Angelicae Dahuricae Radix Inhibits Dust Mite Extract-Induced Atopic Dermatitis-Like Skin Lesions in NC/Nga Mice

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.

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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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Anti-Inflammatory Effects of Formononetin 7-O-phosphate, a Novel Biorenovation Product, on LPS-Stimulated RAW 264.7 Macrophage Cells

Molecules ◽

10.3390/molecules24213910 ◽

2019 ◽

Vol 24 (21) ◽

pp. 3910 ◽

Cited By ~ 2

Author(s):

Min-Seon Kim ◽

Jin-Soo Park ◽

You Chul Chung ◽

Sungchan Jang ◽

Chang-Gu Hyun ◽

...

Keyword(s):

Biological Properties ◽

In Vitro Assays ◽

Raw 264.7 Cells ◽

No Production ◽

Raw 264.7 ◽

Dependent Manner ◽

Macrophage Cells ◽

Anti Inflammatory ◽

Reduced Toxicity

Biorenovation is a microbial enzyme-catalyzed structural modification of organic compounds with the potential benefits of reduced toxicity and improved biological properties relative to their precursor compounds. In this study, we synthesized a novel compound verified as formononetin 7-O-phosphate (FMP) from formononetin (FM) using microbial biotransformation. We further compared the anti-inflammatory properties of FMP to FM in lipopolysaccharide (LPS)-treated RAW264.7 macrophage cells. We observed that cell viabilities and inhibitory effects on LPS-induced nitric oxide (NO) production were greater in FMP-treated RAW 264.7 cells than in their FM-treated counterparts. In addition, FMP treatment suppressed the production of proinflammatory cytokines such as prostaglandin-E2 (PGE2), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in a dose-dependent manner and concomitantly decreased the mRNA expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). We also found that FMP exerted its anti-inflammatory effects through the downregulation of the extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and nuclear factor kappa B (NF-κB) signaling pathways. In conclusion, we generated a novel anti-inflammatory compound using biorenovation and demonstrated its efficacy in cell-based in vitro assays.

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Inhibitory Effect of Centella asiatica Extract on DNCB-Induced Atopic Dermatitis in HaCaT Cells and BALB/c Mice

Nutrients ◽

10.3390/nu12020411 ◽

2020 ◽

Vol 12 (2) ◽

pp. 411 ◽

Cited By ~ 4

Author(s):

Yonghyeon Lee ◽

Hyeon Kyeong Choi ◽

Kaudjhis Patrick Ulrich N’deh ◽

Young-Jin Choi ◽

Meiqi Fan ◽

...

Keyword(s):

Atopic Dermatitis ◽

Allergic Inflammation ◽

Centella Asiatica ◽

Ethanol Extract ◽

Inhibitory Effect ◽

Interferon Γ ◽

Dependent Manner ◽

Hacat Cells ◽

Signaling Mechanism ◽

Tnf Α

Atopic dermatitis (AD) is a chronic inflammatory skin disease caused mainly by immune dysregulation. This study explored the anti-inflammatory and immunomodulatory effects of the Centella asiatica ethanol extract (CA) on an AD-like dermal disorder. Treatment with CA inhibited the expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in a dose-dependent manner in inflammatory stimulated HaCaT cells by interferon-γ (IFN-γ) and TNF-α-triggered inflammation. Eight-week-old BALB/c mice treated with 2,4-dinitrochlorobenzene (DNCB) were used as a mouse model of AD. In AD induce model, we had two types treatment of CA; skin local administration (80 µg/cm2, AD+CA-80) and oral administration (200 mg/kg/d, AD+CA-200). Interestingly, the CA-treated groups exhibited considerably decreased mast cell infiltration in the ear tissue. In addition, the expression of IL-6 in mast cells, as well as the expression of various pathogenic cytokines, such as TNF-α, IL-4, IL-5, IL-6, IL-10, IL-17, iNOS, COX-2, and CXCL9, was reduced in both AD+CA-80 and AD+CA-200 groups. Collectively, our data demonstrate the pharmacological role and signaling mechanism of CA in the regulation of allergic inflammation of the skin, which supports our hypothesis that CA could potentially be developed as a therapeutic agent for AD.

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

The American Journal of Chinese Medicine ◽

10.1142/s0192415x2050055x ◽

2020 ◽

Vol 48 (05) ◽

pp. 1121-1140

Author(s):

Hien T.T. Ngo ◽

Eunson Hwang ◽

Hyungoo Kang ◽

Bom Park ◽

Seul A. Seo ◽

...

Keyword(s):

Atopic Dermatitis ◽

Elevated Serum ◽

Mitogen Activated Protein Kinase ◽

Raw 264.7 Cells ◽

Achillea Millefolium ◽

Raw 264.7 ◽

Hacat Cells ◽

Necrosis Factor Alpha ◽

Cox 2 ◽

Anti Inflammatory

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.

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Purification, characterization, crystal structure and NO production inhibitory activity of three new sesquiterpenoids from homalomena occulta

Acta Crystallographica Section C Structural Chemistry ◽

10.1107/s2053229618013815 ◽

2018 ◽

Vol 74 (11) ◽

pp. 1440-1446

Author(s):

Qi Zhang ◽

Li Ma ◽

Zhaoxia Qu ◽

Guige Hou ◽

Yanan Wang ◽

...

Keyword(s):

Crystal Structure ◽

Single Crystal ◽

2D Nmr ◽

Inhibitory Effect ◽

Raw 264.7 Cells ◽

No Production ◽

Raw 264.7 ◽

X Ray Diffraction ◽

X Ray ◽

Spectroscopic Analyses

Two new isodaucane-type sesquiterpenoids, namely (1R,4S,5S,6R,7S,10R)-isodauc-6,7,10-triol, C15H28O3, (1), and (1R,4S,5S,6S,7S,10R)-isodauc-6,7,10-triol, (2), and a new eudesmane-type sesquiterpenoid, 1β,4β,5α-trihydroxyeudesmane, (3), were obtained from the rhizomes of homalomena occulta with the aid of column chromatography. Their structures were elucidated based on extensive spectroscopic analyses, including 1D NMR, 2D NMR and HRESIMS. The structure of (1) was confirmed by single-crystal X-ray diffraction and the absolute configuration was assigned with respect to that of the precursor. The single-crystal structure reveals that adjacent molecules of (1) embrace through two groups of intermolecular O—H...O hydrogen bonds to generate a two-dimensional sheet with a 63-net topology. The three compounds were evaluated for their activity against lipopolysaccharide-induced production of nitrogen oxide (NO) in RAW 264.7 cells, and (1) showed an inhibitory effect on NO production, with IC50 values of 5.7±0.22 µM.

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Naphthoquinone Derivatives with Anti-Inflammatory Activity from Mangrove-Derived Endophytic Fungus Talaromyces sp. SK-S009

Molecules ◽

10.3390/molecules25030576 ◽

2020 ◽

Vol 25 (3) ◽

pp. 576 ◽

Cited By ~ 1

Author(s):

Hongju Liu ◽

Chong Yan ◽

Changqun Li ◽

Tingting You ◽

Zhigang She

Keyword(s):

Nitric Oxide ◽

Endophytic Fungus ◽

Raw 264.7 Cells ◽

Inflammatory Factors ◽

No Production ◽

Raw 264.7 ◽

Mrna Levels ◽

Tnf Α ◽

Ic50 Values ◽

Oxide Synthase

Twelve 1, 4-naphthoquinone derivatives, including two new (1 and 2) and 10 known (3–12), were obtained from endophytic fungus Talaromyces sp. SK-S009 isolated from the fruit of Kandelia obovata. All structures were identified through extensive analysis of the nuclear magnetic resonance (NMR), mass spectrometry (MS) and circular dichroism (CD), as well as by comparison with literature data. These compounds significantly inhibited the lipopolysaccharide (LPS)-induced nitric oxide (NO) production in the murine macrophage cell line (RAW 264.7 cells). The half maximal inhibitory concentration (IC50) values, except for compound 2, were lower than that of indomethacin (26.3 μM). Compound 9 inhibited the LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA expressions in RAW 264.7 macrophages. Additionally, compound 9 reduced the mRNA levels of pro-inflammatory factors interleukin (IL)1β, IL-6, and tumor necrosis factor (TNF)-α. The results of this study demonstrated that these 1, 4-naphthoquinone derivatives can inhibit LPS-induced inflammation.

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ANTI-INFLAMMATORY ACTIVITY OF TINOCRISPOSIDE BY INHIBITING NITRIC OXIDE PRODUCTION IN LIPOPOLYSACCHARIDES-STIMULATED RAW 264.7 CELLS

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i4.23739 ◽

2018 ◽

Vol 11 (4) ◽

pp. 149 ◽

Cited By ~ 1

Author(s):

Adek Zamrud Adnan ◽

Muhammad Taher ◽

Tika Afriani ◽

Annisa Fauzana ◽

Dewi Imelda Roesma ◽

...

Keyword(s):

Nitric Oxide ◽

Inflammatory Diseases ◽

Positive Control ◽

Inflammatory Activity ◽

Raw 264.7 Cells ◽

No Production ◽

Raw 264.7 ◽

Dependent Manner ◽

Anti Inflammatory

Objective: The aim of this study was to investigate in vitro anti-inflammatory activity of tinocrisposide using lipopolysaccharides (LPS)-stimulated RAW 264.7 macrophage cells. Tinocrisposide is a furano diterpene glycoside that was isolated in our previous study from Tinospora crispa.Methods: Anti-inflammatory effect was quantified spectrometrically using Griess method by measuring nitric oxide (NO) production after the addition of Griess reagent.Results: The sample concentrations of 1, 5, 25, 50, and 100 μM and 100 μM of dexamethasone (positive control) have been tested against the LPS-stimulated RAW 264.7 cells, and the results showed NO level production of 39.23, 34.00, 28.9, 20.25, 16.3, and 13.68 μM, respectively, and the inhibition level of 22.67, 33.00, 43.03, 60.10, 68.00, and 73%, respectively.Conclusions: From the study, it could be concluded that tinocrisposide was able to inhibit the formation of NO in the LPS-stimulated RAW 264.7 cells in concentration activity-dependent manner, with half-maximal inhibition concentration 46.92 μM. It can be developed as anti-inflammatory candidate drug because NO is a reactive nitrogen species which is produced by NO synthase. The production of NO has been established as a mediator in inflammatory diseases.

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Effects of Sibseonsan as an Anti-Inflammatory, Anti-Wrinkle, and Skin Whitening Treatment

Journal of Acupuncture Research ◽

10.13045/jar.2020.00024 ◽

2020 ◽

Vol 37 (2) ◽

pp. 88-93

Author(s):

Na Young Jo

Keyword(s):

Treatment Group ◽

Cell Line ◽

Radical Scavenging ◽

Raw 264.7 Cells ◽

No Production ◽

Raw 264.7 ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Tnf Α ◽

Anti Inflammatory

Background: The purpose of this study was to investigate whether Sibseonsan (SSS) is an effective anti-inflammatory, anti-wrinkling, and whitening agent.Methods: To determine whether SSS had an anti-inflammatory effect, a murine macrophage cell line was used (RAW 264.7) and production of DPPH, NO, TNF-α, and PGE2 were measured. To ascertain potential anti-wrinkle effects of SSS in these cells, collagenase and elastase production were measured. To verify whether SSS had a whitening effect, tyrosinase activity and DOPA staining were performed using a melanoma cell line (B16/F10).Results: There was no significant reduction in survival of SSS-treated RAW 264.7 cells, up to 400 μg/mL. Free radical scavenging (23.96 ± 1.85%) was observed in RAW 264.7 cells treated with SSS at a concentration of 400 μg/mL. The SSS treatment group (400 μg/mL) significantly inhibited NO production compared with the LPS stimulated treatment group. The SSS treatment of macrophage cells appeared to reduce production of TNF-α in a concentration dependent manner. There was a significant reduction in the concentration of PGE2 by about 25% in the SSS treatment (400 μg/mL) group (p = 0.05). Compared with the control, the production of collagenase and elastase in B16/F10 cells treated with SSS (400 μg/mL) was greater by 26.37% and 45.71%, respectively. The SSS treatment (400 μg/mL) group showed a significant reduction by about 17% in tyrosinase production in B16/F10 cells. The SSS treatment group showed little change in DOPA staining. Conclusion: SSS extract may be useful for the treatment and prevention of inflammatory diseases and may have anti-wrinkle and whitening effects. These results may support the use of SSS in clinical practice.

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Anti-Inflammatory Activity of 4-((1R,2R)-3-Hydroxy-1-(4-hydroxyphenyl)-1-methoxypropan-2-yl)-2-methoxyphenol Isolated from Juglans mandshurica Maxim. in LPS-Stimulated RAW 264.7 Macrophages and Zebrafish Larvae Model

Pharmaceuticals ◽

10.3390/ph14080771 ◽

2021 ◽

Vol 14 (8) ◽

pp. 771

Author(s):

Su-Hyeon Cho ◽

SeonJu Park ◽

Hoibin Jeong ◽

Song-Rae Kim ◽

Myeong Seon Jeong ◽

...

Keyword(s):

Nitric Oxide ◽

Inflammatory Responses ◽

Inflammatory Activity ◽

Raw 264.7 Cells ◽

No Production ◽

Raw 264.7 ◽

Dependent Manner ◽

Juglans Mandshurica ◽

Zebrafish Larvae ◽

Anti Inflammatory

Juglans mandshurica Maxim., a traditional folk medicinal plant, is widely distributed in Korea and China. In our previous study, we isolated a new phenylpropanoid compound, 4-((1R,2R)-3-hydroxy-1-(4-hydroxyphenyl)-1-methoxypropan-2-yl)-2-methoxyphenol (HHMP), from J. mandshurica. In the present study, we evaluated the anti-inflammatory activity of HHMP on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and zebrafish larvae. HHMP significantly inhibited LPS-induced nitric oxide (NO) and prostaglandin E2 production in a dose-dependent manner. Moreover, HHMP treatment considerably suppressed LPS-induced expression of inducible nitric oxide synthase and cyclooxygenase-2. We also demonstrated the mechanisms of HHMP inhibition of inflammatory responses in LPS-stimulated RAW 264.7 cells via Western blot analysis and immunofluorescence staining. Furthermore, HHMP significantly inhibited NO production in LPS-stimulated zebrafish larvae. Consequently, we established that HHMP significantly inhibited the LPS-induced activation of NF-κB and MAPK and the nuclear translocation of p65 in RAW 264.7 cells. Taken together, our findings demonstrate the effect of HHMP on LPS-induced inflammatory responses in vitro and in vivo, suggesting its potential to be used as a natural anti-inflammatory agent.

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Anti-Acne Effects of Cembrene Diterpenoids from the Cultured Soft Coral Sinularia flexibilis

Marine Drugs ◽

10.3390/md18100487 ◽

2020 ◽

Vol 18 (10) ◽

pp. 487

Author(s):

Li-Wei Chen ◽

Hsuan-Lien Chung ◽

Ching-Chiung Wang ◽

Jui-Hsin Su ◽

Yu-Ju Chen ◽

...

Keyword(s):

Acne Vulgaris ◽

Adult Population ◽

Wistar Rat ◽

Mitogen Activated Protein Kinase ◽

Raw 264.7 Cells ◽

No Production ◽

Raw 264.7 ◽

Hacat Cells ◽

Sinularia Flexibilis ◽

Cutibacterium Acnes

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.

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