1.Preclinical and clinical studies on Qin-Zhu-Liang-Xue decoction: insights from network pharmacology and implications for atopic dermatitis treatment.
Keke HUANG ; Qingkai LIU ; Ruoxi ZHANG ; Hua NIAN ; Ying LUO ; Yue LUO ; Xiaoya FEI ; Le KUAI ; Bin LI ; Yimei TAN ; Su LI ; Xin MA
Frontiers of Medicine 2025;19(1):134-148
To investigate the protective effects and underlying mechanisms of Qin-Zhu-Liang-Xue decoction (QZLX) in atopic dermatitis (AD) and glucocorticoid resistance, we conducted a single-blinded, randomized controlled clinical trial to evaluate the efficacy and safety of this concoction. Network pharmacology analysis was performed and validated through clinical studies. The efficacy, safety, and mechanism of action of QZLX and glucocorticoid receptor (GR) α recombinant protein were assessed in AD mice induced by 2,4-dinitrofluorobenzene (DNFB). Correlation analysis was performed to determine the clinical relevance of GRα. The trial demonstrated that patients who received QZLX showed considerable improvements in their Scoring Atopic Dermatitis (SCORAD) and Dermatology Life Quality Index (DLQI) scores compared with those who received mizolastine at week 4. Network pharmacological analysis identified GRα as a key target for QZLX in AD treatment. QZLX administration increased the serum GRα expression in AD patients, alleviated AD symptoms in mice, decreased inflammatory cytokine expression, and increased GRα expression without affecting liver or kidney function. In addition, GRα recombinant protein improved AD-like skin lesions in DNFB-induced mice. A negative correlation was observed between GRα expression and clinical parameters, including SCORAD, DLQI, and serum IgE levels. QZLX alleviates AD symptoms through the upregulation of GRα and thus presents a novel therapeutic strategy for the prevention of glucocorticoid resistance in AD management.
Dermatitis, Atopic/drug therapy*
;
Animals
;
Drugs, Chinese Herbal/administration & dosage*
;
Humans
;
Mice
;
Network Pharmacology
;
Male
;
Female
;
Adult
;
Receptors, Glucocorticoid/metabolism*
;
Disease Models, Animal
;
Single-Blind Method
;
Middle Aged
;
Young Adult
2.Prim-O-glucosylcimifugin mitigates atopic dermatitis by inhibiting Th2 differentiation through LCK phosphorylation modulation.
Hang ZHAO ; Xin MA ; Hao WANG ; Xiao-Jie DING ; Le KUAI ; Jian-Kun SONG ; Zhan ZHANG ; Dan YANG ; Chun-Jie GAO ; Bin LI ; Mi ZHOU
Journal of Integrative Medicine 2025;23(3):309-319
OBJECTIVE:
To assess the safety and topical efficacy of prim-O-glucosylcimifugin (POG) and investigate the molecular mechanisms of its therapeutic effects in atopic dermatitis (AD).
METHODS:
The effects of POG on human keratinocyte cell viability and its anti-inflammatory properties were evaluated using cell counting kit-8 assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Subsequently, the impact of POG on the differentiation of cluster of differentiation (CD) 4+ T cell subsets, including T-helper type (Th) 1, Th2, Th17, and regulatory T (Treg), was examined through in vitro experiments. Network pharmacology analysis was used to elucidate POG's therapeutic mechanisms. Furthermore, the therapeutic potential of topically applied POG was further evaluated in a calcipotriol-induced mouse model of AD. The protein and transcript levels of inflammatory markers, including cytokines, lymphocyte-specific protein tyrosine kinase (Lck) mRNA, and LCK phosphorylation (p-LCK), were quantified using immunohistochemistry, RT-qPCR, and Western blot analysis.
RESULTS:
POG was able to suppress cell proliferation and downregulate the transcription of interleukin 4 (Il4) and Il13 mRNA. In vitro experiments indicated that POG significantly inhibited the differentiation of Th2 cells, whereas it exerted negligible influence on the differentiation of Th1, Th17 and Treg cells. Network pharmacology identified LCK as a key therapeutic target of POG. Moreover, the topical application of POG effectively alleviated skin lesions in the calcipotriol-induced AD mouse models without causing pathological changes in the liver, kidney or spleen tissues. POG significantly reduced the levels of Il4, Il5, Il13, and thymic stromal lymphopoietin (Tslp) mRNA in the AD mice. Concurrently, POG enhanced the expression of p-LCK protein and Lck mRNA.
CONCLUSION
Our research revealed that POG inhibits Th2 cell differentiation by promoting p-LCK protein expression and hence effectively alleviates AD-related skin inflammation. Please cite this article as: Zhao H, Ma X, Wang H, Ding XJ, Kuai L, Song JK, Zhang Z, Yang D, Gao CJ, Li B, Zhou M. Prim-O-glucosylcimifugin mitigates atopic dermatitis by inhibiting Th2 differentiation through LCK phosphorylation modulation. J Integr Med. 2025; 23(3): 309-319.
Dermatitis, Atopic/drug therapy*
;
Animals
;
Humans
;
Cell Differentiation/drug effects*
;
Phosphorylation/drug effects*
;
Mice
;
Th2 Cells/drug effects*
;
Keratinocytes/drug effects*
;
Disease Models, Animal
;
Mice, Inbred BALB C
;
Calcitriol/analogs & derivatives*
3.Clinical practice guidelines for the diagnosis and treatment of atopic dermatitis with integrative traditional Chinese and Western medicine.
Xin-Ran DU ; Meng-Yi WU ; Mao-Can TAO ; Ying LIN ; Chao-Ying GU ; Min-Feng WU ; Yi CAO ; Da-Can CHEN ; Wei LI ; Hong-Wei WANG ; Ying WANG ; Yi WANG ; Han-Zhi LU ; Xin LIU ; Xiang-Fei SU ; Fu-Lun LI
Journal of Integrative Medicine 2025;23(6):641-653
Traditional Chinese medicine (TCM) is a well-accepted therapy for atopic dermatitis (AD). However, there are currently no evidence-based guidelines integrating TCM and Western medicine for the treatment of AD, limiting the clinical application of such combined approaches. Therefore, the China Association of Chinese Medicine initiated the development of the current guideline, focusing on key issues related to the use of TCM in the treatment of AD. This guideline was developed in accordance with the principles of the guideline formulation manual published by the World Health Organization. A comprehensive review of the literature on the combined use of TCM and Western medicine to treat AD was conducted. The findings were extensively discussed by experts in dermatology and pharmacy with expertise in both TCM and Western medicine. This guideline comprises 23 recommendations across seven major areas, including TCM syndrome differentiation and classification of AD, principles and application scenarios of TCM combined with Western medicine for treating AD, outcome indicators for evaluating clinical efficacy of AD treatment, integration of TCM pattern classification and Western medicine across disease stages, daily management of AD, the use of internal TCM therapies and proprietary Chinese medicines, and TCM external treatments. Please cite this article as: Du XR, Wu MY, Tao MC, Lin Y, Gu CY, Wu MF, Cao Y, Chen DC, Li W, Wang HW, Wang Y, Wang Y, Lu HZ, Liu X, Su XF, Li FL. Clinical practice guidelines for the diagnosis and treatment of atopic dermatitis with integrative traditional Chinese and Western medicine. J Integr Med. 2025; 23(6):641-653.
Dermatitis, Atopic/drug therapy*
;
Humans
;
Medicine, Chinese Traditional/methods*
;
Integrative Medicine
;
Drugs, Chinese Herbal/therapeutic use*
;
Practice Guidelines as Topic
4.MOR106 alleviates inflammation in mice with atopic dermatitis by blocking the JAK2/STAT3 signaling pathway and inhibiting IL-17C-mediated Tfh cell differentiation.
Limin TIAN ; Xiaohui HUYAN ; Sen YANG ; Mengjie WANG ; Yuenan YANG
Chinese Journal of Cellular and Molecular Immunology 2024;40(1):26-32
Objective To explore the significance of interleukin-17C(IL-17C)-mediated follicular helper T cell (Tfh) differentiation in atopic dermatitis (AD) model. Methods BALB/c mice were divided into control group, AD model group, low-dose MOR106 (anti-IL-17C huIgG1)(MDR106-L)treatment group and high-dose MOR106 (MOR106-H) treatment group, 8 mice in each group. Except for the control group, all the other groups were treated with 2, 4- dinitrochlorobenzene (DNCB) to establish AD models. The low-dose and high-dose MOR106 groups were treated with 5 mg/kg or 10 mg/kg MOR106 respectively. The differentiation of Tfh cell subsets in peripheral blood of mice was analyzed by flow cytometry, and the expression of Janus kinase 2/signal transducer and activator of transcription 3(JAK2/STAT3) signal pathway protein in skin tissue was detected by Western blot analysis. Results Compared with the control group, the dermatitis severity score, mass difference between two ears, spleen mass and spleen index of DNCB group increased significantly, while those of MOR106-L group and MOR106-H group decreased significantly. Compared with the control group, the Tfh subgroup of AD mice showed deregulated differentiation, resulting in a significant increase in the percentage of CD4+CXCR5+IFN-γ+Tfh1 cells, CD4+CXCR5+IL-17A+Tfh17 and CD4+CXCR5+IL-21+Tfh21 cells, and a significant decrease in the percentage of CD4+CXCR5+IL-10+Tfh10 cells and CD4+CXCR5+FOXP3+Tfr cells in peripheral blood. The protein levels of phosphorylated JAK2(p-JAK2) and p-STAT3 were significantly increased. MOR106 effectively reversed these changes of Tfh1, Tfh10, Tfh17, Tfh21 and Tfr cells in peripheral blood of AD mice. Compared with AD group, the levels of p-JAK2 and p-STAT3 protein in low-dose and high-dose MOR106 treatment groups decreased significantly. Conclusion MOR106 can reduce the inflammatory response of AD mice by blocking JAK2/STAT3 signaling pathway and inhibiting the differentiation of Tfh cells mediated by IL-17C.
Animals
;
Mice
;
Dermatitis, Atopic/drug therapy*
;
Interleukin-17
;
T Follicular Helper Cells
;
Janus Kinase 2
;
Dinitrochlorobenzene
;
Inflammation
;
Cell Differentiation
;
Signal Transduction
5.Updated consensus guidelines for management of moderate-to-severe atopic dermatitis in Singapore: Integrating biologics, Janus kinase inhibitors and conventional therapies.
Yik Weng YEW ; Uma ALAGAPPAN ; Derrick AW ; Nisha Suyien CHANDRAN ; Karen Jl CHOO ; Roland CHU ; Hong Yi KOH ; Mark Jean Aan KOH ; Shan Xian LEE ; Ching Yin NEOH ; Siyun Lucinda TAN ; Mark TANG ; Yong-Kwang TAY ; Seth FRANCIS-GRAHAM ; Andrew LIM ; Haur Yueh LEE
Annals of the Academy of Medicine, Singapore 2024;53(11):670-682
INTRODUCTION:
Since 2016, several therapies have been approved for treating atopic dermatitis (AD) in Singapore, including biologics, oral Janus kinase (JAK) inhibitors and topical crisaborole. This study supplements the 2016 Singapore treatment guidelines for AD, focusing on newer therapies for moderate-to-severe disease, while revisiting older treatment regimens to accommodate changes in knowledge and practice.
METHOD:
A modified Delphi panel was held, led by 2 co-chairs. The voting expert panel consisted of 12 dermatologists experienced in managing AD in Singapore. Delphi survey rounds were conducted between 24 July and 27 October 2023. Panellists indicated their agreement with drafted statements using a 5-point Likert scale. Consensus was defined as ≥80% agreement. An expert meeting was held to facilitate the consensus process between rounds 1 and 2 of voting.
RESULTS:
All expert panellists participated in both survey rounds, with a 100% response rate. Thirty-nine statements, classified into general principles, conventional treatments, biologics and JAK inhibitors, were proposed. Of these, 27 statements reached consensus at the end of round 1. After the expert meeting, 17 statements were included in round 2, of which 16 statements reached consensus. One statement did not reach consensus. Key updates are the inclusion of dupilumab and JAK inhibitors as potential first-line treatments for moderate-to-severe AD, in certain populations.
CONCLUSION
This modified Delphi study generated consensus among Singapore dermatology experts, to update treatment guidelines in moderate-to-severe atopic dermatitis. The consensus statements developed are intended to supplement the 2016 Singapore treatment guidelines for AD. Further revisions may be required when new evidence and/or treatments become available.
Dermatitis, Atopic/drug therapy*
;
Humans
;
Singapore
;
Janus Kinase Inhibitors/therapeutic use*
;
Biological Products/therapeutic use*
;
Delphi Technique
;
Consensus
;
Antibodies, Monoclonal, Humanized/therapeutic use*
;
Severity of Illness Index
;
Bridged Bicyclo Compounds, Heterocyclic/therapeutic use*
;
Dermatologic Agents/therapeutic use*
;
Practice Guidelines as Topic
;
Pyrimidines/therapeutic use*
;
Boron Compounds
6.Transdermal delivery of natural products against atopic dermatitis.
Minghui LI ; Yihua XU ; Yanan YU ; Wanshu LI ; Lixia CHEN ; Bo ZHAO ; Yuli GAO ; Jianqing GAO ; Hangjuan LIN
Chinese Journal of Natural Medicines (English Ed.) 2024;22(12):1076-1088
Atopic dermatitis (AD) is a chronic inflammatory skin condition. Natural products have gained traction in AD treatment due to their accessibility, low toxicity, and favorable pharmacological properties. However, their application is primarily constrained by poor solubility, instability, and limited permeability. The transdermal drug delivery system (TDDS) offers potential solutions for transdermal delivery, enhanced penetration, improved efficacy, and reduced toxicity of natural drugs, aligning with the requirements of modern AD treatment. This review examines the application of hydrogels, microneedles (MNs), liposomes, nanoemulsions, and other TDDS-carrying natural products in AD treatment, with a primary focus on their effects on penetration and accumulation in the skin. The aim is to provide valuable insights into the treatment of AD and other dermatological conditions.
Animals
;
Humans
;
Administration, Cutaneous
;
Biological Products/pharmacokinetics*
;
Dermatitis, Atopic/drug therapy*
;
Drug Delivery Systems
;
Hydrogels/chemistry*
;
Skin/metabolism*
;
Skin Absorption
7.Advances in Diagnostic Criteria and Severity Assessment of Atopic Dermatitis.
Acta Academiae Medicinae Sinicae 2023;45(3):493-499
Atopic dermatitis(AD),a chronic and relapsing skin disease,is characterized by dry skin and pruritus,severely affecting the quality of patients' life.Accurately grasping the diagnostic criteria and severity assessment is essential and helps to avoid misdiagnosis and missed diagnosis.Moreover,it facilities the development and adjustment of the therapeutic schedule according to the therapeutic reaction and disease control conditions.This article reviews the research advances in the diagnostic criteria and severity assessment of AD.
Humans
;
Dermatitis, Atopic/drug therapy*
;
Pruritus
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Skin Diseases
;
Severity of Illness Index
8.A multi-center, double-blind, randomized, placebo- and positive-controlled phase II clinical study of benvitimod for the treatment of atopic dermatitis.
Lin CAI ; Yan ZHAO ; Min ZHENG ; Furen ZHANG ; Qing SUN ; Quanzhong LIU ; Jin HU ; Juan SHEN ; Jianzhong ZHANG
Chinese Medical Journal 2023;136(2):251-252
9.Clinical observation on the efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis.
Cheng Yuan LI ; Shuang CHEN ; Wei Lu QIAN ; Liu YANG ; Qiu ZHENG ; Ai Jun CHEN ; Jin CHEN ; Kun HUANG ; Sheng FANG ; Ping WANG ; Li HU ; Xin Ran LIU ; Xiao Qin ZHAO ; Na TAN ; Tao CAI
Chinese Journal of Preventive Medicine 2023;57(10):1590-1595
To investigate the clinical efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis (AD) in China. A small sample self-controlled study before and after treatment was conducted to retrospective analysis patients with moderate to severe AD treated with dupilumab in the department of dermatology of the First Affiliated Hospital of Chongqing Medical University from July 2020 to March 2022. Dupilumab 600 mg was injected subcutaneously at week 0, and then 300 mg was injected subcutaneously every 2 weeks. The condition was evaluated by SCORAD(severity scoring of atopic dermatitis), NRS(numerical rating scale), DLQI(dermatology life quality index) and POEM(patient-oriented eczema measure). The improvement of SCORAD, NRS, DLQI and POEM was analyzed by paired t test and non-parametric paired Wilcoxon. The results showed that a total of 67 patients with moderate to severe AD received dupilumab treatment, of which 41 patients (the course of treatment was more than 6 weeks) had reduced the severity of skin lesions, improved quality of life and reduced pruritus. A total of 23 patients completed 16 weeks of treatment. At 4, 8, 12 and 16 weeks, SCORAD, NRS, DLQI and POEM decreased compared with the baseline, and the differences were statistically significant. SCORAD (50.13±15.19) at baseline, SCORAD (36.08±11.96)(t=6.049,P<0.001) at week 4,SCORAD (28.04±11.10)(t=10.471,P<0.001) at week 8, SCORAD (22.93±9.72)(t=12.428,P<0.001) at week 12, SCORAD (16.84±7.82)(t=14.609,P<0.001) at week 16, NRS 7(6,8) at baseline, NRS 4(3,5)(Z=-3.861,P<0.001) at week 4, NRS 2(1,4)(Z=-4.088,P<0.001) at week 8, NRS 1(0,2)(Z=-4.206,P<0.001) at week 12, NRS 2(0,2)(Z=-4.222,P<0.001) at week 16, DLQI (13.83±5.71) at baseline, DLQI (8.00±4.02)(t=6.325,P<0.001) at week 4, DLQI (5.61±3.50)(t=8.060,P<0.001) at week 8, DLQI (3.96±1.99)(t=8.717,P<0.001) at week 12, DLQI (2.70±1.89)(t=10.355,P<0.001) at week 16, POEM (18.04±6.41) at baseline, POEM (9.70±4.70)(t=7.031,P<0.001) at week 4, POEM (7.74±3.48)(t=8.806,P<0.001) at week 8, POEM (6.35±3.33)(t=10.474,P<0.001) at week 12, POEM (4.26±2.51)(t=11.996,P<0.001) at week 16. In the 16th week, 100%(23 patients), 91.3%(21 patients), 34.8%(8 patients) and 8.7%(2 patients) of 23 patients reached SCORAD30, SCORAD50, SCORAD70, and SCORAD90 statuses, respectively. There were 82.6%(19 patients), 95.7%(22 patients) and 95.7%(22 patients) of 23 patients with NRS, DLQI and POEM improved by≥4 points compared with baseline. Twelve patients with AD who continued to receive dupilumab after 16 weeks showed further improvement in skin lesions. The adverse events were conjunctivitis and injection site reaction. In conclusion, dupilumab is an effective and safe treatment for moderate and severe AD. However, the longer-term efficacy and safety require further studies involving larger sample sizes and a longer follow-up time.
Humans
;
Dermatitis, Atopic/drug therapy*
;
Quality of Life
;
Retrospective Studies
;
Severity of Illness Index
;
Treatment Outcome
10.Clinical observation on the efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis.
Cheng Yuan LI ; Shuang CHEN ; Wei Lu QIAN ; Liu YANG ; Qiu ZHENG ; Ai Jun CHEN ; Jin CHEN ; Kun HUANG ; Sheng FANG ; Ping WANG ; Li HU ; Xin Ran LIU ; Xiao Qin ZHAO ; Na TAN ; Tao CAI
Chinese Journal of Preventive Medicine 2023;57(10):1590-1595
To investigate the clinical efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis (AD) in China. A small sample self-controlled study before and after treatment was conducted to retrospective analysis patients with moderate to severe AD treated with dupilumab in the department of dermatology of the First Affiliated Hospital of Chongqing Medical University from July 2020 to March 2022. Dupilumab 600 mg was injected subcutaneously at week 0, and then 300 mg was injected subcutaneously every 2 weeks. The condition was evaluated by SCORAD(severity scoring of atopic dermatitis), NRS(numerical rating scale), DLQI(dermatology life quality index) and POEM(patient-oriented eczema measure). The improvement of SCORAD, NRS, DLQI and POEM was analyzed by paired t test and non-parametric paired Wilcoxon. The results showed that a total of 67 patients with moderate to severe AD received dupilumab treatment, of which 41 patients (the course of treatment was more than 6 weeks) had reduced the severity of skin lesions, improved quality of life and reduced pruritus. A total of 23 patients completed 16 weeks of treatment. At 4, 8, 12 and 16 weeks, SCORAD, NRS, DLQI and POEM decreased compared with the baseline, and the differences were statistically significant. SCORAD (50.13±15.19) at baseline, SCORAD (36.08±11.96)(t=6.049,P<0.001) at week 4,SCORAD (28.04±11.10)(t=10.471,P<0.001) at week 8, SCORAD (22.93±9.72)(t=12.428,P<0.001) at week 12, SCORAD (16.84±7.82)(t=14.609,P<0.001) at week 16, NRS 7(6,8) at baseline, NRS 4(3,5)(Z=-3.861,P<0.001) at week 4, NRS 2(1,4)(Z=-4.088,P<0.001) at week 8, NRS 1(0,2)(Z=-4.206,P<0.001) at week 12, NRS 2(0,2)(Z=-4.222,P<0.001) at week 16, DLQI (13.83±5.71) at baseline, DLQI (8.00±4.02)(t=6.325,P<0.001) at week 4, DLQI (5.61±3.50)(t=8.060,P<0.001) at week 8, DLQI (3.96±1.99)(t=8.717,P<0.001) at week 12, DLQI (2.70±1.89)(t=10.355,P<0.001) at week 16, POEM (18.04±6.41) at baseline, POEM (9.70±4.70)(t=7.031,P<0.001) at week 4, POEM (7.74±3.48)(t=8.806,P<0.001) at week 8, POEM (6.35±3.33)(t=10.474,P<0.001) at week 12, POEM (4.26±2.51)(t=11.996,P<0.001) at week 16. In the 16th week, 100%(23 patients), 91.3%(21 patients), 34.8%(8 patients) and 8.7%(2 patients) of 23 patients reached SCORAD30, SCORAD50, SCORAD70, and SCORAD90 statuses, respectively. There were 82.6%(19 patients), 95.7%(22 patients) and 95.7%(22 patients) of 23 patients with NRS, DLQI and POEM improved by≥4 points compared with baseline. Twelve patients with AD who continued to receive dupilumab after 16 weeks showed further improvement in skin lesions. The adverse events were conjunctivitis and injection site reaction. In conclusion, dupilumab is an effective and safe treatment for moderate and severe AD. However, the longer-term efficacy and safety require further studies involving larger sample sizes and a longer follow-up time.
Humans
;
Dermatitis, Atopic/drug therapy*
;
Quality of Life
;
Retrospective Studies
;
Severity of Illness Index
;
Treatment Outcome

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