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Background: At present, acupuncture-related practices have been widely used to treat psoriasis. In our study, we investigated the effect and explored the mechanism of electroacupuncture (EA) on acupoints Baihui (DU20) and Xuehai (SP10) for the treatment of psoriasis. Methods: Imiquimod-induced psoriasis-like mouse model was used in this study. Mice were treated with electroacupuncture at DU20 and SP10 (depth of 2-3 mm, frequency of 2/15 Hz, intensity of 0.5-1.0 mA, 10 min/day). The severity of psoriasis-like lesions for each group was assessed. In addition, histological analysis of the lesions were performed. The levels of inflammatory cytokines were determined using Elisa. The expression levels of Substance P (SP) and NK1R were measured using Western blotting. In addition, NK1R inhibitor was administrated to evaluate the target of electroacupuncture in our mouse model. Results: Electroacupuncture significantly alleviated IMQ-induced skin lesions and epidermal thickness, accompanied with reduced keratinocyte proliferation, CD3+, CD4+, and CD8+ T cells infiltration. The reduced levels of inflammatory cytokines was observed after electroacupuncture treatment. In addition, electroacupuncture inhibited the expression levels of SP and NK1R. NK1R inhibitor could ameliorate lesional symptoms and suppress epidermal thickening and CD3+, CD4+, and CD8 + T cell infiltration. Conclusions: Electroacupuncture relieved psoriasis-like inflammation and T cell infiltration. This therapeutic action was likely mediated by the modulation of Substance P and its receptor NK1R.
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ETHNOPHARMACOLOGICAL RELEVANCE: Qing-Re-Chu-Shi Decoction (QRCSD), a traditional Chinese herbal formula, has been employed as a complementary and alternative therapy for inflammatory skin diseases. However, its active constituents and the mechanistic basis of its action on atopic dermatitis remain in adequately understood. AIM OF THE STUDY: Atopic dermatitis (AD) is an allergic dermatitis marked by eczematous lesions and pruritus. The study aimed to elucidate the underlying effects of QRCSD on AD and to identify the components responsible for its therapeutic efficacy in a mouse model. MATERIALS AND METHODS: Network pharmacology and UPLC-mass analysis were used to anticipate the pharmacological mechanisms and to identify active components of QRCSD, respectively. A DNCB-induced AD-like model was established in NC/Nga mice. QRCSD or prednisolone (as a positive control) was administered via gavage every other day from day14 to day 21. Dermatitis severity score, scratching behavior, skin barrier function, spleen index, Th1/Th2 lymphocyte ratio, and serum IgE levels were evaluated. Protein arrays, including 40 inflammatory cytokines, were performed on skin lesions, followed by confirmation experiments of Western blotting in dorsal skin lesions. RESULTS: The construction of a QRCSD-AD-Network and topological analysis firstly proposed potential targets of QRCSD acting on AD. Animal experiments demonstrated that oral administration of QRCSD ameliorated AD-like lesions, reduced epidermal thickness and mast cell count, decreased serum IgE levels, augmented tight junction protein (Claudin 1, Occludin) levels, and regulated the Th1/Th2 balance in the spleen, as well as spleen index. Elevated levels of interleukin (IL)-4, IL-5, IL-6, IL-17, and Eotaxin were revealed in AD-like skin lesions by protein arrays. Western blotting confirmed that the phosphorylation levels of ERK, P38, JNK, STAT3 and P65 were downregulated, and IL-6 expression was also reduced following QRCSD treatment. CONCLUSIONS: The study enhances the understanding of the anti-inflammatory and immunomodulatory effects of QRCSD, showcasing its significant protective role against atopic dermatitis. Treatment with QRCSD may be considered as a viable candidate for complementary and alternative therapy in managing atopic dermatitis.
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Dermatitis Atópica , Ratones , Animales , Dermatitis Atópica/inducido químicamente , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/patología , Dinitroclorobenceno/toxicidad , Piel/patología , Interleucina-6/metabolismo , Citocinas/metabolismo , Antiinflamatorios/efectos adversos , Inmunoglobulina ERESUMEN
Houshiheisan (HSHS), a classic prescription in traditional Chinese medicine (TCM), has shown outstanding efficacy in treating stroke. This study investigated various therapeutic targets of HSHS for ischemic stroke using mRNA transcriptomics. Herein, rats were randomly separated into the sham, model, HSHS 5.25 g/kg (HSHS5.25), and HSHS 10.5 g/kg (HSHS10.5) groups. Rats suffering from stroke were induced by permanent middle cerebral artery occlusion (pMCAO). After seven days of HSHS treatment, behavioral tests were conducted, and histological damage was examined with hematoxylin-eosin (HE). The mRNA expression profiles were identified using microarray analysis and quantitative real-time PCR (qRT-PCR) validated gene expression changes. An analysis of gene ontology and pathway enrichment was conducted to analyze potential mechanisms confirmed using immunofluorescence and western blotting. HSHS5.25 and HSHS10.5 improved neurological deficits and pathological injury in pMCAO rats. The intersections of 666 differentially expressed genes (DEGs) were chosen using transcriptomics analysis in the sham, model, and HSHS10.5 groups. The enrichment analysis suggested that the therapeutic targets of HSHS might regulate the apoptotic process and ERK1/2 signaling pathway, which was related to neuronal survival. Moreover, TUNEL and immunofluorescence analysis indicated that HSHS inhibited apoptosis and enhanced neuronal survival in the ischemic lesion. Western blot and immunofluorescence assay indicated that HSHS10.5 decreased Bax/Bcl-2 ratio and suppressed caspase-3 activation, while the phosphorylation of ERK1/2 and CREB was upregulated in a stroke rat model after HSHS treatment. Effective inhibition of neuronal apoptosis by activating the ERK1/2-CREB signaling pathway may be a potential mechanism for HSHS in the treatment of ischemic stroke.
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BACKGROUND: Psoriasis is a psychosomatic immune skin disease with psychological factors contributing to the disease. Substance P (SP) is highly expressed in the psoriatic lesions of patients and is involved in pathological disease progression. Tribulus terrestris L. has been used as a Chinese herbal medicine for disease prevention for thousands of years. Terrestrosin D (TED) has been identified as the effective monomeric component of Tribulus terrestris L.. PURPOSE: We investigated whether TED could reverse imiquimod-induced psoriatic lesions, and then, investigated its potential mechanism of action both in vivo and in vitro. METHODS: 5% imiquimod cream was applied onto the backs of mice for 6 days to induce psoriasis-like skin lesions. The psoriatic area and severity index (PASI) was then used for scoring disease severity. Pathological changes and Ki-67 expression levels in skin lesions were measured using hematoxylin and eosin (H&E) and immunofluorescence staining after TED administration. The in vivo and in vitro expression levels of inflammatory cytokines, the ratio of DCs, and SP were measured using ProcartaPlex Mouse Cytokine panels, flow cytometry, and western blotting. Behavioral assessments were determined using the open field and elevated plus-maze (EPM) test. RESULTS: TED decreased PASI scores, epidermal thickness, Ki-67 expression levels, the ratio of DCs in the spleen, and secretion of IL-12p70, IL-18, and TNF-α in imiquimod-induced psoriasis-like murine models. Furthermore, TED increased IL-10 secretion levels, improved behavior, and down-regulated the expression levels of SP. Additionally, TED inhibited the in vitro maturation and activation of SP-induced CD11c+ DCs and the release of IL-12p70 and IL-23. CONCLUSION: TED reduced DCs maturation, down-regulated the expression levels of inflammatory factors, and improved skin lesions and behavior of psoriasis-like murine models by inhibiting the interaction between Substance P and Dendritic cells.
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Psoriasis , Sustancia P , Animales , Proliferación Celular , Citocinas , Células Dendríticas , Modelos Animales de Enfermedad , Imiquimod , Ratones , Ratones Endogámicos BALB C , Psoriasis/inducido químicamente , Psoriasis/tratamiento farmacológico , Saponinas , PielRESUMEN
BACKGROUND: psoriasis is a chronic inflammatory skin disease. The accumulation of IL-17 cytokines in the lesions leads to epidermis proliferation. Traditional Chinese medicine has a significant effect on psoriasis treatment. Among them, Tuhuaiyin is a representative prescription, which has an outstanding curative effect in acute and remission stage. METHODS: To reveal the target and molecular mechanism of Tuhuaiyin, systematic pharmacology platform and database screening were used to construct the Tuhuaiyin interaction network with compounds, targets and diseases. The intervention of Tuhuaiyin on keratinocyte proliferation and inflammation was verified in the model of psoriasis-like lesions induced by imiquimod. The effect on the number and function of IL-17-producing cells was detected, and the regulatory effect of Tuhuaiyin on gut microbial was explored. RESULTS: 32 selected active molecules in Tuhuaiyin acted on psoriasis biological processes. Tuhuaiyin significantly alleviates erythema and scales in the psoriasis like mouse model induced by imiquimod. Excessive proliferation of keratinocytes and infiltration of inflammatory cells were restrained in the dermis by using Tuhuaiyin. The expression of IL-17 was down-regulated in skin and peripheral blood. The proportion of IL-17-producing cells was decreased in immune organs. And phosphorylation of JNK inhibited in skin lesions. At the same time, the change of gut microbial diversity in the psoriasis-like model was improved. CONCLUSION: our study predicted and verified the molecular immunological mechanism of Tuhuaiyin, alleviated the abnormal proliferation of keratinocytes by inhibiting the proportion of IL-17-producing cells and the expression of IL-17 cytokines. Taken together, our data identify the therapeutic potential of Tuhuaiyin for psoriasis.
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Medicamentos Herbarios Chinos/uso terapéutico , Microbioma Gastrointestinal/efectos de los fármacos , Imiquimod/toxicidad , Interleucina-17/antagonistas & inhibidores , Farmacología en Red/métodos , Psoriasis/tratamiento farmacológico , Animales , Antineoplásicos/toxicidad , Células CACO-2 , Medicamentos Herbarios Chinos/farmacología , Microbioma Gastrointestinal/fisiología , Humanos , Interleucina-17/biosíntesis , Masculino , Ratones , Ratones Endogámicos BALB C , Psoriasis/inducido químicamente , Psoriasis/metabolismoRESUMEN
INTRODUCTION: The incidence of psoriasis vulgaris is increasing worldwide. Chronic recurrence of the disease, as well as accompanying cardiovascular disease, metabolic syndrome, and depression has affected the physical and mental health of these patients. Psoriasis vulgaris is a difficult and major disease in the dermatology field. Short-term curative effects using conventional therapy for psoriasis vulgaris has made major strides. However, traditional Chinese medicine (TCM) treatment has long-term curative advantages for psoriasis vulgaris but lacks the scientific and clinical evidence for its use. This study intends to demonstrate and provide scientific and clinical evidence for the use of TCM to delay the recurrence of psoriasis vulgaris. METHODS AND ANALYSIS: This will be a prospective, multicenter cohort study. We intend to recruit 1521 psoriasis vulgaris patients from 14 hospitals in Beijing, Tianjin, and Hebei. Treatment will be based on the diagnosis specifications and clinical practice guidelines of TCM and conventional therapy. During inclusion and the subsequent follow-up period, doctors through electronic case reports will collect different therapeutic TCM regimens and conventional therapy that were administered. Information on life condition, skin lesions at each visit, World Health Organization Quality of Life Instruments, Zung Self-rating Anxiety Scale, Zung Self-assessment of Depression, laboratory examinations, incidence of new rash and recurrence during the remission and recurrence stages will be recorded. ETHICS AND DISSEMINATION: The clinical trial protocol for this study was approved by the ethics committee of the Beijing hospital of TCM affiliated to capital medical university (Ethics number: 2019BL02-010-02). We will publish and present our results at national and international conferences and in peer-reviewed journals specialized in dermatology. TRIAL REGISTRATION: This protocol has been registered in clinicaltrials. gov (ChiCTR1900021629).