Anti-inflammatory Effects of Achillea millefolium on Atopic Dermatitis-Like Skin Lesions in NC/Nga Mice

2020 ◽  
Vol 48 (05) ◽  
pp. 1121-1140
Author(s):  
Hien T.T. Ngo ◽  
Eunson Hwang ◽  
Hyungoo Kang ◽  
Bom Park ◽  
Seul A. Seo ◽  
...  

Achillea millefolium L. (AM) is an aromatic herb with a variety of pharmacological properties, such as anti-inflammatory and anti-allergic activities. However, AM’s effects on atopic dermatitis (AD) have not been investigated. This study evaluates the anti-AD activity of 50% ethanol-extracted AM in murine macrophage Raw 264.7 cells, in tumor necrosis factor-alpha/interferon-gamma (TNF-[Formula: see text]/IFN-[Formula: see text])-stimulated human immortal keratinocyte HaCaT cells in vitro, and in Biostir-AD-treated NC/Nga mice in vivo. The results showed that AM significantly downregulated expression of pro-inflammatory cytokines, such as INOS, COX-2, and interleukin (IL)-6 in lipopolysaccharide (LPS)-treated Raw 264.7 cells. The mRNA expressions of INOS, COX-2, and IL-6 decreased by 76.1%, 69.3%, and 31.8%, respectively. Overexpression of chemokines, such as activation-regulated chemokine and macrophage-derived chemokine, regulated on activation of normal T-cell expressed and secreted, and IL-8 was inhibited by 70.01%, 52.91%, 73.53%, and 18.93%, respectively, in TNF-[Formula: see text]/IFN-[Formula: see text]-stimulated HaCaT cells by downregulating the mitogen-activated protein kinase, I[Formula: see text]B[Formula: see text], and the signal transducer and activator of transcription 1 signaling pathways. AD-like symptoms, such as elevated serum immunoglobin E levels, epidermal thickening, high dermatitis severity score, transepidermal water loss, and reduced skin hydration, were relieved by the dietary administration of AM in Biostir-AD-treated NC/Nga mice. In addition, filaggrin expression increased significantly in AM-treated groups. These results suggest that AM could be a useful candidate for AD treatment.

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1941
Author(s):  
So-Yeon Kim ◽  
Sang-Deok Han ◽  
Minju Kim ◽  
Tamanna Jahan Mony ◽  
Eun-Seok Lee ◽  
...  

The mechanism of atopic dermatitis (AD) is modulated by the release of cytokines and chemokines through the mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-κB) signaling pathway. Topical steroids are used to treat AD, but some people need safer anti-inflammatory drugs to avoid side effects. Mentha arvensis has been used as a herbal plant with medicinal properties, but its anti-inflammatory effects have not been elucidated in an AD model. In this study, we investigated the anti-inflammatory effects of M. arvensis essential oil (MAEO) and its underlying molecular mechanism in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and HaCaT cells (human epidermal keratinocyte). Additionally, we examined the ameliorating effects of the MAEO in a dinitrochlorobenzene (DNCB)-induced murine model of AD. We found, in both RAW 264.7 cells and HaCaT cells, MAEO inhibited LPS-stimulated inflammatory mediators such as nitric oxide (NO) and prostaglandin E2 and proinflammatory cytokines, including IL-1β and IL-6, due to the suppression of COX-2 and iNOS expression. In LPS-stimulated macrophages, we also observed that MAEO inhibited the phosphorylation of ERK and P65. Furthermore, MAEO treatment attenuated AD symptoms, including the dermatitis score, ear thickness, epidermal thickness and infiltration of mast cells, in a DNCB-induced animal model of AD. Overall, our findings suggest that MAEO exerts anti-inflammatory and anti-atopic dermatitis effects via inhibition of the ERK/NF-κB signaling pathway.


2020 ◽  
Vol 48 (08) ◽  
pp. 1875-1893
Author(s):  
Da-Sol Kim ◽  
Kyoung-Eun Park ◽  
Yeon-Ju Kwak ◽  
Moon-Kyoung Bae ◽  
Soo-Kyung Bae ◽  
...  

Inflammation regulation is essential for maintaining healthy functions and normal homeostasis of the body. Porphyromonas gingivalis (P. gingivalis) is a gram-negative anaerobic bacterium and a major pathogen that causes oral inflammation and other systemic inflammations. This study aims to examine the anti-inflammatory effects of Agrimonia pilosa Ledeb root extracts (APL-ME) in Porphyromonas gingivalis LPS-induced RAW 264.7 cells and find anti-inflammatory effect compounds of APL-ME. The anti-inflammatory effects of APL-ME were evaluated anti-oxidant activity, cell viability, nitrite concentration, pro-inflammatory cytokines (interleukin-1[Formula: see text], interleukin-6, tumor necrosis factor (TNF)-[Formula: see text], and anti-inflammatory cytokine (interleukin-10 (IL-10)). Also, Inflammation related genes and proteins, cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), expression were decreased by APL-ME and mitogen-activated protein kinase (MAPK) signaling proteins expression was regulated by APL-ME. Liquid chromatography-mass spectrometer (LC/MS)-MS analysis results indicated that several components were detected in APL-ME. Our study indicated that APL-ME suppressed nitrite concentrations, pro-inflammatory cytokines such as IL-1[Formula: see text], IL-6 and TNF-[Formula: see text] in P. gingivalis LPS induced RAW 264.7 cells. However, IL-10 expression was increased by ALP-ME. In addition, protein expressions of COX-2 and iNOS were inhibited APL-ME extracts dose-dependently. According to these results, APL-ME has anti-inflammatory effects in P. gingivalis LPS induced RAW 264.7 cells.


2012 ◽  
Vol 40 (04) ◽  
pp. 813-831 ◽  
Author(s):  
You-Chang Oh ◽  
Won-Kyung Cho ◽  
Yun Hee Jeong ◽  
Ga Young Im ◽  
Min Cheol Yang ◽  
...  

Sipjeondaebotang (SJ) has been used as a traditional drug in east-Asian countries. In this study, to provide insight into the biological effects of SJ and SJ fermented by Lactobacillus, we investigated their effects on lipopolysaccharide (LPS)-mediated inflammation in macrophages. The investigation was focused on whether SJ and fermented SJ could inhibit the production of pro-inflammatory mediators such as prostaglandin (PG) E2 and nitric oxide (NO) as well as the expressions of cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB in LPS-stimulated RAW 264.7 cells. We found that SJ modestly inhibited LPS-induced PGE2, NO and TNF-α production as well as the expressions of COX-2 and iNOS. Interestingly, fermentation significantly increased its inhibitory effect on the expression of all pro-inflammatory mediators. Furthermore, fermented SJ exhibited increased inhibition of p38 MAPK and c-Jun NH2-terminal kinase (JNK) MAPK phosphorylation as well as NF-κB p65 translocation by reduced IκBα degradation compared with either untreated controls or unfermented SJ. High performance liquid chromatography (HPLC) analysis showed fermentation by Lactobacillus increases liquiritigenin and cinnamyl alcohol contained in SJ, which are known for their anti-inflammatory activities. Finally, SJ fermented by Lactobacillus exerted potent anti-inflammatory activity by inhibiting MAPK and NF-κB signaling in RAW 264.7 cells.


2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Hoyoung Lee ◽  
Jun Kyoung Lee ◽  
Hyekyung Ha ◽  
Mee-Young Lee ◽  
Chang-Seob Seo ◽  
...  

We examined whether Angelicae Dahuricae Radix (AR) suppresses the development of atopic dermatitis (AD)-like skin lesions induced byDermatophagoides farinaein NC/Nga mice. To investigate the effect of AR, we measured the AD severity score, measured plasma levels of IgE and histamine, and performed histological analysis in NC/Nga mice. We also confirmed the anti-inflammatory effects of AR by measuring TARC/CCL17 production from LPS-treated RAW 264.7 cells and mRNA levels of TARC and MDC/CCL22 in TNF-α/IFN-γ-treated HaCaT cells. 10 mg/day of AR extract was applied for 4 weeks to NC/Nga mice. Both the AR extract and 0.1% tacrolimus suppressed the development of AD-like skin lesions and reduced dermatitis scores of the back and ear skin. AR extracts caused an inhibition of histological changes induced by repeated application ofD. farinaeand a reduction of IgE and histamine levels in plasma (P<0.05). Furthermore, NO production in LPS-treated RAW 264.7 cells was diminished in a dose-dependent manner, and hTARC production and TARC and MDC mRNA levels in TNF-α/IFN-γ-treated HaCaT cells were diminished by AR. The inhibitory effect of AR on NO, TARC and MDC production may be associated with the suppression of AD-like skin lesions inD. farinae-induced NC/Nga mice.


2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Gyeong-Eun Hong ◽  
Jin-A. Kim ◽  
Arulkumar Nagappan ◽  
Silvia Yumnam ◽  
Ho-Jeong Lee ◽  
...  

Scutellaria baicalensisGeorgi has been used as traditional medicine for treating inflammatory diseases, hepatitis, tumors, and diarrhea in Asia. Hence, we investigated the anti-inflammatory effect and determined the molecular mechanism of action of flavonoids isolated from KoreanS. baicalensisG. in lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophages. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to examine cytotoxicity of the flavonoids at various concentrations of 10, 40, 70, and 100 µg/mL. No cytotoxicity was observed in RAW 264.7 cells at these concentrations. Furthermore, the flavonoids decreased production of inflammatory mediators such as inducible nitric oxide synthase, cyclooxygenase-2, interleukin-6, and tumor necrosis factor-alpha and inhibited phosphorylation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) in LPS-induced RAW 264.7 cells. Moreover, to identify the differentially expressed proteins in RAW 264.7 cells of the control, LPS-treated, and flavonoid-treated groups, two-dimensional gel electrophoresis and mass spectrometry were conducted. The identified proteins were involved in the inflammatory response and included PRKA anchor protein and heat shock protein 70 kD. These findings suggest that the flavonoids isolated fromS. baicalensisG. might have anti-inflammatory effects that regulate the expression of inflammatory mediators by inhibiting the NF-κB signaling pathway via the MAPK signaling pathway in RAW 264.7 cells.


2021 ◽  
Author(s):  
MA Sunil ◽  
vasudevan Sunitha ◽  
Prasanthkumar Santhakumaran ◽  
Mohind C. Mohan ◽  
Midhun Sebastian Jose ◽  
...  

Abstract Catechin, a flavonol belonging to the flavonoid group of polyphenols is present in many plant foods. The present study was done to evaluate the effect of catechin on various inflammatory mediators using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The effect of catechin on total cyclooxygenase (COX) activity, 5-lipoxygenase (5-LOX), myeloperoxidase, nitrite and inducible nitric oxide synthase (iNOS) level, secretion of tumour necrosis factor-α (TNF-α) and interleukin-10 (IL-10) were assessed in LPS-stimulated RAW 264.7 cells. The expression of COX-2, iNOS, TNF-α, nuclear factor-ĸB (NF-κB) and p38 mitogen-activated protein kinase (MAPK) genes were also investigated. The effect was further analyzed using human PBMCs by assessing the level of TNF-α and IL-10. The study demonstrated that the inflammatory mediators such as COX, 5-LOX, nitrite, iNOS, and TNF-α were significantly inhibited by catechin in a dose-dependent manner whereas IL-10 production was up-regulated in RAW 264.7 cells. Moreover, catechin down-regulated the mRNA level expression of COX-2, iNOS, TNF-α, NF-κB and p38 MAPK. The current study ratifies the beneficial effect of catechin as a dietary component in plant foods to provide protection against inflammatory diseases.


Marine Drugs ◽  
2020 ◽  
Vol 18 (10) ◽  
pp. 487
Author(s):  
Li-Wei Chen ◽  
Hsuan-Lien Chung ◽  
Ching-Chiung Wang ◽  
Jui-Hsin Su ◽  
Yu-Ju Chen ◽  
...  

Acne is a skin disease common in adolescents and increasingly common in the adult population. The major pathologic events of acne vulgaris include increased sebum production, retention hyperkeratosis, carrying commensal skin microbiota, and inflammation. In recent years, more than 10,000 compounds have been isolated and identified from marine organisms. The aim of this study was to discover the potential anti-acne activity of fraction 9 + 10 (SF-E) of Sinularia flexibilis extract and six cembrene diterpenoids. We found that the SF-E significantly reduced Cutibacterium acnes-induced edema in Wistar rat ears. The cembrene diterpenoids including 11-dehydrosinulariolide (SC-2), 3,4:8,11-bisepoxy-7-acetoxycembra-15(17)-en-1,12-olide (SC-7), and sinularin (SC-9) reduced nitric oxide (NO) production with 50% inhibitory concentration of 5.66 ± 0.19, 15.25 ± 0.25, and 3.85 ± 0.25 μM, respectively, and inducible NO synthase expression in RAW 264.7 cells. Moreover, treatment with SC-2, SC-7, and SC-9 significantly suppressed lipopolysaccharide- and heat-killed C. acnes-induced expression of proteins involved in mitogen-activated protein kinase pathway in both RAW 264.7 and HaCaT cells. After treatment with SC-2, SC-7, and SC-9, over-proliferation of HaCaT cells was significantly terminated. In summary, SC-2, SC-7, and SC-9 showed anti-inflammatory effects in RAW 264.7 cells, suggesting that these cembrene diterpenoids obtained from S. flexibilis are natural marine products with potential anti-acne activities.


2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Kotha Anilkumar ◽  
Gorla V. Reddy ◽  
Rajaram Azad ◽  
Nagendra Sastry Yarla ◽  
Gangappa Dharmapuri ◽  
...  

Inflammation is the major causative factor of different diseases such as cardiovascular disease, diabetes, obesity, osteoporosis, rheumatoid arthritis, inflammatory bowel disease, and cancer. Anti-inflammatory drugs are often the first step of treatment in many of these diseases. The present study is aimed at evaluating the anti-inflammatory properties of isoorientin, a selective cyclooxygenase-2 (COX-2) inhibitor isolated from the tubers of Pueraria tuberosa, in vitro on mouse macrophage cell line (RAW 264.7) and in vivo on mouse paw edema and air pouch models of inflammation. Isoorientin reduced inflammation in RAW 264.7 cell line in vitro and carrageenan induced inflammatory animal model systems in vivo. Cellular infiltration into pouch tissue was reduced in isoorientin treated mice compared to carrageenan treated mice. Isoorientin treated RAW 264.7 cells and animals showed reduced expression of inflammatory proteins like COX-2, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), 5-lipoxygenase (5-LOX), and interleukin 1-β (IL-1-β) both in vitro and in vivo. The antioxidant enzyme levels of catalase and GST were markedly increased in isoorientin treated mice compared to carrageenan treated mice. These results suggest that isoorientin, a selective inhibitor of COX-2, not only exerts anti-inflammatory effects in LPS induced RAW cells and carrageenan induced inflammatory model systems but also exhibits potent antioxidant properties.


Biomedicines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 11 ◽  
Author(s):  
Adnan Shahidullah ◽  
Ji-Young Lee ◽  
Young-Jin Kim ◽  
Syed Muhammad Ashhad Halimi ◽  
Abdur Rauf ◽  
...  

Diospyrin is a bisnaphthoquinonoid medicinal compound derived from Diospyros lotus, with known anti-cancer, anti-tubercular, and anti-leishmanial activities against Leishmania donovani. However, the effects of diospyrin on lipopolysaccharide (LPS)-induced macrophage activation and inflammation are not fully reported. In this study, the anti-inflammatory effects of diospyrin on LPS-induced macrophages were examined. Diospyrin showed no toxicity in RAW 264.7 at concentrations of up to 10 μM. Diospyrin moderated the production of nitric oxide (NO), monocyte chemotactic protein-1, macrophage inflammatory protein-1β, interleukin (IL)-6, IL-10, granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, vascular endothelial growth factor, leukemia inhibitory factor, and RANTES/CCL5, as well as calcium release in LPS-induced RAW 264.7, at concentrations of up to 10 μM significantly (p < 0.05). Diospyrin also significantly inhibited the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and mRNA expression of C/EBP homologous protein (CHOP), as well as tumor necrosis factor receptor superfamily member 6 (Fas), in LPS-induced RAW 264.7 cells at concentrations of up to 10 μM (p < 0.05). Diospyrin exhibits anti-inflammatory properties mediated via inhibition of NO, and cytokines in LPS-induced mouse macrophages via the ER-stressed calcium-p38 MAPK/CHOP/Fas pathway.


2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Min-Ji Bak ◽  
Van Long Truong ◽  
Hey-Sook Kang ◽  
Mira Jun ◽  
Woo-Sik Jeong

In the present study, the anti-inflammatory effect and underlying mechanisms of wild grape seeds procyanidins (WGP) were examined using lipopolysaccharide- (LPS-) stimulated RAW 264.7 cells. We used nitric oxide (NO) and prostaglandin E2(PGE2) and reactive oxygen species (ROS) assays to examine inhibitory effect of WGP and further investigated the mechanisms of WGP suppressed LPS-mediated genes and upstream expression by Western blot and confocal microscopy analysis. Our data indicate that WGP significantly reduced NO, PGE2, and ROS production and also inhibited the expression of proinflammatory mediators such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expressions. Consistently, WGP significantly reduced LPS-stimulated expression of proinflammatory cytokines such as tumor necrosis factorα(TNF-α) and interleukin- (IL-) 1β. Moreover, WGP prevented nuclear translocation of nuclear factor-κB (NFκB) p65 subunit by reducing inhibitoryκB-α(IκBα) and NFκB phosphorylation. Furthermore, we found that WGP inhibited LPS-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK). Taken together, our results demonstrated that WGP exerts potent anti-inflammatory activity through the inhibition of iNOS and COX-2 by regulating NFκB and p38 MAPK pathway.


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