2,3-Dehydrosilybin Suppresses IL-31-Associated Pruritus Factors in Astrocytes and Microglia

Ji Hyeon Park,Jae Young Shin,Feng Wang,Suping Hao,Da Jeong Shin,Seon Il Jang,Byoung Ok Cho 한국식품영양과학회 2021 한국식품영양과학회 학술대회발표집 Vol.2021 No.10

Chronic pruritus is the main symptom that increases the suffering of patients in hypersensitivity disorder disease. IL-31 is a pruritic cytokine with a primary objective to control itch. A 2,3-dehydrosilybin (DHS) is a type of flavonoid extracted from the seeds of milk thistle. DHS has been reported to have hepatoprotective, angiogenic, and antioxidant effects. This study investigated the effect of DHS pretreatment on IL-31-associated pruritus in astrocytes and microglia. Pretreatment with DHS inhibited the production of IL-31 by lipopolysaccharide (LPS) and interferon gamma (IFN-γ) stimulation in microglia. Pretreatment with DHS inhibited the phosphorylation of MAPK, STAT1 and NF-κB by LPS plus IFN-γ stimulation in microglia. In addition, DHS suppressed the expression of IL-31 receptor A in IL-31-treated astrocytes. DHS also inhibited lipocalin2 production in IL-31 stimulated astrocytes. Taken together, DHS has potential as a therapeutic agent for symptom relief by down-regulating the IL-31-mediated pruritus mechanism in microglia and astrocytes.

감껍질 열수 및 초임계 유체 추출물의 항아토피 효과

조병옥(Byoung Ok Cho),윤홍화(Hong Hua Yin),방숭주(Chong Zhou Fang),신재영(Jae Young Shin),하혜옥(Hye Ok Ha),김상준(Sang Jun Kim),정승일(Seung Il Jeong),장선일(Seon Il Jang) 한국식품과학회 2015 한국식품과학회지 Vol.47 No.3

본 연구에서는 고종시 감껍질을 열수 추출 및 초임계 유체 추출하여 아토피 피부염 증상 억제 효과를 밝히고, 항염 효능을 나타내는 기능성 소재로서의 이용 가능성을 알아보고자 하였다. 그 결과 육안 평가를 통해 피부의 홍반(erythema), 가려움과 피부의 건조상태(pruritus and dry skin), 부종과 혈종(edema and excoriation), 짓무름(erosion), 그리고 태선화(lichenification)와 같은 아토피 피부염 같은 증상이 AD 모델에서 증가하였지만, SPPE와 PPWE를 투여하였을 경우 완화되는 것을 확인할 수 있었으며, SPPE가 PPWE보다 더 뛰어난 효과를 나타내었다. 피부 두께와 염증 세포의 침윤은 AD 모델에서 크게 증가하였지만, SPPE와 PPWE를 투여하였을 경우 감소하는 것을 확인할 수 있었으며, SPPE가 PPWE보다 더 뛰어난 효과를 나타내었다. 혈청 중의 IgE와 IL-4의 수치를 측정한 결과, AD 모델에서 크게 증가하였으나 SPPE와 PPWE를 투여하였을 경우 감소하는 것을 확인할 수 있었으며, SPPE가 PPWE보다 더 뛰어나게 억제하는 효과를 나타내었다. 또한 RAW264.7 세포에 SPPE를 처리하였을 경우 염증매개 인자인 NO, PGE2, IL-6, IL-1β의 생성량이 유의적의로 감소하였고, PPWE의 경우 NO, PGE2, IL-1β의 생성을 억제한 반면 IL-6 생성 억제에는 영향을 나타내지 않았다. 이러한 염증 매개인자 억제 효능은 SPPE가 PPWE보다 더 뛰어나게 억제하는 것을 확인하였다. 따라서 감껍질 추출물은 아토피 피부염 증상 개선과 염증관련 질환 치료를 위한 기능성 천연물 소재로 유용하게 활용될 수 있을 것으로 판단된다. This study aimed to investigate the anti-atopic effect of hot water (PPWE) and supercritical-carbon dioxide fluid extract of persimmon peels (SPPE) on atopic dermatitis (AD)-like skin lesions in hairless mice. Histological analyses demonstrated that SPPE treatment more strongly inhibited the dermal infiltration of inflammatory cells in AD-like skin lesions than that by PPWE. Compared to PPWE, SPPE significantly decreased the dermatitis clinical score and the epidermal thickness and potently suppressed serum IgE and interleukin (IL)-4 production in hairless mice with AD. Furthermore, compared to PPWE, SPPE potently inhibited the production of nitric oxide, prostaglandin E₂, and proinflammatory cytokines such as IL-6 and IL-1β in lipopolysaccharide-stimulated RAW264.7 macrophages. These results suggested that SPPE exhibited anti-atopic dermatitis activity via the regulation of inflammatory responses.

Luteolin and apigenin inhibits itch-related IL-31 and IL-33 cytokines in mouse astrocytes

Seon Il Jang,Denis Nchang Che,Byoung Ok Cho,Jae Young Shin,Hyun Ju Kang,Ji-su Kim,Young-Soo Kim 한국식품영양과학회 2019 한국식품영양과학회 학술대회발표집 Vol.2019 No.10

DLE and Myricitrin attenuate IL-6-induced astrocyte activation and pruritus by targeting STAT3 signaling pathways

Jae Young Shin,Byoung Ok Cho,Ji Hyeon Park,Da Jeong Shin,Feng Wang,Suping Hao,Eun Seo Kang,Seon Il Jang 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.7

Diospyros lotus (date plum) is a deciduous plant native to Asia including Korea and China. In traditional medicine, it has been used as an anticancer, antidiabetic, and antipyretic agent. Recently, the effect of Diospyros lotus on the improvement of sensitive skin was also reported. Chronic pruritus is one of the most difficult to manage symptoms of inflammatory skin disease. Recently, it was found that activation of STAT3 in astrocytes contributes to chronic pruritus. In this study, the effects of Diospyros lotus leaf extract (DLE) and its main component myricitrin on pruritus were investigated in in vitro and in vivo. Astrocytes were pretreated with DLE and myricitrin and stimulated with IL-6 to measure activation of STAT3 and production of lipocalin-2 (LCN2). We also investigated the effects of DLE and myricitrin on itch in chloroquine-induced itch mouse model. DLE and myricitrin blocked STAT3 activation and inhibited the release of LCN2 in astrocytes. Moreover, DLE and myricitrin inhibited the scratching behavior and inhibited the expression of glial fibrillary acidic protein (GFAP) in chloroquine-injected mice. Collectively, these studies suggest that modulation of DLE and myricitrin signaling pathways contribute to pruritus inhibition, thus suggesting potential for the prevention and/or treatment of pruritus caused by hypersensitivity skin conditions.

관절1호방이 Collagen Ⅱ로 유발된 관절염 억제에 관한 연구

한규진 ( Kyu Jin Han ),진광선 ( Kwang Seon Jin ),신혜란 ( Hye Ran Shin ),윤일지 ( Il Ji Yoon ),최승훈 ( Seung Hoon Choi ),오민석 ( Min Seok Oh ) 한방재활의학과학회 2005 한방재활의학과학회지 Vol.15 No.4

Objectives : The aim of this study was to know the immunity responses of Gwanjulbang-1(Quanjiefang-1)(hereinafter referred to GJB-1) to on Rheumatoid Arthritis in Collagen-induced Arthritis(CIA) Mice Methods : For this purpose, experiments were performed to measure the cytotoxicity against mLFC, hFLSs and the production of proinflammatory cytokines IL-1β, IL-6, TNF-α, IFN-γ in hFLSs and the production of pro-inflammatory cytokines IL-4, IL-10 and the value of CD3+(T), CD19+(B), CD3+/CD69+, CD4, γδ T cells, CD4+/CD25+ Results : 1. The cytotoxicity against mLFC, hFLSs were not measured. 2. The production of pro-inflammatory cytokines IFN-γ were reduced in hFLSs. 3. The production of pro-inflammatory cytokines IL-4, IL-10 were increased. 4. Statistically significant value of CD3+(T), CD19+(B), CD3+/CD69+, CD4, γδ T cells, CD4+/CD25+ compared with control group, wild type, MTX. Conclusions : Comparison of the results for this study showed that GJB-1 had immunomodulatory effects of suppressing or enhancing. So we expect that GJB-1 should be used as a effective drugs for not only rheumatoid arthritis but also another auto-immune disease. Therefore we have to survey continuously in looking for the effective substance and mechanism in the future.

신선기보탕(神仙氣步湯)이 Collagen Ⅱ 유발관절염(誘發關節炎)의 발생 및 치료에 미치는 영향

구본길 ( Bon Kil Koo ),신혜란 ( Hye Lan Shin ),진광선 ( Kwang Seon Jin ),윤일지 ( Il Ji Yoon ),오민석 ( Min Suck Oh ) 한방재활의학과학회 2005 한방재활의학과학회지 Vol.15 No.4

Objectives: Cytokines play key roles in spontaneous autoimmune arthritis in CIA(collagen induced arthritis) mice, a model of rheumatoid arthritis. The object of study is to evaluate the effect of IL-6, TNF-α on development of collagen induced arthritis, on humoral and cellular immunity and on the endogenous production of IL-6, TNF-α in DBA/1J mice. Methods: DBA/1J mice were immunized with 100㎍ bovine type II collagen in 0.1㎖ Freund`s complete adjuvant. There are three groups in this study, Which are wild type(WT), CIA-control and CIA-SSKBT(350㎎/㎏). Levels of anti-collagen antibodies, serum IL-6 and TNF-α were measured at the end of study. At week 6, CIA-control group developed arthritis while CIA-SSKBT group showed far less incidence and severity of arthritis. Result and Conclusions: This study shows that SSKBT inhibits inflammatory effect of IL-6, TNF-α.

Antipruritic effect of 2,3-dehydrosilybin in IL-6-induced astrocyte and chloroquine-treated mice by targeting STAT3 signaling pathways

Byoung Ok Cho,Jae Young Shin,Ji Hyeon Park,Feng Wang,Suping Hao,Da Jeong Shin,Seon Il Jang 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.7

Chronic pruritus is a symptom that reduces the quality of life of patients with inflammatory skin disease. Persistent activation of astrocytic signal transducer and activator of transcription 3 (STAT3) contributes to the elevation of chronic pruritus. STAT3 activation increases lipocalin-2 (LCN2) expression and enhances pruritus. A 2,3-dehydrosilybin (DHS) is a type of flavonoid extracted from the seeds of milk thistle. DHS has been reported to have hepatoprotective, angiogenic, and antioxidant effects. In this study, the inhibitory effect of DHS on chronic pruritus was investigated in IL-6-treated astrocytes and chloroquine-injected mice. As a result, DHS prevented STAT3 activation and LCN2 production in IL-6-treated astrocytes. Moreover, DHS inhibited scratching and inhibited the expression of glial fibrillary acidic protein (GFAP) in chloroquine-injected mice. It also reduced the level of inflammatory cytokines in the mice serum. In conclusion, it was demonstrated that DHS suppressed itch through the STAT3 signaling pathway. Thus our results suggest that DHS can prevent and/or treat chronic itch.

Soybean Fermented with Bacillus amyloliquefaciens (Cheonggukjang) Ameliorates Atopic Dermatitis-Like Skin Lesion in Mice by Suppressing Infiltration of Mast Cells and Production of IL-31 Cytokine

( Byoung Ok Cho ),( Jae Young Shin ),( Ji-su Kim ),( Denis Nchang Che ),( Hyun Ju Kang ),( Do-youn Jeong ),( Seon Il Jang ) 한국미생물생명공학회(구 한국산업미생물학회) 2019 Journal of microbiology and biotechnology Vol.29 No.5

The present study was conducted with the aim to investigate the ameliorative effects of a new soybean product (cheonggukjang) fermented with Bacillus amyloliquefaciens SCGB1 (SFBA) in atopic dermatitis (AD) mouse model. Visual evaluation of AD induction in the mice indicated the remarkable control of SFBA in reducing the pathological severity of AD-like skin lesions reported as the SCORAD score of AD clinical symptoms. The results revealed that SFBA reduced dorsal skin and epidermal thickness to a similar extent with prednisolone. Further analysis revealed the dominance of SFBA in restraining mast cell infiltration in the dermis; immunoglobulin-E expression in serum; and TH2 IL-4 cytokine and itch-related IL-31 cytokine in the mice skin and serum. SFBA also suppressed scratching behaviours in mice induced by compound 48/80. Further histological findings also revealed the alleviation of collagen fiber deposition in dermal skin of the AD mice model. These actions of SFBA were examined to be mediated by its suppression of the phosphorylation activation of key signalling molecules such as NF-κB and MAPK responsible for the induction of cytokine production. Thus, SFBA can be considered as a promising functional food for managing clinical, histological and immunological spectra associated with AD.

고욤잎, 감잎 및 뽕잎 복합추출물의 항아토피 효과

조병옥(Byoung Ok Cho),윤홍화(Hong Hua Yin),신재영(Jae Young Shin),방숭주(Chong Zhou Fang),체 데니스 창(Chong Zhou Fang),장선일(Seon Il Jang) 한국식품영양과학회 2016 한국식품영양과학회지 Vol.45 No.4

본 연구는 고욤잎, 감잎 및 뽕잎을 단독으로 사용하기보다 혼합하여 사용할 경우 고욤잎, 감잎 및 뽕잎 복합추출물이 아토피 피부염(AD) 증상을 억제하는지 효과를 밝히고, 항염효능을 나타내는 기능성 소재로서의 이용 가능성을 알아보고자 하였다. 그 결과 육안 평가를 통해 피부의 건조 상태, 스케일링, 미란, 찰과상 및 홍반 같은 아토피 피부염 증상이 AD 모델에서 증가하였지만, 고욤잎, 감잎 및 뽕잎 각각의 추출물과 복합추출물을 투여하였을 경우 완화되는 것을 확인할 수 있었으며, 복합추출물이 고욤잎, 감잎 및 뽕잎 각각의 추출물보다 더 뛰어난 효과를 나타내었다. 피부 두께와 염증세포 및 비만세포의 침윤은 AD 모델에서 크게 증가하였지만, 고욤잎, 감잎 및 뽕잎 단독추출물과 복합추출물을 투여하였을 경우 감소하는 것을 확인할 수 있었으며, 복합추출물이 단독추출물보다 더 뛰어난 효과를 나타내었다. 혈청중의 IgE와 IL-4의 수치를 측정한 결과 AD 모델에서 많이 증가하였으나, 고욤잎, 감잎 및 뽕잎 단독추출물과 복합추출물을 투여하였을 경우 감소하는 것을 확인할 수 있었으며, 복합추출물이 단독추출물보다 더 뛰어나게 억제하는 효과를 나타내었다. HMC-1 세포에 복합추출물을 처리하였을 경우 염증성 사이토카인인 TNF-α와 IL-6의 생성량이 유의적으로 감소하였으며, 또한 RAW 264.7 세포에 복합추출물을 처리하였을 경우 염증 매개 인자인 TNF-α, IL-6, PGE2 및 NO 생성량이 감소하였고, 이러한 염증 매개 인자 억제 효능은 복합추출물이 단독추출물보다 더 뛰어나게 억제하는 것을 확인하였다. 이러한 결과로 미루어볼 때 고욤잎, 감잎 및 뽕잎을 혼합한 복합추출물을 사용할 때 효능이 더 우수한 것을 확인하였고, 아토피 피부염 증상 개선 및 염증관련 질환 치료를 위한 기능성 천연물 소재 및 제품 개발에 응용이 가능할 것으로 생각한다. The present study investigated the anti-atopic effects of mixed extracts from date plum, persimmon, and mulberry leaves (DPME) on atopic dermatitis (AD)-like skin lesions in hairless mice. The in vivo results demonstrated that DPME treatment significantly reduced the dermatitis clinical score and epidermal thickness in AD-like skin lesions. Histological analyses showed that DPME treatment strongly inhibited dermal infiltration of inflammatory cells and activity of mast cells in AD-like skin lesions. DPME treatment inhibited production of serum IgE and interluekin (IL)-4 in hairless mice with AD. Moreover, DPME treatment significantly suppressed production of tumor necrosis factor (TNF)-α and IL-6 cytokines in phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated HMC-1 human mast cells. In addition, DPME treatment reduced production of pro-inflammatory mediators (nitric oxide, prostaglandin E2, TNF-α, and IL-6) in lipopolysaccharide-stimulated RAW 264.7 macrophages. Therefore, the results of this study indicate that the anti-atopic and anti-inflammatory effects of DPME may be involved in the regulation of inflammatory responses, suggesting that DPME may be used as an anti-atopic dermatitis material and natural anti-inflammatory ingredient.

Use of Serum Biomarkers to Aid Antidepressant Selection in Depressive Patients

Hee-Ju Kang,Ju-Wan Kim,Wonsuk Choi,Ju-Yeon Lee,Sung-Wan Kim,Il-Seon Shin,Jae-Min Kim 대한정신약물학회 2024 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.22 No.1

Objective: This study aimed to identify serum biomarkers prospectively associated with remission at 12 weeks in outpatients with depressive disorders receiving stepwise psychopharmacotherapy, according to the main antidepressant used during the treatment period. Methods: This study included 1,024 depressive outpatients initially treated using antidepressant monotherapy, followed by alternating pharmacological strategies during the acute phase (3−12 weeks; 3-week interval). Fourteen serum biomarkers, sociodemographics, and clinical characteristics were evaluated at baseline. Based on the use frequency and mechanism of action, four main antidepressant types were distinguished: escitalopram, other selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), and mirtazapine. A Hamilton Depression Rating Scale score ≤ 7 was take to indicate remission. Results: Lower high-sensitivity C-reactive protein levels were correlated with remission at 12 weeks for all antidepressant types. Lower interleukin (IL)-6 levels and tumor necrosis factor-alpha levels were associated with remission using escitalopram and other SSRIs respectively. Lower IL-1β and leptin levels, predicted remission in association with SSRIs including escitalopram. For SNRIs, remission at 12 weeks was predicted by lower IL-4 and IL-10 levels. For mirtazapine, remission at 12 weeks was associated with lower leptin levels, and higher serotonin and folate levels. Conclusion: Baseline serum status, as estimated by nine serum markers, may help clinicians determine the most appropriate antidepressant to achieve remission in the acute phase of depression.