Water soluble extracts from Actinidia arguta, PG102, attenuates house dust mite-induced murine atopic dermatitis by inhibiting the mTOR pathway with Treg generation

Bae, Min-Jung; Lim, Seonung; Lee, Doo Suk; Ko, Kyoung Ryang; Lee, Wonwoo; Kim, Sun‐Young

doi:10.1016/j.jep.2016.08.004

Cited by 20 publications

(13 citation statements)

References 43 publications

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“…Reduction in IL-17A level could be due to direct suppression of IL-17A-producing cells or due to upregulation of anti-inflammatory mediators. The latter may be a possible explanation based on the previous report describing an increase in regulatory T cell generation by PG102 [ 17 ]. It would be worth further investigating the cellular target of PG102 in psoriasis-like skin inflammation.…”

Section: Discussionmentioning

confidence: 90%

“…PG102 is a botanical extract derived from an edible portion of Actidinia arguta . It has previously been shown to contain potent anti-inflammatory and anti-oxidative activities both in vitro and in vivo [ 15 , 16 , 17 , 29 , 30 ]. Based on these reports, we investigated the effect of PG102 on the murine IMQ-induced psoriasis-like skin inflammation model.…”

Section: Discussionmentioning

confidence: 99%

“…PG102 is a water-soluble extract of hardy kiwifruit Actinidia arguta, which is rich in flavonoids such as isoquercitrin, vitamin C, and organic acids such as quinic acid [ 13 , 14 ]. It has been shown to contain strong anti-inflammatory and anti-oxidative activities, alleviating symptoms of spontaneous dermatitis, and atopic dermatitis in respective animal models by regulating the expression of chemokines and cytokines and by promoting differentiation of regulatory T cells [ 15 , 16 , 17 ]. Its efficacy and safety were not limited to animal studies, exploratory human clinical study involving 90 asymptomatic subjects with atopy (serum total Immunoglobulin E (IgE) > 300 IU/mL) had also shown its potential as a safe immunosuppressive agent [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

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A Water-Soluble Extract from Actinidia arguta Ameliorates Psoriasis-Like Skin Inflammation in Mice by Inhibition of Neutrophil Infiltration

et al. 2018

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Psoriasis is a chronic inflammatory disease with complex etiology involving multiple factors. Current treatment methods are highly limited and there is a strong need for the development of safer and efficacious agents. We have previously shown that a water-soluble extract derived from hardy kiwifruit Actinidia arguta, called PG102, shows potent anti-inflammatory effects. Based on its reported biological activities, the effects of PG102 were examined on imiquimod-induced psoriasis-like skin inflammation. Our results showed that topical application of PG102 ameliorates clinical symptoms of psoriasis, reducing skin thickness and Interleukin (IL)-17A level in draining lymph nodes without causing any adverse effects. Treatment with PG102 on cytokine-stimulated HaCaT cells suppressed hyperproliferation and downregulated the expression of various chemokines and antimicrobial peptides known to induce neutrophil infiltration. These anti-inflammatory activities of PG102 were mediated via inhibition of NF-κB and signal transducer of activation (STAT) signaling. We also found decreased neutrophil chemotaxis both in vitro and in vivo. Taken together, PG102 has potential as a safe and effective reagent for the treatment of psoriasis.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Water-Soluble Extract from Actinidia arguta Ameliorates Psoriasis-Like Skin Inflammation in Mice by Inhibition of Neutrophil Infiltration

et al. 2018

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“…Decreased number of Tregs in inflammatory sites is related with inflammatory disease, including AD. Bae et al, reported that mice having dust mite-induced AD showed reduced Foxp3 expression in both inflamed site and dLN [ 28 ]. Loss of Tregs caused by Foxp3 deficiency caused a multi-organ inflammatory response including skin inflammation resembling AD associated with elevated serum IgE levels, eosinophilia, dysregulated Th1 and Th2 cytokine production, and other autoimmune symptoms [ 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

Bee Venom Phospholipase A2 Ameliorates House Dust Mite Extract Induced Atopic Dermatitis Like Skin Lesions in Mice

Jung

Baek

Kang

et al. 2017

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Atopic dermatitis (AD) is a biphasic inflammatory skin disease that is provoked by epidermal barrier defects, immune dysregulation, and increased skin infections. Previously, we have demonstrated that bvPLA2 evoked immune tolerance by inducing regulatory T cells (Treg), and thus alleviated Th2 dominant allergic asthma in mice. Here, we would like to determine whether treatment with bvPLA2 exacerbates the AD-like allergic inflammations induced by house dust mite extract (DFE) in a murine model. Epidermal thickness, immune cell infiltration, serum immunoglobulin, and cytokines were measured. Ear swelling, skin lesions, and the levels of total serum IgE and Th1/Th2 cytokines were elevated in DFE/DNCB-induced AD mice. Topical application of bvPLA2 elicited significant suppression of the increased AD symptoms, including ear thickness, serum IgE concentration, inflammatory cytokines, and histological changes. Furthermore, bvPLA2 treatment inhibited mast cell infiltration into the ear. On the other hand, Treg cell depletion abolished the anti-atopic effects of bvPLA2, suggesting that the effects of bvPLA2 depend on the existence of Tregs. Taken together, the results revealed that topical exposure to bvPLA2 aggravated atopic skin inflammation, suggesting that bvPLA2 might be a candidate for the treatment of AD.

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“…ex Miq., an edible fruit belonging to the genus Kiwifruit, is widely prescribed in Korea for a variety of inflammatory and allergic diseases. We previously reported that PG102 could effectively ameliorate pathologic conditions in various allergic disease mouse models, including atopic dermatitis, rhinitis, asthma and food allergies by regulating the expression levels of Th1 and Th2 cytokines [26,27,28,29,30]. Consistent with these data, the treating with PG102 of 90 individuals who had abnormally high levels of IgE (>300 IU/mL), significantly reduced the serum levels of IgE, ECP, TARC, IL-4, and IL-5, compared with the placebo group [31].…”

Section: Introductionmentioning

confidence: 99%

Water-Soluble Extract from Actinidia arguta (Siebold & Zucc.) Planch. ex Miq. and Perilla frutescens (L.) Britton, ACTPER, Ameliorates a Dry Skin-Induced Itch in a Mice Model and Promotes Filaggrin Expression by Activating the AhR Signaling in HaCaT Cells

et al. 2019

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With a complex etiology involving multiple factors, the condition known as itch is a primary symptom of many skin diseases. Current treatment methods are ineffective for addressing itches caused by dry skin, for example. We developed a botanical extract, ACTPER, made from a mixture of Actinidia arguta and Perilla frutescens, which have traditionally been used to treat itch. The quality of ACTPER as a research agent was controlled in our experiment by cell-based bioassays, as well as by high-performance liquid chromatography (HPLC), using two chemical markers. In the acetone-induced dry skin mice model, the oral administration of ACTPER alleviated dry skin-related skin properties and itching behavior. The RNA and protein expression of the filament aggregating protein (filaggrin) gene, a key factor involved in the regulation of skin barrier function, was significantly increased, as measured by quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence assay. To understand the underlying mechanism(s) at the molecular level, HaCaT cells, a human keratinocyte-derived cell line, were treated with various concentrations of ACTPER. We found that the protein expression of filaggrin was indeed upregulated by ACTPER in a dose dependent manner. Data from experiments involving the reporter plasmid containing the xenobiotic response element (XRE), and the chemical antagonist for the aryl hydrocarbon receptor (AhR), indicated that the ACTPER-mediated upregulation of filaggrin was controlled through the activation of the AhR signaling pathway. The molecular docking simulation study predicted that ACTPER might contain chemical compounds that bind directly to AhR. Taken together, our results suggest that ACTPER may provide the platform, based upon which a variety of safe and effective therapeutic agents can be developed to treat itch.

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Water soluble extracts from Actinidia arguta, PG102, attenuates house dust mite-induced murine atopic dermatitis by inhibiting the mTOR pathway with Treg generation

Cited by 20 publications

References 43 publications

A Water-Soluble Extract from Actinidia arguta Ameliorates Psoriasis-Like Skin Inflammation in Mice by Inhibition of Neutrophil Infiltration

A Water-Soluble Extract from Actinidia arguta Ameliorates Psoriasis-Like Skin Inflammation in Mice by Inhibition of Neutrophil Infiltration

Bee Venom Phospholipase A2 Ameliorates House Dust Mite Extract Induced Atopic Dermatitis Like Skin Lesions in Mice

Water-Soluble Extract from Actinidia arguta (Siebold & Zucc.) Planch. ex Miq. and Perilla frutescens (L.) Britton, ACTPER, Ameliorates a Dry Skin-Induced Itch in a Mice Model and Promotes Filaggrin Expression by Activating the AhR Signaling in HaCaT Cells

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