Graded brain fMRI response to somatic and visual acupuncture stimulation.

Increased stimulation can enhance acupuncture clinical response; however, the impact of acupuncture stimulation as "dosage" has rarely been studied. Furthermore, acupuncture can include both somatic and visual components. We assessed both somatic and visual acupuncture dosage effects on sensory ratings and brain response. Twenty-four healthy participants received somatic (needle inserted, manually stimulated) and visual (needle video, no manual stimulation) acupuncture over the leg at three different dosage levels (control, low-dose, and high-dose) during functional magnetic resonance imaging (fMRI). Participants reported the perceived deqi sensation for each acupuncture dose level. Blood-oxygen-level dependent imaging data were analyzed by general linear model and multivariate pattern analysis. For both somatic and visual acupuncture, reported deqi sensation increased with increased dosage of acupuncture stimulation. Brain fMRI analysis demonstrated that higher dosage of somatic acupuncture produced greater brain responses in sensorimotor processing areas, including anterior and posterior insula and secondary somatosensory cortex. For visual acupuncture, higher dosage of stimulation produced greater brain responses in visual-processing areas, including the middle temporal visual areas (V5/MT+) and occipital cortex. Psychophysical and psychophysiological responses to both somatic and visual acupuncture were graded in response to higher doses. Our findings suggest that acupuncture response may be enhanced by the dosage of needling-specific and nonspecific components, represented by different neural mechanisms.

Potential role of acupuncture in the treatment of Parkinson's disease: A narrative review.

Background: The prevalence of Parkinson's disease (PD) has grown rapidly compared to that of other neurological disorders. Acupuncture has been used to address the complex symptoms of PD. Recently, similarities in the mechanisms of action between acupuncture and neuromodulation have received considerable attention. This review aims to summarize the evidence regarding these similarities to suggest potential role of acupuncture in the treatment of PD. Methods: The literature from two electronic databases, PubMed and Google Scholar, was searched using the search terms 'Acupuncture', 'Parkinson's disease', 'Vagus nerve stimulation', and 'Brain functional connectivity'. We then explored the evidence for the effectiveness of acupuncture in PD and evaluated the evidence for similarities in the mechanisms of action between acupuncture and neuromodulation. Results: Data suggests that acupuncture treatment is effective for PD symptoms by modulating inflammation and brain functional connectivity (BFC). These acupuncture effects have been shown to be similar to neuromodulation in controlling inflammation and BFC. Based on the shared mechanisms of action, potential acupuncture mechanisms that may ameliorate a wide range of PD symptoms include but are not limited to (1) vagal activation of the anti-inflammatory pathway and (2) BFC enhancement. Conclusion: The development of acupuncture strategies based on shared mechanisms with neuromodulation will provide new treatment options for patients with PD as personalized neuromodulating therapies. Further studies are needed to gather scientific evidence for optimizing parameters in PD patients.

The Mixture of Natural Products SH003 Exerts Anti-Melanoma Effects through the Modulation of PD-L1 in B16F10 Cells.

Melanoma is the most invasive and lethal skin cancer. Recently, PD-1/PD-L1 pathway modulation has been applied to cancer therapy due to its remarkable clinical efficacy. SH003, a mixture of natural products derived from Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii, and formononetin (FMN), an active constituent of SH003, exhibit anti-cancer and anti-oxidant properties. However, few studies have reported on the anti-melanoma activities of SH003 and FMN. This work aimed to elucidate the anti-melanoma effects of SH003 and FMN through the PD-1/PD-L1 pathway, using B16F10 cells and CTLL-2 cells. Results showed that SH003 and FMN reduced melanin content and tyrosinase activity induced by α-MSH. Moreover, SH003 and FMN suppressed B16F10 growth and arrested cells at the G2/M phase. SH003 and FMN also led to cell apoptosis with increases in PARP and caspase-3 activation. The pro-apoptotic effects were further enhanced when combined with cisplatin. In addition, SH003 and FMN reversed the increased PD-L1 and STAT1 phosphorylation levels induced by cisplatin in the presence of IFN-γ. SH003 and FMN also enhanced the cytotoxicity of CTLL-2 cells against B16F10 cells. Therefore, the mixture of natural products SH003 demonstrates therapeutic potential in cancer treatment by exerting anti-melanoma effects through the PD-1/PD-L1 pathway.

The west meets the east - A need for a renaissance in brain, behavior, and immunity research.

Psychoneuroimmunology (PNI)-the burgeoning concept in recent years, can potentially contribute to developing effective treatments for mental health disorders. Despite the advancement in the modern pharmacological approach for mental disorders, especially Western medicine attributed explicitly to interacting with a specific target has given rise to unmet needs, and treatment failure has led to the proliferation and exploration of traditional and alternative therapies. As research into these exciting under-explored traditional treatment approaches continues to evolve at an unprecedented pace, the need to gain vital insights into the potentiality and mechanism of action in neuropsychiatric disorders has resulted in the current Special Issue. This Special Issue is devoted to psychoneuroimmunology, focusing on introducing the recent advances with traditional and alternative medications in East Asia at the interface of immunology, neurosciences, molecular psychiatry and behavioural medicine neurosciences.

Discovering Influential Core-Keywords, Researcher Networks and Research Trends of Acupuncture on Depression Using Bibliometric Analysis.

Depression is a common illness worldwide. Acupuncture is used as an alternative to non-pharmacological therapy. This study aimed to identify the development and global trends in the study of acupuncture therapy for depression over the past two decades using a bibliometric analysis. Articles published between 2001 and 2020 on acupuncture for depression were retrieved from the Web of Science database. Extracted information included authors, organizations, countries, keywords, and journals. The VOSviewer program was used to visualize the impacts and network hubs of the keywords, authors, and affiliations. Analyses of 871 original and review articles revealed that the number of publications has continually increased over the past 20 years. China has published the maximum number of articles, followed by the United States and South Korea. As for research areas, integrative complementary medicine was most well represented in terms of the number of articles. Co-occurrence analysis of keywords indicated that each five sub-group cluster (including "pain related to depressive symptoms," "CAM therapies of depression," "comorbid disease or symptoms of depression," "clinical trials of depression," and "mechanism of acupuncture on depression") has its own impact keyword. The most recent keywords were "protocol" and "systematic review," whereas early keywords were "acupuncture analgesia" and "St john's wort." Co-authorship analysis of authors and organizations revealed 4 influential authors and 2 organizations in the field of acupuncture for depression. The present study provided influential keywords that show comorbid symptoms, treatments, and mechanism. Additionally, it revealed the influential persons or groups related to acupuncture therapy for depression.

Effectiveness and safety of herbal medicine Ukgansan for clinical symptoms in Parkinson's disease: A pilot, randomized, assessor-blinded clinical trial.

Objectives: Parkinson's disease (PD) is a neurodegenerative disease in which patients are suffering various symptoms. Previous experimental studies suggested that herbal medicine Ukgansan (UGS) could be beneficial for PD. The aim of this pilot clinical trial was to evaluate the efficacy of UGS for improving clinical symptoms in patients with PD. Methods: Sixty patients with idiopathic PD were randomly assigned to receive either UGS plus acupuncture or acupuncture alone for 6 weeks. During the trial, all anti-parkinsonian medications were maintained. Subjects were evaluated for various clinical assessments of PD, including the Movement Disorder Society-Sponsored Revision of the Unified PD Rating Scale (MDS-UPDRS) and the 39-item Parkinson's Disease Questionnaire (PDQ-39), until 12 weeks. Results: In MDS-UPDRS between the groups, no significant time x group interaction was found. In the subgroup analysis of participants with anxiety, a significant time x group interaction was found in the PDQ-39 domain of mobility (P = 0.007), activities of daily living (P = 0.042), and the PDQ-39 summary index (P = 0.048). In addition, post-hoc analysis in participants with anxiety showed a significant decrease in the domains of mobility (P = 0.001) and activities of daily living (P = 0.013) at week 7. There were no adverse events associated with UGS. Conclusion: The additional administration of UGS has the potential to significantly improve the quality of life of PD patients with anxiety. In order to create more definitive evidence, clinical trials with more rigorous methodologies should be conducted in future. Clinical trial registration: http://cris.nih.go.kr, identifier: KCT0003444.

Acupuncture attenuates comorbid anxiety- and depressive-like behaviors of atopic dermatitis through modulating neuroadaptation in the brain reward circuit in mice.

Atopic dermatitis (AD) is highly comorbid with negative emotions such as anxiety and depression. Although acupuncture has demonstrated efficacy in AD, its influence on comorbid anxiety and depression remains unclear. We sought to explore the impact and mechanisms of action of acupuncture on comorbid anxiety and depression of AD. AD-like skin lesions were induced by the topical application of MC903 to the mouse cheek. Acupuncture was performed at Gok-Ji (LI11) acupoints. AD-like phenotypes were quantified by lesion scores, scratching behavior, and histopathological changes. The effects of acupuncture on comorbid anxiety and depression-like behaviors were assessed using the elevated plus-maze (EPM), open-field tests (OFT), and tail-suspension test (TST). In addition, biochemical changes in the brain reward regions were investigated by immunoblotting for the expression of tyrosine hydroxylase (TH), dopamine D1 receptor (D1R), phospho-dopamine and cAMP-regulated phosphoprotein-32 kDa (pDARPP-32), phospho-cAMP response element binding protein (pCREB), ΔFosB, and brain-derived neurotrophic factor (BDNF) in the nucleus accumbens, dorsolateral striatum, and ventral tegmental area. Acupuncture effectively improved the chronic itching and robust AD-like skin lesions with epidermal thickening. Additionally, it considerably reduced comorbid anxiety- and depression-like symptoms, as indicated by more time spent in the open arms of the EPM and in the center of the open field and less time spent immobile in the TST. Higher pCREB, ΔFosB, BDNF, and pDARPP-32 levels, and reduced TH and D1R protein expression in the brain reward regions of AD mice were reversed by acupuncture treatment. The beneficial effects of acupuncture on clinical symptoms (scratching behavior) and comorbid psychological distress in AD strongly correlated with dorsal striatal ΔFosB levels. Collectively, these data indicate that acupuncture had a significant, positive impact on comorbid anxiety- and depression-like behaviors by modulating neuroadaptation in the brain reward circuit in mice with AD, providing a novel perspective for the non-pharmacological management of psychiatric comorbidities of AD.

Acupuncture Regulates Symptoms of Parkinson's Disease via Brain Neural Activity and Functional Connectivity in Mice.

Parkinson's disease (PD) is a multilayered progressive brain disease characterized by motor dysfunction and a variety of other symptoms. Although acupuncture has been used to ameliorate various symptoms of neurodegenerative disorders, including PD, the underlying mechanisms are unclear. Here, we investigated the mechanism of acupuncture by revealing the effects of acupuncture treatment on brain neural responses and its functional connectivity in an animal model of PD. We observed that destruction of neuronal network between many brain regions in PD mice were reversed by acupuncture. Using machine learning analysis, we found that the key region associated with the improvement of abnormal behaviors might be related to the neural activity of M1, suggesting that the changes of c-Fos in M1 could predict the improvement of motor function induced by acupuncture treatment. In addition, acupuncture treatment was shown to significantly normalize the brain neural activity not only in M1 but also in other brain regions related to motor behavior (striatum, substantia nigra pars compacta, and globus pallidus) and non-motor symptoms (hippocampus, lateral hypothalamus, and solitary tract) of PD. Taken together, our results demonstrate that acupuncture treatment might improve the PD symptoms by normalizing the brain functional connectivity in PD mice model and provide new insights that enhance our current understanding of acupuncture mechanisms for non-motor symptoms.

A mixture of Panax ginseng and Scrophularia buergeriana improves immune function in an immunosuppressed murine model.

BACKGROUND: Immunomodulatory drugs are currently used for immunosuppressed individuals, but adverse side effects have been reported. Although Panax ginseng and Scrophularia buergeriana are known to have respective pharmacological properties, the potential of a mixture of Panax ginseng and Scrophularia buergeriana (Isam-Tang, IST) as an immunomodulatory drug has not yet been studied. PURPOSE: The present study was designed to assess the immunomodulatory activity of IST and p-coumaric acid (pCA), an active compound of IST, in the immune system. METHODS: The levels of immunostimulatory cytokines, nitrite, inducible nitric oxide synthase (iNOS), NF-kB activation, and proliferation were examined in RAW264.7 cells, primary splenocytes and splenic NK cells isolated from normal mouse spleen, and in cyclophosphamide-induced immunosuppressed mice using ELISA, quantitative real-time PCR, Western blotting, and immunofluorescence staining. RESULTS: IST or pCA treatment increased the production of immunostimulatory cytokines and nitrite and the expression of iNOS in RAW264.7 cells and splenocytes. IST or pCA also induced NF-κB signaling activation and promoted the phagocytic activity of RAW264.7 cells. In addition, the splenocyte proliferation and splenic NK activity were enhanced by IST or pCA. IST or pCA increased the levels of immunostimulatory cytokines in immunosuppressed mice and ameliorated splenic tissue damage. CONCLUSION: These findings suggest that IST supplementation may be used to enhance immune function.

A network pharmacology-based approach to explore mechanism of action of medicinal herbs for alopecia treatment.

Hair loss is one of the most common skin problems experienced by more than half of the world's population. In East Asia, medicinal herbs have been used widely in clinical practice to treat hair loss. Recent studies, including systematic literature reviews, indicate that medicinal herbs may demonstrate potential effects for hair loss treatment. In a previous study, we identified medical herbs used frequently for alopecia treatment. Herein, we explored the potential novel therapeutic mechanisms of 20 vital medicinal herbs for alopecia treatment that could distinguish them from known mechanisms of conventional drugs using network pharmacology analysis methods. We determined the herb-ingredient-target protein networks and ingredient-associated protein (gene)-associated pathway networks and calculated the weighted degree centrality to define the strength of the connections. Data showed that 20 vital medicinal herbs could exert therapeutic effects on alopecia mainly mediated via regulation of various target genes and proteins, including acetylcholinesterase (AChE), phospholipase A2 (PLA2) subtypes, ecto-5-nucleotidase (NTE5), folate receptor (FR), nicotinamide N-methyltransferase (NNMT), and quinolinate phosphoribosyltransferase (QPRT). Findings regarding target genes/proteins and pathways of medicinal herbs associated with alopecia treatment offer insights for further research to better understand the pathogenesis and therapeutic mechanism of medicinal herbs for alopecia treatment with traditional herbal medicine.

The immune-enhancing effects of a mixture of Astragalus membranaceus (Fisch.) Bunge, Angelica gigas Nakai, and Trichosanthes Kirilowii (Maxim.) or its active constituent nodakenin.

ETHNOPHARMACOLOGICAL RELEVANCE: A mixture (SH003) of Astragalus membranaceus (Fisch.) Bunge, Angelica gigas Nakai, and Trichosanthes Kirilowii (Maxim.) has beneficial effects against several carcinomas. There have been few reports on an immune-enhancing activity of SH003 and its active constituent nodakenin. AIM OF THE STUDY: This study aimed at identifying the immune-enhancing effect of SH003 and nodakenin. MATERIALS AND METHODS: The immune-enhancing effect was evaluated using RAW264.7 macrophages, mouse primary splenocytes, and a cyclophosphamide (CP)-induced immunosuppression murine model. RESULTS: The results show that SH003 or nodakenin stimulated the production levels of granulocyte colony-stimulating factor, IL-12, IL-2, IL-6, TNF-α, and nitric oxide (NO) and the expression levels of iNOS in RAW264.7 macrophages. SH003 or nodakenin also enhanced NF-κB p65 activation in RAW264.7 macrophages. SH003 or nodakenin stimulated the production levels of IFN-γ, IL-12, IL-2, TNF-α, and NO and the expression levels of iNOS in splenocytes. SH003 or nodakenin increased the splenic lymphocyte proliferation and splenic NK cell activity. In addition, SH003 or nodakenin increased the levels of IFN-γ, IL-12, IL-2, IL-6, and TNF-α in the serum and spleen of CP-treated mice, alleviating CP-induced immunosuppression. CONCLUSION: Taken together, the results of this study show that SH003 improved immunosuppression through the activation of macrophages, splenocytes, and NK cells. These findings suggest that SH003 could be applied as a potential immunostimulatory agent for a variety of diseases caused or exacerbated by immunodeficiency.

Changes of local microenvironment and systemic immunity after acupuncture stimulation during inflammation: A literature review of animal studies.

An increasing number of studies have demonstrated the underlying mechanisms by which acupuncture therapy mediates both local and systemic immunomodulation. However, the connection between alterations in the local microenvironment and the resulting change in systemic immunity remains unclear. In this review, we focus on cell-specific changes in local immune responses following acupuncture stimulation and their link to systemic immune modulation. We have gathered the most recent evidence for chemo- and mechano-reactive changes in endothelial cells, neutrophils, macrophages, and mast cells in response to acupuncture. Local signaling is then related to the activation of systemic neuro-immunity including the cholinergic, adrenal, and splenic nervous systems and pain-related neuromodulation. This review aims to serve as a reference for further research in this field.

Acupuncture attenuates comorbid anxiety- and depressive-like behaviors of atopic dermatitis through modulating neuroadaptation in the brain reward circuit in mice

Atopic dermatitis (AD) is highly comorbid with negative emotions such as anxiety and depression. Although acupuncture has demonstrated efficacy in AD, its influence on comorbid anxiety and depression remains unclear. We sought to explore the impact and mechanisms of action of acupuncture on comorbid anxiety and depression of AD. AD-like skin lesions were induced by the topical application of MC903 to the mouse cheek. Acupuncture was performed at Gok-Ji (LI11) acupoints. AD-like phenotypes were quantified by lesion scores, scratching behavior, and histopathological changes. The effects of acupuncture on comorbid anxiety and depression-like behaviors were assessed using the elevated plus-maze (EPM), open-field tests (OFT), and tail-suspension test (TST). In addition, biochemical changes in the brain reward regions were investigated by immunoblotting for the expression of tyrosine hydroxylase (TH), dopamine D1 receptor (D1R), phospho-dopamine and cAMP-regulated phosphoprotein-32 kDa (pDARPP-32), phospho-cAMP response element binding protein (pCREB), ΔFosB, and brain-derived neurotrophic factor (BDNF) in the nucleus accumbens, dorsolateral striatum, and ventral tegmental area. Acupuncture effectively improved the chronic itching and robust AD-like skin lesions with epidermal thickening. Additionally, it considerably reduced comorbid anxiety- and depression-like symptoms, as indicated by more time spent in the open arms of the EPM and in the center of the open field and less time spent immobile in the TST. Higher pCREB, ΔFosB, BDNF, and pDARPP-32 levels, and reduced TH and D1R protein expression in the brain reward regions of AD mice were reversed by acupuncture treatment. The beneficial effects of acupuncture on clinical symptoms (scratching behavior) and comorbid psychological distress in AD strongly correlated with dorsal striatal ΔFosB levels. Collectively, these data indicate that acupuncture had a significant, positive impact on comorbid anxiety- and depression-like behaviors by modulating neuroadaptation in the brain reward circuit in mice with AD, providing a novel perspective for the non-pharmacological management of psychiatric comorbidities of AD.

Effect of Acupuncture on Gut-Brain Axis Parameters in Patients with Atopic Dermatitis: A Study Protocol for a Randomized, Participant- and Assessor-Blind, Sham-Controlled Trial.

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).

Lycii radicis cortex inhibits glucocorticoid­induced bone loss by downregulating Runx2 and BMP­2 expression.

Lycii radicis cortex (LRC) has been used to regulate high blood pressure, body temperature, pain and bone disorders in East Asia. Glucocorticoids (GCs), also known as steroids, are potent immunity regulators widely used in the treatment of inflammatory diseases. However, despite their effectiveness, GC usage is strictly controlled due to severe side­effects, such as osteoporosis. However, further research is required as to date, at least to the best of our knowledge, there is no appropriate model to overcome secondary osteoporosis as a side­effect of GC use. Thus, the aim of the present study was to establish an experimental model of osteoporosis induced by GC. Furthermore, the present study aimed to establish the research methodology for medical evaluations of the effectiveness and side­effects of GCs. A secondary osteoporosis animal model was established, and the animals were divided into two groups as follows: The allergic contact dermatitis (ACD)­induced group and the non­ACD­induced group. In the ACD­induced group, a GC topical application group was compared with a GC subcutaneous injection group. The results revealed that the presence of ACD affected the induction of GC­mediated osteoporosis. Therefore, the group exhibiting induced ACD that was treated with a topical application of GC was selected for examining the side­effects of GCs. The effects of LRC on secondary osteoporosis were confirmed in vivo and in vitro. The results indicated that LRC regulated dexamethasone­induced osteoblast apoptotic markers, including caspase­6, caspase­9, X­linked inhibitor of apoptosis, apoptosis inhibitor 1 and apoptosis inhibitor 2, and increased the expression of osteoblast differentiation­related genes, such as Runt­related transcription factor 2 and bone morphogenetic protein 2 in the MC3T3E­1 cell line. LRC also significantly reduced GC­induced osteoporosis and exerted anti­inflammatory effects in vivo. In addition, LRC inhibited the reduction of calbindin­D28k in the kidney. Overall, the results of the present study suggest that the use of LRC alleviates GC­induced secondary osteoporosis.

The Role of Skin Mast Cells in Acupuncture Induced Analgesia in Animals: A Preclinical Systematic Review and Meta-analysis.

While mast cells (MCs) are previously well-known as a pathological indicator of pain, their role in alleviating pain is recently emerged in acupuncture research. Thus, this study systematically reviews the role of MC in acupuncture analgesia. Animal studies on MC changes associated with the acupuncture analgesia were searched in PubMed and EMBASE. The MC number, degranulation ratio and pain threshold changes were collected as outcome measures for meta-analyses. Twenty studies were included with 13 suitable for meta-analysis, most with a moderate risk of bias. A significant MC degranulation after acupuncture was indicated in the normal and was significantly higher in the pain model. In the subgroup analysis by acupuncture type, manual (MA) and electrical (EA, each P < .00001) but not sham acupuncture had significant MC degranulation. Meta-regression revealed the linear proportionality between MC degranulation and acupuncture-induced analgesia (P < .001), which was found essential in MA (P < .00001), but not in EA (P = .45). MC mediators, such as adenosine and histamine, are involved in its mechanism. Taken together, skin MC is an essential factor for acupuncture-induced analgesia, which reveals a new aspect of MC as a pain alleviator. However, its molecular mechanism requires further study. PERSPECTIVE: This systematic review synthesizes data from studies that examined the contribution of skin MC in acupuncture analgesia. Current reports suggest a new role for skin MC and its mediators in pain alleviation and explain a peripheral mechanism of acupuncture analgesia, with suggesting the need of further studies to confirm these findings.

Effect of acupuncture treatment in patients with mild to moderate atopic dermatitis: a randomized, participant- and assessor-blind sham-controlled trial.

BACKGROUND: Atopic dermatitis (AD) is a chronic recurrent inflammatory skin disease that affects 1-3% of adults worldwide. Currently, it is not possible to completely cure AD; therefore, alternative treatments need to be developed to meet the patients' needs. Here, based on our previous pilot study, we conducted the first confirmatory randomized controlled trial to evaluate the effect of acupuncture in patients with mild to moderate AD. METHODS: A randomized, participant- and assessor-blinded, sham-controlled trial was designed with an intervention period twice-weekly for 4 weeks and a 4-week follow-up. We equally allocated 36 participants to the verum acupuncture (VA) and sham acupuncture (SA) groups. The main outcome measure was the change in SCORing Atopic Dermatitis index (SCORAD) score before and after treatment. RESULTS: A total of 36 participants, aged 19 to 38 years, were enrolled, and 35 were included in the intention-to-treat analyses. The mean change in total SCORAD score differed significantly among the two groups at 4 weeks after randomization (P < .0001): the mean difference was - 11.83 (7.05) in the VA group and 0.45 (7.77) in the SA group. The mean SCORAD score substantially decreased 2-weeks after starting the acupuncture treatment and continued to improve for at least 4 weeks after the end of the treatment in the VA group compared to the SA group (each P < .0001). No serious adverse events were observed. CONCLUSIONS: Twice-weekly acupuncture treatment was effective in reducing AD symptoms in patients with mild to moderate AD without serious adverse events. TRIAL REGISTRATION: Clinical Research Information Service Identifier: KCT0002796 .

Peripheral ERK modulates acupuncture-induced brain neural activity and its functional connectivity.

Acupuncture has been widely used as a therapeutic intervention, and the brain network plays a crucial role in its neural mechanism. This study aimed to investigate the acupuncture mechanism from peripheral to central by identifying how the peripheral molecular signals induced by acupuncture affect the brain neural responses and its functional connectivity. We confirmed that peripheral ERK activation by acupuncture plays a role in initiating acupuncture-induced peripheral proteomic changes in mice. The brain neural activities in the neocortex, hippocampus, thalamus, hypothalamus, periaqueductal grey, and nucleus of the solitary tract (Sol) were significantly changed after acupuncture, and these were altered by peripheral MEK/MAPK inhibition. The arcuate nucleus and lateral hypothalamus were the most affected by acupuncture and peripheral MEK/MAPK inhibition. The hypothalamic area was the most contributing brain region in contrast task PLS analysis. Acupuncture provoked extensive changes in brain functional connectivity, and the posterior hypothalamus showed the highest betweenness centrality after acupuncture. After brain hub identification, the Sol and cingulate cortex were selected as hub regions that reflect both degree and betweenness centrality after acupuncture. These results suggest that acupuncture activates brain functional connectivity and that peripheral ERK induced by acupuncture plays a role in initiating brain neural activation and its functional connectivity.