Effects of Berberine and Hwangryunhaedok-Tang on Oral Bioavailability and Pharmacokinetics of Ciprofloxacin in Rats

Hwangryunhaedok-Tang (HR) and berberine-containing single herbs are used to treat bacterial infection and inflammatory diseases in eastern Asia. The combination of berberine-containing herbal medicines and ciprofloxacin can be an excellent antibacterial chemotherapy against multidrug resistance bacteria. To evaluate the pretreatment effect of berberine and HR, vehicle, berberine (25 and 50 mg/kg/day), and HR (1.4 g/kg/day) were daily administered to rats for five consecutive days. On day 6, ciprofloxacin was administered (10 mg/kg, i.v. and 20 mg/kg, p.o.) to rats. To assess cotreatment effect of berberine and ciprofloxacin, berberine (50 mg/kg) and ciprofloxacin (20 mg/kg) were coadministered by single oral gavage. Pharmacokinetic data were estimated by noncompartmental model. Compared with ciprofloxacin alone (control group), coadministration of berberine (50 mg/kg) and ciprofloxacin significantly decreasedCmaxof ciprofloxacin (P<0.05). In addition, the pretreatment of berberine (50 mg/kg/day) and HR (1.4 g/kg/day) significantly decreasedCmaxandAUC0→∞, compared with control group (P<0.05). The oral bioavailability of ciprofloxacin was reduced by cotreatment of berberine and pretreatment of berberine and HR. Our results suggest that the expression of P-glycoprotein and organic anion and/or organic cation transporters (OAT/OCT) could take a role in reduced oral bioavailability of ciprofloxacin by berberine and HR.

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Humoral factors of innate immunity in the saliva of patients with infectious inflammatory respiratory diseases

OTORHINOLARYNGOLOGY 2-3(2) 2019 - OTORHINOLARYNGOLOGY ◽

10.37219/2528-8253-2018-2-13 ◽

2018 ◽

pp. 13-17

Author(s):

Oleg Melnikov ◽

Diana Zabolotnaya ◽

Alexander Bredun ◽

Bogdan Bil ◽

Oksana Rylska ◽

...

Keyword(s):

Innate Immunity ◽

Chronic Rhinosinusitis ◽

Inflammatory Diseases ◽

Activity Level ◽

Chronic Tonsillitis ◽

Control Group ◽

Quantitative Composition ◽

Upper Airways ◽

Humoral Factors ◽

Immune Modulators

Introduction: In recently ears factors of innate immunity both cellular and humoral have been paid considerable attention as they are a protective barrier of a fast response and that is why they are largely concentrated at the intersection of the digestive tract and airways. The data concerning the activity level of factors of innate immunity in the upper airways affected by nonspecific inflammatory processes is insufficient and sparse and therefore the purpose of this research was to study the content of humoral factors of innate immunity in the oropharyngeal secretion (ORS) of patients with chronic infectious inflammatory diseases of the upper airways in remission. Materials and Methods: There was an examination of 16 patients with chronic rhinosinusitis (CRS) of bacterial genesis (15-40 years old), 12 patients with rhinopharyngitis of post-viral genesis (8-16 years old), 12 people with scleroma from 30 tо 52 years of age (atrophic form), 10 patients with chronic tonsillitis in remission (from 10 to 33 years of age) and 11 patients of a control group (practically healthy donors from 12 tо 40 years of age). The content of MIP-1b, defensin-1β, lactoferrin, lysozyme, α-interferon was studied in the nonstimulated OPS. Statistics were carried out using Mann-Whitney U-test. Results: The greatest number of deviations in the decrease in the content of the examined nonspecific protective factors was found in cases of scleroma, chronic tonsillitis and chronic rhinosinusitis (p<0,05). The lack of protective humoral factors of innate immunity can be evidence of local immunodeficiency even in remission, which is a pathophysiological component of the maintenance of chronic inflammation. Conclusion: The decrease int he quantitative composition of factors of innate immunity in the oropharyngeal secretion of patients with chronic infectious inflammatory diseases of the airways is an objective ground not only for a replacement therapy, but also for the use of immune response modifiers from photo-immune modulators to “genuine immune modulators” controlling the state of the factors of both innate immunity and immunoglobulins, primarily of secretory type, the level and functionality of various groups of immunocompetent and accessory cells.

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Salivary mir-27b Expression in Oral Lichen Planus Patients: A Series of Cases and a Narrative Review of Literature

Current Topics in Medicinal Chemistry ◽

10.2174/1568026619666191121144407 ◽

2020 ◽

Vol 19 (31) ◽

pp. 2816-2823 ◽

Cited By ~ 3

Author(s):

Dario Di Stasio ◽

Laura Mosca ◽

Alberta Lucchese ◽

Donatella Delle Cave ◽

Hiromichi Kawasaki ◽

...

Keyword(s):

Lichen Planus ◽

Oral Lichen Planus ◽

Inflammatory Diseases ◽

Biological Fluids ◽

Critical Role ◽

Invasive Procedure ◽

Control Group ◽

Study Group ◽

Immune Functions ◽

Oral Lichen

Background: microRNAs play a critical role in auto-immunity, cell proliferation, differentiation and cell death. miRNAs are present in all biological fluids, and their expression is essential in maintaining regular immune functions and preventing autoimmunity, whereas miRNA dysregulation may be associated with the pathogenesis of autoimmune and inflammatory diseases. Oral lichen planus (OLP) is an inflammatory disease mediated by cytotoxic T cells attack against epithelial cells. The present study aims to perform a specific microRNA expression profile through the analysis of saliva in this disease. Methods: The study group was formed by five patients (mean age 62.8±1.98 years; 3 females/2 males) affected by oral lichen planus and control group by five healthy subjects (mean age 59.8 years±2.3; 3 females/ 2 males); using a low-density microarray analysis, we recorded a total of 98 differentially expressed miRNAs in the saliva of patients with oral lichen planus compared to the control group. The validation was performed for miR-27b with qRT-PCR in all saliva samples of oral lichen planus group. Results: 89 miRNAs were up-regulated and nine down-regulated. In details, levels of miR-21, miR- 125b, miR-203 and miR15b were increased (p<0.001) in study group while levels of miR-27b were about 3.0-fold decreased compared to controls (p<0.001) of miR-27b expression in OLP saliva. QRTPCR validation confirmed the down regulation of miR-27b in all saliva samples. Conclusions: Collecting saliva samples is a non-invasive procedure and is well accepted by all patients. microRNAs can be readily isolated and identified and can represent useful biomarkers of OLP.

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The Immunomodulatory Role of G2013 (α-L-Guluronic Acid) on the Expression of TLR2 and TLR4 in HT29 cell line

Current Drug Discovery Technologies ◽

10.2174/1570163815666180226093711 ◽

2019 ◽

Vol 16 (1) ◽

pp. 91-95 ◽

Cited By ~ 4

Author(s):

Hamid Farhang ◽

Laleh Sharifi ◽

Mohammad Mehdi Soltan Dallal ◽

Mona Moshiri ◽

Zahra Norouzbabaie ◽

...

Keyword(s):

Inflammatory Responses ◽

Inflammatory Diseases ◽

Rna Extraction ◽

Cell Plate ◽

Inhibitory Effect ◽

Control Group ◽

Ht29 Cells ◽

Guluronic Acid ◽

Tlr4 Mrna

Background: The non-steroidal anti-inflammatory drugs (NSAIDs) play crucial role in the controlling of inflammatory diseases. Due to the vast side effects of NSAIDs, its use is limited. G2013 or &#945;-L-Guluronic Acid is a new NSAID with immunomodulatory features. Objectives: Considering the leading role of TLRs in inflammatory responses, in this study, we aimed to evaluate G2013 cytotoxicity and its effect on the expression of TLR2 and TLR4 molecules. Methods: HEK293-TLR2 and HEK293-TLR4 cells were cultured and seeded on 96-well cell plate, and MTT assay was performed for detecting the viability of the cells after treatment with different concentrations of G2013. HT29 cells were grown and treated with low and high doses of G2013. After total RNA extraction and cDNA synthesis, quantitative real-time PCR were performed to assess the TLR2 and TLR4 mRNA synthesis. Results: We found that concentrations of ≤125 &#181;g/ml of G2013 had no apparent cytotoxicity effect on the HEK293-TLR2 and -TLR4 cells. Our results indicated that after G2013 treatment (5 &#181;g/ml) in HT29 cells, TLR2 and TLR4 mRNA expression decreased significantly compared with the untreated control group (p=0.02 and p=0.001 respectively). Conclusion: The results of this study revealed that G2013 can down regulate the TLR2 and TLR4 gene expression and exerts its inhibitory effect. Our findings are parallel to our previous finding which showed G2013 ability to down regulate the signaling pathway of TLRs. However, further studies are needed to identify the molecular mechanism of G2013.<p>

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The struggle with rheumatism through Dracunculus vulgaris Schott: In the light of ethnobotanical information.

Current Molecular Pharmacology ◽

10.2174/1874467213666200502020345 ◽

2020 ◽

Vol 13 ◽

Author(s):

Fatma Tuğçe Gürağaç Dereli ◽

Mert Ilhan ◽

Esra Küpeli Akkol

Keyword(s):

Petroleum Ether ◽

Inflammatory Diseases ◽

Petroleum Ether Extract ◽

Major Constituent ◽

Control Group ◽

Ether Extract ◽

Test Models ◽

Mouse Ear ◽

Gas Chromatography Mass Spectroscopy ◽

Abdominal Constriction

Background: The fruits with the seeds of Dracunculus vulgaris Schott. (Araceae) are used against inflammatory diseases in Turkey. Objective: Present study was designed to justify this folkloric usage type of the plant. Therefore, the aim of this study is to investigate the anti-inflammatory activity of D. vulgaris. Methods: Petroleum ether, ethyl acetate and methanol extracts were prepared from the fruits, successively. Carrageenan-, serotonin-, and prostaglandin E2-induced hind paw edema; acetic acid–induced capillary permeability and 12-O-tetradecanoyl-phorbol-13-acetate–induced mouse ear edema models were used to assess the antiinflammatory activity of the extracts. The analgesic activity was experienced by using p-benzoquinone-induced abdominal constriction test. Results: The petroleum ether extract displayed the highest activities in all of the used test models compared with the control group. Therefore, the constituents of this extract were determined by using gas chromatography–mass spectroscopy (GC–MS). Linoleic acid was found to be major constituent of the petroleum ether extract of D. vulgaris. Conclusion: This study has provided some justification for the folkloric use of the plant.

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CXCL13 concentration in latent syphilis patients with treatment failure

Open Medicine ◽

10.1515/med-2020-0204 ◽

2020 ◽

Vol 15 (1) ◽

pp. 635-643

Author(s):

Yan Zhang ◽

Jun Wang ◽

Yingnan Wei ◽

Huili Liu ◽

Chunli Wu ◽

...

Keyword(s):

Nervous System ◽

Treatment Failure ◽

Leukocyte Count ◽

Inflammatory Diseases ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

System Control ◽

Failure Group ◽

Latent Syphilis ◽

Hiv Negative

AbstractWe aimed to investigate the CXCL13 concentration of the serum and cerebral spinal fluid (CSF) in human immunodeficiency virus (HIV)-negative latent syphilis patients with treatment failure and explore the change in CXCL13 after treatment. Sixty-eight latent syphilis patients with treatment failure (failure group), 68 syphilis patients with successful treatment (seroconversion group) and 18 patients with non-inflammatory diseases of the nervous system (control group) were included and serum and CSF were collected. Enzyme-linked immunosorbent assay was employed to detect the CXCL13 in the serum and CSF. Results showed that the serum CXCL13 concentration was comparable among three groups, and the CSF leukocyte count, IgG index and CXCL13 concentration in the failure group were significantly higher than those in the seroconversion group and control group (P < 0.05, P < 0.01). CSF CXCL13 concentration in the failure group was positively related to the CSF leukocyte count (r = 0.3594, P < 0.001). Of the 68 patients in the treatment failure group, neurosyphilis was found in 17 (25.0%). In conclusion, involvement of nervous system is one of the reasons for the treatment failure in patients with latent syphilis. Detection of CSF CXCL13 concentration is helpful for the diagnosis and therapeutic evaluation of HIV-negative latent syphilis patients with treatment failure and neurosyphilis.

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Phase angle and Mediterranean diet in patients with acne: Two easy tools for assessing the clinical severity of disease

Journal of Translational Medicine ◽

10.1186/s12967-021-02826-1 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Luigi Barrea ◽

Marianna Donnarumma ◽

Sara Cacciapuoti ◽

Giovanna Muscogiuri ◽

Ludovica De Gregorio ◽

...

Keyword(s):

Body Composition ◽

Mediterranean Diet ◽

Phase Angle ◽

Inflammatory Diseases ◽

Bioelectrical Impedance ◽

Dietary Factors ◽

Clinical Severity ◽

Control Group ◽

Cross Sectional ◽

Severe Acne

Abstract Background Acne is a chronic, inflammatory and debilitating skin disorder. Dietary factors and nutritional status are among the exacerbating factors of acne. Phase angle (PhA), a direct measure of Bioelectrical Impedance Analysis (BIA), represents an indicator of the chronic inflammatory state. The Mediterranean diet (MD) is a healthy dietary pattern that can exert anti-inflammatory effects in several inflammatory diseases. We aimed to investigate the difference in PhA and adherence to the MD and their associations with the severity of acne in a sample of naïve treatment patients with acne compared to control group. Materials In this cross-sectional, case–control, observational study, we enrolled 51 patients with acne and 51 control individuals. Body composition was evaluated by a BIA phase-sensitive system (50 kHz BIA 101 RJL, Akern Bioresearch, Florence, Italy, Akern). For adherence to the MD, we have used the PREvención con DIeta MEDiterránea (PREDIMED) questionnaire. The clinical severity of acne was assessed by using the global acne grading system (GAGS), a quantitative scoring system to assess acne severity. Results Patients with acne had a worse body composition, in particular smaller PhA (p = 0.003), and a lower adherence to the MD (p < 0.001) than the control group, in spite of no differences in gender, age and BMI between the two groups. Stratifying patients with acne according to GAGS categories, both PhA (p = 0.006) and PREDIMED score (p = 0.007) decreased significantly in severe acne than mild/moderate acne. The GAGS score was negative correlations with PhA (r = − 0.478, p < 0.001) and PREDIMED score (r = − 0.504, p < 0.001). The results of the multivariate analysis showed PhA and PREDIMED score were the major determinants of GAGS score (p < 0.001). The receiver operator characteristic (ROC) analysis reporting a value of PhA of ≤ 6.1° and a PREDIMED score of ≤ 9 identified patients with acne with the highest clinical severity of the disease. Conclusions Novel correlations were reported between PhA and the degree of adherence to the MD with acne severity. Of interest, PhA and PREDIMED scores might represent possible markers of the severity of acne in a clinical setting. This study highlights how a cooperation between dermatologist and nutritionists might provide a combination key in the complex management of acne patients.

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Expression and Function of Organic Anion Transporting Polypeptides in the Human Brain: Physiological and Pharmacological Implications

Pharmaceutics ◽

10.3390/pharmaceutics13060834 ◽

2021 ◽

Vol 13 (6) ◽

pp. 834

Author(s):

Anima M. Schäfer ◽

Henriette E. Meyer zu Schwabedissen ◽

Markus Grube

Keyword(s):

Organic Anion ◽

Physiological Role ◽

Point Of View ◽

Efflux Transporters ◽

Organic Anion Transporting Polypeptides ◽

Current State ◽

P Glycoprotein ◽

The Central Nervous System ◽

And Function ◽

Uptake Transporters

The central nervous system (CNS) is an important pharmacological target, but it is very effectively protected by the blood–brain barrier (BBB), thereby impairing the efficacy of many potential active compounds as they are unable to cross this barrier. Among others, membranous efflux transporters like P-Glycoprotein are involved in the integrity of this barrier. In addition to these, however, uptake transporters have also been found to selectively uptake certain compounds into the CNS. These transporters are localized in the BBB as well as in neurons or in the choroid plexus. Among them, from a pharmacological point of view, representatives of the organic anion transporting polypeptides (OATPs) are of particular interest, as they mediate the cellular entry of a variety of different pharmaceutical compounds. Thus, OATPs in the BBB potentially offer the possibility of CNS targeting approaches. For these purposes, a profound understanding of the expression and localization of these transporters is crucial. This review therefore summarizes the current state of knowledge of the expression and localization of OATPs in the CNS, gives an overview of their possible physiological role, and outlines their possible pharmacological relevance using selected examples.

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Inhalationally Administered Semifluorinated Alkanes (SFAs) as Drug Carriers in an Experimental Model of Acute Respiratory Distress Syndrome

Pharmaceutics ◽

10.3390/pharmaceutics13030431 ◽

2021 ◽

Vol 13 (3) ◽

pp. 431

Author(s):

Matthias Otto ◽

Jörg Krebs ◽

Peter Welker ◽

René Holm ◽

Manfred Thiel ◽

...

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Distress Syndrome ◽

Lung Mechanics ◽

Systemic Absorption ◽

Control Group ◽

Pharmacokinetic Data ◽

Tnf Α ◽

Semifluorinated Alkanes

Aerosol therapy in patients suffering from acute respiratory distress syndrome (ARDS) has so far failed in improving patients’ outcomes. This might be because dependent lung areas cannot be reached by conventional aerosols. Due to their physicochemical properties, semifluorinated alkanes (SFAs) could address this problem. After induction of ARDS, 26 pigs were randomized into three groups: (1) control (Sham), (2) perfluorohexyloctane (F6H8), and (3) F6H8-ibuprofen. Using a nebulization catheter, (2) received 1 mL/kg F6H8 while (3) received 1 mL/kg F6H8 with 6 mg/mL ibuprofen. Ibuprofen plasma and lung tissue concentration, bronchoalveolar lavage (BAL) fluid concentration of TNF-α, IL-8, and IL-6, and lung mechanics were measured. The ibuprofen concentration was equally distributed to the dependent parts of the right lungs. Pharmacokinetic data demonstrated systemic absorption of ibuprofen proofing a transport across the alveolo-capillary membrane. A significantly lower TNF-α concentration was observed in (2) and (3) when compared to the control group (1). There were no significant differences in IL-8 and IL-6 concentrations and lung mechanics. F6H8 aerosol seemed to be a suitable carrier for pulmonary drug delivery to dependent ARDS lung regions without having negative effects on lung mechanics.

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JAK2 Phosphorylation Signals and Their Associated Cytokines Involved in Chronic Rhinosinusitis with Nasal Polyps and Correlated with Disease Severity

Biomolecules ◽

10.3390/biom11071059 ◽

2021 ◽

Vol 11 (7) ◽

pp. 1059

Author(s):

Yu-Tsai Lin ◽

Wei-Chih Chen ◽

Ming-Hsien Tsai ◽

Jing-Ying Chen ◽

Chih-Yen Chien ◽

...

Keyword(s):

Chronic Rhinosinusitis ◽

Disease Severity ◽

Nasal Polyps ◽

Inflammatory Diseases ◽

Janus Kinase ◽

Sinus Surgery ◽

Control Group ◽

Jak2 Inhibitor ◽

Ifn Γ ◽

Snot 22

Janus kinase 2 (JAK2) is a member of the JAK family that transduces cytokine-mediated signals via the JAKs/STATs (signal transducer and activator of transcription proteins) pathway, which plays an important role in many inflammatory diseases. This study investigates the association of p-JAK2 and JAK2-associated cytokines from nasal polyp (NP) tissue with disease severity, and evaluates the p-JAK2-mediated STATs in chronic rhinosinusitis (CRS) with NP. Sixty-one CRSwNP patients with nasal polyps undergoing endoscopic sinus surgery were enrolled, while the turbinate tissues from 26 nasal obstruction patients were examined as the control group. Elevated levels of p-JAK2 were detected in CRSwNP, and significantly correlated with scores of disease severity (LMK-CT, TPS, and SNOT-22). Expressions of the JAK2-associated cytokines, such as IL-5, IL-6, IL-13, G-CSF, and IFN-γ were significantly higher in CRSwNP than in the controls, while the levels of IL-5, IL-6, IL-13, or G-CSF had positive correlation with scores of disease severity. Moreover, markedly increased expression of p-STAT3 in CRSwNP was observed relative to the control. Taken together, these data showed that the JAK2-associated cytokines including IL-6 and G-CSF may stimulate JAK2 phosphorylation to activate p-STAT3, indicating an association with disease severity and supporting its development of JAK2 inhibitor as a potential therapeutic agent for CRS.

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