Atopic dermatitis (AD) is a relapsing and remitting chronic inflammatory skin disease for which a variety of etiological factors are involved. Treatment strategies should be multifaceted and have few side effects. In this respect, acupuncture has become increasingly popular as a safe, consistently effective, and drug-free therapy that treats multiple AD symptoms. We aim to not only verify the effectiveness of acupuncture but also suggest patient-specific response determinants and a new underlying mechanism implicating the gut-brain axis. We have designed a randomized, participant-blinded, sham-controlled clinical trial for 60 mild to moderate AD patients. In a previous study, we observed that the clinical skin symptoms of AD were closely associated with gastrointestinal (GI) symptoms. From these findings, we developed an intervention with six acupuncture points: three for AD symptoms and three for GI symptoms. Also, since high responders and low responders to the acupuncture treatment could be identified in the previous study, we now aim to explore response-determining factors, with a particular focus on GI symptoms. Therefore, we will precisely evaluate not only AD symptoms using the SCORAD, EASI, and DLQI tools, but also GI symptoms using the GSRS, TDS, BSFS, and AR tools and abdominal examination. AD develops in association with complicated pathophysiological factors, such as skin barrier function, genetic susceptibility, and immunological factors. Moreover, the underlying mechanism by which acupuncture treatment works has not been clearly elucidated. We, therefore, will conduct a simultaneous cross-sectional study with a sample of 40 healthy individuals, wherein potential indicators, such as fMRI, gut microbiota, and serum TARC and ATX, will be investigated to determine the gut-brain axis-associated mechanism of acupuncture. We expect that the results of this study could provide important clinical evidence for the effects of acupuncture and help elucidate the therapeutic mechanisms that underlie acupuncture’s efficacy in AD treatment. This trial is registered with https://clinicaltrials.gov/ct2/show/KCT0005422 (Trial registration: Korean Clinical Trial Registry (http://cris.nih.go.kr; registration number: KCT0005422); date of registration: September 23, 2020).

Rosacea is a chronic erythematous disease with telangiectasia that affects the central area of the face. However, because of the ambiguity in the pathophysiology of rosacea, its treatment has not been clearly elucidated; therefore, new therapeutic options need to be developed. Gyejibokryeong-hwan (GBH) is widely used in clinical practice for various blood circulation disorders, including hot flushes. Therefore, we explored the potential pharmaceutical mechanism of GBH on rosacea and investigated the therapeutic points exclusive to GBH through comparative analysis with chemical drugs recommended in 4 guidelines for rosacea based on network analysis. The active compounds in GBH were identified, and the proteins targeted by these compounds and the genes related to rosacea were searched. Additionally, the proteins targeted by the guideline drugs were also searched to compare their effects. And the pathway/term analysis of common genes was conducted. Ten active compounds were obtained for rosacea. There were 14 rosacea-related genes targeted by GBH, with VEGFA, TNF, and IL-4, which were suggested as core genes. The pathway/term analysis of the 14 common genes revealed that GBH could potentially act on rosacea via 2 pathways: the "interleukin 17 signaling pathway" and the "neuroinflammatory response." Comparison and analysis of the protein targets between GBH and guideline drugs revealed that only GBH separately acts on the "vascular wound healing pathway." GBH has the potential to act on IL-17 signaling pathway, neuroinflammatory response and vascular wound healing pathway. Further studies are needed to determine the potential mechanism of GBH in rosacea.Abbreviations: DL = drug-likeness, GBH = Gyejibokryeong-hwan, GO = gene ontology, IL = interleukin, KEGG = Kyoto encyclopedia of genes and genomes, MMP = matrix metalloproteinase, NF = nuclear factor, NK = natural killer, OB = oral bioavailability, PPI = protein-protein interaction, TCMSP = traditional Chinese medicine systems pharmacology database and analysis platform, TNF = tumor necrosis factor, TRP = transient receptor potential, UV = ultraviolet, VEGFA = vascular endothelial growth factor A.