Serum IL-6 Levels Research Articles

Ciplukan (Physalis angulata Linn) Bioactivity against Bleomycin-Induced Pulmonary Fibrosis in Mice by reducing Subpleural Fibrosis, KL-6 Level and Anti-Inflammatory properties

Pulmonary fibrosis is a fatal lung disease with unknown pathogenesis and limited treatment options. Herbal medicine began to be developed as an antifibrosis drug for this disease. Ciplukan plant (Physalis angulata Linn.), is a wild plant that has been widely used for generations as traditional Indonesian medicine for various diseases; but has never been studied as an antifibrosis. This study aimed to determine Ciplukan herb ethanol extract (CPL) bioactivity as antifibrosis in pulmonary fibrosis disorders in experimental mice model induced by bleomycin. A total of 35 male mice and 35 female mice of the ddy strain was divided into 7 groups respectively with 1 normal control group and 6 experimental animal models of pulmonary fibrosis induced by bleomycin groups. For the pulmonary fibrosis model, bleomycin (BLM) was injected subcutaneously 8 times with a frequency of twice a week for 4 weeks. Furthermore, the mice were given CPL orally starting at week 6 of treatment with 2 different doses, 1.95mg (CPL-1) and 3.9mg (CPL) every day for 4 weeks. Pulmonary fibrosis histopathology was analyzed using HE and MT staining methods. Serum IL-6, KL-6, and TGF-β1 levels determination was carried out using the ELISA method. The administration of CPL significantly reduced the fibrosis score from 2.80±1.095 to 1.67±0.577µm (p=0.026). The CPL also showed anti-inflammatory activity by reducing IL-6 levels from 1916.20±594.27 to 16.81±17.07pg/mL (p=0.003); TGF-β1 levels from 51.25±2.25 to 22.48±0.93ng/mL (p=0.021); and KL-6 levels from 28.09±2.25 to 13.99±0.93ng/mL (p=0.000). CPL was proven to have pulmonary antifibrotic activity in experimental mice model. The pulmonary antifibrotic effect was evidenced by a decrease in pulmonary fibrosis scores also a decrease in KL-6 levels, IL-6 levels, and TGF-β1. The administration of CPL-1 and CPL-2 can provide recovery of pulmonary fibrosis induced by bleomycin.

Serum Interleukin 6 (IL -6) as Prognostic Marker in Egyptian CLL patients.

Background: Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. Currently, several biomarkers are being used as CLL prognosticators, including elevated protein levels, elevated RNA levels, gene mutations, and epigenetic changes. Materials and Methods: This study is a prospective study conducted on 55 patients newly diagnosed with CLL, serum IL-6 level was measured initially and after a 6-month treatment course. Correlation with the course of the disease and the known CLL prognostic parameters was done initially and after 6 months. Results: The initial serum IL-6 level in the patient group (pre-treatment) ranges from 36-91 pg/mL (median 57), and in the patient group (post-treatment) ranges from 1-32 pg/mL (median 2). Serum IL-6 level was positively correlated with WBC count, β2 microglobulin, LDH, ESR, B symptoms, Uric Acid, BM Aspirate (% of lymphocytes), and Binet and Rai staging systems. Conclusion: Serum IL-6 is a useful poor prognostic marker in newly diagnosed CLL patients; its prognostic value goes with the other known prognostic markers such as the BM lymphocyte count, ESR, and LDH.

Serum GAS6, sAXL, IL-10, NO, and BCL-2 levels are decreased in patients with Behçet's disease.

Behçet's disease (BD) is an autoimmune chronic systemic inflammatory disease characterized by a versatile clinical spectrum. Growth arrest specific protein 6 (GAS6)/soluble AXL (sAXL) signaling pathway draws attention in the resolution of inflammation, and its deficiency is associated with chronic inflammatory, autoimmune diseases, as well as clearance of apoptotic cells by phagocytes - efferocytosis. In this study, it was aimed to investigate whether GAS6/sAXL, interleukin (IL)-10, nitric oxide (NO), and BCL-2 levels were associated with inflammation and efferocytosis contributes to the pathogenesis of BD. A total of 37 Behçet patients with ocular involvement and 30 healthy control subjects were included in this study. GAS6, sAXL, IL-10, NO, and BCL-2 levels were quantified using enzyme-linked immunosorbent assay (ELISA) method. Serum GAS6, sAXL, IL-10, NO, and BCL-2 levels were significantly lower in patients with BD compared to the controls (P < 0.005, P < 0.001, P < 0.001, P < 0.001, and P < 0.001, respectively). In correlation analysis, research parameters decreased in patients with BD was significantly correlated with each other: GAS6-IL-10 (r = 0.585, P < 0.001), GAS6-BCL-2 (r = 0.541, P < 0.001), sAXL-BCL-2 (r = 0.696, P < 0.001), IL-10-NO (r = 0.717, P < 0.001), IL-10-BCL-2 (r = 0.759, P < 0.001), and NO-BCL-2 (r = 0.541, P < 0.001). In conclusion, decreased serum BCL-2 level may be an indicator of increased apoptosis in these patients and decreased levels of GAS6/sAXL, IL-10, and NO may indicate insufficient clearance of apoptotic bodies released as a result of increased apoptosis in BD patients.

A Novel IRAK4 Inhibitor DW18134 Ameliorates Peritonitis and Inflammatory Bowel Disease.

IRAK4 is a critical mediator in NF-κB-regulated inflammatory signaling and has emerged as a promising therapeutic target for the treatment of autoimmune diseases; however, none of its inhibitors have received FDA approval. In this study, we identified a novel small-molecule IRAK4 kinase inhibitor, DW18134, with an IC50 value of 11.2 nM. DW18134 dose-dependently inhibited the phosphorylation of IRAK4 and IKK in primary peritoneal macrophages and RAW264.7 cells, inhibiting the secretion of TNF-α and IL-6 in both cell lines. The in vivo study demonstrated the efficacy of DW18134, significantly attenuating behavioral scores in an LPS-induced peritonitis model. Mechanistically, DW18134 reduced serum TNF-α and IL-6 levels and attenuated inflammatory tissue injury. By directly blocking IRAK4 activation, DW18134 diminished liver macrophage infiltration and the expression of related inflammatory cytokines in peritonitis mice. Additionally, in the DSS-induced colitis model, DW18134 significantly reduced the disease activity index (DAI) and normalized food and water intake and body weight. Furthermore, DW18134 restored intestinal damage and reduced inflammatory cytokine expression in mice by blocking the IRAK4 signaling pathway. Notably, DW18134 protected DSS-threatened intestinal barrier function by upregulating tight junction gene expression. In conclusion, our findings reported a novel IRAK4 inhibitor, DW18134, as a promising candidate for treating inflammatory diseases, including peritonitis and IBD.

Level of interleukin 17 in inflammatory bowel disease and its relation with disease activity

BackgroundInflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder of the gastrointestinal tract (GIT).It results in progressive intestinal epithelium structural and functional damage that necessitates lifetime medication.Thereis imbalance in the production of T helper 1 (Th1), Th2 and Th17 cytokines. This plays a crucial role in the chronic inflammatory process and the defective immune response to pathogenic agents; thus promoting the recurrence of the disease.Our aim of this study was to detect serum IL-17 levels in IBD patients and its relation with disease activity.MethodsThis was a single center case control study, conducted at hepatology and gastroenterology unit, Mansoura specialized Medical Hospital, Egypt.Patients who were included were aged 18–65 years, diagnosed either Ulcerative Colitis (UC)or Crohn’s Disease (CD) based on previous colonoscopy.IBD activity was measured for UC using the MAYO score and CD using the CD activity index (CDAI). Fifty five patients were UC, 24 patients were CD, 21 patients were control.Patients who were excluded were under 15 years old, with history of GIT malignancy, or any serious comorbidities. Study protocol was approved by Institution Research Board (IRB) of Mansoura Medical College.All patients were subjected to full history taking, routine physical examination, colonoscopy and laboratory investigations including serum IL-17 levels by ELISA besides CBC, CRP, ESR and fecal calprotectin.ResultsSerum IL-17 level was increased significantly among UC; median (min-max) = 72(21–502)pg/ml, in CD 54.5(25–260) versus control 19 (14–35), P < 0.001.However, it was not correlated to the disease activity either Mayo score of UC or CDAI of CD.There was significant correlation to the extent of inflammation in UC affecting the colon (either proctosigmoiditis, left sided colitis or pan colitis), also to the type of CD (either inflammatory, stricturing or fistulizing) by P < 0.05.It was not correlated significantly with any of the IBD activity markers (CRP, ESR, or fecal calprotectin).Yet there was negative significant correlation with Hb level (r =-0.28, p = 0.005).There was not significant association between median serum level of IL-17 & duration of disease (P = 0.6).However, median IL-17 was higher among hospitalized cases than non-hospitalized (73 & 55, pg/ml respectively; p < 0.002). AUC was significantly differentiating between IBD and control group = 0.993 with the best-detected cut off point from curve 32 pg/ml yielding sensitivity of 97.5% and specificity of 95.2%.ConclusionSerum IL-17 increases in colonic inflammation significantly more than in control group, however its increase is not correlated to IBD activity.

Association of high disease activity and serum IL-6 levels with the incidence of inflammatory major organ events in Behçet disease: a prospective registry study.

Little is known about the relationship between the disease activity of Behçet disease (BD) and the incidence of inflammatory major organ events. In this prospective registry study, we investigated the association between the Behçet Disease Current Activity Form (BDCAF) and incidence of inflammatory major organ events, defined as the inflammation of the ocular, central nervous, intestinal, and vascular systems in BD. We enrolled participants from Japanese multicenter prospective cohorts. The BDCAF was evaluated annually. BD-related symptoms, including inflammatory major organ events, were monitored. The association between BDCAF and inflammatory major organ events was analyzed by time-to-event analysis. An unsupervised clustering of the participants' BDCAF, therapeutic agents, and multiple serum cytokines was also performed to examine their association with inflammatory major organ events. A total of 260 patients were included. The patients had a median BDCAF score of 2 [Interquartile range, 1-3] at the enrolment and remained disease active at 1- and 2-year follow-ups, indicating residual disease activity in BD. Patients with a BDCAF score of 0 had a longer inflammatory major organ event-free survival at 52 weeks than those with a score of 1 or higher (p=2.2 x 10-4). Clustering analysis revealed that patients who did not achieve remission despite treatment with tumor necrosis factor inhibitors had high serum inflammatory cytokine levels and incidences of inflammatory major organ events. Among the elevated cytokines, IL-6 was associated with inflammatory major organ events. This study suggests that treatment strategies targeting overall disease activity and monitoring residual serum IL-6 may help prevent inflammatory major organ events in BD.

Palmatine Attenuated Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting M1 Phenotype Macrophage Polarization via NAMPT/TLR2/CCR1 Signaling.

The present work was conducted to research the potential mechanism of palmatine (PAL) on lipopolysaccharide (LPS)-caused acute lung injury (ALI). Network pharmacology and bioinformatic analyses were carried out. Mice were intragastrically treated with PAL and intratracheally stimulated with LPS. LPS-induced RAW264.7 cells were employed for the in vitro model. The MPO activity, W/D ratio, neutrophils, total cell number in BALF, and histopathological alteration were examined. The levels of TNF-α, IL-1β, IL-6, IL-18, IL-4, and IL-10 in serum, BALF, and supernatant were examined by ELISA. The mRNA expressions of iNOS, CD68, Arg1, Ym1, and CD206 and protein expressions of NAMPT, TLR2, CCR1, and NLRP3 inflammasome were detected by PCR, WB, and immunofluorescence. The NAMPT inhibitor FK866, TLR2 inhibitor C29, CCR1 inhibitor BX471, NAMPT-overexpression (OE) plasmid, and TLR2-OE plasmid were used for mechanism research. As a result, PAL relieved the symptoms of ALI. PAL inhibited M1 phenotype indices and promoted M2 phenotype indices in both LPS-induced mice and RAW264.7 cells. PAL also inhibited the expressions of NAMPT, TLR2, CCR1, and NLRP3 inflammasome. The treatments with FK866, NAMPT-OE plasmid, C29, TLR2-OE plasmid, and BX471 proved that PAL exerted its effect via NAMPT/TLR2/CCR1. Molecular docking suggested that PAL might combine with NAMPT. In conclusion, PAL ameliorated LPS-induced ALI by inhibiting M1 phenotype macrophage polarization via NAMPT/TLR2/CCR1 signaling.

Brodalumab for moderate-severe hidradenitis suppurativa: An open-label multicentric cohort study in real clinical practice.

The use of biological therapy is becoming increasingly common in patients with hidradenitis suppurativa (HS). Levels of serum TNF-alfa and IL17 support the role of an immune system dysregulation in the pathogenesis of HS. Brodalumab targets the receptor A of IL-17, thus having a promising role in the treatment of HS. A multicenter retrospective observational open-label study was conducted in two tertiary hospitals. Adults with moderate to severe HS under treatment with brodalumab 210 mg at week 0, 1, 2 and then every 2 weeks were included and assessed at weeks 0 and 16 which was the median follow-up time. Demographic and disease-related variables as well as response parameters (HiSCR and IHS4) and safety data were recorded and analysed. A total of 16 patients (75% males) were included in our study. 50% of patients presented an inflammatory phenotype and mean BMI was 28.37. HiSCR was achieved in 50% of patients and mean IHS4 decreased from 24.13 to 16.81 (p = 0.002). No differences were found between those who achieved HiSCR and those who did not. Grade 2 adverse events were reported in three patients with no fatal outcomes and treatment discontinuation was advised in four patients. Brodalumab seems to be effective and safe in patients with moderate to severe HS, even in those that did not respond to adalimumab, which, at the moment, is the only widely approved biologic for this indication. Thus, it stands as an interesting option for the treatment of HS.

Evaluation of interleukin-8 levels in the diagnosis of invasive pulmonary aspergillosis in patients with haematological malignancies.

This study aimed to determine the level of interleukin (IL)-8 in diagnosing of invasive pulmonary aspergillosis (IPA). We conducted this study with 50 controls and 25 IPA patients with haematological malignancies. Demographic data, haematological diagnoses, chemotherapy regimen, galactomannan level, fungal culture, and computed tomography findings of the patients were evaluated prospectively. IL-8 levels were studied with the ELISA method. The mean age of patients in the case group was 60.84±15.38 years, while that of the controls was 58.38±16.64 years. Of the patients, 2/25 were classified as having 'proven', 13/25 as 'probable', and 10/25 as 'possible' invasive aspergillosis (IA). Serum IL-8 levels were found to be significantly higher in the case group compared to the controls. There was a negative correlation between serum IL-8 levels and neutrophil counts and a positive correlation with the duration of neutropenia. A significant cutoff value for serum IL-8 parameter in detecting IPA disease was obtained as ≥274 ng/l; sensitivity was 72%; specificity was 64%; PPV was 50%; and NPV was 82%. In the subgroup analysis, there was no significant difference in serum IL-8 levels between the case group and the patients in the neutropenic control group, while a significant difference was found in with the patients in the non-neutropenic control group. Serum IL-8 levels in neutropenic patients who develop IPA are not adequate in terms of both the diagnosis of the disease and predicting mortality. New, easily applicable methods with high sensitivity and specificity in diagnosing IPA are still needed.

Association of adipokine levels with obesity in periodontal health and disease: A systematic review with meta-analysis and meta-regression.

This study aimed to investigate the levels of serum, gingival crevicular fluid (GCF), and salivary adipokines and their possible relationship with periodontitis and obesity. An electronic search was conducted in the following databases: PubMed/ Medline, Scopus, and EBSCOhost through February 2023. Two independent reviewers screened the titles, abstracts, and full text of all the studies. Studies comparing the levels of adipokines in GCF, serum, and/or saliva in subjects with obesity and periodontitis (group 1), subjects with normal weight and periodontitis (group 2), and subjects with obesity and gingival health (group 3) were included. Meta-analyses and meta-regression were performed on the data from included studies. Seventeen studies with study participants ranging from 30 to 120 were included with subjects in each group ranging from 10 to 40. There was a significant increase in levels of serum TNF-α, leptin, IL-6, and CRP between groups 1 and 2 (p < .05). In GCF, TNF-α and resistin levels were significantly higher (p < .05) in Group 1 vs. 2. Serum level of leptin was higher for group 1 vs. 3 (p < .05). Meta-regression analysis revealed that the obesity definition (body mass index (BMI) cut-off value >25 or >30) was significant for serum resistin (p < .05) and GCF resistin (p < .05) between group 1 and 2. The current analysis indicates that both periodontitis and obesity can modulate the pro-inflammatory cytokines at systemic and local levels. This bidirectional interaction of periodontitis and obesity via the inflammation pathway seems likely plausible. Further studies are required to elucidate this mechanism in more detail.

Abstract LB329: Interleukin6 as a Potential Prognostic Marker and Therapeutic Target in Oral Squamous Cell Carcinoma

Abstract This study investigates the role of interleukin (IL)-6 in oral squamous cell carcinoma (OSCC), evaluating its potential as a prognostic marker and therapeutic target. This study involved 95 untreated OSCC patients, with pre-surgical serum IL-6 levels measured by Electro chemiluminescence immunoassay (ECLIA). Patients were categorized into high (78 patients) and low (17 patients) IL-6 groups based on a cutoff value of 8 pg/mL.A strong correlation was observed between higher IL-6 levels and lower overall survival (P&amp;lt;0.0001) and disease-free survival (P=0.0283). Serum IL-6 levels also showed a strong positive correlation with certain blood test markers such as neutrophil and lymphocyte fractions and C-reactive protein (CRP), and a negative correlation with albumin levels. These findings suggest a link between systemic inflammation, malnutrition, and the Inflammation-based prognostic score (IBPS).Further analysis through microarray assessed the gene expression in primary tumor tissues, revealing 513 genes with more than a two-fold change in the high IL-6 group compared to controls. Gene Ontology analysis indicated increased metabolic activity in the high IL-6 group and suppressed inflammation and immune-related molecules in the low IL-6 group.Immunohistochemical staining for IL-6 in tumor tissues showed its presence mainly in the stroma, particularly in cancer-associated fibroblasts (CAFs) identified by vimentin and α-SMA positivity. Both OSCC cell lines and CAFs established from OSCC tissues demonstrated high IL-6 secretion, especially in cell lines derived from lymph node metastases. Furthermore, cell lines from primary, lymph node, and lung metastases exhibited high IL-6 secretion, with HRAS mutations also identified. Knockdown of HRAS using siRNA reduced IL-6 secretion.Finally, in vivo experiments using an anti-IL-6 receptor antibody showed that blocking IL-6 signaling reduced the proliferation of OSCC cell lines.The study concludes that IL-6 is a useful prognostic and therapeutic target in OSCC. The wide applicability of IL-6 testing and the clinical use of anti-human IL-6R antibody drugs, combined with aggressive nutritional intervention, suggest a potential paradigm shift in OSCC treatment. Citation Format: Hiroyuki Goda, Tomoko Adachi, Koh-ichi Nakashiro, Nobuyuki Kuribayashi, Daisuke Uchida. Interleukin6 as a Potential Prognostic Marker and Therapeutic Target in Oral Squamous Cell Carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB329.

Sodium Cromolyn Modulates Carrageenan-Induced Acute Inflammation Through the Interleukin-6 Levels

Background: Previous studies have indicated that sodium cromolyn does not negatively affect steroidal and nonsteroidal anti-inflammatory drugs (NSAIDs). Objective: This study aimed to investigate the anti-inflammatory effects of sodium cromolyn on carrageenan-induced paw edema in rats and assess its impact on IL-6, an anti-inflammatory cytokine. Methods: The carrageenan-induced paw edema model is widely used for studying inflammatory mechanisms and evaluating anti-inflammatory drugs. The test groups received intraperitoneal injections of sodium cromolyn at doses of 25, 50, and 100 mg/kg alongside a positive control group (indomethacin at 5 mg/kg) and a negative control group (which received the solvent, saline). Thirty minutes after drug administration, carrageenan (1% w/v) was injected into the right hind paws of the rats. Changes in paw volume were measured using a plethysmometer at 0.5, 1, 2, and 3 hours post-carrageenan injection. Blood and paw tissue samples were collected three hours after carrageenan administration, and IL-6 levels were determined using the standard rat Interleukin-6 ELISA kit. Results: The plasma and tissue IL-6 levels in the group treated with cromolyn (25 mg/kg) were significantly higher than those in the positive control group (indomethacin 5 mg/kg). Sodium cromolyn at a dose of 25 mg/kg had a negligible effect on reducing paw edema and IL-6 levels in serum and paw tissues compared to indomethacin (5 mg/kg). The IL-6 levels in plasma and tissues for the group receiving 50 mg/kg of cromolyn were not significantly different from those in the indomethacin group (5 mg/kg). However, IL-6 levels in the group treated with 100 mg/kg of cromolyn were significantly lower than those in the indomethacin group. Among the groups treated with sodium cromolyn, the highest and lowest IL-6 levels were observed in the groups receiving 25 mg/kg and 100 mg/kg of sodium cromolyn, respectively. The anti-inflammatory effects of sodium cromolyn at doses of 25 mg/kg, 50 mg/kg, and 100 mg/kg were analyzed, revealing that 25 mg/kg of cromolyn sodium was not significantly effective at any time point (P &lt; 0.05). Additionally, no significant differences (P &lt; 0.05) were observed between the 50 mg/kg and 100 mg/kg doses at any study hour. Sodium cromolyn at a 50 mg/kg dose was as effective as indomethacin (5 mg/kg) in significantly reducing paw edema. Conclusions: Sodium cromolyn, at doses of 50 and 100 mg/kg, effectively reduced paw edema and the concentration of serum and paw tissue IL-6 (P &lt; 0.05), demonstrating significant anti-inflammatory activity. Sodium cromolyn at a 50 mg/kg dose is recommended as the anti-inflammatory dose of this drug.

Bio-inspired deposition of gold nanoparticles onto the surface of kaolin for in vitro management of human ovarian cancer and modulation of the inflammatory response in adenomyosis-induced mice in vivo via the MAPK signaling pathway

A mild and eco-friendly protocol has been developed for the preparation of kaolin-decorated Au nanoparticles mediated by Ephedra root extract as a green reducing and stabilizing agents without any toxic substrates. Structural features of the prepared Au NPs/Kaolin were assessed through FE-SEM, TEM, and XRD techniques. TEM images show the good deposition of Au NPs over the surface of extract-modified kaolin without aggregation. Towards the medicinal application, its antioxidant efficacy was assessed by the DPPH method, and the corresponding IC50 value was obtained as 104 μg/mL. Cytotoxicity of the nanoformulated bio-composite was ascertained through MTT analysis against human ovarian carcinoma cells, i.e., PA-1 and SK-OV-3. The IC50 in those studies was 250 and 119 μg/mL against PA-1and SK-OV-3 cells, respectively. In the in vivo design, tamoxifen was used to induce the experimental adenomyosis model in mice. After treatment, the thymus, spleen, uterine, and body weights of all animals were measured. Then, inflammatory factor expression and myometrial infiltration were determined by qRT-PCR, ELISA, and histology examination in the uterus. Western blotting, qRT-PCR, and immune histochemical (IHC) staining were applied to analyze the MAPK/ERK signaling pathway protein expression. Au NPs/Kaolin bio-nanocomposite ameliorated the adenomyosis symptoms by raising the thymus and spleen index and decreasing the myometrial infiltration. The raised levels of TNF-α, IL-6, and IL-1β in adenomyosis model mice uterus and serum were also reduced after Au NPs/Kaolin bio-nanocomposite treatment. The adenomyosis amelioration of Au NPs/Kaolin bio-nanocomposite was gained by preventing the MAPK/ERK signaling pathway, including decreasing the expressions of protein and mRNA of p-p38/p38, p-JNK/JNK, and p-ERK/ERK.

Mechanistic insights into the hepatoprotective properties of Mallotus phillipensis fruit: Targeting proinflammatory cytokines and free radicals using isolated compound

Ethnopharmacological relevance:Mallotus phillipensis (MP) belongs to the endangered plants of great medicinal value. Widely used in the Ayurvedic healthcare system, parts of the plant which are rich in secondary metabolites are used in the treatment of several diseases like eczema, bronchitis, worm infestation, diabetes, kidney stones, cancer, and malaria. In ethnomedicine, MP has been reported to be traditionally used in the treatment and healing of jaundice and inflammatory conditions in the Ayurveda system. This plant was thus selected to explore its hepatoprotective activity. ObjectiveThis study was undertaken to investigate the protective property of MP and a flavanone i.e. 7,4′-Dihydroxy-3′′,3′′-dimethyl-(5,6-pyrano-2′′-one)-8′′′-(3′′′,3′′′-dimethylallyl)-flavanone (A4) previously identified and obtained from the same plant on CCl4-induced liver injury in animal models to validate the folkloric claims. Traditional medicinal plants have the potential to provide phytoconstituents capable of healing liver cells. In this regard, MP is used in various traditional medicinal systems to treat several diseases. Though it has been studied for its hepatoprotective potential, activity on the isolated compounds is yet to be reported to confirm the active principle. Therefore, the study assessed the hepatoprotective effect of ethyl acetate and methanol extracts and a flavanone isolated from MP fruit extract. MethodsMethanol and ethyl acetate fractions of MP fruits at two different doses (300 mg/kg and 500 mg/kg) and a flavanone (A4-50 mg/kg) isolated from MP were tested for hepatoprotective potential in rats. At 50 mg/kg dosage/ day orally, silymarin was used as a standard drug. The effect on liver enzymes and serum cytokines was also verified in animal models. Histopathology and antioxidant tests were performed on liver tissue. Elemental analysis, 1H- &13C NMR, MS, IR and UV spectral data were used to characterize the structure of isolated flavanone (A4). ResultsThe ethyl acetate and methanol fractions of MP fruit and the isolated compound A4 i.e. flavanone showed strong hepatoprotective effects, as evidenced by their ability to impede the rise in serum transaminases. They also decreased the serum IL-1, IL-6 and TNF-α levels and showed significant antioxidant potential. The effect was found to be in decreasing order as MEA 500 > MPM 500 > MEA 300 > A4 > MPM 300. ConclusionsThe results indicate that MP fruit fractions with methanol, ethyl acetate and A4 can lessen CCL4-induced liver damage. This may be because of their antioxidant and cytokine-inhibitory properties.

Studying of anti-inflammatory and antioxidant effects of tectorigenin in ovalbumin-induced asthma mice models.

Allergic asthma is an important respiratory system problem characterized by airway inflammation, breathlessness, and bronchoconstriction. Allergic asthma and its outcomes are triggered by type 2 allergic immune responses. Tectorigenin is a methoxy-isoflavone with anti-inflammatory effects. In this study, we investigated the effects of tectorigenin on the pathophysiology of allergic asthma in an animal model. Asthmatic mice were treated with tectorigenin. Then airway hyperresponsiveness (AHR), eosinophil percentage, levels of interleukin (IL)-33, IL-25, IL-13, IL-5, IL-4, total and ovalbumin (OVA)-specific immunoglobulin (Ig)E, and lung histopathology were evaluated. Tectorigenin significantly (P 〈 0.05) reduced eosinophil infiltration (41 ± 7%) in the broncho-alveolar lavage fluid (BALF), serum IL-5 level (41 ± 5, pg/mL), and bronchial and vascular inflammation (scores of 1.3 ± 0.2 and 1.1 ± 0.3, respectively) but had no significant effects on AHR, serum levels of IL-33, -25, -13, and -4 (403 ± 24, 56 ± 7, 154 ± 11, and 89 ± 6 pg/mL, respectively), total and OVA-specific IgE (2684 ± 265 and 264 ± 19 ng/mL, respectively), goblet cell hyperplasia, and mucus production. Tectorigenin could control inflammation and the secretion of inflammatory mediators of asthma, so it can be regarded as a potential antiasthma treatment with the ability to control eosinophilia-related problems.

Mechanism of Jiaotai Pills in treatment of depression by UHPLC-TOF-MS combined with network pharmacology and experimental validation

This study aims to analyze the constituents of Jiaotai Pills migrating to the blood in normal rats by UHPLC-TOF-MS technique and reveal the underlying mechanism of Jiaotai Pills in the treatment of depression by network pharmacology and animal experiments. UHPLC-TOF-MS technique was used to detect the constituents of Jiaotai Pills in the blood of rats after intragastric administration. The intersection target of the constituents and depression was screened by DisGeNET and SwissTargetPrediction database, and the protein-protein interaction(PPI) network was constructed. Key targets were imported into the DAVID platform for Gene Ontology(GO) analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway annotation. Combined with constituents, targets, and pathways, the &quot;constituent-target-pathway&quot; network was constructed by Cytoscape 3.9.1 software, through which the key targets and pathways of Jiaotai Pills against depression were predicted. The depression model of chronic unpredictable mild stress(CUMS) was established on rats. After that, behavioral experiments were conducted. The expression of inflammatory factors in serum and the neurotransmitters in the brain were detected by ELISA, and the expression of key targets in the hippocampus was detected by Western blot. The results showed that a total of 17 constituents of Jiaotai Pills were identified in the blood, including 10 alkaloids. There were 124 intersection targets between constituents of Jiaotai Pills and depression disorder. A total of 52 core targets were screened according to PPI results, including NLRP3 and caspase-1, etc. KEGG enrichment analysis mainly involved 15 typical pathways such as NOD-like receptor pathway. The results of animal experiments showed that Jiaotai Pills significantly improved the depression-like behavior of CUMS depressive model on rats, decreased the levels of IL-1β, TNF-α and IL-6 in serum, and increased the expression of neurotransmitters such as 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) in the brain. Besides, Jiaotai Pills also down-regulated the expression of NLRP3 and caspase-1 proteins in the hippocampus and inhibited the NLRP3-mediated NOD-like receptor signaling pathway. In conclusion, Jiaotai Pills may play a role in the treatment of depression by inhibiting the NLRP3 inflammasome and the NOD-like receptor pathway mediated by NLRP3.

Maqin Xiaoke Granule Alleviates Acute Bronchitis Induced by Smoking Combined With Streptococcus pneumoniae by Regulating NLRP3/p38 MAPK/Glycerophospholipid Pathway

Objective: To explore the efficacy and mechanism of action of Maqin Xiaoke Granules (MQs) in the treatment of acute bronchitis (AB). Methods: The rat model of AB was established by mixed smoke and Streptococcus pneumoniae nasal infection. The pathological changes of lung tissue and bronchus were observed by hematoxylin-eosin (HE) staining and scored. The mRNA expression levels of NOD-like receptor thermal protein domain associated protein 3 ( NLRP3) and p38 mitogen-activated protein kinase ( p38 MAPK) in lung tissue were detected by real-time fluorescence quantitative polymerase chain reaction, and the expression levels of inflammatory factors (tumor necrosis factor-α [ TNF-α], interleukin-6 [ IL-6], interleukin-1β [ IL-1β], interleukin-10 [ IL-10]) in serum and lung homogenate were detected by enzyme-linked immunosorbent assay. The therapeutic effect of MQ on rats with AB was preliminarily evaluated. Metabolic profiling of rat serum was performed by ultra high-performance liquid chromatography-quadrupole-time of flight-mass spectrometry/mass spectrometry, combining P &lt; .05, variable important in projection &gt; 1, fold change &gt; 1.5 and screening for differential metabolites based on univariate and multivariate statistical analyses, and then analyzing the possible metabolic pathways with the help of MetaboAnalyst 5.0 database, to analyze the mechanism of MQ’s action on the treatment of AB at the metabolic level. Results: MQ significantly ameliorated the pathological injury of bronchial and lung tissues in model rats, reduced the mRNA levels of NLRP3 and p38 MAPK ( P &lt; .05, .01), lowered the levels of TNF-α, IL-6, and IL-1β in serum and lung homogenates ( P &lt; .05, .01), and elevated IL-10 in serum and lung homogenates ( P &lt; .0001, .01) levels, and to regulate abnormal metabolites in rats with AB via the glycerophospholipid metabolic pathway. Conclusion: MQ significantly improved AB induced by mixed smoke combined with Streptococcus pneumoniae, and the mechanism of its induction may be related to the dysregulation of glycerophospholipid metabolism, and this study provides a reference for the rational clinical application of MQ.

Analgesic and anti-inflammatory effects of galangin: a potential pathway to inhibit transient receptor potential vanilloid 1 receptor activation.

Galangin, commonly employed in traditional Chinese medicine for its diverse medicinal properties, exhibits potential in treating inflammatory pain. Nevertheless, its mechanism of action remains unclear. Mice were randomly divided into 4 groups for 7 days: a normal control group, a galangin-treated (25 and 50 mg/kg), and a positive control celecoxib (20 mg/kg). Analgesic and anti-inflammatory effects were evaluated using a hot plate test, acetic acid-induced writhing test, acetic acid-induced vascular permeability test, formalininduced paw licking test, and carrageenan-induced paw swelling test. The interplay between galangin, transient receptor potential vanilloid 1 (TRPV1), NF-κB, COX-2, and TNF-α proteins was evaluated via molecular docking. COX- 2, PGE2, IL-1β, IL-6, and TNF-α levels in serum were measured using ELISA after capsaicin administration (200 nmol/L). TRPV1 expression in the dorsal root ganglion was analyzed by Western blot. The quantities of substance P (SP) and calcitonin gene-related peptide (CGRP) were assessed using qPCR. Galangin reduced hot plate-induced licking latency, acetic acid-induced contortions, carrageenantriggered foot inflammation, and capillary permeability in mice. It exhibited favorable affinity towards TRPV1, NF- κB, COX-2, and TNF-α, resulting in decreased levels of COX-2, PGE2, IL-1β, IL-6, and TNF-α in serum following capsaicin stimulation. Galangin effectively suppressed the upregulation of TRPV1 protein and associated receptor neuropeptides CGRP and SP mRNA, while concurrently inhibiting the expression of NF-κB, TNF-α, COX-2, and PGE2 mRNA. Galangin exerts its anti-inflammatory pain effects by inhibiting TRPV1 activation and regulating COX-2, NF-κB/TNF-α expression, providing evidence for the use of galangin in the management of inflammatory pain.

Mesenchymal Stem Cells and Curcumin Effectively Mitigate Freund's Adjuvant- induced Arthritis via their Anti-inflammatory and Gene Expression of COX-1, IL-6 and IL-4.

Rheumatoid arthritis (RA) is a type of arthritis that damages joints and can affect the thymus and the spleen. RA is an autoimmune disorder in which the immune system targets the body's own tissues. The causes of RA are unknown, although a genetic link is thought to be involved. The objective of this research was to evaluate the effect of curcumin, mesenchymal stem cells (MSCs), and their combination on the disruption of serum cytokines, ankle joint, thymus and spleen histopathology, and affected genes in complete Freund's adjuvant (CFA)-induced arthritis in male and female Wistar rats. Experimental animals were organized into 16 groups (6 animals for each), eight groups including male rats and the other eight groups including females rats. The groups are normal control, CMC, curcumin, MSCs, CFA, CFA/curcumin, CFA/ MSCs and the arthritic group treated with MSCs and curcumin. One subcutaneous injection of 0.1 mL CFA was given to rats into the right hind leg footpad to induce RA. The arthritic rats were intravenously injected three times with bone marrow-derived MSCs (BM-MSCs) and/or treated orally with curcumin daily (100 mg per kg body weight per day) for 21 days. Curcumin and BM-MSCs work together to dramatically (P < 0.05) restore the high serum PGE2 and IL-17 levels and lower the IL-13 level in arthritic rats to normal levels. Deleterious effects on the spleen and thymus histological structure were counteracted. Gene expression of COX-1 and IL-6 was increased and IL-4 was decreased; these changes were improved by the combination treatment (P < 0.05). Based on these findings, additive therapeutic effects on RA occur from the combined treatment of curcumin and BM-MSCs compared with their individual use (P < 0.05). Thus, it can be said that both curcumin and BM-MSCs are effective at reducing inflammation while also having beneficial effects on the ankle joint, thymus and spleen.

A combination of gliclazide and metformin attenuates obesity-induced polycystic ovary syndrome in female Wistar rats

Presently, it is known that the progression of obesity concomitantly leads to polycystic ovary syndrome and infertility. This study aimed to evaluate the potential effects of metformin (M; insulin secretagogues) and gliclazide (G; insulin sensitizer) alone and their combination at different doses to treat obesity-induced PCOS. High high-fat diet was given to all female Wistar rats for nine weeks to induce obesity except for the normal control group which received a normal chow diet. Estradiol valerate (0.8 mg/kg) was also given to all obese rats to induce polycystic ovarian syndrome. After the induction, M (100, 300 mg/kg) and G (5, 10 mg/kg) were given orally either individually or in combination for 28 days. The notable (p < 0.0001) reduction in body weight and blood glucose level was observed in treatment groups in contrast to disease control (DCG). The marked (p < 0.05–0.0001) decrease in hemocylated hemoglobin, serum insulin, cholesterol, triglycerides, and testosterone was observed in treated groups, notably in combination groups (M100+G10 mg/kg) in contrast to DCG. There was a considerable (p < 0.01–0.0001) increase in progesterone E2, estradiol, luteinizing, and follicle-stimulating hormones in treated groups as compared to DCG. Treatment with M and G treated groups also exhibited marked (p < 0.05–0.0001) increases in SOD, CAT, and GSH while decreased in NO and MDA levels in ovary tissue as evidenced by the histological study of the ovary. Treatment with M and G alone and in combination significantly (p < 0.0001) restored the serum IL-6, NrF2, and NF-κB levels as compared to DCG. The results inveterate that the M and G combination (M100+G10, and M300+G10) was useful in treating obesity-induced infertility due to antioxidant properties, hypolipidemic effects, and modulation of inflammatory markers.