OBJECTIVE: Psoriasis, a common chronic inflammatory skin condition with genetic underpinnings, is traditionally managed with cupping therapy. Although used historically, the precise mechanical effects and therapeutic mechanisms of cupping in psoriasis remain largely unexamined. This study aimed to evaluate cupping therapy's efficacy for psoriasis and investigate its role in modulating inflammatory responses and cellular metabolism. METHODS: Psoriasis was induced in mice using topical imiquimod (IMQ). The effects of cupping on psoriatic lesions were assessed using the Psoriasis Area and Severity Index score, histology, immunohistochemistry, and immunofluorescence staining. polymerase chain reaction sequencing (RNA-seq) and Western blotting were conducted to examine changes in mRNA expression and the AMP-activated protein kinase (AMPK) signaling pathway. RESULTS: Cupping therapy significantly reduced inflammation, epidermal thickness, and inflammatory cell infiltration in mice with IMQ-induced psoriasis. Immunohistochemistry and immunofluorescence showed lower expression of inflammatory markers and a shift in T-cell populations. RNA-seq and Western blotting indicated that cupping upregulated Piezo1 and activated the AMPK pathway, improving energy metabolism in psoriatic skin. CONCLUSION Cupping therapy reduces epidermal hyperproliferation and inflammation in psoriasis, rebalancing the local immune microenvironment. Mechanistically, cupping promotes calcium influx via Piezo1, activates AMPK signaling, and supports metabolic homeostasis, suggesting therapeutic potential for psoriasis. Please cite this article as: Xi RF, Liu X, Wang Y, Lu HZ, Yuan SJ, Guo DJ, Zhu JY, Li FL, Duan YJ. Mechanosensory activation of Piezo1 via cupping therapy: Harnessing neural networks to modulate AMPK pathway for metabolic restoration in a mouse model of psoriasis. J Integr Med. 2025; 23(6):721-732.
Animals ; Psoriasis/chemically induced* ; Mice ; AMP-Activated Protein Kinases/metabolism* ; Disease Models, Animal ; Cupping Therapy/methods* ; Signal Transduction ; Imiquimod ; Ion Channels/genetics* ; Male ; Mechanotransduction, Cellular

Aim To investigate the anti-tumor effect of celastrol(CEL)on colorectal cancer and the possible targets/mechanisms. Methods The cytotoxic activities of CEL were evaluated against A549, HCT-116, HepG2 by CCK-8 method. Western blotting was used to detect the expression level of STAT3 and its upstream and downstream proteins(JAK2, Survivin, MCL-1)in HCT-116 cells before and after CEL treatment Flow cytometry was applied to assess CEL's apoptosis and cell-cycle arrest effect in HCT-116 cells. SPR detection and molecular docking analysis were performed to further assess the binding ability between CEL and STAT3 protein. Lastly, human colorectal cancer organoid culture was constructed to verify the anti-tumor effect of CEL. Results CEL showed significant cytotoxicity to A549(IC50 = 2.37±0.02 μmol·L-1), HCT-116(IC50 = 1.40±0.21 μmol·L-1)and HepG2(IC50 = 2.52±0.02 μmol·L-1). Additionally, CEL could effectively decrease the level of p-STAT3 and the downstream gene expression of STAT3(Survivin and MCL-1)in a concentration-dependent manner; however, CEL did not affect the total level of STAT3 and upstream kinases JAK2. Moreover, CEL could induce apoptosis of HCT-116 cells concentration-dependently and arrest the cell cycle. According to the SPR analysis, CEL showed a strong binding affinity with the KD value(the equilibrium dissociation constant)of 60.38 μmol·L-1. Molecular docking analysis also suggested that CEL bound to the SH2 domain of STAT3. Lastly, CEL showed much better activity than the positive drug oxaliplatin(L-OHP)on all the colorectal cancer organoids. Conclusions CEL shows a significant anti-colorectal cancer effect, potentially caused by a direct target inhibiting STAT3, inducing apoptosis, and blocking the cell cycle.

Objective:This study explores the key core targets of Guishenwan in the treatment of thin endometrium and related signaling pathways through the method of network pharmacology，and further uses animal experiments to verify the obtained targets and verify that Guishenwan are effective for thin endometrium. Method:Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） was used to retrieve the effective chemical components，active component targets and target abbreviations of the eight Chinese medicines in Guishenwan，the GeneCards database and Online Mendelian Inheritance in Man（OMIM）database were used to retrieve thin endometrial related targets gene.Use Wayne software to take the intersection of the drug target of Guishenwan and the disease target of the thin endometrium，and import the intersection target into the STRING database and Cytoscape 3.7.2 software for visual analysis to obtain the "drug-disease" protein protein interaction（PPI） network， then input the intersection target into Enrichr database and DAVID database for gene ontology（GO） enrichment analysis and Kyoto encyclopedia of genes and genomes（KEGG） enrichment analysis. Using the obtained possible core and key targets as the theoretical basis，a thin endometrial model in rats was established. After Guishenwan and estrogen intervention for 21 days，the endometrial thickness of rats was observed by hematoxylin-eosin staining（HE） staining. Western blot and quantitative real time polymerase chain reaction（Real-time PCR） detect the protein and mRNA expression levels of the four core key targets of epidermal growth factor receptor（EGFR），matrix metalloproteinase 9（MMP9），interleukin-1beita（IL-1β） and mitogen activated protein kinase 14（MAPK14）. Result:The Venn software obtained 130 intersection targets in total， imported 130 intersection targets into the STRING database and Cytoscape database，and obtained a protein interaction network diagram including 33 nodes and 107 edges. DAVID 6.8 database for GO analysis. The function annotation analysis involving 167 biological processes（BP），22 cell components（CC），39 molecular functions（MF）. DAVID 6.8 database for KEGG enrichment analysis， and thin endometrium related A total of 34 pathways. Western blot and Real-time PCR were used to analyze the expression results of EGFR，MMP9，IL-1β，MAPK14 protein and genes in the endometrial tissues of the 6 groups of rats. Guishenwan can enhance the expression of EGFR，MMP9，IL-1β，MAPK14 protein and mRNA on the thin endometrium. Conclusion:According to the theoretical analysis of network pharmacology and the results of animal experiments，it is found that Guishenwan can effectively improve the related indicators of thin endometrium，and promote the expression of EGFR，MMP9，IL-1β，MAPK14 protein and genes. The intimal tissue proliferates and improves the symptoms of thin intima.

Objective::To investigate the antihypertensive effect of Tianmu Jiangya powder and its related antihypertensive mechanism by using SHR rats as a model, and protein expressions provide an experimental basis for the clinical application of Tianmu Jiangya powder in the treatment of hypertension. Method::Sixty male SHR rats were randomly divided into six groups according to body weight after one week of adaptive feeding: model group, valsartan group (12 mg·kg^-1), captopril group (9 mg·kg^-1), hydrochlorothiazide group (6 mg·kg^-1), Tianmu Jiangya powder low and high-dose group (0.36, 1.44 g·kg^-1), WKY rats were used as the normal group, and the intragastric administration lasted for 16 weeks. Softron BP-2010A intelligent non-invasive blood pressure meter was used to measure the systolic blood pressure (SBP)and heart rate (HR) of rat tail arteries. Adobe Photoshop CS5 software was used to analyze the left auricle and claw fixed selected areas to evaluate the effect on blood stasis syndrome. Vevo 2100 small animal ultrasound imaging system detects left ventricular ejection fraction (LVEF), left ventricular shortening (FS), left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), left ventricular end-systole dimension (LVIDs), left ventricular end-diastole dimension (LVIDd), interventricular septum end-systolic depth (IVSs), and interventricular septum end-diastolic depth (IVSd). Then the rats were sacrificed and the materials were taken (blood, heart, aorta, liver, kidney, tibia), and the weight of heart, liver, kidney and tibia length were measured and recorded. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of the heart and thoracic aorta. Separation of serum and plasma, and determination of nitric oxide (NO) in serum by nitrate reductase method. Radioimmunoassay was used to detect plasma adrenaline/3 methoxyadrenaline (MN), urea (UREA), and uric acid (UA) contents. The expression of nitric oxide synthase(iNOS) and vascular endothelial growth factor(VEGF) protein in thoracic aorta of each group was detected and analyzed by immunohistochemical method. Result::Compared with normal group, the SBP and HR of the rats in model group were significantly increased (P<0.05). The r value of the claw was significantly reduced and the g value was significantly increased at 8 and 16 weeks (P<0.05). LVEF and FS significantly decreased, LVESV, LVIDs, IVSd increased significantly (P<0.05). Heart weight, heart weight /tibia length, liver weight and liver weight /tibia length, plasma of MN, UREA, and UA contents significantly increased, and promoted the expression of iNOS and VEGF proteins in the aortic (P<0.05). Compared with the model group, the Tianmu Jiangya powder administration group could continuously reduce SBP in SHR rats, maintain HR stability (P<0.05), significantly increase the claw of r value, lower the claw of g value(P<0.05). LVEF, FS significantly increased, LVEDV, LVESV, LVIDd and LVIDs significantly decreased (P<0.05), significantly increased serum NO content, decreased liver weight, liver weight/tibia length, plasma MN, UREA, UA content (P<0.05), and down-regulated the expression of iNOS and VEGF protein in the aorta(P<0.05). Conclusion::Tianmu Jiangya powder has a certain antihypertensive effect, and its mechanism may be mainly related to protecting heart function, improving vascular endothelial function, reducing catecholamines and sedative analgesia.