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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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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. ...
... Sung et al. [36] also investigated the anti-inflammatory effect of I. verum fruit extract and its main compound trans-anethole in the human keratinocyte HaCaT cell line. The authors observed that trans-anethole exhibited anti-inflammatory activity in the studied cells, which was evidenced by the reduced protein expression of TARS, MDC, IL-4, and IL-1β without any accompanying cytotoxic effect. ...
... Ethanol extract of the I. verum fruit [36] Inhibitory activity against nuclear factor (NF-κB) translocation into the nucleus, phosphorylation and IκBα degradation ...
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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.
... Moreover, T + I can activate numerous intracellular signaling pathways, such as NF-κB and MAPK pathways, which are associated with inflammatory diseases like atopic dermatitis (Basu et al., 2019;Cho et al., 2020). The keratinocytes in patients with atopic dermatitis secrete chemokines and cytokines that stimulate the development of ISDs, which is triggered by MAPK signaling (Sung et al., 2012;Lim et al., 2016). The protein expression of phosphorylated ERK, JNK, and p38 were dramatically reduced in T + I-induced keratinocytes after BT-AuNPs pretreatment, implying that BT-AuNPs inhibit T + I-stimulated MAPK pathway activation. ...
... The protein expression of phosphorylated ERK, JNK, and p38 were dramatically reduced in T + I-induced keratinocytes after BT-AuNPs pretreatment, implying that BT-AuNPs inhibit T + I-stimulated MAPK pathway activation. The MAPK signaling is important in immune responses and collaborates with NF-κB to modulate inflammatory pathways (Kim et al., 2010;Sung et al., 2012). Our results indicated that BT-AuNPs also markedly suppressed the protein expression of phosphorylated IκB-α and p65, suggesting that BT-AuNPs might inhibit T + I-stimulated NF-κB signaling activation which includes release and phosphorylation of IκB, NF-κB translocation into the nucleus, and activation of the inflammatory response (Mi et al., 2022c). ...
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Introduction: Recently, nanotechnology has emerged as a potential technique for skin generation, which has several treatment advantages, such as decreased drug cytotoxicity and enhanced skin penetration. Boehmeria tricuspis (BT) belongs to the Urticaceae family and is rich in phenolic and flavonoid compounds. In this study, we biosynthesized gold nanoparticles (BT-AuNPs) using BT extract to explore their anti-inflammatory and skin-moisturizing properties in keratinocytes. Methods: Field-emission transmission electron microscopy, energydispersive X-ray spectrometry, dynamic light scattering, and Fourier-transforminfrared spectroscopy were used to examine the synthesized BT-AuNPs. qRT-PCR, western blot, and ELISA were applied for investigating the effect of BT-AuNPs on anti-inflammation and moisturizing activity in HaCaT cells. Results: At concentrations below 200 μg/mL, BT-AuNPs had no cytotoxic effect on keratinocytes. BT-AuNPs dramatically alleviated the expression and secretion of inflammatory chemokines/cytokine, such as IL-6, IL-8, TARC, CTACK, and RANTES in keratinocytes stimulated by tumor necrosis factor-α/interferon-γ (T + I). These anti-inflammatory properties of BT-AuNPs were regulated by inhibiting the NF-κB and MAPKs signaling pathways. Furthermore, BT-AuNPs greatly promoted hyaluronic acid (HA) production by enhancing the expression of hyaluronic acid synthase genes (HAS1, HAS2, and HAS3) and suppressing the expression of hyaluronidase genes (HYAL1 and HYAL2) in HaCaT cells. Discussion: These results suggest that BT-AuNPs can be used as a promising therapeutic alternative for treating skin inflammation. Our findings provide a potential platform for the use of BT-AuNPs as candidates for treating inflammatory skin diseases and promoting skin health.
... 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.
... 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.
... To investigate the anti-inflammatory effects of HEs, bioactive fractions, or compounds in in vitro AD studies, a variety of cell lines or primary culture cells have been used with stimulators as follows. Keratinocytes: Human keratinocyte HaCaT cell lines were applied in in vitro studies of AD with TNF-α or TNF-α/IFN-γ as the stimulator Sung et al., 2011a;Sung et al., 2011b;Choi et al., 2012a;Sung et al., 2012;Choi et al., 2014;Lim et al., 2014;Park et al., 2015;Yang et al., 2015a;Choi et al., 2016;Lim et al., 2016;Sung et al., 2016;. Langerhans cells: Langerhans cells derived from mice were stimulated with peptidoglycan (PEG) in an AD study (Matsui et al., 2010). ...
Article
Atopic dermatitis (AD) is an allergic disorder characterized by skin inflammation. It is well known that the activation of various inflammatory cells and the generation of inflammatory molecules are closely linked to the development of AD. There is accumulating evidence demonstrating the beneficial effects of herbal extracts (HEs) on the regulation of inflammatory response in both in vitro and in vivo studies of AD. This review summarizes the anti-atopic effects of HEs and its associated underlying mechanisms, with a brief introduction of in vitro and in vivo experiment models of AD based on previous and recent studies. Thus, this review confirms the utility of HEs for AD therapy.
... Illicium verum commonly known as star anise belongs to the family of Illiciaceae. Traditionally it is used as an herbal medicine in traditional Chinese and Ayurveda formulations for treatment of skin inflammation, rheumatoid arthritis, asthma, and bronchitis [12][13] . Syzygium aromaticum commonly known as clove is an aromatic herb belongs to the family of Myrtaceae. ...
... The shikimic acid found in flower lawing is a precursor in the production of oseltamivir (Tamiflu®), an antiviral medication used to treat influenza A and influenza B [74]. Bunga Lawang extract inhibits TNF-and IFN-induced production of chemokines and cytokines in human keratinocytes, demonstrating anti-inflammatory action [75]. ...
Article
In Indonesia, the number of cases infected with Covid-19 peaked between mid-June and August 2021, resulting in the denial of hospital treatment to some people due to insufficient capacity. Therefore, people treat themselves by using natural ingredients. This study aims to identify plants that can treat Covid-19 with self-medication. This study took a description approach to investigate people using traditional herbs in self-medication for COVID-19 recovery. Snowball sampling is the approach used. Interviews and an online system (gform) were used to collect data. The number of samples collected allows for a more thorough analysis of the 104 respondents. The results showed that women (51.0%), people aged between 56 and 65 (52.9%), Banten residents (32.7%), secondary education (57. 7%), and people with comorbidities (86.5). %) were all interested in using traditional herbal medicine. Reduction of symptoms and results of laboratory tests were used to measure recovery. The most common comorbidities were hypertension (7-14 days to recovery), diabetes mellitus (15-21 days to recovery), and cardiovascular disease (7-14 days and 15-21 days to recovery). The Zingiberaceae family dominates traditional herbs. The most widely used traditional ingredients are Empon-Empon, which consists of red ginger, turmeric, nutmeg, aromatic ginger, bay leaves, lemongrass, galangal, cinnamon, and cloves. The average healing time is 7-14 days (32.7%). In conclusion people who utilized herbal medicines reported a speedy recovery and reduction in the severity of their symptoms. Keywords: Covid-19, Empon-Empon, herbal medicine, self-medication, traditional ingredients
... Atopic dermatitis patients may experience an overexpression of inflammatory factors if their keratinocytes are activated [16,20]. TNFα/IFN-γ are commonly applied in the modeling of AD cell models [26,27]. We used this model as a model for in vitro experiments. ...
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The main pathogenic factor in atopic dermatitis (AD) is Th2 inflammation, and levels of serum CCL17 and CCL22 are related to severity in AD patients. Fulvic acid (FA) is a kind of natural humic acid with anti-inflammatory, antibacterial, and immunomodulatory effects. Our experiments demonstrated the therapeutic effect of FA on AD mice and revealed some potential mechanisms. FA was shown to reduce TARC/CCL17 and MDC/CCL22 expression in HaCaT cells stimulated by TNF-α and IFN-γ. The inhibitors showed that FA inhibits CCL17 and CCL22 production by deactivating the p38 MAPK and JNK pathways. After 2,4-dinitrochlorobenzene (DNCB) induction in mice with atopic dermatitis, FA effectively reduced the symptoms and serum levels of CCL17 and CCL22. In conclusion, topical FA attenuated AD via downregulation of CCL17 and CCL22, via inhibition of P38 MAPK and JNK phosphorylation, and FA is a potential therapeutic agent for AD.
... Molecules 2023, 28, 293 2 of 14 dendritic cells, and T cells, through the production of various inflammatory mediators, such as cytokines and chemokines. The stimulation of keratinocytes with tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) leads to the expression of pro-inflammatory cytokines, chemokines, and adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1), and these factors contribute to the infiltration of inflammatory cells into sites of inflammation in the skin [12]. ...
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Atopic dermatitis (AD) is a common chronic inflammatory skin disease. Bisdemethoxycurcumin (BDMC) is an ingredient from the rhizome of the traditional Chinese herbal medicine turmeric. BDMC has been reported to have important pharmacological properties, such as anti-inflammatory, antioxidant, antitumor and antiproliferative activities. However, its effect on atopic dermatitis has not been reported. The purpose of our study was to demonstrate the effectiveness of BDMC on TNF-α/IFNγ-stimulated HaCaT cells and on 2,4-dinitrochlorobenzene (DNCB)-induced AD mice. Our studies showed in vitro that BDMC was able to significantly inhibit the mRNA expression of chemokines and cytokines in TNF-α/IFN-γ-stimulated HaCaT cells and alleviate their inflammatory response. Our studies found in vivo that BDMC was able to significantly improve the symptoms of DNCB-induced AD skin lesions, decrease the number of scratches, ear thickness, and spleen index, improve inflammatory cells and mast cell infiltration and decrease skin thickness. Moreover, it was also able to inhibit the mRNA expression levels of chemokines and inflammatory cytokines and the activation of the MAPK and NF-κB signaling pathways. Thus, the results indicated that BDMC can improve atopic dermatitis in mice and that further clinical studies are warranted on its treatment of AD.
... Like several other plant extracts [14] [15], AEGL can be used for the treatment of inflammation as they have been proven to decrease IFN-γ activity. The down regulation of the expression of TNF-α/IFN-γ through the blockade of several pathways is associated with the inhibition of ERK1/2 phosphorylation [13] [16]. ...
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Background: The pathophysiology of the inflammatory process reveals intricate signaling which includes the IL-1β, IL-6, and TNFα pathways that could serve as drug targets. Aim: This study determined the effect of the aqueous extract of Gongronema latifolium (AEGL) leaves on the expression of IFNγ, IL-10, CD3, and CD56 in rabbits. Materials and Methods: ELISA tests were performed to determine the effect of the AEGL on the expression of a pro-inflammatory cytokine (IFNγ), an anti-inflammatory cytokine (IL-10), and CD3 and CD56 cell surface markers in rabbits. Twenty cross-bred male rabbits with an average weight range of 1.0 - 1.5 kg were selected. The rabbits were separated into four groups of four rabbits each treated as follows: Grp1 is the untreated control; Grp2 is the treated control; and Grp3, Grp4, and Grp5 were treated with 200, 400, and 600 mg/kg of AEGL respectively for 28 days. Results: The AEGL showed its greatest inhibitory effect in Group 4 on IL-10 (118.5 pg/ml), and IFNγ (332 pg/ml) on days 14 and 21 respectively. AEGL also showed the highest inhibition of CD3 expression on days 14 and 21 (0 pg/ml) in Group 3; and CD56 expression on day 21 (630.5 pg/ml) in Group 4. Conclusion: AEGL showed exhibited strong T cell mediated anti- inflammatory, and immunomodulatory activity in test rabbits within the 28-day period which can be confirmed by cell based assays. Specifically at 400 mg/kg, AEGL exhibited the greatest anti-inflammatory activity which is suggestive of its maximum effective dose. Keywords Inflammation, Cell Surface Markers, Antioxidant Activity, Cytokine, Hepatic Toxicity, Medicinal Plant, Gongronema latifolium
... 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.
... 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.
... 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.
... 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.
... 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.
... 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.
... The yeast contains protein which is responsible to produce fever by an inflammatory reaction, in addition to other pro-inflammatory cytokines in the brain, which is responsible for increasing body temperature including interleukin (IL-1β and IL-6), interferon (IFN-α), tumor necrosis factor (TNF-α), prostaglandins (PGE2 and PGI2) [38]. For the management of pyrexia, standard drug paracetamol is used to reduce the level of prostaglandins by inhibiting cyclooxygenase enzymes, which release antiinflammatory signals from the brain at the site of injury. ...
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The current investigation was designed to evaluate the analgesic, antipyretic, and anti-inflammatory effects of various extracts (methanol, ethanol, and aqueous) of dried fruit of Illicium verum hook.f, using 3 different doses (150, 250, and 350 mg/kg p.o) to verify the traditional uses of this spice. In the hot plate model of analgesia, ethanol extract showed a significant reduction in pain in a dose-dependent manner compared to the control group. The maximum effect was observed at 350 mg/kg dosage i.e., 16.90±0.17 s compared to the control group i.e., 5.03±0.05 s. The antipyretic activity was assessed in rats by Brewer’s yeast induction. The methanol and ethanol extracts produced a significant reduction in rectal temperature compared to the control group throughout the three doses. The maximum effect was observed at 350 mg/kg dosage of ethanol extract i.e., 37.1±0.8* compared to the control i.e., 39.1±0.3. In the paw edema model, methanol and ethanol extracts disclosed a significant reduction in paw edema at 350 mg/kg of dose. The maximum effect was observed at 350 mg/kg dosage of ethanol extract i.e., 0.25±0.23* compared to the control i.e., 0.97±0.4. In a behavioral study, locomotor activity (rearing) and exploratory activity (grooming) in mice was reduced significantly at higher doses (350 mg/kg p.o) involving the three extracts. However, scratching was increased non-significantly at all doses compared to the control group. This study concluded that various extracts of Illicium verum hook.f showed significant analgesic, antipyretic, and anti-inflammatory effects at different doses in a dose-dependent manner with varying potencies. The ethanol extract was found to be more potent among all, followed by methanol and aqueous extracts, whereas maximum effects were observed at 350 mg/kg of dose.
... 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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COVID-19 caused by the severe acute respiratory coronavirus 2 (SARS-CoV2) is likely to cause oxidative stress like other RNA viruses. The cytokine storm mechanism includes pulmonary alveolar membranes hyalinization, hyper-inflammation and lethal respiratory distress. Persons with diabetes, asthma and heart problems already have oxidative stress; viral infection increases stress and, thus contribute to COVID-19 severity. Traditional Indian spices will serve as boosters of energy and immunity and prepare the body for the prevention of infection and immunization. The spices which were included in this article are: Ginger (Zingiber officinale L.), Cumin (Cuminum cyminum L.), Cloves (Syzygium aromaticum L.), Black cumin (Nigella sativa L.), Bay leaves (Cinnamomum tamala (Buch.-Ham.) T. Nees and C. H. Eberm., Laurus nobilis L.), Fenugreek (Trigonella foenum-graecum L.), Asafoetida (Ferulaassa-foetida L.), Coriander (Coriandrum sativum L.), Nutmeg and Mace (Myristica fragrans Houtt.), Turmeric (Curcuma longa L.), Garlic (Allium Sativum L.), Allspice (Pimenta officinalis (L.) Merr.), Peppermint (Mentha × piperita L./Mentha balsamea Wild), Pepper (Capsicum frutescens L., Capsicum baccatum L., Capsicum annuum L.), Star anise (Illicium verum Hook. f.), Ajwain (Trachyspermum ammi (L.) Sprague ex Turrill), Black pepper (Piper nigrum L.), Cinnamon (Cinnamomum verum J.S. Presl.), Cardamom (Alpinia cardamomum (L.) Roxb.; Amomum cardamomum L.), Mustard (Brassica nigra (L.) Koch) and Fennel (Foeniculum vulgare Mill). The use of spices can help in decreasing the severity and help in the prevention of coronavirus infection. These spices contain polyphenols, flavonoids, saponins and alkaloids. The antioxidant, anti- inflammatory and immunomodulatory effects of spices can potentiate health functionality by acting on various pathological processes. The risks of coronavirus (COVID-19) can be mitigated with a special reference the respiratory health by the use of these spices every day, which strengthens the natural protection mechanism (immunity) of the body. Spices acting as immunity boosters not only helps to stay healthy from seasonal flu, but also possesses anti-viral properties to combat coronavirus. The Ministry of Ayush, Government of India also endorses these immunity boosting spices and their proper use. In this study, numerous conventional spices and their bioactive components and effects have been compiled and discussed to help improve our immune system and also play a key role in the battle against microbial infections, like COVID-19. This paper will help researchers and industries to recognize and analyze possible spices that can satisfy their interests for various applications, including the development of herbal/Ayurvedic antiviral drugs.
... 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.
... 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.
... 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.
... 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.
... 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.
... 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.
... 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.
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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.
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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.
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We investigated the protective effect of the bioactive compound eckol on inflammatory-related skin lesions in vitro. HaCaT cells were stimulated with tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) mixture, and treated with various concentration of eckol (25, 50, and 100 µg/ml). The expression of pro-inflammatory cytokines and chemokines were analyzed by enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR), respectively. Mitogen-activated protein kinase (MAPKs) and nuclear factor-kappa B (NF-κB) signaling pathways regulate immune and inflammation responses. Phosphorylation of MAPKs and NF-κB, indicating activation of respective signaling pathways, was examined by western blot analysis. Treatment of TNF-α and IFN-γ promoted the mRNA expression and production of pro-inflammatory cytokines and chemokines in HaCaT cells. However, eckol significantly suppressed the these mediators. Furthermore, activation of TNF-α/IFN-γ-induced MAPKs and NF-κB signaling pathway was inhibited by eckol treatment. Eckol also hampered the TNF-α/IFN-γ-mediated nuclear translocation of NF-κB p65 in HaCaT cells. Taken together, our findings demonstrate that eckol shows effective protective activity against TNF-α/IFN-γ-induced skin inflammation.
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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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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.
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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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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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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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Thymus and activation-regulated chemokine (TARC/CCL17) contributes not only to the recruitment of leukocytes, but is also involved in immune disorders, such as atopic dermatitis (AD) and bronchial asthma. We have previously reported that the levels of TARC were high in patients with AD and that lesional epidermis were strongly immunoreactive for TARC. In this paper, the effects of transforming growth factor (TGF)-β1 on the expression of TARC/CCL17 were examined in HaCaT cells, a human keratinocytes (KCs) cell line, co-stimulated with TNF-α and IFN-γ. We found that TGF-β1 down-regulated the TARC synthesis and secretion of HaCaT cells co-stimulated with TNF-α and IFN-γ in a dose-dependent manner. TGF-β1 at a concentration of 10ng/ml maximally inhibited this secretion. Northern blot analysis showed a similar inhibitory effect of TGF-β1 on TARC mRNA expression by HaCaT cells. The TGF-β1-induced down-regulation of TARC/CCL17 in HaCaT cells suggests that TGF-β1 might regulate the TARC-related inflammatory processes, which may be important for understanding the pathogenesis of allergic diseases.
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The various solvent fractions of star-anise (Illicium verum) and black caraway (Carum nigrum), along with their spice powders and volatile oils, were prepared and evaluated for antioxygenic activity, using different methods. Star-anise powder and its ethanol/water (80:20)-soluble fraction showed strong antioxygenic activity in refined sunflower oil while the petroleum ether fraction exhibited marginal antioxygenic activity and the water-soluble fraction was practically devoid of any activity in sunflower oil. The black caraway powder showed marginal antioxygenic activity while its ethanol/water fraction (80:20) showed strong antioxygenic activity and all other fractions showed slight pro-oxygenic activity in refined sunflower oil. Both the spice powders and their extracts were also evaluated for antioxidant activity by linoleic acid peroxidaton, β-carotene-linoleate and 1, 1-diphenyl-2-picryl hydrazyl (DPPH) methods. Both the star-anise and black caraway powders, as well as their ethanol/water extracts, exhibited strong antioxygenic activity. Volatile oils from both the spices exhibited antioxygenic activity and the activity did not seem to be concentration-dependent. Volatile oils from star-anise showed relatively higher antioxygenic activity than did those from black caraway. Gas chromatography–mass spectroscopy (GC–MS) studies on star-anise and black caraway volatile oils resulted in the identification of 25 and 22 compounds, respectively, representing 94–97% of the total content.
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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.
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The fruit of Illicium verum Hook. f. (Chinese star anise) has long been used in traditional Chinese medicine and food industry with the actions of dispelling cold, regulating the flow of Qi and relieving pain. A bibliographic investigation was carried out by analyzing recognized books including Chinese herbal classic, and worldwide accepted scientific databases (Pubmed, SciFinder, Scopus and Web of Science) were searched for the available information on I. verum. I. verum is an aromatic evergreen tree of the family Illiciaceae. It is sometimes contaminated with highly toxic Japanese star anise (I. anisatum L.) and poisonous star anise (I. lanceolatum A. C. Smith), which contain several neurotoxic sesquiterpenes. Traditional uses of I. verum are recorded throughout Asia and Northern America, where it has been used for more than 10 types of disorders. Numerous compounds including volatiles, seco-prezizaane-type sesquiterpenes, phenylpropanoids, lignans, flavonoids and other constituents have been identified from I. verum. Modern pharmacology studies demonstrated that its crude extracts and active compounds possess wide pharmacological actions, especially in antimicrobial, antioxidant, insecticidal, analgesic, sedative and convulsive activities. In addition, it is the major source of shikimic acid, a primary ingredient in the antiflu drug (Tamiflu). This review summarizes the up-to-date and comprehensive information concerning the botany, traditional use, phytochemistry and pharmacology of I. verum together with the toxicology, and discusses the possible trend and scope for future research of I. verum.
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Cinnamomum cassia (C. cassia) has been traditionally used to treat allergic disease as well as dyspepsia, gastritis, and blood circulation disturbances. However, the antiallergic properties of C. cassia have not been fully verified using scientific tools. This study investigated the effectiveness of C. cassia extract (CCE) as an antiallergic agent in atopic dermatitis model and underlying mechanism. The effect of CCE on mite antigen-treated NC/Nga mice was evaluated by examining skin symptom severity, levels of serum IgE, tumor necrosis factor-α (TNF-α), and histamine, skin histology, and mRNA expression of cytokines in the skin lesions. Moreover, the effect of CCE on TNF-α-and interferon-γ (IFN-γ)-induced chemokine production in human keratinocytes was investigated using ELISA. CCE treatment of NC/Nga mice reduced the dermatitis score and the levels of serum IgE, histamine, and TNF-α. Histological examination showed inhibition of the thickening of the epidermis/dermis and reduced dermal infiltration of inflammatory cells. In skin lesions, mRNA expression of IL-4, TNF-α, and thymus and activation-regulated chemokine (TARC) was inhibited by CCE treatment. The production of TARC, macrophage-derived chemokine, and RANTES from IFN-γ-and TNF-α-stimulated human keratinocytes was suppressed by CCE treatment in a dose-dependent manner. CCE inhibits the development of atopic dermatitis-like skin lesions in NC/Nga mice by suppressing the T-helper 2 cell response.