scholarly journals Effect of Neferine on DNCB-Induced Atopic Dermatitis in HaCaT Cells and BALB/c Mice

2021 ◽  
Vol 22 (15) ◽  
pp. 8237
Author(s):  
Chung-Chi Yang ◽  
Yen-Ling Hung ◽  
Wen-Chin Ko ◽  
Yi-Ju Tsai ◽  
Jia-Feng Chang ◽  
...  

Atopic dermatitis (AD) is a chronic and persistent inflammatory skin disease characterized by eczematous lesions and itching, and it has become a serious health problem. However, the common clinical treatments provide limited relief and are accompanied by adverse effects. Therefore, there is a need to develop novel and effective therapies to treat AD. Neferine is a small molecule compound isolated from the green embryo of the mature seeds of lotus (Nelumbo nucifera). It has a bisbenzylisoquinoline alkaloid structure. Relevant studies have shown that neferine has many pharmacological and biological activities, including anti-inflammatory, anti-thrombotic, and anti-diabetic activities. However, there are very few studies on neferine in the skin, especially the related effects on inflammatory skin diseases. In this study, we proved that it has the potential to be used in the treatment of atopic dermatitis. Through in vitro studies, we found that neferine inhibited the expression of cytokines and chemokines in TNF-α/IFN-γ-stimulated human keratinocyte (HaCaT) cells, and it reduced the phosphorylation of MAPK and the NF-κB signaling pathway. Through in vivo experiments, we used 2,4-dinitrochlorobenzene (DNCB) to induce atopic dermatitis-like skin inflammation in a mouse model. Our results show that neferine significantly decreased the skin barrier damage, scratching responses, and epidermal hyperplasia induced by DNCB. It significantly decreased transepidermal water loss (TEWL), erythema, blood flow, and ear thickness and increased surface skin hydration. Moreover, it also inhibited the expression of cytokines and the activation of signaling pathways. These results indicate that neferine has good potential as an alternative medicine for the treatment of atopic dermatitis or other skin-related inflammatory diseases.

2017 ◽  
Vol 2017 ◽  
pp. 1-10
Author(s):  
Joonhyoung Yang ◽  
Sangyeon Min ◽  
Seungug Hong

Background. Atopic Dermatitis (AD) is one of the most common chronic inflammatory skin diseases. Objective. This experiment aimed to study the effects of Fermented Flax Seed Oil (FFSO) on symptoms such as redness, eczema, and pruritus induced by AD. Materials and Methods. AD-induced NC/Nga mice were used to observe the immunological and therapeutic effects of FFSO on skin in vivo. Raw 264.7 cells were used to investigate the effects of FFSO in cells. Fc receptor expression and concentration of beta-hexosaminidase were measured. Nitric oxide assay, Western blotting, real-time PCR, image analysis, and statistical analysis were performed in vitro. Results. In the immunohistochemical results, p-ERK 1/2 expression decreased, fibrogenesis strongly increased, and distribution reduction is observed. Distribution of IL-4-positive cells in the corium near the basal portion of the epithelium in the AT group was reduced. FFSO treatment reduced the number of cells showing NF-κB p65 and iNOS expression. The level of LXR in the AT group was higher than that in the AE group, and elevation of PKC expression was significantly reduced by FFSO treatment. Conclusion. FFSO could alleviate symptoms of AD such as epithelial damage, redness, swelling, and pruritus.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1043.3-1044
Author(s):  
S. Borthakur ◽  
P. Mande ◽  
D. Rios ◽  
P. Halvey ◽  
A. Boisvert ◽  
...  

Background:Current treatment approaches for autoimmune conditions comprise primarily of systemic immunosuppressants or cytokine blockade. The concentration of therapeutic molecules to the tissues that are the sites of autoimmune and inflammatory diseases is a promising approach with the potential to induce therapeutic benefit and avert risks associated with systemic immunotherapies. Pandion Therapeutics is developing a bifunctional antibody platform that can drive localized immune modulation by combining a “tether antibody” that targets a tissue of choice and “an effector end” that activates specific regulatory immune pathways to restore immune-homeostasis.Objectives:Here we report the engineering of a skin-tethered PD-1 agonist and a skin-tethered CD39 that inhibit T cell activation and function and deplete local ATP, respectively, modulating different arms of the immune system in a tissue specific manner.Methods:Biophysical assays were performed to characterize Skin-tethered immune effectors for drug-like properties and in vitro and in vivo assays for target binding, cellular activity and tissue specific-localization. Moreover, these bifunctionals were tested in pathway-relevant preclinical models such as Vitiligo and Contact Hypersensitivity.Results:Biophysical characterization of the bifunctional molecules showed desired drug like properties including specificity, stability, and manufacturability. The skin tethered bifunctionals showed effector activity in in vitro assays and selectively localized to the skin. Skin localization strikingly correlated with a tether-dependent efficacy compared to a non-tether control.Conclusion:We believe that this therapeutic approach has the potential to drive the resolution of cutaneous inflammation, providing an opportunity for developing new targeted therapies for autoimmune and inflammatory skin diseases.Disclosure of Interests:Susmita Borthakur Shareholder of: Pandion Therapeutics Inc., Employee of: Pandion therapeutics Inc., Purvi Mande: None declared, Daniel Rios: None declared, Patrick Halvey: None declared, Angela Boisvert: None declared, MIchael Rowe: None declared, Anisha Agrawal: None declared, Minasri Borah: None declared, Mike Cianci: None declared, Joanne L. Viney Shareholder of: Pandion therapeutics Inc., Consultant of: Harpoon, Finch, Quench, HotSpot, Employee of: Pandion Therapeutics Inc., Katalin Kis-Toth: None declared, Kevin L. Otipoby Shareholder of: Pandion Therapeutics Inc., Employee of: Pandion Therapeutics Inc., Ivan Mascanfroni: None declared, Nathan Higginson-Scott Shareholder of: Pandion Therapeutics Inc., Consultant of: Mediar Tx, Employee of: Pandion Therapeutics Inc.


Plants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1230
Author(s):  
Sumin Pyeon ◽  
Ok-Kyung Kim ◽  
Ho-Geun Yoon ◽  
Shintae Kim ◽  
Kyung-Chul Choi ◽  
...  

Atopic dermatitis (AD) is a chronic inflammatory skin disease caused by immune hypersensitivity reaction. The cause of AD is unclear, but its symptoms have a negative effect on quality of life; various treatment methods to alleviate these symptoms are underway. In the present study, we aimed to evaluate in vitro antioxidant and anti-inflammatory effects of Rubus coreanus water extract (RCW) on AD. Total phenolic compounds and flavonoid content of RCW were 4242.40 ± 54.84 mg GAE/g RCE and 1010.99 ± 14.75 mg CE/g RCW, respectively. RCW reduced intracellular reactive oxygen species level and increased the action of antioxidant enzymes, such as catalase, superoxide dismutase, and glutathione peroxidase in tumor necrosis factor-α (TNF-α)/interferon-γ (IFN-γ)-stimulated HaCaT cells. Moreover, mRNA expression of the pro-inflammatory cytokines, including TNF-α, interleukin-1β, and interleukin-6, was downregulated by RCW in the TNF-α/IFN-γ-stimulated cells. The levels of inflammatory chemokines (thymus- and activation-regulated chemokine; eotaxin; macrophage-derived chemokine; regulated on activation, normal T-cell expressed and secreted; and granulocyte-macrophage colony-stimulating factor) and intercellular adhesion molecule-1 were decreased in the TNF-α/IFN-γ-stimulated HaCaT cells after RCW treatment. Additionally, the mRNA expression levels of filaggrin and involucrin, proteins that form the skin, were increased by RCW. Furthermore, RCW inhibited the nuclear factor kappa-light-chain-enhancer of the activated B cells pathway in the TNF-α/IFN-γ-stimulated HaCaT cells. Collectively, the present investigation indicates that RCW is a potent substance that inhibits AD.


2022 ◽  
Vol 23 (1) ◽  
pp. 553
Author(s):  
Ga-Yul Min ◽  
Ji-Hye Kim ◽  
Tae-In Kim ◽  
Won-Kyung Cho ◽  
Ju-Hye Yang ◽  
...  

Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with a type 2 T helper cell (Th2) immune response. The IndigoPulverata Levis extract (CHD) is used in traditional Southeast Asian medicine; however, its beneficial effects on AD remain uninvestigated. Therefore, we investigated the therapeutic effects of CHD in 2,4-dinitrochlorobenzene (DNCB)-induced BALB/c mice and tumor necrosis factor (TNF)-α- and interferon gamma (IFN)-γ-stimulated HaCaT cells. We evaluated immune cell infiltration, skin thickness, and the serum IgE and TNF-α levels in DNCB-induced AD mice. Moreover, we measured the expression levels of pro-inflammatory cytokines, mitogen-activated protein kinase (MAPK), and the nuclear factor-kappa B (NF-κB) in the mice dorsal skin. We also studied the effect of CHD on the translocation of NF-κB p65 and inflammatory chemokines in HaCaT cells. Our in vivo results revealed that CHD reduced the dermis and epidermis thicknesses and inhibited immune cell infiltration. Furthermore, it suppressed the proinflammatory cytokine expression and MAPK and NF-κB phosphorylations in the skin tissue and decreased serum IgE and TNF-α levels. In vitro results indicated that CHD downregulated inflammatory chemokines and blocked NF-κB p65 translocation. Thus, we deduced that CHD is a potential drug candidate for AD treatment.


Pharmaceutics ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 684 ◽  
Author(s):  
Christian Gorzelanny ◽  
Christian Mess ◽  
Stefan W. Schneider ◽  
Volker Huck ◽  
Johanna M. Brandner

Although, drugs are required in the various skin compartments such as viable epidermis, dermis, or hair follicles, to efficiently treat skin diseases, drug delivery into and across the skin is still challenging. An improved understanding of skin barrier physiology is mandatory to optimize drug penetration and permeation. The various barriers of the skin have to be known in detail, which means methods are needed to measure their functionality and outside-in or inside-out passage of molecules through the various barriers. In this review, we summarize our current knowledge about mechanical barriers, i.e., stratum corneum and tight junctions, in interfollicular epidermis, hair follicles and glands. Furthermore, we discuss the barrier properties of the basement membrane and dermal blood vessels. Barrier alterations found in skin of patients with atopic dermatitis are described. Finally, we critically compare the up-to-date applicability of several physical, biochemical and microscopic methods such as transepidermal water loss, impedance spectroscopy, Raman spectroscopy, immunohistochemical stainings, optical coherence microscopy and multiphoton microscopy to distinctly address the different barriers and to measure permeation through these barriers in vitro and in vivo.


2019 ◽  
Vol 6 (10) ◽  
pp. 191184 ◽  
Author(s):  
Fangbin Hu ◽  
Weikang Liu ◽  
Liuliu Yan ◽  
Fanhui Kong ◽  
Kun Wei

Astaxanthin is a xanthophyll carotenoid with high beneficial biological activities, such as antioxidant function and scavenging oxygen free radicals, but its application is limited because of poor water solubility and low bioavailability. Here, we prepared and optimized poly(lactic-co-glycolic acid) (PLGA) nanoparticles loaded with astaxanthin using the emulsion solvent evaporation technique and investigated the anti-photodamage effect in HaCaT cells. The four-factor three-stage Box–Behnken design was used to optimize the nanoparticle formulation. The experimental determination of the optimal nanoparticle size was 154.4 ± 0.35 nm, the zeta potential was 22.07 ± 0.93 mV, encapsulation efficiency was 96.42 ± 0.73% and drug loading capacity was 7.19 ± 0.12%. The physico-chemical properties of the optimized nanoparticles were characterized by dynamic light scattering, scanning electron microscopy, transmission electron microscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry and thermo-gravimetric analyser. In vitro study exhibited the excellent cell viability and cellular uptake of optimized nanoparticles on HaCaT cells. The anti-photodamage studies (cytotoxicity assay, reactive oxygen species content and JC-1 assessment) demonstrated that the optimized nanoparticles were more effective and safer than pure astaxanthin in HaCaT cells. These results suggest that our PLGA-coated astaxanthin nanoparticles synthesis method was highly feasible and can be used in cosmetics or the treatment of skin diseases.


2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Mouna Moutia ◽  
Norddine Habti ◽  
Abdallah Badou

Allium Sativum L. (garlic), which is a species of the onion family, Alliaceae, is one of the most used plants in traditional medicine worldwide. More than 200 chemicals with diverse properties have been found in garlic extracts. Several garlic compounds were suggested to be efficient in improving various pathologies including certain types of cancer. This paper is an overview of data about garlic biological activities in vitro and/or in vivo on immune cells, on the development of certain inflammatory diseases, and on different types of carcinomas and sarcomas. Garlic and its compounds were found to have notable antioxidant properties. Garlic therapeutic potential has also been studied in several inflammatory diseases such as allergic-airway inflammation, inflammatory bowel disease, arthritic rheumatism, and atherosclerosis. Furthermore, garlic was found to be able to maintain the immune system homeostasis and to exhibit beneficial effects on immune cells especially through regulation of proliferation and cytokine gene expression. Finally, we will show how major garlic components such as sulfur compounds and polyphenols might be responsible for the garlic biological activities revealed in different situations. If identified, specific compounds present in garlic could potentially be used in therapy.


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