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

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Purpose::Vibrio vulnificus ( V. Vulnificus) infection is characterized by rapid onset, aggressive progression, and challenging treatment. Bacterial resistance poses a significant challenge for clinical anti-infection treatment and is thus the subject of research. Enhancing host infection tolerance represents a novel infection prevention strategy to improve patient survival. Our team initially identified cytochrome P4501A1 (CYP1A1) as an important target owing to its negative modulation of the body's infection tolerance. This study explored the superior effects of the CYP1A1 inhibitor bergamottin compared to antibiotic combination therapy on the survival of mice infected with multidrug-resistant V. Vulnificus and the protection of their vital organs. Methods::An increasing concentration gradient method was used to induce multidrug-resistant V. Vulnificus development. We established a lethal infection model in C57BL/6J male mice and evaluated the effect of bergamottin on mouse survival. A mild infection model was established in C57BL/6J male mice, and the serum levels of creatinine, urea nitrogen, aspartate aminotransferase, and alanine aminotransferase were determined using enzyme-linked immunosorbent assay to evaluate the effect of bergamottin on liver and kidney function. The morphological changes induced in the presence of bergamottin in mouse organs were evaluated by hematoxylin and eosin staining of liver and kidney tissues. The bacterial growth curve and organ load determination were used to evaluate whether bergamottin has a direct antibacterial effect on multidrug-resistant V. Vulnificus. Quantification of inflammatory factors in serum by enzyme-linked immunosorbent assay and the expression levels of inflammatory factors in liver and kidney tissues by real-time quantitative polymerase chain reaction were performed to evaluate the effect of bergamottin on inflammatory factor levels. Western blot analysis of IκBα, phosphorylated IκBα, p65, and phosphorylated p65 protein expression in liver and kidney tissues and in human hepatocellular carcinomas-2 and human kidney-2 cell lines was used to evaluate the effect of bergamottin on the nuclear factor kappa-B signaling pathway. One-way ANOVA and Kaplan-Meier analysis were used for statistical analysis. Results::In mice infected with multidrug-resistant V. Vulnificus, bergamottin prolonged survival ( p = 0.014), reduced the serum creatinine ( p = 0.002), urea nitrogen ( p = 0.030), aspartate aminotransferase ( p = 0.029), and alanine aminotransferase ( p = 0.003) levels, and protected the cellular morphology of liver and kidney tissues. Bergamottin inhibited interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α expression in serum (IL-1β: p = 0.010, IL-6: p = 0.029, TNF-α: p = 0.025) and inhibited the protein expression of the inflammatory factors IL-1β, IL-6, TNF-α in liver (IL-1β: p = 0.010, IL-6: p = 0.011, TNF-α: p = 0.037) and kidney (IL-1β: p = 0.016, IL-6: p = 0.011, TNF-α: p = 0.008) tissues. Bergamottin did not affect the proliferation of multidrug-resistant V. Vulnificus or the bacterial load in the mouse peritoneal lavage fluid ( p = 0.225), liver ( p = 0.186), or kidney ( p = 0.637). Conclusion::Bergamottin enhances the tolerance of mice to multidrug-resistant V. Vulnificus infection. This study can serve as a reference and guide the development of novel clinical treatment strategies for V. Vulnificus.

Aim To investigate the protective effect of Jujing formula on retina of mice with dry age-related macular degeneration(AMD).Methods The mouse model of dry AMD was induced by intraperitoneal in-jection of sodium iodate,and the prognosis was given to the Jujing formula.Retinal thickness was detected by optical coherence tomography(OCT),the retinal morphological changes were observed by hematoxylin-eosin(HE)staining,and the apoptosis of retinal cells was detected by in situ terminal transferase labeling(TUNEL)staining.Combination of tumor necrosis fac-tor-α(TNF-α),interleukin-6(IL-6)and interleukin-1β(IL-1 β)in eyeballs and serum,superoxide dis-mutase(SOD),glutathione(GSH)and malondialde-hyde(MDA)were evaluated to assess the protective effects of Jujing formula on retinal injury in mice with dry AMD.Results The results of OCT,HE and TUNEL staining showed that Jujing formula significant-ly improved the retinal injury induced by sodium iodate in mice with dry AMD,increased the retinal thickness(P＜0.05),reduced the apoptosis of retinal cells(P＜0.01),and increased the levels of GSH,IL-6 and SOD activity in eyeballs and serum(P＜0.01).The levels of TNF-α,IL-6,IL-1β and MDA were reduced(P＜0.01).Conclusions Jujing formula has certain therapeutic effects on retinal injury in dry AMD,which may be related to inhibiting inflammatory response and enhancing antioxidant capacity.

This study aimed to evaluate the efficacy and safety of various Chinese patent medicines in the treatment of inflammatory response in chronic glomerulonephritis(CGN) based on network Meta-analysis. Randomized controlled trial(RCT) of oral Chinese patent medicines for improving inflammatory response in patients with CGN was retrieved from databases such as CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, and Web of Science from database inception to March 2023. All investigators independently screened the literature, extracted data, and evaluated the quality. Stata 16.0 and RevMan 5.4.1 software were used to analyze the data of the literature that met the quality standards. Finally, 71 RCTs were included, involving 7 Chinese patent medicines. The total sample size was 6 880 cases, including 3 441 cases in the test group and 3 439 cases in the control group. The network Meta-analysis showed that(1) in terms of reducing TNF-α, the top 3 optimal interventions according to the surface under the cumulative ranking curve(SUCRA) were Shenyanshu Capsules/Granules/Tablets+conventional western medicine, Huangkui Capsules+conventional western medicine, and Bailing Capsules+conventional western medicine.(2) In terms of reducing hs-CRP, the top 3 optimal interventions according to SUCRA were Yishen Huashi Granules+conventional western medicine, Huangkui Capsules+conventional wes-tern medicine, and Bailing Capsules+conventional western medicine.(3) In terms of reducing IL-6, the top 3 optimal interventions according to SUCRA were Yishen Huashi Granules+conventional western medicine, Bailing Capsules+conventional western medicine, and Shenyan Kangfu Tablets+conventional western medicine.(4) In terms of reducing 24hUTP, the top 3 optimal interventions according to SUCRA were Shenyan Kangfu Tablets+conventional western medicine, Bailing Capsules+conventional western medicine, and Huangkui Capsules+conventional western medicine.(5) In terms of reducing Scr, the top 3 optimal interventions according to SUCRA were Bailing Capsules+conventional western medicine, Shenyanshu Capsules/Granules/Tablets+conventional western medicine, and Yishen Huashi Granules+conventional western medicine.(6) In terms of reducing BUN, the top 3 optimal interventions according to SUCRA were Yishen Huashi Granules+conventional western medicine, Shenyanshu Capsules/Granules/Tablets+conventional western medicine, and Bailing Capsules+conventional western medicine.(7) In terms of improving the clinical total effective rate, the top 3 optimal interventions according to SUCRA were Huangkui Capsules+conventional western medicine, Kunxian Capsules+conventional western medicine, and Yishen Huashi Granules+conventional western medicine. The results showed that the combination of conventional western medicine and Chinese patent medicine could reduce the expression of serum inflammatory factors TNF-α, hs-CRP, and IL-6 and inhibit the inflammatory response. The combination of conventional western medicine and Chinese patent medicine was superior to conventional western medicine alone in reducing Scr, BUN, and 24hUTP, and improving the clinical total effective rate of treatment. Due to the limitation of the quantity and quality of literature included, the above conclusions need to be validated by more high-quality studies.
Humans ; Tumor Necrosis Factor-alpha ; Network Meta-Analysis ; Nonprescription Drugs ; C-Reactive Protein ; Interleukin-6 ; Drugs, Chinese Herbal/therapeutic use* ; Glomerulonephritis/drug therapy*

OBJECTIVE: Psoriasis is a common chronic inflammatory skin disease that is prone to recurrence, and the proinflammatory factor, cysteine-rich protein 61 (Cyr61), is important in its pathophysiology. Long-term clinical practice has shown that Sancao Formula (SC), a Chinese herbal compound, is effective in the treatment of psoriasis, but the precise mechanism remains unknown. In this study, we investigate the mechanism by which SC extract alleviates imiquimod (IMQ)-induced psoriasis. METHODS: The expression of Cyr61 in psoriatic lesions and normal healthy skin was detected using immunohistochemical analysis to investigate the biological role of Cyr61 in models of psoriatic inflammation. A psoriatic mouse model was established by topical application of IMQ, and the effect of topical application of SC extract was evaluated using the psoriasis area and severity index (PASI) score, hematoxylin-eosin staining, and histopathological features of the skin. Next, a HaCaT cell inflammation model was established using interferon-γ (IFN-γ), and the effect of SC extract on the mRNA and protein levels of Cyr61 and intercellular cell adhesion molecule-1 (ICAM-1) was confirmed using Western blot and quantitative real-time polymerase chain reaction analyses. RESULTS: Immunohistochemical staining showed that the expression of Cyr61 in psoriatic lesions was higher than that in normal skin samples (78.26% vs 41.18%, P < 0.05), and the number of Cyr61-positive cells in psoriatic lesions was also significantly higher than in normal skin (18.66 ± 2.51 vs 4.33 ± 1.52, P < 0.05). Treatment in mice with IMQ-induced psoriasis showed that SC extract could significantly improve the inflammatory phenotype, PASI score (10.875 ± 0.744 vs 3.875 ± 0.582, P < 0.05), and pathological features compared with those in IMQ model group; SC treatment was also associated with decreased levels of Cyr61 and ICAM-1. In the IFN-γ-induced inflammatory cell model, the mRNA and protein levels of Cyr61 and ICAM-1 were upregulated, while the SC extract downregulated the levels of Cyr61 and ICAM-1. CONCLUSION The results provide a theoretical basis for the involvement of Cyr61 in the pathogenesis of psoriasis, and suggest that SC should be used to target Cyr61 for the prevention of psoriasis recurrence.
Animals ; China ; Cysteine-Rich Protein 61/metabolism* ; Disease Models, Animal ; Drugs, Chinese Herbal/therapeutic use* ; Imiquimod/adverse effects* ; Inflammation/drug therapy* ; Intercellular Adhesion Molecule-1/genetics* ; Interferon-gamma ; Mice ; Mice, Inbred BALB C ; Psoriasis/pathology* ; RNA, Messenger/therapeutic use*

This study aims to establish an ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) method for the determination of emodin-8-O-β-D-glucoside(EG) and its metabolites in plasma, and to investigate the toxicokinetics(TK) behavior of them in rats. To be specific, the TK of EG and its metabolites from the first to the last administration in the repeated dose toxicity study was determined, and the kinetic parameters were calculated. The exposure of EG prototype and metabolites in rat plasma after oral administration of different doses of EG was evaluated. The result showed that the prototype of EG and its metabolites aloe-emodin-8-O-β-D-glucoside, emodin, aloe-emodin, and hydroxyemodin could be detected in rats after oral administration of high-, medium-, and low-dose EG. The area under the curve(AUC) of the prototype and metabolites after the first and last administration was in positive correlation with the dose. The time to the maximum concentration(T_(max)) of EG and metabolites in the three administration groups was <6 h, and the longest in vivo residence time was 12 h. The T_(max) and in vivo residence time of EG were prolonged with the increase in the dose. The metabolites emodin, aloe-emodin, and hydroxyemodin all had two peaks. Both hydroxyemodin and aloe-emodin exhibited increased plasma exposure, slow metabolism, and accumulation in vivo. In addition, aloe-emodin-8-O-β-D-glucoside and emodin disappeared with the increase in dose, suggesting the change of the metabolic pathway of EG in vivo in the case of high-dose administration. The mechanism of high-dose EG in vivo needs to be further explored. This study preliminarily elucidates the TK behavior of EG in rats, which is expected to support clinical drug use.
Animals ; Anthraquinones ; Chromatography, High Pressure Liquid/methods* ; Emodin/toxicity* ; Glucosides/toxicity* ; Mass Spectrometry ; Rats ; Toxicokinetics

Farnesyl diphosphate synthase(FPPS) is a key enzyme at the branch point of the sesquiterpene biosynthetic pathway, but there are no reports on the transcriptional regulation of FPPS promoter in Pogostemon cabin. In the early stage of this study, we obtained the binding protein PcFBA-1 of FPPS gene promoter in P. cabin. In order to explore the possible mechanism of PcFBA-1 involved in the regulation of patchouli alcohol biosynthesis, this study performed PCR-based cloning and sequencing analysis of PcFBA-1, analyzed the expression patterns of PcFBA-1 in different tissues by fluorescence quantitative PCR and its subcellular localization using the protoplast transformation system, detected the binding of PcFBA-1 protein to the FPPS promoter in vitro with the yeast one-hybrid system, and verified its transcriptional regulatory function by dual-luciferase reporter gene assay. The findings demonstrated that the cloned PcFBA-1 had an open reading frame(ORF) of 1 131 bp, encoding a protein of 376 amino acids, containing two conserved domains named F-box-like superfamily and FBA-1 superfamily, and belonging to the F-box family. Moreover, neither signal peptide nor transmembrane domain was contained, implying that it was an unstable hydrophilic protein. In addition, as revealed by fluorescence quantitative PCR results, PcFBA-1 had the highest expression in leaves, and there was no significant difference in expression in roots or stems. PcFBA-1 protein was proved mainly located in the cytoplasm. Furthermore, yeast one-hybrid screening and dual-luciferase reporter gene assay showed that PcFBA-1 was able to bind to FPPS promoter both in vitro and in vivo to enhance the activity of FPPS promoter. In summary, this study identifies a new transcription factor PcFBA-1 in P. cabin, which directly binds to the FPPS gene promoter to enhance the promoter activity. This had laid a foundation for the biosynthesis of patchouli alcohol and other active ingre-dients and provided a basis for metabolic engineering and genetic improvement of P. cabin.
Amino Acid Sequence ; Cloning, Molecular ; Geranyltranstransferase/genetics* ; Pogostemon ; Transcription Factors/genetics*

According to the polarity of different components in Sanpian Decoction, two fingerprints were established. Then the substance benchmark freeze-dried powder of 15 batches of Sanpian Decoction was prepared, followed by the determination of the fingerprints, index component content, and dry extract rates, the identification of attribution of characteristic peaks, and the calculation of similarities between these fingerprints and the reference(R), the content and transfer rate ranges of ferulic acid, sinapine thiocyanate, liquiritin, and glycyrrhizic acid, and the dry extract rate range. The results showed that the similarities of 15 batches of the substance benchmark fingerprints with R were all greater than 0.900.Further summarization of the characteristic peaks revealed that there were a total of 20 characteristic peaks in fingerprint 1, among which, eight were from Sinapis Semen, four from Paeoniae Radix Alba, six from Chuanxiong Rhizoma, and two from Glycyrrhizae Radix et Rhizoma. A total of 16 characteristic peaks were observed in fingerprint 2, including one from Sinapis Semen, three from Paeoniae Radix Alba, eight from Chuanxiong Rhizoma, and four from Glycyrrhizae Radix et Rhizoma. The average dry extract rate of 15 batches of substance benchmarks was 18.25%, with a dry extract rate range of 16.28%-20.76%. The index component content and transfer rate ranges were listed as follows: 0.15%-0.18% and 38.81%-58.05% for ferulic acid; 0.26%-0.42% and 36.51%-51.02% for sinapine thiocyanate; 0.09%-0.15% and 48.80%-76.61% for liquiritin; 0.13%-0.24% and 23.45%-35.61% for glycyrrhizic acid. The fingerprint, dry extract rate, and index component content determination was combined for analyzing the quality value transfer of substance benchmarks in the classic prescription Sanpian Decoction.The established quality evaluation method for the substance benchmarks was stable and feasible, which has provided a basis for the quality control of Sanpian Decoction and the follow-up development of related preparations.
Benchmarking ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Glycyrrhizic Acid/analysis* ; Paeonia ; Quality Control ; Thiocyanates

OBJECTIVE: This study investigated the potential mechanisms behind the beneficial effects of Fructus Zanthoxyli (FZ) against type 2 diabetes mellitus (T2DM) based on network pharmacology and experimental validation. METHODS: Ultra-high-performance liquid chromatography coupled with hybrid quadrupole-orbitrap high-resolution mass spectrometry, and gas chromatography-mass spectrometry were used to identify the constituents of FZ. Next, the differentially expressed genes linked to the treatment of diabetes with FZ were screened using online databases (including Gene Expression Omnibus database and Swiss Target Prediction online database), and the overlapping genes and their enrichment were analyzed by Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, the pathway was verified by in vitro experiments, and cell staining with oil red and Nile red showed that the extract of FZ had a therapeutic effect on T2DM. RESULTS: A total of 43 components were identified from FZ, and 39 differentially expressed overlapping genes were screened as the possible targets of FZ in T2DM. The dug component-target network indicated that PPARA, PPARG, PIK3R3, JAK2 and GPR88 might be the core genes targeted by FZ in the treatment of T2DM. Interestingly, the enrichment analysis of KEGG showed that effects of FZ against T2DM were closely correlated with the adenosine monophosphate-activated protein kinase (AMPK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathways. In vitro experiments further confirmed that FZ significantly inhibited palmitic acid-induced lipid formation in HepG2 cells. Moreover, FZ treatment was able to promote the AMPK and PI3K/Akt expressions in HepG2 cells. CONCLUSION Network pharmacology combined with experimental validation revealed that FZ extract can improve the glycolipid metabolism disorder of T2DM via activation of the AMPK/PI3K/Akt pathway.
Humans ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinase/metabolism* ; Diabetes Mellitus, Type 2/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; AMP-Activated Protein Kinases/metabolism* ; Glycolipids/therapeutic use* ; Network Pharmacology ; Plant Extracts/therapeutic use* ; Drugs, Chinese Herbal/therapeutic use*