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Journal of Ethnopharmacology Sep 2022Jiu-Wei-Yong-An (JWYA) formula is a traditional Chinese medicine (TCM) prescription used to treat atopic dermatitis (AD) in the clinic. JWYA is considered to have...
ETHNOPHARMACOLOGICAL RELEVANCE
Jiu-Wei-Yong-An (JWYA) formula is a traditional Chinese medicine (TCM) prescription used to treat atopic dermatitis (AD) in the clinic. JWYA is considered to have anti-inflammatory and antipruritic properties. However, the mechanism of JWYA remains unclear.
AIM OF THE STUDY
This study aimed to investigate the effect of JWYA on an experimental mouse AD model.
MATERIALS AND METHODS
Mice were sensitized with 2,4-dinitrochlorobenzene (DNCB) and intragastrically administered with JWYA for 14 days. The therapeutic effect was assessed using a grade four dermatitis score, skin moisture, thickness measurements, and a mouse behavior tests. H&E and toluidine blue staining were used to observe epidermal inflammatory thickening and mast cells in mouse skin lesions. Serum IgE levels and skin TNF-α and IL-4 levels were determined using ELISAs. The TNF-α, IL-1β, IL-4, IL-13, IL-31, IL-33, and IFN-γ mRNA expression levels in skin lesions were detected using qPCR. Network pharmacology analysis based on serum active components was performed to elucidate the mechanism, and the results were verified by Western blotting. Finally, we tested the binding affinity between the active ingredients of JWYA and JAK1 via molecular docking.
RESULTS
JWYA improved the skin lesions of AD mice, relieved itching and reduced skin thickening. Additionally, JWYA decreased the serum IgE level and the levels of TNF-α, IL-1β, IL-4, IL-13, IL-31, IL-33, and IFN-γ in skin. Moreover, JWYA inhibited the activation of JAK1/STAT3 and MAPK (p38, ERK, and JNK) signaling. Molecular docking showed that kaempferol, luteolin, and forsythin have high affinity for JAK1.
CONCLUSIONS
JWYA alleviates AD-like skin lesions and inhibited inflammation and skin itch. The effect of JWYA is attributed to blocking the JAK1/STAT3 and MAPK signaling pathways. We suggest that JWYA may be an alternative therapy for the treatment of AD.
Topics: Animals; Cytokines; Dermatitis, Atopic; Dinitrochlorobenzene; Immunoglobulin E; Interleukin-13; Interleukin-33; Interleukin-4; MAP Kinase Signaling System; Mice; Mice, Inbred BALB C; Molecular Docking Simulation; Plant Extracts; Skin; Tumor Necrosis Factor-alpha
PubMed: 35659915
DOI: 10.1016/j.jep.2022.115428 -
International Journal of Molecular... Aug 2023Atopic dermatitis (AD) is a common skin disease worldwide. The major causes of AD are skin barrier defects, immune dysfunction, and oxidative stress. In this study, we...
Atopic dermatitis (AD) is a common skin disease worldwide. The major causes of AD are skin barrier defects, immune dysfunction, and oxidative stress. In this study, we investigated the anti-oxidation and anti-inflammation effects of extract (CAE) and its regulation of the skin barrier and immune functions in AD. In vitro experiments revealed that CAE decreased the reactive oxygen species levels and inhibited the translocation of nuclear factor-κB (NF-κB), further reducing the secretion of interleukin (IL)-1β and IL-6 induced by interferon-γ (IFN-γ)/tumor necrosis factor-α (TNF-α). Moreover, CAE decreased IFN-γ/TNF-α-induced NLR family pyrin domain-containing 3 (NLRP3), caspase-1, high-mobility group box 1 (HMGB1), and receptor for advanced glycation end products (RAGE) expression levels. It also restored the protein levels of skin barrier function-related markers including filaggrin and claudin-1. In vivo experiments revealed that CAE not only reduced the redness of the backs of mice caused by 2,4-dinitrochlorobenzene (DNCB) but also reduced the levels of pro-inflammatory factors in their skin. CAE also reduced transepidermal water loss (TEWL) and immune cell infiltration in DNCB-treated mice. Overall, CAE exerted anti-oxidation and anti-inflammation effects and ameliorated skin barrier dysfunction, suggesting its potential as an active ingredient for AD treatment.
Topics: Mice; Animals; Dermatitis, Atopic; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Coffea; Tumor Necrosis Factor-alpha; Dinitrochlorobenzene; Skin; Antioxidants; Cytokines; Mice, Inbred BALB C
PubMed: 37569742
DOI: 10.3390/ijms241512367 -
International Immunopharmacology May 2023Ursolic acid (UA) is a triterpenoid compound found in natural plants. It has been reported to have anti-inflammatory, antioxidant, and immunomodulatory properties....
BACKGROUND
Ursolic acid (UA) is a triterpenoid compound found in natural plants. It has been reported to have anti-inflammatory, antioxidant, and immunomodulatory properties. However, its role in atopic dermatitis (AD) is unknown. This study aimed to evaluate the therapeutic effect of UA in AD mice and explore the underlying mechanisms.
METHODS
Balb/c mice were treated with 2, 4-dinitrochlorobenzene (DNCB) to induce AD-like lesions. During modeling and medication administration, dermatitis scores and ear thickness were measured. Subsequently, histopathological changes, levels of T helper cytokines, and oxidative stress markers levels were evaluated. Immunohistochemistry staining was used to assess changes in the expression of the nuclear factor of kappa B (NF-κB) and NF erythroid 2-related factor 2 (Nrf2). Furthermore, CCK8 assay, reactive oxygen species (ROS) assay, real-time PCR, and western blotting were employed to evaluate the effects of UA on ROS levels, inflammatory mediator production, and the NF-κB and Nrf2 pathways in TNF-α/IFN-γ-stimulated HaCaT cells.
RESULTS
The results showed that UA significantly reduced dermatitis score and ear thickness, effectively inhibited skin proliferation and mast cell infiltration in AD mice, and decreased the expression level of T helper cytokines. Meanwhile, UA improved oxidative stress in AD mice by regulating lipid peroxidation and increasing the activity of antioxidant enzymes. In addition, UA inhibited ROS accumulation and chemokine secretion in TNF-α/IFN-γ-stimulated HaCaT cells. It might exert anti-dermatitis effects by inhibiting the TLR4/NF-κB pathway and activating the Nrf2/HO-1 pathway.
CONCLUSION
Taken together, our results suggest that UA may have potential therapeutic effects on AD and could be further studied as a promising drug for AD treatment.
Topics: Animals; Mice; Dermatitis, Atopic; NF-kappa B; Dinitrochlorobenzene; NF-E2-Related Factor 2; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha; Antioxidants; Reactive Oxygen Species; Skin; Signal Transduction; Cytokines; Triterpenes; Mice, Inbred BALB C; Ursolic Acid
PubMed: 36996741
DOI: 10.1016/j.intimp.2023.110079 -
Antioxidants (Basel, Switzerland) Apr 2023is widely used pharmacologically in Traditional Chinese Medicine and Ayurvedic medicine as a diuretic, antipyretic, or choleretic and to treat ulcers, snakebites, and...
is widely used pharmacologically in Traditional Chinese Medicine and Ayurvedic medicine as a diuretic, antipyretic, or choleretic and to treat ulcers, snakebites, and edema. Previous studies have shown that phytochemicals from have physiological activities such as anti-inflammatory, anti-tumor, and anti-wrinkle properties. Nevertheless, research on the anti-atopic dermatitis (AD) effect of extract is limited. This study was undertaken to assess the in vitro and in vivo anti-atopic and antioxidant activities of a 95% EtOH extract of roots (NPR). PI-induced RBL-2H3 cells and two typical hapten mice (oxazolone-induced BALB/c mice and 2,4-dinitrochlorobenzene (DNCB)-induced SKH-1 hairless mice) were used to investigate the effect of NPR extract on AD. The expressions of AD-related inflammatory cytokines, skin-related genes, and antioxidant enzymes were analyzed by ELISA, immunoblotting, and immunofluorescence, and skin hydration was measured using Aquaflux AF103 and SKIN-O-MAT instruments. The chemical composition of NPR extract was analyzed using an HPLC-PDA system. In this study, NPR extracts were shown to most efficiently inhibit IL-4 in PI-induced RBL-2H3 cells and AD-like skin symptoms in oxazolone-BALB/c mice compared to its whole and aerial extracts. NPR extract markedly reduced DNCB-induced increases in mast cells, epidermal thickness, IL-4 and IgE expressions, and atopic-like symptoms in SKH-1 hairless mice. In addition, NPR extract suppressed DNCB-induced changes in the expressions of skin-related genes and skin hydration and activated the Nrf2/HO-1 pathway. Three phenolic acids (chlorogenic acid, 3,5-dicaffeoylquinic acid, and 3,4-dicaffeoylquinic acid) were identified by HPLC-PDA in NPR extract. The study shows that NPR extract exhibits anti-atopic activities by inhibiting inflammatory and oxidative stress and improving skin barrier functions, and indicates that NPR extract has potential therapeutic use for the prevention and treatment of AD.
PubMed: 37107248
DOI: 10.3390/antiox12040873 -
FASEB Journal : Official Publication of... Oct 2023PYR-41 is an irreversible and cell permeable inhibitor of ubiquitin-activating enzyme E1, and has been reported to inhibit the degradation of IκB protein. Previous...
PYR-41 is an irreversible and cell permeable inhibitor of ubiquitin-activating enzyme E1, and has been reported to inhibit the degradation of IκB protein. Previous studies have shown that PYR-41 has effects on anti-inflammatory, but whether it has therapeutic effects on allergic dermatitis is unclear. The aim of this research was to explore the therapeutic effects of PYR-41 on atopic dermatitis. The effects of PYR-41 on the activation of NF-κB signaling pathway and the expression of inflammatory genes in HaCat cells were tested by western blot and qPCR. A mouse model was built, and the AD-like skin lesions were induced by 2,4-dinitrochlorobenzene (DNCB). Then, the treatment effects of PYR-41 were examined by skin severity score, ear swelling, ELISA, and qPCR. The results showed that PYR-41 can significantly reduce the K63-linked ubiquitination level of nuclear factor-κB essential modulator (NEMO) and tumor necrosis factor receptor associated factor 6 (TRAF6), inhibit the proteasomal degradation of IκBα, thereby activate TNF-α-induced NF-κB signaling pathway in HaCat cells. In addition, DNCB-treated mice have significant reduction in symptoms after treated by PYR-41, including reduced ear thickening and reduced skin damage. Serum tests showed that PYR-41 significantly reduced the expression of IgE, IFN-γ, and TNF-α. In conclusion, the current results suggest that PYR-41 has potential to reduce the symptoms of atopic dermatitis.
Topics: Animals; Mice; Ubiquitin-Activating Enzymes; Dermatitis, Atopic; Dinitrochlorobenzene; Tumor Necrosis Factor-alpha; NF-kappa B; Skin Diseases
PubMed: 37738047
DOI: 10.1096/fj.202200951RRR -
Molecules (Basel, Switzerland) Dec 2022Atopic dermatitis (AD) is a common chronic inflammatory skin disease. Bisdemethoxycurcumin (BDMC) is an ingredient from the rhizome of the traditional Chinese herbal...
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.
Topics: Animals; Mice; Dermatitis, Atopic; Dinitrochlorobenzene; Keratinocytes; Tumor Necrosis Factor-alpha; Skin; Cytokines; Chemokines; NF-kappa B; RNA, Messenger; Mice, Inbred BALB C
PubMed: 36615486
DOI: 10.3390/molecules28010293 -
Life Sciences May 2024Ursodeoxycholic acid (UDCA) is a hydrophilic dihydroxy bile acid used for cholestatic liver disease and exhibits antioxidant, antitumor, and anti-inflammatory effects....
AIMS
Ursodeoxycholic acid (UDCA) is a hydrophilic dihydroxy bile acid used for cholestatic liver disease and exhibits antioxidant, antitumor, and anti-inflammatory effects. However, its potential effects on atopic dermatitis (AD) have not been elucidated. This study aimed to evaluate the efficacy of UDCA in inhibiting the inflammatory response and alleviating lesions in AD-like mice.
MAIN METHODS
To investigate the efficacy of UDCA in AD-like inflammatory responses, tumor necrosis factor-alpha (TNF-α)- and interferon-gamma (IFN-γ)-stimulated HaCaT cells and anti-dinitrophenyl immunoglobulin E (DNP-IgE)- and human serum albumin (HSA)-stimulated RBL-2H3 cells were used to investigate the levels of inflammatory factors and their mechanisms. AD-like lesions were induced by applying DNCB/DFE to mice. The effect of UDCA administration in AD-like mice was analyzed by assessing organ weight, serum IgE and inflammatory cytokine levels, and histopathological changes using immunohistochemical and immunofluorescent staining.
KEY FINDINGS
In HaCaT cells, UDCA significantly diminished TARC, MDC, MCP-1, and IL-6 expression by inhibiting the phosphorylation of nuclear NF-κB and cytoplasmic IκB, and also increased the levels of skin barrier protein. In RBL-2H3 cells, UDCA reduced β-hexosaminidase and IL-4 levels. In AD-like mice, UDCA suppressed organ hypertrophy, ear edema, SCORAD index, DFE-specific IgE levels, inflammatory cytokine levels, skin hypertrophy, mast cell invasion, skin barrier loss, and thymic stromal lymphopoietin-positive areas.
SIGNIFICANCE
UDCA suppressed the expression of pro-inflammatory cytokines by keratinocytes and mast cells. It also alleviated atopy by suppressing symptoms without organ toxicity in AD-like mice. UDCA may be an effective and safe treatment for AD.
Topics: Humans; Animals; Mice; Rats; Dermatitis, Atopic; Skin; Dinitrochlorobenzene; Ursodeoxycholic Acid; Cytokines; NF-kappa B; Immunoglobulin E; Hypertrophy; Mice, Inbred BALB C
PubMed: 38490296
DOI: 10.1016/j.lfs.2024.122560 -
Clinical Immunology (Orlando, Fla.) Nov 2022Atopic dermatitis (AD), a type of skin inflammation, is associated with immune response mediated by T-helper 2 (Th2) cells, and mast cells. Vasicine is an alkaloid...
Atopic dermatitis (AD), a type of skin inflammation, is associated with immune response mediated by T-helper 2 (Th2) cells, and mast cells. Vasicine is an alkaloid isolated from Adhatoda vasica, a popular Ayurvedic herbal medicine used for treating inflammatory conditions. In the present study, the anti-AD effects of vasicine were evaluated on 2,4-dinitrochlorobenzene-induced AD-like skin lesions in BALB/c mice. The potential anti-allergic effects of vasicine were also assessed using the passive cutaneous anaphylaxis (PCA) test. The results showed that the oral administration of vasicine improved the severity of AD-like lesional skin by decreasing histopathological changes and restoring epidermal thickness. Vasicine also inhibited the infiltration of mast cells in the skin and reduced the levels of pro-Th2 and Th2 cytokines as well as immunoglobulin E in the serum. Finally, vasicine inhibited the expression of pro-Th2 and Th2 cytokines in skin tissues, indicating the therapeutic potential of vasicine for AD.
Topics: Alkaloids; Animals; Anti-Allergic Agents; Cytokines; Dermatitis, Atopic; Dinitrochlorobenzene; Immunoglobulin E; Mice; Mice, Inbred BALB C; Passive Cutaneous Anaphylaxis; Quinazolines; Skin; Skin Diseases
PubMed: 36049600
DOI: 10.1016/j.clim.2022.109102 -
Chinese Journal of Integrative Medicine Jul 2022To evaluate the therapeutic effects of acupoint autohemotherapy (A-AHT) on 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis (AD) in mice focusing on...
OBJECTIVE
To evaluate the therapeutic effects of acupoint autohemotherapy (A-AHT) on 1-chloro-2,4-dinitrobenzene (DNCB)-induced atopic dermatitis (AD) in mice focusing on regulating T helper 1/T helper 2 (Th1/Th2) immune responses.
METHODS
Thirty BALB/c mice were divided into 5 groups by a random number table, including normal control (NC), AD model (AD), A-AHT, sham A-AHT (sA-AHT), and acupoint injection of normal saline (A-NS) groups, 6 mice per group. Mice were challenged by DNCB for the establishment of experimental AD model. On the 8th day, except for the NC and AD groups, the mice in the other groups received management once every other day for a total of 28 days. For the A-AHT and sA-AHT groups, 0.05 mL of autologous whole blood (AWB) was injected into bilateral Zusanli (ST 36) and Quchi (LI 11) and sham-acupoints (5 mm lateral to ST 36 and LI 11), respectively. The A-NS group was administrated with 0.05 mL of normal saline by acupoint injection into ST 36 and LI 11. Dermatitis severity for dorsal skin of mice was determined using the Severity Scoring of Atopic Dermatitis (SCORAD) every week. The total immunoglobulin E (IgE), interleukin-4 (IL-4), and interferon-gamma (IFN-γ) cytokine levels in serum were examined by enzyme-linked immunosorbent assay (ELISA). Spleen Th1/Th2 expression were analyzed via flow cytometry and immunohistochemical assay was used to detect T-box expressed in T cell (T-bet) and GATA-binding protein 3 (GATA3) expressions in skin lesions of mice.
RESULTS
Compared with the AD group, both A-AHT and sA-AHT reduced the SCORAD index and serum IgE level (P<0.05 or P<0.01); A-AHT, sA-AHT and A-NS down-regulated serum IL-4 level and upregulated IFN-γ/IL-4 ratio (P<0.05 or P<0.01); A-AHT regulated the Th1/Th2 shift specifically and increased the related transcription factors such as T-bet expression and T-bet/GATA3 ratio (P<0.05).
CONCLUSION
A-AHT showed significant effectiveness on the AD model mice, through regulating Th1/Th2 immune responses.
Topics: Acupuncture Points; Animals; Dermatitis, Atopic; Dinitrobenzenes; Dinitrochlorobenzene; Immunoglobulin E; Interferon-gamma; Interleukin-4; Mice; Mice, Inbred BALB C; Saline Solution
PubMed: 35776292
DOI: 10.1007/s11655-022-3579-7 -
Biomedicine & Pharmacotherapy =... May 2021Atopic dermatitis (AD) is a chronic inflammatory skin disorder that affects 10-20% of the world's population. Therefore, the discovery of drugs for the treatment of AD...
Atopic dermatitis (AD) is a chronic inflammatory skin disorder that affects 10-20% of the world's population. Therefore, the discovery of drugs for the treatment of AD is important for human health. Hispidulin (HPD; also known as scutellarein 6-methyl ether or dinatin) is a natural flavone that exerts anti-inflammatory effects. In the present study, the effectiveness of HPD on AD-like skin inflammation was investigated. We used a mouse AD model through repeated exposure of mice to 2,4-dinitrochlorobenzene and house dust mite extract (Dermatophagoides farinae extract, DFE) to the ears. In addition, tumor necrosis factor-α and interferon-γ-activated keratinocytes (HaCaT cells) were used to investigate the underlying mechanism of HPD action. Oral administration of HPD alleviated AD-like skin inflammations: it reduced ear thickness; serum immunoglobulin (Ig)E, DFE-specific IgE, and IgG2a levels; and inflammatory cell infiltration. HPD reduced the expression of pro-inflammatory cytokines and chemokines through inhibition of signal transducer and activator of transcription 1 nuclear factor-κB in HaCaT cells. Taken together, these results suggest that HPD could be a potential drug candidate for the treatment of AD.
Topics: Animals; Anti-Allergic Agents; Antigens, Dermatophagoides; Dermatitis, Atopic; Dinitrochlorobenzene; Eosinophils; Female; Flavones; Immunoglobulins; Keratinocytes; Mast Cells; Mice; Mice, Inbred BALB C; Pyroglyphidae; Skin
PubMed: 33761595
DOI: 10.1016/j.biopha.2021.111359