, and activation-regulated chemokine (TARC/CCL17) and macrophage-derived chemokine (MDC/CCL22), in human HaCaT keratinocyte cells treated to interferon (IFN)-γ or tumor necrosis factor (TNF)-α (10 ng/mL each). The effect of the PYE on extracellular signal-regulated kinase (ERK) and other mitogen-activated protein kinases (MAPKs) was related to its suppression of TARC and MDC production by blocking NF-κB activation in HaCaT cells. Furthermore, astaxanthin and xanthophyll from P. yezoensis were identified as anti-AD candidate compounds. These results suggest that the PYE may improve AD and contained two carotenoids by regulating pro-inflammatory chemokines.
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Star anise (Illicium verum) is a medium-sized plant that is native to Asia as well as one of the most important medicinal plants used in Chinese herbal medicine. Star anise has bioactive compounds having antioxidant and anti-inflammatory properties. The antioxidant activity of Star anise (Illicium verum) methanolic extract was studied by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′azinobis-(3-ethylbenzthiazoline-6-sulfonic acid (ABTS) assay. The current study aims to investigate the effect of Star anise (Illicium verum) methanolic extract as ant-inflammatory by reducing the concentration of pro-inflammatory cytokines TNF-α and IL 1beta and reducing the oxidative stress by acting as a scavenger because inflammation and oxidative stress can induce each other. The highest free radical scavenging activities were exerted by the APTS method (95.1±0.33 Trolox/g) whereas, the free radical scavenging activities were exerted by ABTS was 77.7±0.30 Trolox/g. The anti-inflammatory activity of the Star anise (Illicium verum) methanolic extract was studied by its ability to inhibit pro-inflammatory cytokines productions (Tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β)) and reduce oxidative stress at different concentrations. Star anise (Illicium verum) methanolic extract significantly reduce the pro-inflammatory TNF-α and IL-1β production (p<0.05) compared with negative control which is treated with lipopolysaccharide (LPS) and has a similar effect in reducing pro-inflammatory cytokines production similar to the positive control which treated with ascorbic acid. Star anise (Illicium verum) methanolic extract significantly reduces oxidative stress (p<0.05) by reducing antioxidant enzyme activity catalase and glutathione-peroxidase compared with the LPS treated group. In conclusion Star anise (Illicium verum) methanolic extract act as strong antioxidant and anti-inflammatory medicinal plant.
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Anethole is the main fragrance and bioactive compound of anise, fennel, and star anise spices and more than other 20 plant species. It is widely used as flavor agent in food industry and other industries, in cosmetics, perfumery, and pharmaceuticals. In the last few years, various studies have revealed multiple beneficial effects of anethole for human health, such as anti-inflammatory, anticarcinogenic and chemopreventive, antidiabetic, immunomodulatory, neuroprotective, or antithrombotic, that are mediated by the modulation of several cell signaling pathways, mainly NF-kB and TNF-α signaling, and various ion channels. This chapter aims to review the scientific data and attempts to provide an insight into pharmacological activity of anethole and its therapeutic potential in human chronic diseases.
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Objectives : Illicium verum Hook. f. has been known to possess antimicrobial, antioxidant, antifungal, anti-inflammatory, insecticidal, analgesic, sedative, convulsive activities, it has been rarely conducted to evaluate the immuno-biological activity. The present study was examined to evaluate the anti-inflammatory effects of the Illicium verum Hook. f. water extracts (IVE) in vivo and in vitro. Methods : Cell viability was measured by MTT assay. The relative levels of NO were measured with Griess reagent. iNOS, COX-2, NF-{\kappa}B and target proteins were detected by immunoblot analysis, and levels of cytokines were analyzed by ELISA kit. Anti-edema effect was determined in the carrageenan (CA)-induced paw edema model in rats. Results : All dosages of IVE used in MTT assay had no significant cytotoxicity. The increases of NO production and iNOS expression were detected in LPS-treated cells compared with control. However, these increases were attenuated by treatment with IVE. Also, IVE reduced the elevated production of TNF-{\alpha}, IL-1{\beta} and IL-6 by LPS. IVE inhibited the p-I{\kappa}B and translocation of NF-{\kappa}B to nuclear. Furthermore, IVE significantly inhibited the increases of hind paw swelling, skin thicknesses and inflammatory cell infiltrations induced by CA injection. Therefore, IVE will be favorably inhibited the acute edematous inflammations. Conclusion : These results provide evidences that anti-inflammatory effect of IVE is partly due to the reduction of some inflammatory mediators by suppression of NF-{\kappa}B pathway.
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The effect of Illicium verum extracts (IVE) or Eucommia ulmoides leaf extracts (ELE) on nutrient availability, duodenal and jejunal antioxidant ability of Duroc ×Landrace × Yorkshire (DLY) and Chinese native Licha‐black (LCB) piglets was investigated. Ninety‐six piglets (48 DLY and 48 LCB respectively) without significant difference in body weight (11.22 ± 0.32 kg) were used in a 2 × 4 factorial design. Animals were randomly allocated to four treatments, and each had four replicates with three DLY and three LCB piglets. Treatments were basal diet (CON) and basal diet with 500 mg/kg IVE, 250 mg/kg ELE and 50 mg/kg chlortetracycline (CHL) respectively. Animals were placed individually for 7‐days adaptation following 42‐days test. Results showed the significant interaction (p < 0.05) between dietary treatments and pig species in activity of total superoxide dismutase (T‐SOD) and glutathione peroxidase (GSH‐Px), content of malondialdehyde (MDA), and α‐tumour necrosis factor (TNF‐α), nuclear factor erythroid 2‐related factor 2 (Nrf2) and Nrf2/TNF‐α at mRNA and protein level in duodenum and jejunum of DLY and LCB piglets. The IVE and ELE increased (p < 0.05) activity of GSH‐Px and T‐SOD, and the Nrf2/TNF‐α at mRNA and protein level, however, the decreased (p < 0.05) MDA content, and TNF‐α at mRNA and protein level in duodenum and jejunum were observed. The CHL decreased (p < 0.05) activity of GSH‐Px and T‐SOD, TNF‐α and Nrf2 at mRNA and protein level in duodenum, but increased (p < 0.05) MDA content and Nrf2/TNF‐α in jejunum. DLY piglets had higher (p < 0.05) nutrient digestibility (organic matter, crude protein and gross energy), availability (biological value and net protein utilization), MDA content, and TNF‐α at mRNA and protein level in jejunum, and had lower (p < 0.05) activity of GSH‐Px and T‐SOD, and Nrf2 and Nrf2/TNF‐α at mRNA and protein level in duodenum and jejunum than LCB. In conclusion, the 500 mg/kg IVE and 250 mg/kg ELE improved the nutrient availability, and the improvement of antioxidant capacity is realized by activating the Nrf2/TNF‐α of duodenum and jejunum. The CHL had adverse effects on antioxidant ability of DLY and LCB piglets. The results showed that the nutrient digestion and absorption capacity of DLY were stronger than that of LCB piglets, but the antioxidant capacity was lower than that of LCB piglets. Therefore, the IVE and ELE are recommended as a new potential alternative to antibiotics in piglets’ diets.
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DZ2002, a reversible S-adenosyl-L-homocysteine hydrolase (SAHH) inhibitor with immunosuppressive properties and potent therapeutic activity against various autoimmune diseases in mice. The present study was designed to characterize the potential therapeutic effects of DZ2002 on murine model of psoriasis and reveal the correlated mechanisms. In this report, we demonstrated that in vitro, DZ2002 significantly decreased the expression of pro-inflammatory cytokines and adhesion molecule including IL-1α, IL-1β, IL-6, IL-8, TNF-α and ICAM-1 by inhibiting the phosphorylation of p38 MAPK, ERK and JNK in TNF-α/IFN-γ-stimulated HaCaT human keratinocytes. Topical administration of DZ2002 alleviated the imiquimod (IMQ)-induced psoriasis-like skin lesions and inflammation in mice, the therapeutic effect was comparable with the Calcipotriol. Moreover, the inflammatory skin disorder was restored by DZ2002 treatment characterized by reducing both of the CD3(+) T cell accumulation and the psoriasis-specific cytokines expression. Further, we found that DZ2002 improved IMQ-induced splenomegaly and decreased the frequency of splenic IL-17-producing T cells. Our finding offered the convincing evidence that SAHH inhibitor DZ2002 might attenuate psoriasis by simultaneously interfering the abnormal activation and differentiation of keratinocytes and accumulation of IL-17-producing T cells in skin lesions.
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Genistein is one of the main components of soybeans and has been reported to be a potential candidate for the treatment of obesity, cancer, osteoporosis and cardiovascular diseases. Recently, genistein has been shown to have therapeutic effects on some chronic skin diseases, but its underlying mechanisms remain unclear. In this study, we evaluated the role of genistein in alleviating squaric acid dibutylester (SADBE)-induced allergic contact dermatitis (ACD) in mice, and elucidated the potential molecular mechanisms in human keratinocyte (HaCaT) cell line. The impacts of genistein on the production of pro-inflammatory chemokines and cytokines including CXCL9, TSLP, TNF-α, IL-1β and IL-6 in the skin and serum of ACD mice were assessed, as well as the phosphorylation of components in the MAPK and JAK-STAT3 signaling pathways in the skin and dorsal root ganglions (DRGs). The results showed that genistein exerted protective effects on skin damage and inflammatory cell infiltration. Moreover, genistein significantly inhibited the increased expressions of pro-inflammatory factors in skin and peripheral blood, and down-regulated the levels of p-ERK, p-p38 and p-STAT3 in skin and DRGs. Furthermore, genistein inhibited the phosphorylation of ERK and STAT3 to downregulate the expression of cytokines and chemokines, and feedback downregulate phospho-p38 in TNF-α/IFN-γ-induced HaCaT cells. The genistein-mediated inhibitory effect on the MAPK pathway can be reversed by siMAP2K2 but not by siMAP2K4. Altogether, our findings demonstrated that genistein exhibits strong antipruritic and anti-inflammatory effects in ACD mice by inhibiting the production of pro-inflammatory cytokines and intracellular MAP2K2/ERK cell signaling, which makes genistein a potentially valuable candidate for the treatment of skin conditions and systemic syndromes in the setting of contact dermatitis.
Article
Ethnopharmacological relevance: Rhus coriaria L. (R. coriaria) is a medicinal herb native to the middle east and Mediterranean region and well-known as "sumac" or "sicilian sumac". This herb has a wide range of traditional applications, covering its topical use to treat skin burns or eczemas and to promote wound healing. Aim of the study: The present research aims to investigate the potential anti-inflammatory activity of Rhus coriaria L. fruit extracts in human keratinocytes (HaCaT cells), evaluating extracts prepared using different techniques. Materials and methods: Water (WRC), ethanol-water (EWRC) and two types of ethanol extracts (mERC and ERC) were prepared. The HaCaT cells were challenged by TNF-α (10 ng/mL) and IL-8, ICAM-1, VEGF, and MMP-9 release, as well as NF-κB translocation, were measured by ELISA assays. The most active extracts were chemically profiled through HPLC-UV-DAD analysis. Results: Althought all the extracts inhibited the TNF-α-induced IL-8 release, just mERC and EWRC suppressed NF-κB activation, ICAM-1, and MMP-9 secretion. EWRC showed higher inhibition on ICAM-1 and MMP-9 with IC50s of 1.76 ± 0.24 and 1.24 ± 0.33 μg/mL, respectively (mean ± s.d.). On the contrary, mERC significantly decreased VEGF levels whereas EWRC did not show any effect. The HPLC-UV profile of the extracts revealed higher amount of anthocyanins in EWRC in comparison with mERC. Conclusions: Our results suggest the potential positive effect of R. coriaria fruit extracts, mostly mERC, as preventive agent in the treatment of keratinocyte inflammation through their inhibitory effect on the production of skin pro-inflammatory mediators.
Article
Ethnopharmacological relevance Qingxue jiedu Formulation (QF) is composed of two classic prescriptions which have been clinically used for more than 5 centuries and appropriately modified through basic theory of traditional Chinese medicine for treating various skin inflammation such as atopic dermatitis (AD), acute dermatitis and rash. Although QF possesses a prominent clinical therapeutic effect, seldom pharmacological studies on its anti-AD activity are conducted. Aim of the study We used AD mice model to investigate the anti-AD activities of QF, as well as its underlying molecular mechanisms which involved signal transducer and activator of transcription 3 (STAT3), nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Materials and methods 2,4-dinitrofluorobenzene (DNFB)-induced AD mice were used to collect serum and skin tissues for consequential determination. The levels of various inflammatory factors [interleukin (IL)-12, Interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-4, IL-6 and immunoglobulin E (IgE)] were determined by enzyme-linked immunosorbent assay (ELISA). Real-time polymerase chain reaction (RT-PCR) was contributed to detect the effects of relevant inflammatory factors on mRNA. The roles of STAT3, NF-κB and MAPK signaling pathways in AD response were analyzed by Western blotting (WB), and the thickening of mice dorsal skin and inflammatory cell infiltration were observed by hematoxylin and eosin (H&E) staining. Results QF significantly reduced the skin thickening, inflammatory cell infiltration and other symptoms in AD mice. The levels of IL-12, TNF-α, IL-4, IL-6 and IgE were decreased, while IFN-γ was increased by QF in the ELISA analysis. QF lessened the levels of lL-6 and elevated IFN-γ on the mRNA level. In addition, WB analysis showed QF thoroughly inhibited the activation of NF-κB, STAT3 and phosphorylation of JAK1, JAK2, JAK3, while partially suppressed MAPK signaling pathways. Conclusions QF inhibited the activations of STAT3, MAPK and NF-κB signaling pathways and possessed a significant therapeutic effect on AD. Therefore, QF deserves our continuous attention and research as a prominent medicine for AD.
Nature is a rich source of natural drug-like compounds with almost zero side effects. Phytochemicals better known as “Natural Products” are found abundantly in a number of plants. Since time immemorial, spices have been widely used in Indian cuisine as flavoring and colouring agents. Most of these spices and condiments are derived from various biodiversity hotspots in India (which contributes 75% of global spice production) and form the crux of India’s multidiverse and multicultural cuisine. Apart from their aroma, flavor and taste, these spices and condiments are known to possess several medicinal properties also. Most of these spices find considerable mention in Ayurveda, the indigenous system of medicine, as panaceas for several aliments. The antimicrobial, antioxidant, antiproliferative, antihypertensive and antidiabetic properties of several of these natural products are well documented in Ayurveda. These phytoconstituemts are known to act as functional immunoboosters, immunomodulators as well as anti-inflammatory agents. As anticancer agents, their mechanistic action involves cancer cell death via induction of apoptosis, necrosis and autophagy. The present review provides a comprehensive and collective update on the potential of 65 commonly used spices as well as their bioactive constituents as anticancer agents. The review also provides an in-depth update of all major in vitro, in vivo, clinical and pharmacological studies done on these spices with special emphasis on the potential of these spices and their bioactive constituents as potential functional foods for prevention, treatment and management of cancer.
Article
Plant extracts are considered to be an effective alternative to antibiotics in response to weaning stress in piglets. This study evaluated the effect of Illicium verum extracts (IVE) or Eucommia ulmoides leaf extracts (ELE) on growth performance, serum and liver antioxidant ability of nursery piglets, as well as the difference of IVE and ELE on Duroc × Landrace × Yorkshire (DLY) and Chinese native Licha‐black (LCB) piglets. A total of 96 nursery piglets (48 DLY and 48 LCB piglets) with an average body weight of 11.22 ± 0.32 kg were randomly divided into four treatments in a 2 × 4 factorial design. Each treatment had four replicates with 3 DLY and 3 LCB piglets per replicate respectively. Treatments included: basal diet, basal diet + 500 mg/kg IVE, basal diet + 250 mg/kg ELE and basal diet + 50 mg/kg chlortetracycline (CHL). All piglets were housed individually for the 42 days trial period after 7 days adaptation. Results showed that there were significant interactions (p < .05) between piglets species and dietary treatments in average daily gain (ADG) and feed efficiency, serum and hepatic glutathione peroxidase (GSH‐Px) and malondialdehyde (MDA), hepatic integral optical density (IOD) of α‐tumour necrosis factor (TNF‐α), hepatic relative mRNA expressions of nuclear factor erythroid 2‐related factor 2 (Nrf2)/TNF‐α and protein expression of TNF‐α. Regardless of piglets species, supplementation with IVE and ELE increased (p < .05) ADG and feed efficiency, T‐SOD and GSH‐Px in serum and liver, hepatic IOD of Nrf2, hepatic mRNA and protein expression of Nrf2/TNF‐α. However, CHL treatment resulted in lower (p < .05) serum GSH‐Px and hepatic mRNA and protein expression of Nrf2/TNF‐α, and higher hepatic MDA and IOD of TNF‐α. Compared to LCB, DLY piglets had higher (p < .05) ADG and feed efficiency, serum and hepatic MDA, and protein expression of TNF‐α, but lower (p < .05) ADFI, liver index, serum and hepatic GSH‐Px, hepatic IOD of TNF‐α, mRNA expressions of Nrf2/TNF‐α were observed. In conclusion, Illicium verum (500 mg/kg) and Eucommia ulmoides leaf (250 mg/kg) extracts can increase the growth performance and antioxidant ability of DLY and LCB piglets, while chlortetracycline produces undesirable side‐effects on the antioxidant ability of DLY and LCB piglets. Illicium verum and Eucommia ulmoides leaf extracts produced different antioxidant effects in DLY and LCB piglets with the Chinese native Licha‐black pig responding better than Duroc × Landrace × Yorkshire.
Article
Star anise essential oil (SAO) is volatile oil extracted from star anise fruits (Illicium verum Hook. f) with a highly anise flavour and is widely used in food and pharmaceutical industries because of its antimicrobial and antioxidant properties. With the growing public concern about food safety, research concerning safe and effective food preservatives has gained increasing attention. In the past few years, many papers have reported the in vitro antifungal and antioxidant activities of SAO. This paper aims to provide evidences that SAO may be used for prolonging shelf life of food products. For such purpose, this paper reviews the advances of research on the chemical composition, antifungal and antioxidant activities of SAO. The functional bioactive components in SAO and the antifungal mechanism of action are also summarized. SAO may have good potential as food preservative in food industry.
Article
In this study, the anti-inflammatory mechanisms of Quercetin (Que) on atopic dermatitis (AD)-like skin lesions was examined. The left ear of mice was applied with MC903, followed by Que. administration daily on the ear for 8 days. Then macroscopic and histologic examination was performed to detect the severity of skin lesions. In the skin section of AD mice, we observed that Que. could reduce the expression of CCL17, CCL22, IL-4, IL-6, IFN-γ and TNF-α. In vitro, the anti-inflammatory effects of Que. were examined on human keratinocytes (HaCaT cells) treated with IFN-γ/TNF-α. To unveil the lncRNAs' regulatory role on Que-activated anti-inflammatory function, the next-generation high-throughput sequencing was performed in HaCat cells with or without Que. treatment, which profiled the expression of lncRNAs and mRNAs, the results illustrated that lnc-C7orf30-2, a lncRNA expressed differentially, was correlated with IL-6 expression. Silencing of lnc-C7orf30-2 by RiboTM lncRNA Smart Silencer proved its role on IL-6 expression. Therefore, the results here demonstrated that topical administration of Que. plays a beneficial role in controlling AD symptoms, which may serve as potential candidate for AD treatment.
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Indian subcontinent, unique for its Unity in Diversity, is made up of 28 provinces and 8 union territories and is known to have amazing diversity of approximately 1402 million people with a wide variety of races and ethnicity staying together harmonically since the ancient time. It is not surprising that India with 15 major languages and about 100 dialects would have a wide variety of cuisines, with each province having its own cooking tradition and taste. Indian ways of food preparation are not the cuisine of a single nationality, but a collective combination of different cuisines from a number of countries with cultural identities that have been heavily influenced by religious and regional particularities. Above the region-specific nature of Indian cuisine, there exists certain common features among the diverse culinary practices. India’s history, rulers, trade partners, and moreover, the religious and cultural traditions have great influence on its cuisines. From the ancient ages, Indian Ayurveda (the medicinal practices for the well-being of humanity) is considered as a method of science of life in a holistic way. Ayurvedic Science signifies the importance of natural medicines using herbals that also includes spices. Spices and herbs are found not only to attribute flavour to bland meals, but also influence human metabolic processes and defence mechanisms. Spices have a diverse array of natural phytochemicals that have complementary and overlapping actions that include antioxidant effects, modulation of detoxifying enzymes, stimulation of immune system, reduction of inflammation, modulation of steroid metabolism, and antibacterial as well as antiviral effects. In this review, efforts have been made to take a cursory glance on the traditional Indian spices and herbs being used since the prehistoric times in the preparation of foods. The medicinal, nutritional, and especially immunostimulant properties of different spices and herbs have been reviewed. The great biodiversity observed in India by virtue of its enormous variety of flora and fauna owe to its wide range of climatic conditions and topographical characteristics. While in the colder northern states, dishes are prepared commonly with the warming aromatic spices, and in contrast, to combat the hot climate in the southern Indian states, the foods prepared are generally lighter to make them easy for the digestive system. Natural anti-inflammatory compounds are abundant in different Indian spices that not only add flavour, but also impart different immuno-boosting effects. Anti-inflammatory compounds are plentifully present in Indian spices and herbs, and their additive or synergistic actions protect the human body against a variety of threats. Some of the important bioactive compounds possessing nutritional/immunostimulant values include piperine from black pepper, curcumin from turmeric, allyl sulphides from garlic, eugenol from cloves, capsaicin from red pepper, etc. Moreover, natural polyphenols found in some common herbs used in different Indian cuisines, i.e. coriander, bay, mint, curry leaves, etc., have been found with immunostimulant properties in combating a multitude of disorders.KeywordsIndian cuisineSpicesHerbsFermented foodBioactiveImmunostimulant propertiesAnti-inflammatory
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Illicium verum has been widely used in many Asian countries as a spice and pharmaceutical treatment for many diseases. In this study, the antioxidant properties of the ethanol extracts fractionated by hexane, ethyl ether, chloroform and ethyl acetate, and supercritical CO 2 extracts of the plant were evaluated using 1,1-diphenyl-2-picryhydrazyl (DPPH) radical scavenging effect, the total equivalent antioxidant capacity and a reducing power assay. In addition, the amount of total phenolic content and the flavonoid content were also determined. The ethyl acetate fractions contained substantially higher levels of total phenolics (4.5 g gallic acid / 100 g dry weight) and total flavonoids (6.9 g quercetin/100 g dry weight) than the other extracts, and possessed significant antioxidant activities. The chemical components of the various extracts were analyzed by gas chromatography-mass spectrometry (GC-MS); anisyl acetone and anisyl aldehyde were evidenced to provide the slight antioxidant activities. Based on the results, it can be concluded that the ethyl acetate extracts of I. verum show a marked antioxidant potential and that they could be developed as a natural source of antioxidants.
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The present study shows for the first time the chemical profile and the in vitro properties (antioxidant and inhibition of nitric oxide [NO] production) of the aromatic plant Pimpinella anisoides V Brig. (Family Apiaceae). The ethanolic extract of the fruits is characterized by 23 major components. Fourteen monoterpenes, two sesquiterpenes, one fatty acid, five methyl esters and one aldehyde were identified. Among them the most abundant components were the monoterpenes trans-anethole (54.5%), limonene (13.5%), and sabinene (4.4%). The extract showed significant antioxidant activity (50% inhibitory concentration [IC(50)], 3.02 mg/mL) using the 2,2-diphenyl-1-picrylhydrazyl test. The test for inhibition of NO production was performed using the murine monocytic macrophage cell line RAW 264.7. The ethanolic extract had significant activity with an IC(50) value of 72.7 microg/mL, and this might indicate that it would have an anti-inflammatory effect in vivo. Among the pure compounds that most effectively inhibited lipopolysaccharide-induced NO production were the most abundant constituents, trans-anethole and limonene, with IC(50) values of 102.7 microg/mL and 70.1 microg/mL, respectively. The cytotoxic effect of P. anisoides extract and pure compounds in the presence of lipopolysaccharide (1 microg/mL) was evaluated but found to be negligible.
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We have examined the expression of chemokines and their receptors in the atopic dermatitis–like (AD-like) lesions of NC/Nga mice. Such lesions develop when the mice are kept in conventional conditions, but not when they are kept isolated from specific pathogens. The thymus- and activation-regulated chemokine TARC is unexpectedly highly expressed in the basal epidermis of 14-week-old mice with lesions, whereas it is not expressed in the skin without lesions. Production of TARC by keratinocytes was confirmed by culturing murine keratinocytic cell line cells (PAM212) with TNF-α, IFN-γ, or IL-1β. Expression of another Th2 chemokine, macrophage-derived chemokine (MDC), was observed in the skin from mice kept in both conventional and pathogen-free conditions, but expression of MDC was increased severalfold in the skin with lesions. The cellular origin of MDC was identified to be dermal dendritic cells. Infiltration of the skin by IL-4–producing T cells and mast cells, and the increase of CCR4 mRNA in the skin, coincided with the development of AD lesions. These observations indicate that TARC and MDC actively participate in the pathogenesis of AD-like lesions in NC/Nga mice and that these Th2 chemokines could be novel targets for intervention therapy of AD in humans.
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In contrast to mouse epidermal cells, human skin keratinocytes are rather resistant to transformation in vitro. Immortalization has been achieved by SV40 but has resulted in cell lines with altered differentiation. We have established a spontaneously transformed human epithelial cell line from adult skin, which maintains full epidermal differentiation capacity. This HaCaT cell line is obviously immortal (greater than 140 passages), has a transformed phenotype in vitro (clonogenic on plastic and in agar) but remains nontumorigenic. Despite the altered and unlimited growth potential, HaCaT cells, similar to normal keratinocytes, reform an orderly structured and differentiated epidermal tissue when transplanted onto nude mice. Differentiation-specific keratins (Nos. 1 and 10) and other markers (involucrin and filaggrin) are expressed and regularly located. Thus, HaCaT is the first permanent epithelial cell line from adult human skin that exhibits normal differentiation and provides a promising tool for studying regulation of keratinization in human cells. On karyotyping this line is aneuploid (initially hypodiploid) with unique stable marker chromosomes indicating monoclonal origin. The identity of the HaCaT line with the tissue of origin was proven by DNA fingerprinting using hypervariable minisatellite probes. This is the first demonstration that the DNA fingerprint pattern is unaffected by long-term cultivation, transformation, and multiple chromosomal alterations, thereby offering a unique possibility for unequivocal identification of human cell lines. The characteristics of the HaCaT cell line clearly document that spontaneous transformation of human adult keratinocytes can occur in vitro and is associated with sequential chromosomal alterations, though not obligatorily linked to major defects in differentiation.
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The cell surface expression and function of the LFA-1 ligand, intercellular adhesion molecule 1 (ICAM-1), on epidermal keratinocytes (EK) was studied. ICAM-1 expression on the surface of cultured EK was either absent or weak, but was induced by treating EK with rIFN-gamma or TNF for 4-48 h. IFN-gamma and TNF were synergistic. IFN-gamma treatment increased T lymphoblast adhesion from less than 2% to 20-40%, with a concentration dependence similar to that seen for ICAM-1 induction. All of the adhesion to EK was inhibited by LFA-1 and ICAM-1 mAbs, but not by HLA-DR, CD2, or LFA-3 mAbs. There was no difference in the level of T lymphoblast adhesion to IFN-gamma-treated allogeneic or autologous EK. ICAM-1 purified from the HeLa epithelioid cell line and reconstituted into planar membranes also supported efficient adhesion of T lymphoblasts that was blocked by LFA-1 mAb bound to the T lymphoblasts or ICAM-1 mAb bound to the planar membranes. T lymphoblasts adherent to EK or ICAM-1 planar membranes were isolated by panning, and surface markers were analyzed by immunofluorescence flow cytometry. The adherent T cells were a phenotypically skewed subpopulation. They were enriched for CD8+ cells and expressed 1.5-2.5-fold higher LFA-1 and CD2 compared with the unseparated population.
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In chronic inflammatory diseases, such as asthma, rheumatoid arthritis, inflammatory bowel disease, and psoriasis, several cytokines recruit activated immune and inflammatory cells to the site of lesions, thereby amplifying and perpetuating the inflammatory state.1 These activated cells produce many other mediators of inflammation. What causes these diseases is still a mystery, but the disease process results from an interplay of genetic and environmental factors. Genes, such as those for atopy in asthma and for HLA antigens in rheumatoid arthritis and inflammatory bowel disease, may determine a patient's susceptibility to the disease and the disease's severity, but environmental factors, often unknown, . . .
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Anethole, a chief constituent of anise, camphor, and fennel, has been shown to block both inflammation and carcinogenesis, but just how these effects are mediated is not known. One possibility is TNF-mediated signaling, which has also been associated with both inflammation and carcinogenesis. In the present report we show that anethole is a potent inhibitor of TNF-induced NF-kappaB activation (an early response) as monitored by electrophoretic mobility shift assay, IkappaBalpha phosphorylation and degradation, and NF-kappaB reporter gene expression. Suppression of IkappaBalpha phosphorylation and NF-kappaB reporter gene expression induced by TRAF2 and NIK, suggests that anethole acts on IkappaBalpha kinase. Anethole also blocked the NF-kappaB activation induced by a variety of other inflammatory agents. Besides NF-kappaB, anethole also suppressed TNF-induced activation of the transcription factor AP-1, c-jun N-terminal kinase and MAPK-kinase. In addition, anethole abrogated TNF-induced apoptosis as measured by both caspase activation and cell viability. The anethole analogues eugenol and isoeugenol also blocked TNF signaling. Anethole suppressed TNF-induced both lipid peroxidation and ROI generation. Overall, our results demonstrate that anethole inhibits TNF-induced cellular responses, which may explain its role in suppression of inflammation and carcinogenesis. Oncogene (2000).
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Atopic dermatitis is a chronic inflammatory skin disease associated with cutaneous hyperreactivity to environmental triggers and is often the first step in the atopic march that results in asthma and allergic rhinitis. The clinical phenotype that characterizes atopic dermatitis is the product of interactions between susceptibility genes, the environment, defective skin barrier function, and immunologic responses. This review summarizes recent progress in our understanding of the pathophysiology of atopic dermatitis and the implications for new management strategies.
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The prevalence of allergic diseases has increased all over the world during the last two decades. Dietary change is considered to be one of the environmental factors that cause this increase and worsen allergic symptoms. If this is the case, an appropriate intake of foods or beverages with anti-allergic activities is expected to prevent the onset of allergic diseases and ameliorate allergic symptoms. Flavonoids, ubiquitously present in vegetables, fruits or teas possess anti-allergic activities. Flavonoids inhibit histamine release, synthesis of IL-4 and IL-13 and CD40 ligand expression by basophils. Analyses of structure-activity relationships of 45 flavones, flavonols and their related compounds showed that luteolin, ayanin, apigenin and fisetin were the strongest inhibitors of IL-4 production with an IC(50) value of 2-5 microM and determined a fundamental structure for the inhibitory activity. The inhibitory activity of flavonoids on IL-4 and CD40 ligand expression was possibly mediated through their inhibitory action on activation of nuclear factors of activated T cells and AP-1. Administration of flavonoids into atopic dermatitis-prone mice showed a preventative and ameliorative effect. Recent epidemiological studies reported that a low incidence of asthma was significantly observed in a population with a high intake of flavonoids. Thus, this evidence will be helpful for the development of low molecular compounds for allergic diseases and it is expected that a dietary menu including an appropriate intake of flavonoids may provide a form of complementary and alternative medicine and a preventative strategy for allergic diseases. Clinical studies to verify these points are now in progress.
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Atopic dermatitis is a chronically relapsing inflammatory skin disease. Animal models induced by relevant allergens play a very important role in the elucidation of the disease. The patients with atopic dermatitis are highly sensitized with mite allergens such as Dermatophagoides farinae (Df). Therefore, in the present study, we tried to develop a novel model for atopic dermatitis by repeated application with Df extract ointment. Df extract ointment was repeatedly applied to the back of NC/Nga mice together with barrier disruption. Atopic dermatitis-like skin lesions were evaluated by dermatitis scores, skin histology and immunological parameters. The effect of corticosteroid and calcineurin inhibitor was also examined. Repeated application of Df extract ointment caused rapid increase in dermatitis scores. Clinical (skin dryness, erythema, edema and erosion) and histological symptoms (dermal and epidermal thickening, hyperkeratosis, parakeratosis and inflammatory cell infiltration) in this model were very similar to those in human atopic dermatitis. Serum total and Df-specific IgE levels were elevated in this model compared with normal mice, and draining lymph node cells isolated from the mice that exhibited dermatitis produced significant amounts of interleukin-5, interleukin-13 and interferon-gamma after re-stimulation with Df. Furthermore, current first-line drugs for the treatment of human atopic dermatitis, corticosteroid and tacrolimus ointments, were effective against the clinical and histological symptoms in this model. These results suggest that the model we have established is useful for not only elucidating the pathogenesis of atopic dermatitis but also for evaluating therapeutic agents.
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The CC-chemokine TARC is known to be a ligand for the CCR4 receptor which in turn is known to be expressed selectively on the Th2-subset of lymphocytes. Atopic dermatitis is generally believed to be a Th2-type disease, and TARC has been shown to be expressed in the skin lesions of a murine model of AD. IL-10 is an interleukine generally known for its ability to inhibit cytokine production, however it has been found to be highly expressed in the skin from AD patients. We show in this report that IL-10 is able to augment the TARC inducing effects of TNFα and IFNγ in HaCaT cells, a property that may be important in the determination of the composition of the cells of the inflammation in the skin of AD patients. In addition, we show that the IL10 agonist IT 9302, a nona-peptide from the carboxylic end of IL-10, has the same effect on TARC production from HaCaT cells.
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Essential oil from dried Star anise fruits (Illicium verum H.) was extracted with liquid CO2. The yield and the time of extraction were compared with that of the conventional steam distillation method. Extraction with liquid CO2 yielded 9.8% more essential oil than steam distillation. The anethole contents in oils obtained by the two methods were not significantly different and were in the range of 89–92% of the total oil. The particle size of 0.425–0.710 mm and the time of 90 min were found to be optimum for both steam distillation and liquid CO2 extraction. Two mathematical models were used to describe the relationship between the yield and time of extraction. Langmuir's adsorption model fitted the data better than the simple exponential model. Extraction of essential oil from Star anise fruits with liquid CO2 was better than steam distillation in terms of energy saving, product yield and product quality.
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Casuarinin is a naturally occurring tannin that is isolated from the leaves of Hippophae rhamnoides. It has been shown to have anti-oxidant, anti-cancer, anti-viral, and anti-inflammatory activities. The aim of this study was to investigate the possible mechanism by which casuarinin inhibits TNF-α/IFN-γ-induced Th2 chemokines expression in the human keratinocytes cell line HaCaT. We found that casuarinin suppressed TNF-α/IFN-γ-induced expression of TARC and MDC mRNA and protein in HaCaT cells. Casuarinin significantly inhibited TNF-α/IFN-γ-induced activation of NF-κB, STAT1, and p38 MAPK. Furthermore, we observed that p38 MAPK contributes to inhibition of TNF-α/IFN-γ-induced TARC and MDC production by blocking NF-κB and STAT1 activation in HaCaT cells. Taken together, these results suggest that casuarinin may exert anti-inflammatory responses by suppressing TNF-α/IFN-γ-induced expression of TARC and MDC via blockage of p38 MAPK activation and subsequent activation of NF-κB and STAT1. We propose that it could therefore be used as a therapeutic agent against inflammatory skin diseases.
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Cinnamomum cassia Blume (Aceraceae) has been traditionally used to treat various inflammatory diseases such as gastritis. However, the anti-inflammatory mechanism of Cinnamomum cassia has not been fully elucidated. This study examined the anti-inflammatory mechanism of 95% ethanol extract (Cc-EE) of Cinnamomum cassia. The effect of Cc-EE on the production of inflammatory mediators in RAW264.7 cells and peritoneal macrophages was investigated. Molecular mechanisms underlying the effects, especially inhibitory effects, was elucidated by analyzing the activation of transcription factors and their upstream signaling, and by evaluating the kinase activity of target enzymes. Cc-EE of Cinnamomum cassia diminished the production of nitric oxide (NO), tumor necrosis factor (TNF)-α, and prostaglandin (PG)E(2), in lipopolysaccharide (LPS)-activated RAW264.7 cells and peritoneal macrophages in a dose-dependent manner. Cc-EE also blocked mRNA expression of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, and TNF-α by suppressing the activation of nuclear factor (NF)-κB, and simultaneously inhibited its upstream inflammatory signaling cascades, including spleen tyrosine kinase (Syk) and Src. Consistent with these findings, the extract directly blocked the kinase activities of Src and Syk. Cc-EE exerts strong anti-inflammatory activity by suppressing Src/Syk-mediated NF-κB activation, which contributes to its major ethno-pharmacological role as an anti-gastritis remedy. Future work will be focused on determining whether the extract can be further developed as an anti-inflammatory drug.
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Keratinocytes may play an important role in the pathogenesis of skin disease in atopic dermatitis. Caffeoyl derivatives are demonstrated to have anti-inflammatory and anti-oxidant effects. However, the effect of 3,4,5-tricaffeoylquinic acid prepared from Aconium koreanum on the pro-inflammatory cytokine-stimulated keratinocyte responses remains uncertain. In human keratinocytes, we investigated the effect of 3,4,5-tricaffeoylquinic acid on the tumor necrosis factor (TNF)-α-stimulated production of inflammatory mediators in relation to the nuclear factor (NF)-κB and cell signaling Akt, which regulates the transcription genes involved in immune and inflammatory responses. 3,4,5-Tricaffeoylquinic acid inhibited the TNF-α-stimulated production of cytokines (IL-1β and IL-8) and chemokine (CCL17 and CCL27) in keratinocytes. Bay 11-7085 (an inhibitor of NF-κB activation) and Akt inhibitor attenuated the TNF-α-induced formation of inflammatory mediators. 3,4,5-Tricaffeoylquinic acid, Bay 11-7085, Akt inhibitor and N-acetylcysteine inhibited the TNF-α-induced activation of NF-κB, activation of Akt, and formation of reactive oxygen and nitrogen species. The results show that 3,4,5-tricaffeoylquinic acid seems to attenuate the TNF-α-stimulated inflammatory mediator production in keratinocytes by suppressing the activation of Akt and NF-κB pathways which may be mediated by reactive oxygen species. The findings suggest that 3,4,5-tricaffeoylquinic acid may exert an inhibitory effect against the pro-inflammatory mediator-induced skin disease.
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Hippophae rhamnoides has been extensively used in oriental traditional medicines for treatment of asthma, skin diseases, gastric ulcers, and lung disorders. In this study, we isolated casuarinin from the leaves of H.rhamnoides and examined the effect of casuarinin on the TNF-α-induced ICAM-1 expression in a human keratinocytes cell line HaCaT. Pretreatment with casuarinin inhibited TNF-α-induced protein and mRNA expression of ICAM-1 and subsequent monocyte adhesiveness in HaCaT cells. Casuarinin significantly inhibited TNF-α-induced NF-κB activation. In addition, casuarinin inhibited activation of ERK and p38 MAPK in a dose-dependent manner. Furthermore, pretreatment with casuarinin decreased TNF-α-induced pro-inflammatory mediators, such as IL-1β, IL-6, IL-8, and MCP-1. These results demonstrated that casuarinin exerts its anti-inflammatory activity by suppressing TNF-α-induced expression of ICAM-1 and pro-inflammatory cytokines/chemokines via blockage of activation of NF-κB and ERK/p38 MAPK and can be used as a therapeutic agent against inflammatory skin diseases.
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Environmental and endogenous stresses to skin are considered causative reasons for skin cancers, premature ageing, and chronic inflammation. Screening of substances with preventive and/or curative properties is currently based on mechanistic studies of their effects towards stress-induced responses in skin cell cultures. We compared effects of plant polyphenols (PPs) on the constitutive, UVA-, LPS-, or TNF-alpha-induced inflammatory responses in cultured normal human epidermal keratinocytes (NHEK) and immortalized HaCaT cells. Representatives of three classes of PPs, flavonoids, stilbenoids, and phenylpropanoids were studied. Their effects on mRNA were determined by qRT-PCR; protein expression was assayed by Western blot and bioplexed ELISA; phosphorylation of Akt1, ERK1/2, EGFR, and NFkappaB was quantified by intracellular ELISA or Western blot. PPs or their combination with UVA or LPS induced strong up-regulation of stress responses in HaCaT but not in NHEK. In addition, compared to NHEK, HaCaT responded to TNF-alpha with higher synthesis of MCP-1, IP-10 and IL-8, concomitant with stronger NFkappaB activation. PPs down-regulated the chemokine release from both cell types, although with distinct effects on NFkappaB, Akt1, ERK, and EGFR activation. Results of pharmacological screenings obtained by using HaCaT should be cautiously considered while extending them to primary keratinocytes from human epidermis.