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Food Science and Biotechnology Jan 2024Atopic dermatitis (AD) is an inflammatory skin disease showing skin barrier dysfunction, eczematous lesions, severe itching, and abnormal immune responses. The aim of...
UNLABELLED
Atopic dermatitis (AD) is an inflammatory skin disease showing skin barrier dysfunction, eczematous lesions, severe itching, and abnormal immune responses. The aim of this study was to determine whether an herb combination of (LE), (HC), and (SP) has a superior anti-AD effect. Forty-two compounds were identified in LE, HC, SP, and a combined herb extract of LE, HC, and SP (LHS) using ultra-high-pressure liquid chromatography (UHPLC)-Orbitrap mass spectrometer (MS). The concentration of flavonoid glycosides including orientin (luteolin-8--glucoside), quercetin-3--rhamnoside, and luteolin-7--glucoside in the LHS was increased than in individual extracts. Furthermore, the treatment of LHS most effectively inhibited the increase of epidermal thickness, the number of mast cells, and the release of immunoglobulin E compared with that with each extract. These results suggest that the potential anti-AD effects of the LHS are due to the changes of bioactive compounds by the combination of herbs.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s10068-023-01329-7.
PubMed: 38186620
DOI: 10.1007/s10068-023-01329-7 -
Journal of Ethnopharmacology Apr 2024Qing-Re-Chu-Shi Decoction (QRCSD), a traditional Chinese herbal formula, has been employed as a complementary and alternative therapy for inflammatory skin diseases....
ETHNOPHARMACOLOGICAL RELEVANCE
Qing-Re-Chu-Shi Decoction (QRCSD), a traditional Chinese herbal formula, has been employed as a complementary and alternative therapy for inflammatory skin diseases. However, its active constituents and the mechanistic basis of its action on atopic dermatitis remain in adequately understood.
AIM OF THE STUDY
Atopic dermatitis (AD) is an allergic dermatitis marked by eczematous lesions and pruritus. The study aimed to elucidate the underlying effects of QRCSD on AD and to identify the components responsible for its therapeutic efficacy in a mouse model.
MATERIALS AND METHODS
Network pharmacology and UPLC-mass analysis were used to anticipate the pharmacological mechanisms and to identify active components of QRCSD, respectively. A DNCB-induced AD-like model was established in NC/Nga mice. QRCSD or prednisolone (as a positive control) was administered via gavage every other day from day14 to day 21. Dermatitis severity score, scratching behavior, skin barrier function, spleen index, Th1/Th2 lymphocyte ratio, and serum IgE levels were evaluated. Protein arrays, including 40 inflammatory cytokines, were performed on skin lesions, followed by confirmation experiments of Western blotting in dorsal skin lesions.
RESULTS
The construction of a QRCSD-AD-Network and topological analysis firstly proposed potential targets of QRCSD acting on AD. Animal experiments demonstrated that oral administration of QRCSD ameliorated AD-like lesions, reduced epidermal thickness and mast cell count, decreased serum IgE levels, augmented tight junction protein (Claudin 1, Occludin) levels, and regulated the Th1/Th2 balance in the spleen, as well as spleen index. Elevated levels of interleukin (IL)-4, IL-5, IL-6, IL-17, and Eotaxin were revealed in AD-like skin lesions by protein arrays. Western blotting confirmed that the phosphorylation levels of ERK, P38, JNK, STAT3 and P65 were downregulated, and IL-6 expression was also reduced following QRCSD treatment.
CONCLUSIONS
The study enhances the understanding of the anti-inflammatory and immunomodulatory effects of QRCSD, showcasing its significant protective role against atopic dermatitis. Treatment with QRCSD may be considered as a viable candidate for complementary and alternative therapy in managing atopic dermatitis.
Topics: Mice; Animals; Dermatitis, Atopic; Dinitrochlorobenzene; Skin; Interleukin-6; Cytokines; Anti-Inflammatory Agents; Immunoglobulin E
PubMed: 38176665
DOI: 10.1016/j.jep.2024.117702 -
Biomedicine & Pharmacotherapy =... Jan 2024Atopic dermatitis (AD) is one of the most common skin autoimmune diseases needing continuous anti-inflammatory management. Pterostilbene is reported to exhibit...
Atopic dermatitis (AD) is one of the most common skin autoimmune diseases needing continuous anti-inflammatory management. Pterostilbene is reported to exhibit anti-inflammatory activity with higher bioavailability and stability than its parent compound, resveratrol. In this study, a series of synthetic pterostilbene analogs were designed by the hybridization of pterostilbene with chalcones or benzoyl chloride. Seventeen analogs derived from pterostilbene were synthesized with differences in the positions of hydroxyl, methoxyl, or fluoro moieties. These compounds were screened by the inhibitory effect on the overexpressed Th2-associated cytokines/chemokines in the activated human keratinocytes (HaCaT). The anti-IL-5 and anti-CCL5 activity of these compounds led to the identification of three effective compounds: 3a ((E)- 4-(3,5-dimethoxystyryl)phenyl benzoate), 3d ((E)- 4-(3,5-dimethoxystyryl)phenyl 2-methoxybenzoate), and 3g ((E)- 4-(3,5-dimethoxystyryl)phenyl 2-fluorobenzoate). These benzoyl pterostilbenes also significantly decreased Th1/Th17-associated proinflammatory mediators in the activated macrophages (differentiated THP-1). The result showed that the conditioned medium of benzoyl pterostilbene-treated macrophages reduced the phosphorylated STAT3 in the keratinocytes, indicating the blockade of crosstalk between resident and immune cells. Compounds 3d and 3g generally showed greater skin absorption than 3a. The flux of 3g across barrier-defective skins mimicking the AD skin was 3-fold higher than that of across intact skin. The dinitrochlorobenzene (DNCB)-induced AD mouse model manifested that topical delivery with 3g improved the pathological signs through inhibiting cytokines/chemokines (IL-5, TNF-α, CCL17, and CCL22) and macrophage recruitment. The epidermal thickness was reduced from 76 to 55 µm after topical 3g delivery. The therapeutic activity of 3g was comparable to that of tacrolimus (TAC) used as a positive control. The benzoyl pterostilbenes attenuated the inflammation via the MAPK and c-Jun signaling. Furthermore, this study provided experimental evidence of benzoyl pterostilbene analogs for therapeutic potential on AD.
Topics: Animals; Mice; Humans; Dermatitis, Atopic; Macrophage Activation; Skin; Keratinocytes; Inflammation; Cytokines; Chemokines; Anti-Inflammatory Agents; Mice, Inbred BALB C
PubMed: 38159374
DOI: 10.1016/j.biopha.2023.116073 -
Inflammation Jun 2024A topic dermatitis (AD) is a common chronic and recurrent skin disorder. The protective effects of sodium butyrate (NaB), a metabolite of short-chain fatty acid...
A topic dermatitis (AD) is a common chronic and recurrent skin disorder. The protective effects of sodium butyrate (NaB), a metabolite of short-chain fatty acid breakdown by the gut microbiota, have been widely reported in numerous inflammatory diseases. However, the effect of NaB treatment alone on AD has not been reported. In the current study, AD was induced in BALB/c mice with 2,4-dinitrochlorobenzene (DNCB) for 28 days with NaB (200 mg/kg) treatment by gavage. NaB attenuated AD-induced skin bleeding, scarring, dryness, abrasions and erosions. In addition, NaB inhibited inflammatory cells infiltration and attenuated the expression of inflammatory cytokines and chemokines. Mechanistically, NaB reduced histone deacetylase 3 (HDAC3) expression and NF-κB p65 nuclear translocation by increasing the lysine acetylation levels of STAT1 and NF-κB p65 in AD. Taken together, our study suggests that NaB inhibits inflammatory mediators and ameliorates AD by inhibiting HDAC3 expression, thereby upregulating STAT1 and NF-κB p65 lysine acetylation levels and reducing NF-κB p65 nuclear translocation. Therefore, this study provides a new theoretical basis for NaB in the treatment of AD.
Topics: Animals; Histone Deacetylases; STAT1 Transcription Factor; Mice; Butyric Acid; Mice, Inbred BALB C; Dermatitis, Atopic; NF-kappa B; Inflammation; Signal Transduction; Transcription Factor RelA
PubMed: 38159175
DOI: 10.1007/s10753-023-01955-7 -
Inflammation Apr 2024The mouse model of 2,4-dinitrochlorbenzene (DNCB)-induced human-like atopic dermatitis (hlAD) has been widely used to test novel treatment strategies and compounds....
The mouse model of 2,4-dinitrochlorbenzene (DNCB)-induced human-like atopic dermatitis (hlAD) has been widely used to test novel treatment strategies and compounds. However, the study designs and methods are highly diverse, presenting different hlAD disease patterns that occur after sensitization and repeated challenge with DNCB on dorsal skin. In addition, there is a lack of information about the progression of the disease during the experiment and the achieved pheno- and endotypes, especially at the timepoint when therapeutic treatment is initiated. We here examine hlAD in a DNCB-induced BALB/cJRj model at different timepoints: (i) before starting treatment with dexamethasone, representing a standard drug control (day 12) and (ii) at the end of the experiment (day 22). Both timepoints display typical AD-associated characteristics: skin thickening, spongiosis, hyper- and parakeratosis, altered cytokine and gene expression, increased lipid mediator formation, barrier protein and antimicrobial peptide abnormalities, as well as lymphoid organ hypertrophy. Increased mast cell infiltration into the skin and elevated immunoglobulin E plasma concentrations indicate a type I allergy response. The DNCB-treated skin showed an extrinsic moderate sub-acute hlAD lesion at day 12 and an extrinsic mild sub-acute to chronic pheno- and endotype at day 22 with a dominating Th2 response. A dependency of the filaggrin formation and expression in correlation to the disease severity in the DNCB-treated skin was found. In conclusion, our study reveals a detailed classification of a hlAD at two timepoints with different inflammatory skin conditions and pheno- and endotypes, thereby providing a better understanding of the DNCB-induced hlAD model in BALB/cJRj mice.
Topics: Dermatitis, Atopic; Animals; Dinitrochlorobenzene; Mice; Filaggrin Proteins; Disease Models, Animal; Mice, Inbred BALB C; Skin; Cytokines; Dexamethasone; Inflammation; Female
PubMed: 38150167
DOI: 10.1007/s10753-023-01943-x -
Frontiers in Immunology 2023Atopic dermatitis (AD) is one of the most common inflammatory skin diseases with complex pathogenesis involving epidermal barrier dysfunction, skin microbiome...
Atopic dermatitis (AD) is one of the most common inflammatory skin diseases with complex pathogenesis involving epidermal barrier dysfunction, skin microbiome abnormalities and type-2-skewed immune dysregulation. Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that plays critical roles in various biological processes. However, the role of STAT3 in epidermal keratinocytes in AD remains unclear. In this study, we generated an epidermal keratinocyte-specific -deficient mouse strain (termed cKO mice). After topical 2,4-dinitrochlorobenzene (DNCB) treatment, cKO mice developed worsened AD-like skin inflammation with increased Ki67 cells, decreased filaggrin and loricrin expression, and downregulated S100A9 and LL37. The dominant microbial population in cKO mice changed from to . DNCB-treated cKO mice displayed more infiltrating type-2 inflammatory cells, including mast cells, eosinophils, and CD4T cells, accompanied by increased skin IL-4 and serum IgE levels. Moreover, thymic stromal lymphopoietin (TSLP), mainly produced by keratinocytes, was highly expressed in the ear skin of cKO mice and chemoattracted more TSLPR cells. TSLP blockade significantly alleviated DNCB-induced AD-like skin inflammation in cKO mice. Thus, epidermal keratinocyte-specific STAT3 deficiency can aggravate AD-like skin inflammation in mice, possibly through TSLP dysregulation.
Topics: Animals; Mice; Cytokines; Dermatitis, Atopic; Dinitrochlorobenzene; Inflammation; Keratinocytes; STAT3 Transcription Factor; Thymic Stromal Lymphopoietin; Up-Regulation
PubMed: 38053996
DOI: 10.3389/fimmu.2023.1273182 -
Nutrition Research and Practice Dec 2023, commonly referred to as the maitake mushroom, has been studied extensively to explore its potential health benefits. However, its anti-inflammatory effects in skin...
BACKGROUND/OBJECTIVES
, commonly referred to as the maitake mushroom, has been studied extensively to explore its potential health benefits. However, its anti-inflammatory effects in skin disorders have not been sufficiently elucidated. This study aimed to elucidate the anti-inflammatory role of the ethanol extract of in atopic dermatitis (AD) using in vivo and in vitro models.
MATERIALS/METHODS
We investigated its impact on skin and spleen inflammatory responses in extract (DFE)/1-chloro-2,4 dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in a mouse model. Additionally, we determined the immunosuppressive response and mechanism of by inducing atopic-like immune reactions in keratinocytes through tumor necrosis factor (TNF)-α/interferon (IFN)-γ stimulation.
RESULTS
Our study revealed that ameliorates clinical symptoms in an AD-like mouse model. These effects contributed to the suppression of Th1, Th2, Th17, and Th22 immune responses in the skin and spleen, leading to protection against cutaneous inflammation. Furthermore, inhibited the production of antibodies immunoglobulin (Ig)E and IgG2a in the serum of AD mice. Importantly, the inhibitory effect of on inflammatory cytokines in TNF-α/IFN-γ-stimulated AD-like keratinocytes was associated with the suppression of MAPK (Mitogen Activated Protein Kinase) pathway activation.
CONCLUSIONS
Collectively, these findings highlight the potential of as a novel therapeutic agent for AD treatment and prevention.
PubMed: 38053833
DOI: 10.4162/nrp.2023.17.6.1056 -
International Immunopharmacology Jan 2024Atopic dermatitis (AD) is a chronic, inflammatory cutaneous disease driven by immune dysregulation. Catalpol is an iridoids, possessing anti-inflammatory, antioxidant,...
Atopic dermatitis (AD) is a chronic, inflammatory cutaneous disease driven by immune dysregulation. Catalpol is an iridoids, possessing anti-inflammatory, antioxidant, and neuroprotective activities. It can be added to food as a dietary supplement. To evaluate the effects and mechanisms of catalpol on AD, both in vitro and in vivo studies were conducted. It was found that catalpol downregulated the phosphorylation of Lyn and Syk to inhibit various downstream pathways, including intracellular Ca elevation, cytokines generation, and histamine release, which ultimately controlled mast cell (MCs) degranulation. The results showed that catalpol alleviated AD-like skin lesions and MC infiltration via regulation of pro-Th2 and Th2 cytokines in vivo. Furthermore, this compound reduced the levels of IgE in AD mice and improved allergic reactions in PCA mice. The results provided that catalpol was potentially developed as a dietary supplement to improve AD and other atopic diseases.
Topics: Mice; Animals; Dermatitis, Atopic; Mast Cells; Dinitrochlorobenzene; Immunoglobulin E; Skin; Cytokines; Mice, Inbred BALB C
PubMed: 38041954
DOI: 10.1016/j.intimp.2023.111274 -
International Journal of Biological... Jan 2024Bactrocera minax is a disastrous pest of citrus crops in China. Numerous studies focused on the molecular mechanism of odorant perception of B. minax, but the molecular...
Molecular and functional characterization of an antenna-enriched glutathione S-transferase BminGSTd3 involved in undecanol degradation in the citrus fruit fly, Bactrocera minax (Enderlein) (Diptera Tephritidae).
Bactrocera minax is a disastrous pest of citrus crops in China. Numerous studies focused on the molecular mechanism of odorant perception of B. minax, but the molecular mechanism of odorant degradation remains unclear. Glutathione S-transferases (GSTs) are considered as a class of odorant-degrading enzymes involved in degrading odorant molecules in insects' olfactory system. Here, we identified a delta-class GST gene, BminGSTd3, from B. minax. It was predominantly expressed in adult's olfactory organ antennae. The bacterially expressed recombinant BminGSTd3 was able to catalyze the conjugation of glutathione (GSH) with 2, 4-dinitrochlorobenzene (CDNB). Spectrophotometric analysis showed that undecanol can inhibit catalytic activities of BminGSTd3. Metabolic assays exhibited that undecanol can be depleted by BminGSTd3. Undecanol is believed to be an important B. minax sex pheromone component. The other components of the pheromone remain unclear. To understand how BminGSTd3 specifically recognizes undecanol, a 3D model of BminGSTd3 was constructed by homology modeling. Molecular docking based on this model revealed that E64 and S65 are the key amino acids recognizing undecanol, and this was proven by site-directed mutagenesis and intrinsic fluorescence assays. We suggest that BminGSTd3 is an undecanol metabolizing GST in B.minax, and E64 and S65 may serve as the key binding sites.
Topics: Animals; Tephritidae; Citrus; Glutathione Transferase; Molecular Docking Simulation; Drosophila; Glutathione
PubMed: 38040156
DOI: 10.1016/j.ijbiomac.2023.128514 -
Veterinary and Animal Science Dec 2023The aim of this study was to investigate the effects of different diet types, forms, and contents of ajwain essential oil (AEO) on various physiological characteristics...
The aim of this study was to investigate the effects of different diet types, forms, and contents of ajwain essential oil (AEO) on various physiological characteristics of broiler chickens, including cell-mediated immunity responses, intestinal morphology, and microflora. A total of 1500 one-day-old male broiler chickens were allocated to different treatments based on a 2 × 3 × 2 factorial arrangement, considering diet types (corn and corn-wheat), contents of AEO (0, 150, and 300 mg/kg of diet), and forms of AEO (conventional and encapsulated). The results indicated that the broiler chickens fed the diet containing 150 ppm EO demonstrated reduced skin thickness in response to a 2,4-dinitrochlorobenzene challenge, 24 h after injection, compared to those receiving a diet without EO ( < 0.05). Increasing the EO content led to an increase in the villous height to crypt depth ratio in the jejunum of broiler chickens receiving 300 ppm EO ( < 0.05). Moreover, there was a slight improvement in the villous height to crypt depth ratio in the jejunum of broiler chickens fed the corn-wheat diet ( = 0.07). Broiler chickens fed the 300 ppm EO showed a lower total bacterial population compared to those fed the 150 ppm EO ( < 0.05). Finally, the use of EO at a content of 150 ppm improved cellular immune response, while EO at a content of 300 ppm improved the morphology and overall population of intestinal bacteria. Furthermore, the inclusion of wheat-corn diets exhibited enhanced morphological characteristics of the intestines. However, the forms of AEO did not exert any significant influence on the physiological traits.
PubMed: 38022719
DOI: 10.1016/j.vas.2023.100321