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               Discovery of metabolic biomarkers associated with the efficacy of a mixed

               Chinese herbal formula in atopic dermatitis patients


                                                                        3,4
                                                    1,2
                                #,1
               Shu-Mei Chang,  Yen-Ying Kung,  Sien-Hung Yang,  Chao-Hsiung Lin,*  Shu-Ling
                                                                                              ,5
                   ,1
               Fu*

               1  Institute of Traditional Medicine, College of Medicine, National Yang Ming Chiao Tung
                 University, Taipei 11221, Taiwan
               2  Center for Traditional Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan
               3  School of Traditional Chinese Medicine, College of Medicine, Chang Gung University,
                 Taoyuan 33302, Taiwan
               4  Division of Chinese Internal Medicine, Center for Traditional Chinese Medicine, Chang
                 Gung Memorial Hospital, Taoyuan 33378, Taiwan
               5  Department of Life Sciences and Institute of Genome Sciences, College of Life Sciences,
                 National Yang Ming Chiao Tung University, Taipei 11221, Taiwan
               * E-mail: chaohsiunglin@nycu.edu.tw; slfu@nycu.edu.tw

               Abstract
                  Atopic dermatitis (AD) is a chronic skin disease characterized by dry skin, red rashes, and
               intense itching. Despite some conventional treatments for AD, many patients still suffer from
               inadequate treatment responses and side effects; thus, more effective, safe, and cost-effective
               treatment options are urgently needed. Chinese medicine is often used as a complementary
               treatment, and a mixed Chinese herbal formula (CHF) has shown potential in alleviating AD
               symptoms, though the potential mechanisms remain unclear. Metabolomics, the latest omics
               tool, represents the downstream layer that reveals biochemical changes associated with disease
               and treatment. In this study, we conducted metabolomics analysis in a randomized, double-
               blind, placebo-controlled clinical trial that evaluated the effect of a mixed CHF. Eighty-four
               AD patients were randomly assigned in a 2:1 ratio to receive either CHF or placebo over a 12-
               week  period.  Clinical  and  plasma  metabolic  data  were  collected  to  identify  treatment-
               responsive  metabolites  and  to  evaluate  their  associations  with  clinical  improvement.  In
               preliminary results, specific metabolites associated with treatment response were identified, and
               some of them overlapped with previously identified AD-related markers, such as lauric acid,
               aspartate, 6-carboxyhexanoate, and N-acetylglycine. Notably, the levels of these metabolites in
               CHF-responsive AD patients exhibited a recovery trend toward healthy controls. In summary,
               we  observed  a  subgroup  of  patients  who  responded  favorably  to  the  CHF  treatment  and
               identified key metabolites associated with this response. These findings provide a molecular
               basis for the potential efficacy of CHF and facilitate the development of personalized treatment
               strategies for AD patients.

               Keywords: Atopic dermatitis; Chinese herbal formula; Metabolomics
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