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Nutrition Research and Practice Oct 2023Atopic dermatitis (AD) is a chronic disease with an increasing incidence globally; therefore, there is a growing demand for natural compounds effective in treating...
BACKGROUND/OBJECTIVES
Atopic dermatitis (AD) is a chronic disease with an increasing incidence globally; therefore, there is a growing demand for natural compounds effective in treating dermatitis. In this study, the protective effects of leaves with and without chlorophyll (LLE and LLE[Ch-]) on AD were investigated in animal models of AD and HaCaT cells. Further, we investigated whether LLE and LLE(Ch-) show any differences in physiological activity.
MATERIALS/METHODS
AD was induced by 2,4-dinitrochlorobenzene (DNCB) for three weeks, while NC/Nga mice were fed LLE or LLE(Ch-) extracts for 7 weeks. Serum immunoglobulin E (IgE) and cytokine (tumor necrosis factor [TNF]-α, interleukin [IL]-6, and IL-4) concentrations and the degree of DNA fragmentation in lymphocytes were examined. A histopathological examination (haematoxylin & eosin staining and blue spots of toluidine) of the dorsal skin of mice was performed. To elucidate the mechanism of action, the expression of the thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) were measured in HaCaT cells.
RESULTS
Serum IgE and cytokines (TNF-α and IL-6) levels as well as DNA fragmentation of lymphocytes were significantly decreased in AD-induced mice treated with LLE or LLE(Ch-) compared to those of the control group. The epidermal thickness of the dorsal skin and mast cell infiltration in the LLE group significantly reduced compared to that in the control group. The LLE extracts showed no cytotoxicity up to 1,000 µg/mL in HaCaT cells. LLE or LLE(Ch-)-treated group showed a reduction of TARC and MDC in TNF-α-and IFN-γ-stimulated HaCaT cells.
CONCLUSIONS
These results suggest that LLE potentially improves inflammation by reducing the expression of chemokines that inhibit T helper 2 cell migration. LLE(Ch-) showed similar effects to LLE on blood levels of IgE, TNF-α and IL-6 and protein expression in HaCat cells, but the ultimate effect of skin improvement was not statistically significant. Therefore, both LLE and LLE(Ch-) can be used as functional materials to alleviate AD, but LLE(Ch-) appears to require more research to improve inflammation.
PubMed: 37780223
DOI: 10.4162/nrp.2023.17.5.855 -
Pharmaceuticals (Basel, Switzerland) Sep 2022Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritus, dry skin and redness on the face and inside elbows or knees. Most patients with...
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritus, dry skin and redness on the face and inside elbows or knees. Most patients with AD are children and youths, but it can also develop in adults. In the therapeutic aspect, treatment with corticosteroids for AD has several side effects, such as weight loss, atrophy and acne. In the current study, we examined the anti-inflammatory effect of leaves on HaCaT keratinocytes and 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis-like symptoms in BALB/c mice. We observed that treatment exhibited significant inhibition in the production of inflammatory mediators and proinflammatory cytokines, such as IL-1β, in LPS-induced HaCaT keratinocytes by downregulating the NLRP3 inflammasome activation. Moreover, inhibited the activation of JNK, AP-1 and p65, which resulted in the deformation of NLRP3 in LPS-stimulated HaCaT cells. In mice with DNCB-induced AD-like skin lesions, the administration of ameliorated the clinical symptoms, such as the dermatitis score, thickness of lesional ear skin and TEWL. Furthermore, could attenuate the activation of the immune system, such as reducing the spleen index, concentration of the IgE levels and expression of the NLRP3 inflammasome in ear tissues. Therefore, our results suggest that exerts anti-atopic dermatitis effects by inhibiting the NLRP3 inflammasome-mediated IL-1β.
PubMed: 36297328
DOI: 10.3390/ph15101217 -
Frontiers in Immunology 2023We have integrated dermal dendritic cell surrogates originally generated from the cell line THP-1 as central mediators of the immune reaction in a human full-thickness...
We have integrated dermal dendritic cell surrogates originally generated from the cell line THP-1 as central mediators of the immune reaction in a human full-thickness skin model. Accordingly, sensitizer treatment of THP-1-derived CD14, CD11c immature dendritic cells (iDCs) resulted in the phosphorylation of p38 MAPK in the presence of 1-chloro-2,4-dinitrobenzene (DNCB) (2.6-fold) as well as in degradation of the inhibitor protein kappa B alpha (IκBα) upon incubation with NiSO (1.6-fold). Furthermore, NiSO led to an increase in mRNA levels of IL-6 (2.4-fold), TNF-α (2-fold) and of IL-8 (15-fold). These results were confirmed on the protein level, with even stronger effects on cytokine release in the presence of NiSO: Cytokine secretion was significantly increased for IL-8 (147-fold), IL-6 (11.8-fold) and IL-1β (28.8-fold). Notably, DNCB treatment revealed an increase for IL-8 (28.6-fold) and IL-1β (5.6-fold). Importantly, NiSO treatment of isolated iDCs as well as of iDCs integrated as dermal dendritic cell surrogates into our full-thickness skin model (SM) induced the upregulation of the adhesion molecule clusters of differentiation (CD)54 (iDCs: 1.2-fold; SM: 1.3-fold) and the co-stimulatory molecule and DC maturation marker CD86 (iDCs ~1.4-fold; SM:~1.5-fold) surface marker expression. Noteworthy, the expression of CD54 and CD86 could be suppressed by dexamethasone treatment on isolated iDCs (CD54: 1.3-fold; CD86: 2.1-fold) as well as on the tissue-integrated iDCs (CD54: 1.4-fold; CD86: 1.6-fold). In conclusion, we were able to integrate THP-1-derived iDCs as functional dermal dendritic cell surrogates allowing the qualitative identification of potential sensitizers on the one hand, and drug candidates that potentially suppress sensitization on the other hand in a 3D human skin model corresponding to the 3R principles ("replace", "reduce" and "refine").
Topics: Humans; Dinitrochlorobenzene; Interleukin-8; Langerhans Cells; Interleukin-6; Dendritic Cells; Cytokines
PubMed: 38022577
DOI: 10.3389/fimmu.2023.1276151 -
Journal of Exercise Rehabilitation Aug 2019In general, exercise can help improve overall health and prevent diseases. However, individuals with atopic dermatitis (AD) often lose the desire for physical exercise...
In general, exercise can help improve overall health and prevent diseases. However, individuals with atopic dermatitis (AD) often lose the desire for physical exercise owing to itching caused by sweating. In the present study, we have evaluated the effect of low-intensity tower climbing resistance exercise (TCRE) on extract (DFE; house dust mite extract)- and 2,4-dinitrochlorobenzene-induced AD-like skin lesions in a BALB/c model. Histopathological examination showed reduced thickness of the epidermis/dermis and dermal infiltration of inflammatory cells in the ears. TCRE downregulated serum Ig levels and suppressed mRNA expression of pro-inflammatory cytokines in the ear tissue, and reduced the size and weight of draining lymph nodes (dLNs) and nondraining lymph nodes (ndLNs), along with expression of pro-inflammatory cytokines in CD4 T cells from dLNs and ndLNs. Taken together, we showed that low-intensity TCRE reduced AD symptoms. These results will help improve treatment of AD, and will be of interest to dermatologists as well as to patients with AD.
PubMed: 31523671
DOI: 10.12965/jer.1938276.138 -
Antioxidants (Basel, Switzerland) May 2021This study aimed to investigate the anti-inflammatory, antioxidant, and anti-atopic dermatitis (AD) effects of haplopine, which is one of the active components in...
This study aimed to investigate the anti-inflammatory, antioxidant, and anti-atopic dermatitis (AD) effects of haplopine, which is one of the active components in Haplopine (12.5 and 25 μM) inhibited the mRNA expressions of inflammatory cytokines IL-6, TSLP, GM-CSF, and G-CSF and the protein expressions of IL-6 and GM-CSF in TNF-α/INF-γ-stimulated HaCaT cells. In HO-induced Jukat T cells, haplopine (25 and 50 μM) suppressed the productions of proinflammatory cytokines (IL-4, IL-13, and COX-2) and increased the mRNA and protein expressions of oxidative stress defense enzymes (SOD, CAT, and HO-1) in a concentration-dependent manner. In vivo, haplopine significantly attenuated the development of AD symptoms in 2,4-dinitrochlorobenzene (DNCB)-stimulated Balb/c mice, as evidenced by reduced clinical dermatitis scores, skin thickness measurements, mast cell infiltration, and serum IgE concentrations. These findings demonstrate that haplopine should be considered a novel anti-atopic agent with the potential to treat AD.
PubMed: 34069696
DOI: 10.3390/antiox10050806 -
International Journal of Molecular... Jan 2022Oral melatonin supplement has been shown to improve dermatitis severity in children with AD, but the mechanism of the effect is unclear, and it is uncertain whether...
Oral melatonin supplement has been shown to improve dermatitis severity in children with AD, but the mechanism of the effect is unclear, and it is uncertain whether melatonin has a direct immunomodulatory effect on the dermatitis. Topical melatonin treatment was applied to DNCB-stimulated Balb/c mice, and gross and pathological skin findings, serum IgE, and cytokine levels in superficial lymph nodes were analyzed. Secretion of chemokines and cell proliferative response after melatonin treatment in human keratinocyte HaCaT cells were also studied. We found that in DNCB-stimulated Balb/c mice, topical melatonin treatment improved gross dermatitis severity, reduced epidermal hyperplasia and lymphocyte infiltration in the skin, and decreased IP-10, CCL27, IL-4, and IL-17 levels in superficial skin-draining lymph nodes. Melatonin also reduced cytokine-induced secretion of AD-related chemokines IP-10 and MCP-1 and decreased IL-4-induced cell proliferation in HaCaT cells. Melatonin seems to have an immunomodulatory effect on AD, with IP-10 as a possible target, and topical melatonin treatment is a potentially useful treatment for patients with AD.
Topics: Administration, Topical; Animals; Cytokines; Dermatitis, Atopic; Dinitrochlorobenzene; Disease Models, Animal; Eczema; Female; Immunomodulating Agents; Immunomodulation; Keratinocytes; Male; Melatonin; Mice; Mice, Inbred BALB C; Severity of Illness Index; Skin
PubMed: 35163297
DOI: 10.3390/ijms23031373 -
Experimental and Therapeutic Medicine Sep 2021Atopic dermatitis (AD), also referred to as atopic eczema, is a long-term inflammatory condition that is characterized by itchy, red, swollen and cracked skin....
Atopic dermatitis (AD), also referred to as atopic eczema, is a long-term inflammatory condition that is characterized by itchy, red, swollen and cracked skin. Accumulating evidence suggests that AD is caused by genetic factors, environmental exposure and immune system dysfunction; however, its underlying molecular mechanism remains unclear. Current treatment strategies aim to decrease the severity and frequency of flares. Heme oxygenase-1 (HO-1) is a nuclear factor erythroid 2-related factor 2 (Nrf2)-regulated gene that plays crucial roles against stress, inflammation and oxidation, and exerts cytoprotective effects. Previous studies have reported that treatment of AD induces high expression levels of HO-1 and Nrf2, indicating that HO-1 may play an important role in the treatment of AD. The present study constructed the recombinant protein, cell-penetrating peptide-HO-1 (CPP-HO-1), which was expressed in and isolated with a 6xHis-tag using HiTrap His column (1 ml). AD was established using 4-dinitrochlorobenzene (DNCB) in mice. It was observed that the CPP-HO-1 fusion protein decreased the severity of AD, inhibited scratching in mice and decreased skin inflammation. Taken together, the results of the present study suggested that the CPP-HO-1 fusion protein may play a protective role against DNCB-induced AD in mice.
PubMed: 34306205
DOI: 10.3892/etm.2021.10373 -
Asian Pacific Journal of Allergy and... Aug 2022Olive (Olea europaea Linn) leaves contain a phenolic compound oleuropein (Ole) has antioxidant, anti-inflammatory, and immunomodulatory activities. However, whether Ole...
BACKGROUND
Olive (Olea europaea Linn) leaves contain a phenolic compound oleuropein (Ole) has antioxidant, anti-inflammatory, and immunomodulatory activities. However, whether Ole might be an effective treatment for atopic dermatitis (AD) remains unknown.
OBJECTIVE
This study investigated the functional role of oleuropein in a 2,4-dinitrochlorobenzene-induced AD-like mouse model, with a focus on allergic inflammation.
METHODS
We evaluated cytokine gene expression, COX-2 inflammatory protein production, and Th2 related cytokine regulation of mast cells and eosinophils that infiltrated AD-like skin lesions.
RESULTS
A topical application of Ole significantly reduced Th2-related cytokine gene expression (IL-4 and IL-5) and inflammatory COX-2 protein production in AD-like skin lesions. Additionally, Ole suppressed serum IgE levels. Furthermore, Ole effectively reduced ear swelling and epidermal and dermal thickening.
CONCLUSIONS
These results suggested that, mechanistically, Ole treatment improved allergic inflammation by blocking the Th2-driven inflammatory axis. In conclusion, our findings indicated that Ole showed promise in treating AD by regulating serum IgE and Th2 cytokine levels. Although the effects of Ole on AD in humans require clinical trials, our results provided insights into how AD treatments might be improved.
PubMed: 35964244
DOI: 10.12932/AP-200122-1309 -
International Journal of Molecular... Nov 2021Oleanolic acid (OA) is a pentacyclic triterpenoid, abundantly found in plants of the family, and is well known for its beneficial pharmacological activities....
Oleanolic acid (OA) is a pentacyclic triterpenoid, abundantly found in plants of the family, and is well known for its beneficial pharmacological activities. Previously, we reported the inhibitory effect of OA on mast cell-mediated allergic inflammation. In this study, we investigated the effects of OA on atopic dermatitis (AD)-like skin lesions and its underlying mechanism of action. We evaluated the inhibitory effect of OA on AD-like responses and the possible mechanisms using a 1-chloro-2,4-dinitrochlorobenzene (DNCB)-induced AD animal model and tumor necrosis factor (TNF)-α/interferon (IFN)-γ-stimulated HaCaT keratinocytes. We found that OA has anti-atopic effects, including histological alterations, on DNCB-induced AD-like lesions in mice. Moreover, it suppressed the expression of Th2 type cytokines and chemokines in the AD mouse model and TNF-α/IFN-γ-induced HaCaT keratinocytes by blocking the activation of serine-threonine kinase Akt, nuclear factor-κB, and the signal transducer and activator of transcription 1. The results demonstrate that OA inhibits AD-like symptoms and regulates the inflammatory mediators; therefore, it may be used as an effective and attractive therapeutic agent for allergic disorders, such as AD. Moreover, the findings of this study provide novel insights into the potential pharmacological targets of OA for treating AD.
Topics: Animals; Cell Line; Cytokines; Dermatitis, Atopic; Dinitrochlorobenzene; Disease Models, Animal; Humans; In Vitro Techniques; Inflammation; Irritants; Keratinocytes; Mice; Mice, Inbred ICR; NF-kappa B; Oleanolic Acid; Signal Transduction
PubMed: 34769428
DOI: 10.3390/ijms222112000 -
Frontiers in Pharmacology 2021Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by complex immune dysregulation and closely related to the gut microbiome. The present study...
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by complex immune dysregulation and closely related to the gut microbiome. The present study investigated the microbiome-mediated effect of (SHCGT) on AD-like symptoms induced by 2,4-dinitrochlorobenzene (DNCB) in BALB/c mice. DNCB was applied regularly to the ear and dorsal skin of BALB/c mice, and SHCGT was administered orally daily for 2 weeks. The composition of the gut microbiota was analyzed using 16S rRNA sequencing, and the effect of gut microbiome-derived metabolites, specifically short-chain fatty acids (SCFAs), was evaluated in tumor necrosis factor-alpha (TNF-α)- and interferon-gamma (IFN-γ)-treated HaCaT cells. SHCGT alleviated DNCB-induced symptoms of AD and the immune response to AD by decreasing the plasma immunoglobulin E level and splenic interleukin-4, interleukin-10, TNF-α, and IFN-γ levels. The gut microbiome composition and the damaged gut epithelial barrier in mice with AD were also significantly altered by SHCGT, and the reduced SCFA levels therein were elevated. We found that SFCAs directly inhibited the mRNA expression of IL-6 and ICAM-1 in TNF-α- and INF-γ-treated HaCaT cells. The finding that SHCGT regulates the gut microbiome and improves DNCB-induced AD in mice suggests that this herbal medicine has therapeutic potential in patients with AD.
PubMed: 34616298
DOI: 10.3389/fphar.2021.722730