scholarly journals Pharmacokinetic Analysis of Carnosic Acid and Carnosol in Standardized Rosemary Extract and the Effect on the Disease Activity Index of DSS-Induced Colitis

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 773
Author(s):  
Jacob P. Veenstra ◽  
Bhaskar Vemu ◽  
Restituto Tocmo ◽  
Mirielle C. Nauman ◽  
Jeremy J. Johnson

Rosemary extract (RE) is an approved food preservative in the European Union and contains dietary phytochemicals that are beneficial for gastrointestinal health. This study investigated the effects of RE on dextran sodium sulfate (DSS)-induced colitis and also determined the pharmacokinetics of dietary phytochemicals administered to mice via oral gavage. Individual components of rosemary extract were separated and identified by LC–MS/MS. The pharmacokinetics of two major diterpenes from RE, carnosic acid (CA) and carnosol (CL), administered to mice via oral gavage were determined. Then, the effect of RE pre-treatment on the disease activity index (DAI) of DSS-induced colitis in mice was investigated. The study determined that 100 mg/kg RE significantly improved DAI in DSS-induced colitis compared to negative control. Sestrin 2 protein expression, which increased with DSS exposure, was reduced with RE treatment. Intestinal barrier integrity was also shown to improve via fluorescein isothiocyanate (FITC)–dextran administration and Western blot of zonula occludens-1 (ZO-1), a tight junction protein. Rosemary extract was able to improve the DAI of DSS-induced colitis in mice at a daily dose of 100 mg/kg and showed improvement in the intestinal barrier integrity. This study suggests that RE can be an effective preventative agent against IBD.

Nutrients ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 227
Author(s):  
Napapan Kangwan ◽  
Sarawut Kongkarnka ◽  
Nitsara Boonkerd ◽  
Kridsada Unban ◽  
Kalidas Shetty ◽  
...  

This study aimed to investigate the protective effect of probiotics and synbiotics from traditional Thai fermented tea leaves (Miang) on dextran sulfate sodium (DSS)-induced colitis in mice, in comparison to sulfasalazine. C57BL/6 mice were treated with probiotics L. pentosus A14-6, CMY46 and synbiotics, L. pentosus A14-6 combined with XOS, and L. pentosus CMY46 combined with GOS for 21 days. Colitis was induced with 2% DSS administration for seven days during the last seven days of the experimental period. The positive group was treated with sulfasalazine. At the end of the experiment, clinical symptoms, pathohistological changes, intestinal barrier integrity, and inflammatory markers were analyzed. The probiotics and synbiotics from Miang ameliorated DSS-induced colitis by protecting body weight loss, decreasing disease activity index, restoring the colon length, and reducing pathohistological damages. Furthermore, treatment with probiotics and synbiotics improved intestinal barrier integrity, accompanied by lowing colonic and systemic inflammation. In addition, synbiotics CMY46 combined with GOS remarkedly elevated the expression of IL-10. These results suggested that synbiotics isolated from Miang had more effectiveness than sulfasalazine. Thereby, they could represent a novel potential natural agent against colonic inflammation.


2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1134-1134
Author(s):  
Hao Li ◽  
Gary Wang ◽  
Gurjit Sidhu ◽  
Yavuz Yagiz ◽  
Liwei Gu

Abstract Objectives Muscadine wine has a unique polyphenol profile consisting of anthocyanin 3, 5-diglucosides, ellagitannins, ellagic acids, and flavonols. This study aimed to determine whether dealcoholized muscadine wine (DMW) alleviated inflammatory bowel diseases (IBD) in IL-10−/− mice. Methods DMW was prepared by concentrating muscadine wine to 10% of its original volume. Male IL-10−/− and wild-type C57BL/6 mice (6∼7-week-old) were fed an AIN-93M diet containing DMW (5.5%, v/w) or wine-free diet for 154 days. Body weight, food intake, stool consistency, rectum bleeding, and disease activity index of mice were recorded twice a week. Colon, spleen, and serum were collected after euthanasia for histological and biochemical analysis. Fluorescence of serum were measured 4 hours after oral gavage of fluorescein isothiocyanate (FITC)-dextran to determine the intestinal permeability. Results IL-10−/− mice developed ulcerative colitis, inflammation, and impaired gut barrier spontaneously whereas wild type mice remained healthy. DMW in diet preserved colon length and decreased colon histology score by 21.2% in IL-10−/− mice (P < 0.05). IL-10−/− mice on DMW diet had a significantly lower disease activity index than those on wine-free diet. Serum level of keratinocyte chemokine, IL-1β, and TNF-α were decreased by 31.8%, 62.8%, and 29.3% (P < 0.05), respectively, by DMW in IL-10−/− mice, whereas IL-6 remained unchanged. Compared to the wine-free diet, concentration of FITC-dextran in the serum of IL-10−/− mice were decreased by 18% by DMW (P < 0.05), indicating improved intestinal barrier function. DMW had no effect on wild type mice. IL-10−/− mice had comparable body weight to wild type ones although their overall food intake was lower. Conclusions DMW alleviated colon inflammation via inhibiting the secretion of inflammatory cytokines and preserving intestinal barrier. Muscadine wine has a potential to manage IBD in patients. Funding Sources This research is supported by NIFA 2018–07,941.


Lupus ◽  
2020 ◽  
Vol 29 (2) ◽  
pp. 182-190
Author(s):  
W Batista Cicarini ◽  
R C Figueiredo Duarte ◽  
K Silvestre Ferreira ◽  
C de Mello Gomes Loures ◽  
R Vargas Consoli ◽  
...  

We have explored the relationship between possible hemostatic changes and clinical manifestation of the systemic lupus erythematosus (SLE) as a function of greater or lesser disease activity according to Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) criteria. Endothelial injury and hypercoagulability were investigated in patients with SLE by measuring thrombomodulin (TM), D-dimer (DDi) and thrombin generation (TG) potential. A total of 90 participants were distributed into three groups: 1) women with SLE presenting with low disease activity (laSLE) (SLEDAI-2K ≤ 4), 2) women with SLE presenting with moderate to high disease activity (mhaSLE) (SLEDAI-2K > 4), and 3) a control group comprising healthy women. Levels of TM and DDi were higher both in the laSLE and mhaSLE groups compared to controls and in mhaSLE compared to the laSLE group. With respect to TG assay, lagtime and endogen thrombin potential, low concentrations of tissue factor provided the best results for discrimination among groups. Analysis of these data allow us to conclude that TM, DDi and TG are potentially useful markers for discriminating patients with very active from those with lower active disease. Higher SLE activity may cause endothelial injury, resulting in higher TG and consequently a hypercoagulability state underlying the picture of thrombosis common in this inflammatory disease.


Gut Microbes ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 1946368
Author(s):  
Angélica Cruz-Lebrón ◽  
Ramona Johnson ◽  
Claire Mazahery ◽  
Zach Troyer ◽  
Samira Joussef-Piña ◽  
...  

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Priscila B. S. Medeiros ◽  
Roberta G. Salomão ◽  
Sara R. Teixeira ◽  
Diane M. Rassi ◽  
Luciana Rodrigues ◽  
...  

Abstract Background Systemic lupus erythematosus (SLE) is an independent risk factor for cardiovascular events. The present study determined the prevalence of subclinical atherosclerosis in childhood-onset SLE using the carotid intima-media thickness (CIMT) measurement and investigated associations between traditional and nontraditional risk factors for atherosclerosis, such as medications, SLE Disease Activity Index - SLEDAI-2 K and SLICC-ACR damage index and CIMT. Methods Cross-sectional prospective study between 2017 and 2018. CIMT was assessed by ultrasonography. Data were collected by chart review, nutritional evaluation and laboratory tests and analyzed by Fisher, Wilcoxon-Mann-Whitney tests, multiple linear and log binomial regression. Results Twenty-eight patients (mean age 13.9 years, SD 3) were enrolled. The prevalence of subclinical atherosclerosis was 32% (95% CI 14.8, 49.4). The mean CIMT was 0.43 ± 0.035 mm. The most common traditional risk factors observed were dyslipidemia (82.1%), uncontrolled hypertension (14.2%), obesity (14.3%), and poor diet (78.6%). Uncontrolled hypertension (p = 0.04), proteinuria (p = 0.02), estimated glomerular filtration rate < 75 ml /min/1.73 m2 (p = 0.02) and SLEDAI-2 K > 5 (P = 0.04) were associated with subclinical atherosclerosis. SLEDAI-2 K > 5 maintained association with CIMT after adjusting for control variables. Conclusion Subclinical atherosclerosis is frequently observed in cSLE, mainly in patients with moderate to severe disease activity.


2010 ◽  
Vol 37 (4) ◽  
pp. 829-834 ◽  
Author(s):  
TAMAR F. BRIONEZ ◽  
SHERVIN ASSASSI ◽  
JOHN D. REVEILLE ◽  
CHARLES GREEN ◽  
THOMAS LEARCH ◽  
...  

Objective.To investigate the role of psychological variables in self-reported disease activity in patients with ankylosing spondylitis (AS), while controlling for demographic and medical variables.Methods.Patients with AS (n = 294) meeting modified New York criteria completed psychological measures evaluating depression, resilience, active and passive coping, internality, and helplessness. Demographic, clinical, and radiologic data were also collected. Univariate and multivariate analyses were completed to determine the strength of the correlation of psychological variables with disease activity, as measured by the Bath AS Disease Activity Index (BASDAI).Results.In the multivariate regression analysis, the psychological variables contributed significantly to the variance in BASDAI scores, adding an additional 33% to the overall R-square beyond that accounted for by demographic and medical variables (combined R-square 18%). Specifically, arthritis helplessness and depression accounted for the most significant portion of the variance in BASDAI scores in the final model.Conclusion.Arthritis helplessness and depression accounted for significant variability in self-reported disease activity beyond clinical and demographic variables in patients with AS. These findings have important clinical implications in the treatment and monitoring of disease activity in AS, and suggest potential avenues of intervention.


2021 ◽  
pp. annrheumdis-2021-219876
Author(s):  
Evgeniy Nasonov ◽  
Saeed Fatenejad ◽  
Eugen Feist ◽  
Mariana Ivanova ◽  
Elena Korneva ◽  
...  

ObjectiveTo evaluate the efficacy and safety of olokizumab (OKZ) in patients with active rheumatoid arthritis despite treatment with methotrexate (MTX).MethodsIn this 24-week multicentre, placebo-controlled, double-blind study, patients were randomised 1:1:1 to receive subcutaneously administered OKZ 64 mg once every 2 weeks, OKZ 64 mg once every 4 weeks, or placebo plus MTX. The primary efficacy endpoint was the proportion of patients achieving an American College of Rheumatology 20% (ACR20) response at week 12. The secondary efficacy endpoints included percentage of subjects achieving Disease Activity Score 28-joint count based on C reactive protein <3.2, Health Assessment Questionnaire Disability Index at week 12, ACR50 response and Clinical Disease Activity Index ≤2.8 at week 24. Safety and immunogenicity were assessed throughout the study.ResultsA total of 428 patients were randomised. ACR20 responses were more frequent with OKZ every 2 weeks (63.6%) and OKZ every 4 weeks (70.4%) than placebo (25.9%) (p<0.0001 for both comparisons). There were significant differences in all secondary efficacy endpoints between OKZ-treated arms and placebo. Treatment-emergent serious adverse events (TESAEs) were reported by more patients in the OKZ groups compared with placebo. Infections were the most common TESAEs. No subjects developed neutralising antidrug antibodies.ConclusionsTreatment with OKZ was associated with significant improvement in signs, symptoms and physical function of rheumatoid arthritis without discernible differences between the two regimens. Safety was as expected for this class of agents. Low immunogenicity was observed.Trial registration numberNCT02760368.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1129.1-1129
Author(s):  
A. Baillet ◽  
X. Romand ◽  
A. Pfimlin ◽  
M. Dalecky ◽  
M. Dougados

Background:Standardization of clinical practice has been proven to be effective in management of chronic diseases. This is particularly true at the time where the concept of treat to target is becoming more and more important in the field of axial spondyloarthritis (ax-SpA).Objectives:To propose a list of variables to be collected at the time of the diagnosis and over the follow-up of patients with axial spondyloarthritis (ax-SpA) for an optimal management in daily practice.Methods:The process comprised (1) the evaluation of the interest of 51 variables proposed for the assessment of axSpA via a systematic literature research, (2) a consensus process involving 78 hospital-based or office-based rheumatologists, considering the collection of the variable in a 4 grade scale from ”potentially useful” to “mandatory”, (3) a consensus on optimal timeline for periodic assessment of the selected variables on a 5 grade scale from “at each visit” to “never to be re-collected”.Results:The systematic literature research retrieved a total of 14,133 abstracts, of which 213 were included in the final qualitative synthesis. Concerning the data to be collected at the time of the diagnosis and during follow-up, we proposed to differentiate the results based on a) the way of collection of the variables (e.g. questionnaires by the patient, interview by the physician, physical examination, investigations) b) the usefulness these variables in daily practice based on the opinion of the rheumatologists ” c) the optimal timeline between 2 evaluations of the variable based on the opinion of the rheumatologists. In the initial systematic review, symptoms of heart failure history of inflammatory bowel disease, psoriasis or uveitis, patient global visual analogic scale, spine radiographs, modified Schöber test, coxo-femoral rotations, swollen joint count, urine strip test, BASDAI and ASDAS global scores were considered very useful and nocturnal back pain/morning stiffness, sacro-iliac joints radiographs and CRP were considered mandatory (Figure 1). Timeline between 2 evaluations of variables to collect in the periodic review are summarized inFigure 2.Figure 1.Core sets of items to collect and report in the systematic review in axial spondyloarthritis management in daily practice ASDAS=Ankylosing Spondylitis Disease Activity Score, BASDAI=Bath Ankylosing Spondylitis Disease Activity Index, BASFI=Bath Ankylosing Spondylitis Functionnal Index, BASMI=Bath Ankylosing Spondylitis Metrology Index, CRP=C Reactive Protein, CT=computerized tomography, FIRST=Fibromyalgia Rapid Screening Tool, HLA=Human Leukocyte Antigen, MRI=Magnetic resonance imaging, PET=positron emission tomography.Figure 2.Periodic review timeline of variables to collectASDAS=Ankylosing Spondylitis Disease Activity Score, BASDAI=Bath Ankylosing Spondylitis Disease Activity Index, Spondylitis Metrology Index, CRP=C Reactive Protein, IBD = inflammatory bowel diseases, PRO = Patient Reported OutcomesConclusion:Using an evidence-based and an expert consensus approaches, this initiative defined a core set of variables to be collected and reported at the time of the diagnosis and during follow-up of patients with ax-SpA in daily practice.Acknowledgments:this study has been conducted in two parts: the first one (evidence-based) was conducted thanks to a support from Abbvie France. AbbVie did not review the content or have influence on this manuscript. The second part of this initiative (consensus) has been conducted thanks to a support from the scientific non-profit organization: Association de Recherche Clinique en RhumatologieDisclosure of Interests:Athan Baillet Consultant of: Athan BAILLET has received honorarium fees from Abbvie for his participation as the coordinator of the systematic literature review, Xavier Romand Consultant of: Xavier ROMAND has received honorarium fees from Abbvie, Arnaud Pfimlin Consultant of: Arnaud PFIMLIN has received honorarium fees from Abbvie, Mickael Dalecky Consultant of: Mickael DALECKY has received honorarium fees from Abbvie, Maxime Dougados Grant/research support from: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Speakers bureau: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma


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