OBJECTIVE: To compare the clinical efficacy between thermo-electroacupuncture at yaosanzhen and oral celecoxib in the treatment of chronic lumbar muscle strain with cold dampness. METHODS: A total of 80 patients with chronic lumbar muscle strain of cold dampness were randomly divided into an observation group (40 cases, 1 case dropped out) and a control group (40 cases, 2 cases were excluded). The observation group was treated with thermo-electroacupuncture at yaosanzhen (bilateral Shenshu [BL23], Dachangshu [BL25], Weizhong [BL40]), disperse-dense wave was selected, with a pulse cycle of 0.08 s, current intensity of 1-3 mA, with needles heated to approximately 45 ℃, the duration was 25 min per session, once a day. The control group was given oral celecoxib capsules, once daily, 200 mg each time. Six sessions as one course, with a 1-day interval between courses, 2 courses were required in both groups. The TCM syndrome score, visual analogue scale (VAS) score, Oswestry disability index (ODI) score, and Japanese Orthopedic Association (JOA) score before and after treatment in both groups were compared. The serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), thromboxane B2 (TXB2) and C-reactive protein (CRP) were detected using ELISA method before and after treatment in both groups. The clinical efficacy was evaluated in both groups after treatment. RESULTS: After treatment, the TCM syndrome scores, VAS scores, ODI scores and serum levels of TNF-α, IL-6, TXB2, CRP in both groups were reduced compared with those before treatment (P<0.01), while the JOA scores were increased (P<0.01)；the TCM syndrome score, VAS score, ODI score and serum levels of TNF-α, IL-6, TXB2, CRP in the observation group were lower than those in the control group (P<0.01, P<0.05), and the JOA score was higher than that in the control group (P<0.01). The total effective rate of the observation group was 92.3% (36/39), which was superior to 78.9% (30/38) in the control group (P<0.05). CONCLUSION Thermo-electroacupuncture at yaosanzhen can alleviate pain symptom in patients with chronic lumbar muscle strain of cold dampness, regulate lumbar function, reduce the levels of inflammatory factors, and the therapeutic effect is superior to oral celecoxib.
Humans ; Male ; Female ; Middle Aged ; Adult ; Electroacupuncture ; Acupuncture Points ; Sprains and Strains/genetics* ; Cold Temperature ; Tumor Necrosis Factor-alpha/blood* ; Interleukin-6/blood* ; Aged ; Treatment Outcome ; Young Adult ; C-Reactive Protein/metabolism* ; Chronic Disease/therapy* ; Lumbosacral Region/physiopathology*

OBJECTIVE: To observe the effects of Huayu Tongluo (transforming stasis and unblocking collaterals) moxibustion on learning-memory ability and hippocampal mammalian sterile 20-like kinase 1 (Mst1)/nuclear factor κB (NF-κB) p65 pathway related to inflammatory response in rats with vascular dementia (VD). METHODS: A total of 60 male Wistar rats of SPF grade were randomly divided into a sham operation group (12 rats) and a modeling group (48 rats). VD model was established by the method of modified bilateral common carotid artery permanent ligation in the modeling group. Thirty-six rats with successful modeling were randomly divided into a model group, a moxibustion group and a western medication group, with 12 rats in each group. Huayu Tongluo moxibustion was applied at "Dazhui" (GV14), "Baihui" (GV20) and "Shenting" (GV24) in the moxibustion group, 20 min each time, once a day, 7 day-intervention was as one course, and 1 day-interval was taken between two courses, for a total of 3 courses. In the western medication group, piracetam was given 0.72 mg/kg by intragastric administration, twice a day, the course of intervention was same as that of the moxibustion group. The learning-memory ability was detected by Morris water maze test; the morphology of hippocampal CA1 region was observed by HE staining; the mRNA expression of Mst1, M1 microglia markers CD86, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) was detected by real-time PCR; the levels of IL-6 and TNF-α in hippocampus were detected by ELISA; and the protein expression of Mst1 and NF-κB p65 in hippocampus was detected by Western blot in rats of each group. RESULTS: Compared with the sham operation group, the escape latency was prolonged in the model group (P<0.05); compared with the model group, the escape latency was shortened in the moxibustion group and the western medication group (P<0.05). The cells in the CA1 region of hippocampus were disordered, cell collapse and irregular nuclei could be observed in the model group; compared with the model group, the cell arrangement in the CA1 region of hippocampus was more regular, and the damage was improved in the moxibustion group and the western medication group. Compared with the sham operation group, the mRNA expression of Mst1, CD86, IL-6 and TNF-α, as well as the protein expression of Mst1, NF-κB p65 in hippocampus were increased in the model group (P<0.05). Compared with the model group, the mRNA expression of Mst1, CD86, IL-6 and TNF-α, as well as the protein expression of Mst1, NF-κB p65 in hippocampus were decreased in the moxibustion group and the western medication group (P<0.05). Compared with the sham operation group, the levels of IL-6 and TNF-α in hippocampus were increased in the model group (P<0.05). Compared with the model group, the levels of IL-6 and TNF-α in hippocampus were decreased in the moxibustion group and the western medication group (P<0.05). CONCLUSION Huayu Tongluo moxibustion can improve the learning-memory ability of VD rats, the mechanism may be related to regulating the activation of microglia through Mst1/NF-κB p65 pathway, reducing the release of pro-inflammatory factors i.e. IL-6 and TNF-α, so as to alleviating the damage of inflammatory factors in the hippocampus of VD rats.
Animals ; Male ; Rats ; Moxibustion ; Hippocampus/metabolism* ; Rats, Wistar ; Dementia, Vascular/genetics* ; Memory/drug effects* ; Humans ; Transcription Factor RelA/genetics* ; Learning ; Protein Serine-Threonine Kinases/genetics* ; Acupuncture Points ; Interleukin-6/genetics* ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal

OBJECTIVE: To compare the clinical efficacy between penetrating needling of three eye acupoints combined with sodium hyaluronate eye drops and sodium hyaluronate eye drops alone for the treatment of dry eye. METHODS: A total of 156 patients (312 eyes) with dry eye were randomly assigned to an observation group and a control group, with 78 patients (156 eyes) in each group. The control group was treated with sodium hyaluronate eye drops, one drop per eye, four times daily, for 4 weeks. In addition to the sodium hyaluronate treatment, the observation group received penetrating needling of three eye acupoints. Acupoints included bilateral Cuanzhu (BL2), Sizhukong (TE23), Sibai (ST2), and Jingming (BL1). Needling was performed once daily, four times a week, for 4 weeks. The subjective ocular symptom scores, neuropathic pain symptom inventory-eye (NPSI-Eye) scores, ocular surface disease index (OSDI) scores, corneal fluorescein staining (FL) scores, tear break-up time (BUT), SchirmerⅠtest (SⅠT), central tear meniscus height (TMH), and tear levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) were evaluated before and after treatment in the two groups. Clinical efficacy was also compared between the two groups. RESULTS: After treatment, both groups showed significant improvements in subjective ocular symptom scores, NPSI-Eye scores, OSDI scores, FL scores, and reductions in tear IL-6 and TNF-α levels (P<0.01). Additionally, BUT, SⅠT, and TMH were increased significantly in both groups (P<0.01). After treatment, the subjective ocular symptom scores, NPSI-Eye score, OSDI score, FL score, and tear levels of IL-6 and TNF-α in the observation group were lower than those in the control group (P<0.01, P<0.05), while BUT, SⅠT, and TMH were significantly improved compared to the control group (P<0.01). The markedly effective rate and total effective rate in the observation group were 83.3% (65/78) and 100.0% (78/78), respectively, which were higher than 52.6% (41/78, P<0.01) and 92.3% (72/78, P<0.05) in the control group. CONCLUSION The penetrating needling of three eye acupoints combined with sodium hyaluronate eye drops can effectively alleviate symptoms of dry eye, reduce inflammatory response, and has superior efficacy to sodium hyaluronate eye drops alone.
Humans ; Hyaluronic Acid/administration & dosage* ; Male ; Female ; Dry Eye Syndromes/genetics* ; Middle Aged ; Acupuncture Points ; Ophthalmic Solutions/administration & dosage* ; Adult ; Aged ; Treatment Outcome ; Acupuncture Therapy ; Interleukin-6/genetics* ; Young Adult ; Tumor Necrosis Factor-alpha/metabolism*

OBJECTIVE: To observe the effect of electroacupuncture combined with enhanced recovery after surgery (ERAS) protocol on promoting intestinal function in patients after gastric cancer surgery. METHODS: Forty-four patients who underwent radical gastrectomy for gastric cancer were randomly divided into an experimental group (22 cases, 3 cases were excluded) and a control group (22 cases, 4 cases were excluded). Both groups received treatment under ERAS protocol, the experimental group was given electroacupuncture at bilateral Neiguan (PC6), Hegu (LI4), Zusanli (ST36) and Quchi (LI11), disperse-dense wave was selected, with frequency of 2 Hz/100 Hz. The control group received placebo electroacupuncture intervention, with the same acupoints as the experimental group, electrode pads were placed on the acupoints without electrical stimulation. Each session lasted 30 min, starting from 1 h after surgery, once every 24 h, until the patient resumed anal flatus. The intestinal sound rate of both groups was observed 24 h before surgery and 24, 48 h after surgery. The bowel sound recovery time (BSRT), time to first anal flatus, time to first defecation, and tolerance to oral enteral nutrition suspension were compared between the two groups. The levels of serum C-reactive protein (CRP), interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12, IL-17, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were measured 24 h before surgery and 24 h after surgery in both groups. RESULTS: The intestinal sound rate 24 h after surgery was decreased compared with that 24 h before surgery in the two groups (P<0.05), the intestinal sound rate 24, 48 h after surgery in the experimental group was higher than that in the control group (P<0.05). The BSRT in the experimental group was earlier than that in the control group (P<0.05) .The levels of serum CRP, IL-6, IL-10 24 h after surgery in the experimental group were higher than those 24 h before surgery (P<0.05), while the levels of serum CRP, IL-4, IL-6, IL-10, IFN-γ in the control group were higher than those 24 h before surgery (P<0.05); the levels of serum CRP、IL-4、IFN-γ 24 h after surgery in the experimental group were lower than those in the control group (P<0.05) .The tolerance rate of oral enteral nutrition suspension in the experimental group was 84.2% (16/19), which was higher than 50.0% (9/18) in the control group (P<0.05). CONCLUSION Electroacupuncture combined with ERAS protocol can improve the intestinal motility, shorten the BSRT, enhance the tolerance of oral intake, and reduce inflammatory response in patients after gastric cancer surgery.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Acupuncture Points ; C-Reactive Protein/metabolism* ; Electroacupuncture ; Gastrectomy ; Interleukin-10 ; Interleukin-6 ; Intestines/physiopathology* ; Stomach Neoplasms/therapy*

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the intestinal flora in rats with chronic obstructive pulmonary disease (COPD) and explore its possible mechanism based on the gut-lung axis theory. METHODS: A total of 30 male SD rats of SPF grade were randomly divided into a normal control (NC) group, a model group and an EA group, 10 rats in each one. In the model group and the EA group, COPD model was established by intratracheal instillation of lipopolysaccharide combined with cigarette fumigation. In the EA group, EA was applied at bilateral "Feishu" (BL13) and "Zusanli" (ST36), with disperse-dense waves, in frequency of 4 Hz/20 Hz, current of 1-3 mA, 20 min a time, once a day for 14 days continuously. Before and after modeling, as well as after intervention, body weight was observed; after intervention, the lung function indexes (forced expiratory volume in 0.1 second [FEV_0.1], FEV_0.1/forced vital capacity [FVC]%, forced expiratory volume in 0.3 second [FEV_0.3] and FEV_0.3/FVC%) were measured, serum levels of inflammatory factors (tumor necrosis factor-α[TNF-α], interleukin-6[IL-6], interleukin-1β[IL-1β] and interleukin-10[IL-10]) were detected by ELISA, histopathology of lung and colon tissues was observed by HE staining, the intestinal flora were analyzed by 16S rRNA, and the correlations between lung function and intestinal flora were analyzed. RESULTS: Compared with the NC group, in the COPD group, the body weight and lung function indexes were reduced (P<0.01); the lung and colon tissues were damaged, the mean linear intercept (MLI) of alveolus and inflammatory cell numbers of 100 μm² in lung tissue were increased (P<0.01); the serum levels of TNF-α, IL-6 and IL-1β were increased (P<0.01, P<0.05), and the serum level of IL-10 was decreased (P<0.01); α-diversity indexes of intestinal flora were increased (P<0.01); the relative abundance of Bacteroidetes, Proteobacteria and Oscillospira, Bacteroides, Coprococcus was increased (P<0.01), the relative abundance of Firmicutes, Actinobacteria, Tenericutes, TM7 and Lactobacillus, Allobaculum, Bifidobacterium, YRC22 was decreased (P<0.01, P<0.05); 31 different expressed metabolic pathways were identified between the two groups. Compared with the COPD group, in the EA group, the body weight and lung function indexes were increased (P<0.01); the damage of lung and colon tissues was improved, the MLI of alveolus was decreased (P<0.05); the serum levels of TNF-α, IL-6 and IL-1β were decreased (P<0.05), and the serum level of IL-10 was increased (P<0.05); α-diversity indexes of intestinal flora were decreased (P<0.01); the relative abundance of Bacteroidetes, Proteobacteria and Oscillospira, Bacteroides, Coprococcus was decreased (P<0.01, P<0.05), the relative abundance of Firmicutes, Actinobacteria, Tenericutes, TM7 and Lactobacillus, Allobaculum, Bifidobacterium, YRC22 was increased (P<0.01); 35 different expressed metabolic pathways were identified between the two groups. The lung function was positive related with Actinobacteria, Tenericutes, TM7 and YRC22, and was negative related with Bacteroidetes, Proteobacteria and Oscillospira, Bacteroides, Coprococcus. CONCLUSION EA may ameliorate lung function and tissue injury of COPD by regulating intestinal flora dysbiosis and inflammatory response, suggesting an anti-inflammatory effect mediated via "gut-lung" axis.
Animals ; Pulmonary Disease, Chronic Obstructive/genetics* ; Male ; Electroacupuncture ; Rats ; Rats, Sprague-Dawley ; Lung/metabolism* ; Gastrointestinal Microbiome ; Humans ; Interleukin-6/immunology* ; Tumor Necrosis Factor-alpha/immunology* ; Intestines/microbiology* ; Interleukin-10/immunology*

OBJECTIVE: To observe the clinical efficacy of warming acupuncture combined with western medication for oligoasthenoteratozoospermia of kidney-yang insufficiency and its effects on the levels of interleukin (IL)-6 and IL-10 in seminal plasma. METHODS: A total of 60 patients with oligoasthenoteratozoospermia of kidney-yang insufficiency were randomly divided into a combination group and a medication group, with 30 cases in each group. The medication group was treated with levocarnitine oral solution orally, 10 mL once, 3 times a day. On the basis of the treatment in the medication group, warming acupuncture was applied at Baihui (GV20), Guanyuan (CV4) and Mingmen (GV4) in the combination group, once every other day, 3 times a week. Both groups were treated for 12 weeks. Before and after treatment, the TCM syndrome score was observed, the semen routine indexes (the sperm concentration, progressive [PR] sperm motility, PR + non-progressive [NP] sperm motility and sperm malformation rate), the serum sex hormones indexes (follicle-stimulating hormone [FSH], luteinizing hormone [LH], testosterone [T] and estradiol [E₂]), as well as the IL-6 and IL-10 levels in seminal plasma were detected, and the clinical efficacy was evaluated after treatment in the two groups. RESULTS: After treatment, except for the hyposexuality score in the medication group, the each item scores and total scores of TCM syndrome were decreased compared with those before treatment (P<0.01, P<0.05), the sperm malformation rates, serum FSH and LH levels, IL-6 levels in the seminal plasma were decreased compared with those before treatment (P<0.01, P<0.05), the PR sperm motility, PR + NP sperm motility, serum T levels, IL-10 levels in the seminal plasma were increased compared with those before treatment (P<0.01, P<0.05) in the two groups; the sperm concentration was increased compared with that before treatment in the combination group (P<0.01). After treatment, compared with the medication group, except for the hyposexuality and frequent nocturia scores, the each item scores and total score of TCM syndrome were lower (P<0.01, P<0.05); the sperm concentration, PR sperm motility and PR + NP sperm motility, serum T level, IL-10 level in the seminal plasma were higher (P<0.01, P<0.05); sperm malformation rate, serum FSH and LH levels, IL-6 level in the seminal plasma were lower (P<0.01, P<0.05) in the combination group. The total effective rate was 83.8% (25/30) in the combination group, which was superior to 60.0% (18/30) in the medication group (P<0.05). CONCLUSION Warming acupuncture combined with western medication can effectively treat oligoasthenoteratozoospermia of kidney-yang insufficiency, regulate the levels of sex hormones, and its mechanism may be related to the down-regulation of IL-6 level and the up-regulation of IL-10 level in seminal plasma.
Humans ; Male ; Interleukin-10/genetics* ; Interleukin-6/genetics* ; Adult ; Semen/metabolism* ; Acupuncture Therapy ; Oligospermia/drug therapy* ; Yang Deficiency/physiopathology* ; Kidney/physiopathology* ; Young Adult ; Asthenozoospermia/drug therapy* ; Combined Modality Therapy ; Treatment Outcome

BACKGROUND: Inflammation plays a critical role in severe cerebral venous thrombosis (CVT) pathogenesis, but the benefits of anti-inflammatory therapies remain unclear. This study aimed to investigate the association between steroid therapy combined with anticoagulation and the prognosis of acute/subacute severe CVT patients. METHODS: A prospective cohort study enrolled patients with acute/subacute severe CVT at Xuanwu Hospital (July 2020-January 2024). Patients were allocated into steroid and non-steroid groups based on the treatment they received. Functional outcomes (modified Rankin scale [mRS]) were evaluated at admission, discharge, and 6 months after discharge. Serum high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), cerebrospinal fluid (CSF) IL-6, and intracranial pressure were measured at admission and discharge in the steroid group. Fundoscopic Frisén grades were assessed at admission and 6 months after discharge. Univariate and multivariate logistic regression were used to evaluat associations between steroid use and favorable outcomes (mRS ≤2) at the 6-month follow-up. Paired tests assessed changes in hs-CRP and other variables before and after treatment, and Spearman's correlations were used to analyze relationships between these changes and functional improvements. RESULTS: A total of 107 and 58 patients in the steroid and non-steroid groups, respectively, were included in the analysis. Compared with the non-steroid group, the steroid group had a higher likelihood of achieving an mRS score of 0-2 (93.5% vs . 82.5%, odds ratio [OR] = 2.98, P  = 0.037) at the 6-month follow-up. After adjusting for confounding factors, the result remained consistent. Pulsed steroid therapy did not increase mortality during hospitalization or follow-up, nor did it lead to severe steroid-related complications (all P  >0.05). Patients in the steroid group showed a significant reduction in serum hs-CRP, IL-6, CSF IL-6, and intracranial pressure at discharge compared to at admission, as well as a significant reduction in the fundoscopic Frisén grade at the 6-month follow-up compare to at admission (all P  <0.001). A reduction in serum inflammatory marker levels during hospitalization positively correlated with improvements in functional outcomes ( P  <0.05). CONCLUSION: Short-term steroid use may be an effective and safe adjuvant therapy for acute/subacute severe CVT when used alongside standard anticoagulant treatments, which are likely due to suppression of the inflammatory response. However, these findings require further validation in randomized controlled trials. TRAIL REGISTRATION ClinicalTrials.gov , NCT05990894.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Anticoagulants/therapeutic use* ; C-Reactive Protein/metabolism* ; Interleukin-6/metabolism* ; Intracranial Thrombosis/drug therapy* ; Prospective Studies ; Steroids/therapeutic use* ; Venous Thrombosis/drug therapy*

This study aims to investigate the antipyretic effects and mechanisms of ethanol extracts from Arisaematis Rhizoma fermented with bile from different sources on a rat model of fever induced by a dry-yeast suspension. The rat model of fever was established by subcutaneous injection of 20% dry-yeast suspension into the rat back. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6) in the serum, as well as prostaglandin E_2(PGE_2) and cyclic adenosine monophosphate(cAMP) in the hypothalamus, were determined by ELISA. Metabolomics analysis was then performed on serum and hypothalamus samples based on UPLC-Q-TOF MS to explore the potential biomarkers and metabolic pathways. The results showed that the body temperatures of rats significantly rose 4 h after modeling. After oral administration of high-dose ethanol extracts of Arisaematis Rhizoma fermented with bovine bile(NCH) and porcine bile(ZCH), the body temperatures of rats declined(P<0.05), and the NCH group showed better antipyretic effect than the ZCH group. Additionally, compared with the model group, the NCH and ZCH groups showed lowered levels of IL-1β, IL-6, TNF-α, PGE_2, and cAMP(P<0.01). The results of serum and hypothalamus metabolomics analysis indicated that both NCH and ZCH exerted antipyretic effects by regulating phenylalanine metabolism, sphingolipid metabolism, arachidonic acid metabolism, and steroid hormone biosynthesis. Collectively, both NCH and ZCH can play an obvious antipyretic role in the rat model of dry yeast-induced fever, and the underlying mechanism might be closely associated with inhibiting inflammation and regulating metabolic disorders. Moreover, NCH demonstrates better antipyretic effect.
Animals ; Rats ; Male ; Fermentation ; Rats, Sprague-Dawley ; Rhizome/metabolism* ; Drugs, Chinese Herbal/chemistry* ; Bile/chemistry* ; Antipyretics/chemistry* ; Fever/metabolism* ; Cattle ; Swine ; Tumor Necrosis Factor-alpha/metabolism* ; Ethanol/chemistry* ; Interleukin-6/blood* ; Interleukin-1beta/blood*

This study investigates the material basis and mechanism of Arisaematis Rhizoma Preparatum in the treatment of chronic obstructive pulmonary disease(COPD) using animal experiments, component analysis, network pharmacology, and molecular docking. A mouse model of COPD was constructed by cigarette smoke and lipopolysaccharide(LPS). Blood gas analysis was performed to measure the pH and partial pressure of carbon dioxide(PCO_2) in the blood of the mice. Lung tissue sections were analyzed using HE staining, and the effects of Arisaematis Rhizoma Preparatum water extract on inflammatory factors(TNF-α, IL-6, and IL-1β) and the PI3K/AKT signaling pathway in the lung tissue of COPD model mice were studied by qPCR and Western blot. The composition of the Arisaematis Rhizoma Preparatum water extract was analyzed using UPLC Q-Exactive Orbitrap MS. The SwissTargetPrediction database was used to predict the targets of the chemical components in Arisaematis Rhizoma Preparatum. GeneCards, OMIM, TTD, PharmGKB and DrugBank disease databases were used to screen for COPD targets, and the potential targets of Arisaematis Rhizoma Preparatum in treating COPD were identified. A protein-protein interaction(PPI) network of intersection targets was constructed and analyzed using the STRING database and Cytoscape 3.9.0, and core genes were screened. GO functional analysis and KEGG pathway enrichment analysis were performed using R language, and molecular docking verification was conducted using AutoDock Vina software. The results of the animal experiments showed that Arisaematis Rhizoma Preparatum water extract improved pulmonary ventilation function in COPD model mice, reduced lung inflammatory cells, decreased alveolar cavities, and improved lung tissue condition. The levels of inflammatory factors TNF-α, IL-6 and IL-1β were decreased, and the phosphorylation levels of PI3K and AKT were inhibited. Fifty-two chemical components were identified from Arisaematis Rhizoma Preparatum, and 440 intersection targets related to COPD were found. Nine key components were screened, including hydroxyphenylethylamine, L-tyrosine, L-tyrosyl-L-alanine, 3,4,5-trihydroxy-1-cyclohexene-1-carboxylic acid, methyl azelate, zingerone, 6-gingerol, linoleamide, and linoleoyl ethanolamine. Five core targets were identified, including AKT1, TNF, STAT3, ESR1, and IL1B. The PI3K/AKT pathway was identified as the key pathway for the treatment of COPD with Arisaematis Rhizoma Preparatum. Molecular docking results showed that 75% of the binding energies of key components and core targets were less than-5 kcal·mol~(-1), indicating good binding affinity. In conclusion, Arisaematis Rhizoma Preparatum may improve pulmonary ventilation function, enhance lung pathological morphology, and reduce pulmonary inflammation in COPD model mice by inhibiting the PI3K/AKT signaling pathway and downregulating TNF-α, IL-6, and IL-1β inflammatory factors. The material basis may be associated with L-tyrosyl-L-alanine, 3,4,5-trihydroxy-1-cyclohexene-1-carboxylic acid, zingerone and 6-gingerol, and AKT1 and TNF may be the primary targets.
Animals ; Pulmonary Disease, Chronic Obstructive/metabolism* ; Network Pharmacology ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Rhizome/chemistry* ; Humans ; Molecular Docking Simulation ; Chromatography, High Pressure Liquid ; Disease Models, Animal ; Signal Transduction/drug effects* ; Lung/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Interleukin-6/immunology*

A combination of the "disease-syndrome-symptom" approach was used to study the syndrome characterization and features of dampness-heat obstruction syndrome in papain-induced knee osteoarthritis(KOA) model rats during the disease process. Forty-eight male SD rats were randomly divided into sham and model groups. The KOA model was established by injecting a mixture of papain and L-cysteine into the joint cavity on days 1, 3, and 5. During the 8 weeks following model establishment, the rats were assessed weekly for the plantar mechanical pain threshold, knee joint diameter, local skin temperature of the knee joint, weight-bearing difference between the two hind feet, and the modified Lequesne MG score of the knee joint. Samples were collected at 1, 2, 4, 6, and 8 weeks after model establishment to observe the gross lesions in cartilage and synovium. Histopathological changes in joint tissues were examined using hematoxylin-eosin, Masson's trichrome, and Senna red O-solid green staining. ELISA and immunohistochemical analysis were performed to detect the levels of interleukin(IL)-1β, IL-6, tumor necrosis factor(TNF)-α, prostaglandin E2(PGE2), and the expression of aquaporins(AQP) 1 and 3 in serum and synovium. The results showed that the ink score of articular cartilage in the model group significantly increased from 4 to 8 weeks, the cartilage Mankin's score and the percentage of Masson-positive area in cartilage increased significantly from 1 to 8 weeks. The percentage of red-stained area for cartilage proteoglycans decreased significantly from 1 to 8 weeks. The synovitis score from 1 to 6 weeks and the percentage of blue-stained collagen fibers in the synovium from 1 to 8 weeks increased significantly, with statistically significant differences compared to the sham group. The mechanical pain threshold in the model group significantly decreased from 1 to 8 weeks, the knee joint diameter significantly increased from 1 to 6 weeks, and the local skin temperature of the knee joint, the weight-bearing difference between the two hind feet, and the modified Lequesne MG score from 1 to 5 weeks significantly increased, all with statistically significant differences compared to the sham group. The levels of IL-1β, IL-6, TNF-α, and PGE2 in serum and synovium of the model group significantly increased from 1 to 6 weeks. Serum TNF-α and PGE2, and synovial IL-1β, also significantly increased at 8 weeks. The levels of cartilage AQP1 and AQP3 significantly increased from 1 to 4 weeks, while synovial AQP1 and AQP3 increased significantly from 1 to 6 weeks, with all differences statistically significant compared to the sham group. In conclusion, papain-induced KOA rats exhibited pathological changes, including articular cartilage degeneration and synovial inflammation, within 1 week of induction. The KOA rats showed characteristics of dampness-heat obstruction syndrome, such as joint pain, swelling, elevated skin temperature, and decreased function, as well as increased inflammatory factors and AQP1、AQP3 in serum and joint tissues within 5 to 6 weeks of disease onset. These results provide an experimental model for studying the syndromes of KOA with dampness-heat obstruction syndrome.
Animals ; Male ; Rats, Sprague-Dawley ; Rats ; Osteoarthritis, Knee/physiopathology* ; Disease Models, Animal ; Humans ; Interleukin-1beta/metabolism* ; Interleukin-6/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Knee Joint/pathology*