The Protective Effects of 18β-Glycyrrhetinic Acid on Imiquimod-Induced Psoriasis in Mice via Suppression of mTOR/STAT3 Signaling

Psoriasis is recognized as an autoimmune and inflammatory dermatosis, which is estimated to affect 2-3% of the population worldwide. 18β-Glycyrrhetinic acid (GA), one of the main ingredients of Licorice (Glycyrrhiza glabra L.), has been shown to have numerous pharmacological effects such as antioxidative, antitumor, and anti-inflammatory activities. However, it remains to be explored whether GA has antipsoriatic effect on psoriasis. In this study, we evaluated the protective effect of GA on psoriasis and its mechanisms of action in imiquimod-induced psoriasis-like mouse model. Results indicated that GA dramatically improved psoriatic lesions and reduced psoriasis area and severity index scores. GA also suppressed the mRNA levels of IL-6, TNF-α, IL-17, IL-23, and IL-1β in the skin and increased the proportion of CD4+ Foxp3+ regulatory T cells (Tregs) in both lymph nodes and spleens. Its anti-inflammatory and immunomodulatory activities may be related to its suppression of the STAT3 and mTOR signaling. In conclusion, GA ameliorated the symptoms of psoriasis, at least in part, through inhibition of inflammatory cytokines and STAT3/mTOR signaling and activation of Tregs in both lymph nodes and spleens. These effects are expected to be beneficial in the treatment and prevention of psoriasis.

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The protective effects of 18β-glycyrrhetinic acid against inflammation microenvironment in gastric tumorigenesis targeting PGE2-EP2 receptor-mediated arachidonic acid pathway

European Journal of Inflammation ◽

10.1177/2058739218762993 ◽

2018 ◽

Vol 16 ◽

pp. 205873921876299 ◽

Cited By ~ 4

Author(s):

Donghui Cao ◽

Jing Jiang ◽

Dan Zhao ◽

Menghui Wu ◽

Houjun Zhang ◽

...

Keyword(s):

Arachidonic Acid ◽

Glycyrrhetinic Acid ◽

Prostaglandin E ◽

Protective Effects ◽

Cox 2 ◽

Anti Inflammatory ◽

Acid Pathway ◽

Ep2 Receptor ◽

Arachidonic Acid Pathway

Accumulating epidemiological and clinical evidence shows that inflammation is an important risk factor for gastrointestinal diseases. Glycyrrhiza glabra, a traditional Chinese medicine, has been shown to safely suppress gastric cancer; however, the anti-inflammatory mechanisms in gastric tumorigenesis have been poorly investigated. Therefore, this study is committed to demonstrate the in vivo anti-inflammatory effect of 18β-glycyrrhetinic acid (GRA), the main active component of G. glabra. The lymphocytes and macrophages were heavily infiltrated in the transgenic mice that highly expressed cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase (mPGES)-1; however, a significant reduction was observed after treatment with GRA. In addition, GRA downregulated the protein levels of COX-2, GαS, EP2, and β-catenin, which were involved in the arachidonic acid pathway. In conclusion, our study showed the potential protective effects of GRA against inflammatory environment that might be involved in gastric tumorigenesis in vivo through the PGE2-EP2 receptor-mediated arachidonic acid pathway.

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Metformin ameliorates scleroderma via inhibiting Th17 cells and reducing mTOR-STAT3 signaling in skin fibroblasts

Journal of Translational Medicine ◽

10.1186/s12967-021-02860-z ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Jeonghyeon Moon ◽

Seon-yeong Lee ◽

Jeong Won Choi ◽

A Ram Lee ◽

Jin Hee Yoo ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Th17 Cells ◽

Skin Fibroblasts ◽

Inflammatory Factors ◽

Metformin Treatment ◽

Protective Effects ◽

Stat3 Signaling ◽

Tnf Α ◽

Anti Inflammatory ◽

Pro Inflammatory Cytokines

AbstractScleroderma is an autoimmune disease that causes dermal fibrosis. It occurs when collagen accumulates in tissue as a result of persistent inflammation. Th17 cells and pro-inflammatory cytokines such as IL-1β, IL-6, IL-17, and TNF-α play important roles in the pathogenesis of scleroderma. Because metformin, a medication used to treat diabetes, has effective immunoregulatory functions, we investigated its therapeutic function in scleroderma. Mice in a model of bleomycin-induced scleroderma were treated with metformin for 2 weeks. Histological assessment demonstrated protective effects of metformin against scleroderma. Metformin decreased the expression of pro-inflammatory factors in dermal tissue and lymphocytes. It also decreased mRNA expression of pro-inflammatory cytokines (IL-1β, IL-6, IL-17, and TNF-α) and fibrosis-inducing molecules both in vivo and in vitro. These results suggest that metformin treatment has anti-inflammatory effects on lymphocytes via the inhibition of IL-17 and cytokines related to Th17 differentiation, such as IL-1β, IL-6, and TNF-α. To investigate how metformin modulates the inflammatory process in skin fibroblasts, we measured mTOR-STAT3 signaling in skin fibroblasts and found that phosphorylated mTOR and phosphorylated STAT3 protein expression were decreased by metformin treatment. These results suggest that metformin has potential to treat scleroderma by inhibiting pro-inflammatory cytokines and anti-inflammatory activity mediated by mTOR-STAT3 signaling.

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Attenuation of Proinflammatory Responses byS-[6]-Gingerol via Inhibition of ROS/NF-Kappa B/COX2 Activation in HuH7 Cells

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/146142 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 23

Author(s):

Xiao-Hong Li ◽

Kristine C. Y. McGrath ◽

Van H. Tran ◽

Yi-Ming Li ◽

Colin C. Duke ◽

...

Keyword(s):

Ros Generation ◽

Inflammatory Factor ◽

Mrna Levels ◽

Protective Effects ◽

Nf Kappa B ◽

Huh7 Cells ◽

Proinflammatory Responses ◽

Ros Scavenger ◽

Anti Inflammatory

Introduction. Hepatic inflammation underlies the pathogenesis of chronic diseases such as insulin resistance and type 2 diabetes mellitus.S-[6]-Gingerol has been shown to have anti-inflammatory properties. Important inflammatory mediators of interleukins include nuclear factorκB (NFκB) and cyclooxygenase 2 (COX2). We now explore the mechanism of anti-inflammatory effects ofS-[6]-gingerol in liver cells.Methods. HuH7 cells were stimulated with IL1βto establish anin vitrohepatic inflammatory model.Results.S-[6]-Gingerol attenuated IL1β-induced inflammation and oxidative stress in HuH7 cells, as evidenced by decreasing mRNA levels of inflammatory factor IL6, IL8, and SAA1, suppression of ROS generation, and increasing mRNA levels of DHCR24. In addition,S-[6]-gingerol reduced IL1β-induced COX2 upregulation as well as NFκB activity. Similar to the protective effects ofS-[6]-gingerol, both NS-398 (a selective COX2 inhibitor) and PDTC (a selective NFκB inhibitor) suppressed mRNA levels of IL6, IL8, and SAA1. Importantly, PDTC attenuated IL1β-induced overexpression of COX2. Of particular note, the protective effect ofS-[6]-gingerol against the IL1β-induced inflammatory response was similar to that of BHT, an ROS scavenger.Conclusions. The findings of this study demonstrate thatS-[6]-gingerol protects HuH7 cells against IL1β-induced inflammatory insults through inhibition of the ROS/NFκB/COX2 pathway.

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Metformin Ameliorates Scleroderma Via Inhibiting Th17 Cells and Reducing mTOR-STAT3 Signaling in Skin Fibroblasts

10.21203/rs.3.rs-139863/v1 ◽

2021 ◽

Author(s):

Jeonghyeon Moon ◽

Seon-yeong Lee ◽

Jeong Won Choi ◽

Aram Lee ◽

Jin Hee Yoo ◽

...

Keyword(s):

Inflammatory Cytokines ◽

Th17 Cells ◽

Skin Fibroblasts ◽

Inflammatory Factors ◽

Metformin Treatment ◽

Protective Effects ◽

Stat3 Signaling ◽

Tnf Α ◽

Anti Inflammatory ◽

Pro Inflammatory Cytokines

Abstract Scleroderma is an autoimmune disease that causes dermal fibrosis. It occurs when collagen accumulates in tissue as a result of persistent inflammation. Th17 cells and pro-inflammatory cytokines such as IL-1β, IL-6, IL-17, and TNF-α play important roles in the pathogenesis of scleroderma. Because metformin, a medication used to treat diabetes, has effective immunoregulatory functions, we investigated its therapeutic function in scleroderma. Mice in a model of bleomycin-induced scleroderma were treated with metformin for 2 weeks. Histological assessment demonstrated protective effects of metformin against scleroderma. Metformin decreased the expression of pro-inflammatory factors in dermal tissue and lymphocytes. It also decreased mRNA expression of pro-inflammatory cytokines (IL-1β, IL-6, IL-17, and TNF-α) and fibrosis-inducing molecules both in vivo and in vitro. These results suggest that metformin treatment has anti-inflammatory effects on lymphocytes via the inhibition of IL-17 and cytokines related to Th17 differentiation, such as IL-1β, IL-6, and TNF-α. To investigate how metformin modulates the inflammatory process in skin fibroblasts, we measured mTOR-STAT3 signaling in skin fibroblasts and found that mTOR and STAT3 protein expression were decreased by metformin treatment. These results suggest that metformin has potential to treat scleroderma by inhibiting pro-inflammatory cytokines and anti-inflammatory activity mediated by mTOR-STAT3 signaling.

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The protective effects of Fuzhengzhiyanghefuzhiyang decoction (FZHFZY) on imiquimod-induced psoriasis in mice through suppression of P38/Erk/NF-κB signaling

10.21203/rs.3.rs-342314/v1 ◽

2021 ◽

Author(s):

Haiming Chen ◽

Yue Lu ◽

Bin Tang ◽

Xiong Li ◽

Hongyu Zhang ◽

...

Keyword(s):

Mechanism Of Action ◽

Severity Index ◽

Raw264.7 Cells ◽

Mrna Levels ◽

Protective Effects ◽

Mice Model ◽

Raw264.7 Macrophages ◽

Tnf Α

Abstract Background Psoriasis is a chronic immune-mediated skin disease affecting approximately 2–3% of world's population. Fuzhenghefuzhiyang decoction (FZHFZY), a Chinese medicine formula created by Prof. Lu Chuanjian, has been shown to have remarkable anti-psoriasis effect in clinical practice. However, the mechanism of action of FZHFZY is unknown. The purpose of this study was to investigate the protective effects of FZHFZY in psoriasis-like skin inflammation both in vitro and in vivo and elucidate the mechanism of action of FZHFZY. Methods In vivo study, we evaluated the protective effect of FZHFZY in imiquimod-induced psoriasis-like mice model. Results indicated that FZHFZY can obviously decrease psoriasis area and severity index (PASI) scores. FZHFZY also suppressed the mRNA levels of IL-6, TNF-α, IL-23 and IL-8 in the skin and its anti-inflammatory activity may be related to its suppression of the P38/Erk/NF-κB signaling. In addition, immunohistochemistry (IHC) data showed that FZHFZY can suppress the expression of F4/80 which is the marker of macrophages in the psoriasis skin. Therefore, we designed to investigate the roles and underlying mechanisms of FZHFZY in LPS-stimulated RAW264.7 macrophages in vitro. Results Our results revealed FZHFZY treatment could significantly inhibit inflammation by modulating the expression of mediators, such as IL-6, TNF-α, IL-23 and IL-8, which expression was increased remarkably in the activated RAW264.7 cells. Our results also showed that FZHFZY inhibited the P38/Erk/NF-κB signaling pathways in RAW264.7 cells induced by LPS. Conclusions Taken together, our present study demonstrates that FZHFZY alleviated inflammatory response by suppressing the P38/Erk/NF-κB signaling in imiquimod-induced psoriasis-like mice model and LPS-stimulated RAW264.7.

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Anti-Inflammatory and Barrier-Protective Effects of Berberine

Zeitschrift für Gastroenterologie ◽

10.1055/s-0031-1304768 ◽

2011 ◽

Vol 49 (10) ◽

Author(s):

Lena John ◽

Anja Fromm ◽

Michael Fromm ◽

Jörg-Dieter Schulzke ◽

Maren Amasheh

Keyword(s):

Protective Effects ◽

Anti Inflammatory

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Red wine extract, resveratrol, on maintenance of organ function following trauma-hemorrhage

Functional Foods in Health and Disease ◽

10.31989/ffhd.v2i10.76 ◽

2012 ◽

Vol 2 (10) ◽

pp. 351

Author(s):

Fu-Chao Liu ◽

Huang-Ping Yu

Keyword(s):

Intracellular Signaling ◽

Red Wine ◽

Antioxidant Properties ◽

Neutrophil Function ◽

Protective Effects ◽

Organ Function ◽

Mitogen Activated Protein ◽

Ros Formation ◽

Anti Inflammatory ◽

And Control

Resveratrol, is a polyphenol that can be extracted from grapes and red wine, possess potential anti-inflammatory effects, which would result in the reduction of cytokine production, the alteration of the expression of adhesion molecule molecules, and the inhibition of neutrophil function. Resveratrol might also act as an antioxidant, anti-aging, and control of cell cycle and apoptosis. Resveratrol has been shown to have protective effects for patients in shock-like states. Such protective phenomenon is reported to be implicated in a variety of intracellular signaling pathways including the regulation of the mitogen-activated protein kinases (MAPK)/ hemeoxygenase-1 (HO-1) pathway, activates estrogen receptor (ER), and the mediation of pro-inflammatory cytokines, reactive oxygen species (ROS) formation and reactive. Moreover, through anti-inflammatory effects and antioxidant properties, the resveratrol is believed to maintain organ function following trauma-hemorrhage.Key words: resveratrol, anti-inflammatory, trauma-hemorrhage.

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Protective Effect of Psoralea corylifolia L. Seed Extract against Palmitate-Induced Neuronal Apoptosis in PC12 Cells

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/5410419 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 3

Author(s):

Yunkyoung Lee ◽

Hee-Sook Jun ◽

Yoon Sin Oh

Keyword(s):

Pc12 Cells ◽

Molecular Mechanisms ◽

Neuronal Cell ◽

Marker Genes ◽

Heme Oxygenase 1 ◽

Mrna Levels ◽

Protective Effects ◽

Psoralea Corylifolia ◽

Antioxidant Genes ◽

Bax Protein

The extract of Psoralea corylifolia seeds (PCE) has been widely used as a herbal medicine because of its beneficial effect on human health. In this study, we investigated the protective effects and molecular mechanisms of PCE on palmitate- (PA-) induced toxicity in PC12 cells, a neuron-like cell line. PCE significantly increased cell viability in PA-treated PC12 cells and showed antiapoptotic effects, as evidenced by decreased expression of cleaved caspase-3, cleaved poly(ADP-ribose) polymerase, and bax protein as well as increased expression of bcl-2 protein. In addition, PCE treatment reduced PA-induced reactive oxygen species production and upregulated mRNA levels of antioxidant genes such as nuclear factor (erythroid-derived 2)-like 2 and heme oxygenase 1. Moreover, PCE treatment recovered the expression of autophagy marker genes such as beclin-1 and p62, which was decreased by PA treatment. Treatment with isopsoralen, one of the major components of PCE extract, also recovered the expression of autophagy marker genes and reduced PA-induced apoptosis. In conclusion, PCE exerts protective effects against lipotoxicity via its antioxidant function, and this effect is mediated by activation of autophagy. PCE might be a potential pharmacological agent to protect against neuronal cell injury caused by oxidative stress or lipotoxicity.

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Structural Characterization and Assessment of Anti-Inflammatory and Anti-Tyrosinase Activities of Polyphenols from Melastoma normale

Molecules ◽

10.3390/molecules26133913 ◽

2021 ◽

Vol 26 (13) ◽

pp. 3913

Author(s):

Rui-Jie He ◽

Jun Li ◽

Yong-Lin Huang ◽

Ya-Feng Wang ◽

Bing-Yuan Yang ◽

...

Keyword(s):

Enzyme Inhibitors ◽

Enzyme Inhibitor ◽

Structure Identification ◽

No Production ◽

Protective Effects ◽

Successful Isolation ◽

Ic50 Values ◽

Development And Utilization ◽

Inhibitory Activities ◽

Anti Inflammatory

Polyphenols, widely distributed in the genus Melastoma plants, possess extensive cellular protective effects such as anti-inflammatory, anti-tyrosinase, and anti-obesity, which makes it a potential anti-inflammatory drug or enzyme inhibitor. Therefore, the aim of this study is to screen for the anti-inflammatory and enzyme inhibitory activities of compounds from title plant. Using silica gel, MCI, ODS C18, and Sephadex LH-20 column chromatography, as well as semipreparative HPLC, the extract of Melastoma normale roots was separated. Four new ellagitannins, Whiskey tannin C (1), 1-O-(4-methoxygalloyl)-6-O-galloyl-2,3-O-(S)-hexahydroxydiphenoyl-β-d-glucose (2), 1-O-galloyl-6-O-(3-methoxygalloyl)-2,3-O-(S)-hexahydroxydiphenoyl-β-d-glucose (3), and 1-O-galloyl-6-O-vanilloyl-2,3-O-(S)-hexahydroxydiphenoyl-β-d-glucose (4), along with eight known polyphenols were firstly obtained from this plant. The structures of all isolates were elucidated by HRMS, NMR, and CD analyses. Using lipopolysaccharide (LPS)-stimulated RAW2 64.7 cells, we investigated the anti-inflammatory activities of compounds 1–4, unfortunately, none of them exhibit inhibit nitric oxide (NO) production, their IC50 values are all > 50 μM. Anti-tyrosinase activity assays was done by tyrosinase inhibition activity screening model. Compound 1 showed weak tyrosinase inhibitory activity with IC50 values of 426.02 ± 11.31 μM. Compounds 2–4 displayed moderate tyrosinase inhibitory activities with IC50 values in the range of 124.74 ± 3.12–241.41 ± 6.23 μM. The structure–activity relationships indicate that hydroxylation at C-3′, C-4′, and C-3 in the flavones were key to their anti-tyrosinase activities. The successful isolation and structure identification of ellagitannin provide materials for the screening of anti-inflammatory drugs and enzyme inhibitors, and also contribute to the development and utilization of M. normale.

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Comparing the protective effects of resveratrol, curcumin and sulforaphane against LPS/IFN-γ-mediated inflammation in doxorubicin-treated macrophages

Scientific Reports ◽

10.1038/s41598-020-80804-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Haidy A. Saleh ◽

Eman Ramdan ◽

Mohey M. Elmazar ◽

Hassan M. E. Azzazy ◽

Anwar Abdelnaser

Keyword(s):

Nitric Oxide ◽

Inflammatory Response ◽

Raw 264.7 Cells ◽

Inos Mrna ◽

No Production ◽

Raw 264.7 ◽

Mrna Levels ◽

Protective Effects ◽

Tnf Α ◽

Ifn Γ

AbstractDoxorubicin (DOX) chemotherapy is associated with the release of inflammatory cytokines from macrophages. This has been suggested to be, in part, due to DOX-mediated leakage of endotoxins from gut microflora, which activate Toll-like receptor 4 (TLR4) signaling in macrophages, causing severe inflammation. However, the direct function of DOX on macrophages is still unknown. In the present study, we tested the hypothesis that DOX alone is incapable of stimulating inflammatory response in macrophages. Then, we compared the anti-inflammatory effects of curcumin (CUR), resveratrol (RES) and sulforaphane (SFN) against lipopolysaccharide/interferon-gamma (LPS/IFN-γ)-mediated inflammation in the absence or presence of DOX. For this purpose, RAW 264.7 cells were stimulated with LPS/IFN-γ (10 ng/mL/10 U/mL) in the absence or presence of DOX (0.1 µM). Our results showed that DOX alone is incapable of stimulating an inflammatory response in RAW 264.7 macrophages. Furthermore, after 24 h of incubation with LPS/IFN-γ, a significant increase in tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and inducible nitric oxide synthase (iNOS) mRNA levels was observed. Similarly, nitric oxide (NO) production and TNF-α and IL-6 protein levels were significantly upregulated. Moreover, in LPS/IFN-γ-treated macrophages, the microRNAs (miRNAs) miR-146a, miR-155, and miR-21 were significantly overexpressed. Interestingly, upon testing CUR, RES, and SFN against LPS/IFN-γ-mediated inflammation, only SFN was able to significantly reverse the LPS/IFN-γ-mediated induction of iNOS, TNF-α and IL-6 and attenuate miR-146a and miR-155 levels. In conclusion, SFN, at the transcriptional and posttranscriptional levels, exhibits potent immunomodulatory action against LPS/IFN-γ-stimulated macrophages, which may indicate SFN as a potential treatment for DOX-associated inflammation.

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