scholarly journals Immune-Stimulatory and Therapeutic Activity of Tinospora cordifolia: Double-Edged Sword against Salmonellosis

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Sultan Alsuhaibani ◽  
Masood A. Khan
Keyword(s):  
Antioxidant Enzymes ◽  
Bacterial Load ◽  
Tinospora Cordifolia ◽  
Liver Inflammation ◽  
Inflammation Markers ◽  
Methanolic Extracts ◽  
Cytokine Levels ◽  
Culture Supernatants ◽  
Broth Dilution

The present study was aimed at determining the activity of aqueous and methanolic extracts of Tinospora cordifolia (AETC and METC) against Salmonella typhimurium. In vitro anti-Salmonella activity of T. cordifolia was determined through the broth dilution and agar well diffusion assays. The immune-stimulating potential of AETC or METC was determined by measuring the cytokine levels in the culture supernatants of treated murine J774 macrophages. Antibacterial activity of AETC or METC was determined by treating S. typhimurium-infected macrophages and BALB/C mice. The toxicity of AETC or METC was determined by measuring the levels of liver inflammation markers aspartate transaminase (AST) and alanine transaminase (ALT) and antioxidant enzymes. Macrophages treated with AETC or METC secreted greater levels of IFN-γ, TNF-α, and IL-1β. METC showed greater activity against S. typhimurium infection in macrophages and mice as well. Treatment with METC resulted in increased survival and reduced bacterial load in S. typhimurium-infected mice. Moreover, METC or AETC treatment reduced the liver inflammation and rescued the levels of antioxidant enzymes in S. typhimurium-infected mice. The results of the present study suggest that the use of T. cordifolia may act as a double-edged sword in combating salmonellosis.

scholarly journals Cytokine Levels in the In Vitro Response of T Cells to Planktonic and Biofilm Corynebacterium amycolatum

2019 ◽  
Vol 68 (4) ◽  
pp. 457-464
Author(s):  
ALINA OLENDER ◽  
AGNIESZKA BOGUT ◽  
AGNIESZKA MAGRYŚ ◽  
JACEK TABARKIEWICZ
Keyword(s):  
T Cells ◽  
Conditioned Medium ◽  
Statistical Significance ◽  
Jurkat T Cells ◽  
Cytokine Levels ◽  
Planktonic Form ◽  
In Vitro Response ◽  
Anti Inflammatory ◽  
Culture Supernatants

Unravelling of the interplay between the immune system and non-diphtheria corynebacteria would contribute to understanding their increasing role as medically important microorganisms. We aimed at the analysis of pro- (TNF, IL-1β, IL-6, IL-8, and IL-12p70) and anti-inflammatory (IL-10) cytokines produced by Jurkat T cells in response to planktonic and biofilm Corynebacterium amycolatum. Two reference strains: C. amycolatum ATCC 700207 (R-CA), Staphylococcus aureus ATCC 25923 (R-SA), and ten clinical strains of C. amycolatum (C-CA) were used in the study. Jurkat T cells were stimulated in vitro by the planktonic-conditioned medium (PCM) and biofilm-conditioned medium (BCM) derived from the relevant cultures of the strains tested. The cytokine concentrations were determined in the cell culture supernatants using the flow cytometry. The levels of the cytokines analyzed were lower after stimulation with the BCM when compared to the PCM derived from the cultures of C-CA; statistical significance (p < 0.05) was observed for IL-1β, IL-12 p70, and IL-10. Similarly, planktonic R-CA and R-SA stimulated a higher cytokine production than their biofilm counterparts. The highest levels of pro-inflammatory IL-8, IL-1β, and IL-12p70 were observed after stimulation with planktonic R-SA whereas the strongest stimulation of anti-inflammatory IL-10 was noted for the BCM derived from the mixed culture of both reference species. Our results are indicative of weaker immunostimulatory properties of the biofilm C. amycolatum compared to its planktonic form. It may play a role in the persistence of biofilm-related infections. The extent of the cytokine response can be dependent on the inherent virulence of the infecting microorganism.

scholarly journals Anti-Acetylcholinesterase Activities of Mono-Herbal Extracts and Exhibited Synergistic Effects of the Phytoconstituents: A Biochemical and Computational Study

Molecules ◽  
2019 ◽  
Vol 24 (22) ◽  
pp. 4175 ◽  
Author(s):  
Acharya Balkrishna ◽  
Subarna Pokhrel ◽  
Meenu Tomer ◽  
Sudeep Verma ◽  
Ajay Kumar ◽  
...  
Keyword(s):  
Methanolic Extract ◽  
Computational Study ◽  
Synergistic Effects ◽  
Tinospora Cordifolia ◽  
Herbal Extracts ◽  
Ache Inhibition ◽  
Product Release ◽  
Methanolic Extracts ◽  
Common Strategy

Alzheimer’s disease (AD), a neurodegenerative disease, is the most common form of dementia. Inhibition of acetylcholinesterase (AChE) is a common strategy for the treatment of AD. In this study, aqueous, hydro-methanolic, and methanolic extracts of five potent herbal extracts were tested for their in vitro anti-AChE activity. Among all, the Tinospora cordifolia (Giloy) methanolic fraction performed better with an IC50 of 202.64 µg/mL. Of the HPLC analyzed components of T. cordifolia (methanolic extract), palmatine and berberine performed better (IC50 0.66 and 0.94 µg/mL, respectively) as compared to gallic acid and the tool compound “galantamine hydrobromide” (IC50 7.89 and 1.45 µg/mL, respectively). Mode of inhibition of palmatine and berberine was non-competitive, while the mode was competitive for the tool compound. Combinations of individual alkaloids palmatine and berberine resulted in a synergistic effect for AChE inhibition. Therefore, the AChE inhibition by the methanolic extract of T. cordifolia was probably due to the synergism of the isoquinoline alkaloids. Upon molecular docking, it was observed that palmatine and berberine preferred the peripheral anionic site (PAS) of AChE, with π-interactions to PAS residue Trp286, indicating that it may hinder the substrate binding by partially blocking the entrance of the gorge of the active site or the product release.

scholarly journals PM2.5 Mediated Alterations In The In Vitro Human Granuloma Resulting In Reactivation Of Mycobacteria

2021 ◽  
Author(s):  
Athisankaran Punniyamurthy ◽  
Sumedha Sharma ◽  
Khushpreet Kaur ◽  
Uma Nahar Saikia ◽  
Ravindra Khaiwal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Particulate Matter ◽  
Mycobacterium Bovis ◽  
Bacterial Load ◽  
Granuloma Formation ◽  
Human Pbmcs ◽  
Cytokine Levels ◽  
Mycobacterial Antigens

Abstract Exposure to pollutants diminishes the immune response to mycobacterial antigens relevant to contain the infection in the granuloma, thus leading to reactivation of latent bacilli. Present study was therefore designed based on the hypothesis that exposure to particulate matter pollutant PM2.5 affects the granuloma formation and reactivation of latent mycobacterial bacilli contained in the granuloma. For the extraction of PM2.5, based on initial standardizations, teflon filter was selected over the quartz filter. Two different approaches were used to study the effect of PM2.5 on the human PBMCs granuloma formed by Mycobacterium bovis BCG at MOI 0.1. In the first approach, granuloma formed in the presence of PM2.5 was loosely packed and ill-defined with significant downregulation of dormancy associated mycobacterial genes, upregulation of reactivation associated rpfB gene along with a significant increase in TNFα level without any change in the bacterial load in terms of CFUs. In the second approach, PM2.5 treatment of already established human PBMCs granuloma formed with M. bovis BCG also led to its disruption. Although, in these conditions, downregulation of dormancy associated genes was observed but there was also a decrease in the expression of reactivation associated rpfB gene without any change in the cytokine levels. Therefore, it can be inferred that in the presence of PM2.5, there is poor granuloma formation along with a change in mycobacterial gene expression characteristics of active bacilli and alteration in host immune response without any significant changes following treatment of already established granuloma with the pollutant.

scholarly journals In VitroandIn VivoActivities of Contezolid (MRX-I) againstMycobacterium tuberculosis

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Carolyn Shoen ◽  
Michelle DeStefano ◽  
Barry Hafkin ◽  
Michael Cynamon
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Bacterial Load ◽  
Clinical Isolates ◽  
Content Type ◽  
Dilution Assay ◽  
Broth Dilution

ABSTRACTThein vitroactivity of contezolid (MRX-I) against clinical isolates ofMycobacterium tuberculosiswas evaluated using a microtiter broth dilution assay. MRX-I was as effective as linezolid (LZD)in vitro. MRX-I and LZD were subsequently studied in BALB/c mice infected intranasally withM. tuberculosisErdman. MRX-I and LZD at 100 mg/kg significantly reduced the bacterial load in lungs compared to the untreated early and late controls.

scholarly journals Antipseudomonal Bacteriophage Reduces Infective Burden and Inflammatory Response in Murine Lung

2015 ◽  
Vol 60 (2) ◽  
pp. 744-751 ◽  
Author(s):  
Rishi Pabary ◽  
Charanjit Singh ◽  
Sandra Morales ◽  
Andrew Bush ◽  
Khalid Alshafi ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage Fluid ◽  
Bacterial Load ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Clinical Strain ◽  
Infection Model ◽  
Attractive Alternative ◽  
Content Type ◽  
Cytokine Levels

ABSTRACTAs antibiotic resistance increases, there is a need for new therapies to treat infection, particularly in cystic fibrosis (CF), wherePseudomonas aeruginosais a ubiquitous pathogen associated with increased morbidity and mortality. Bacteriophages are an attractive alternative treatment, as they are specific to the target bacteria and have no documented side effects. The efficacy of phage cocktails was establishedin vitro. TwoP. aeruginosastrains were taken forward into an acute murine infection model with bacteriophage administered either prophylactically, simultaneously, or postinfection. The infective burden and inflammation in bronchoalveolar lavage fluid (BALF) were assessed at various times. With low infective doses, both control mice and those undergoing simultaneous phage treatment clearedP. aeruginosainfection at 48 h, but there were fewer neutrophils in BALF of phage-treated mice (median, 73.2 × 104/ml [range, 35.2 to 102.1 × 104/ml] versus 174 × 104/ml [112.1 to 266.8 × 104/ml],P< 0.01 for the clinical strain; median, 122.1 × 104/ml [105.4 to 187.4 × 104/ml] versus 206 × 104/ml [160.1 to 331.6 × 104/ml],P< 0.01 for PAO1). With higher infective doses of PAO1, all phage-treated mice clearedP. aeruginosainfection at 24 h, whereas infection persisted in all control mice (median, 1,305 CFU/ml [range, 190 to 4,700 CFU/ml],P< 0.01). Bacteriophage also reduced CFU/ml in BALF when administered postinfection (24 h) and both CFU/ml and inflammatory cells in BALF when administered prophylactically. A reduction in soluble inflammatory cytokine levels in BALF was also demonstrated under different conditions. Bacteriophages are efficacious in reducing both the bacterial load and inflammation in a murine model ofP. aeruginosalung infection. This study provides proof of concept for future clinical trials in patients with CF.

scholarly journals Administration of GDF3 Into Septic Mice Improves Survival via Enhancing LXRα-Mediated Macrophage Phagocytosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Peng Wang ◽  
Xingjiang Mu ◽  
Hongyan Zhao ◽  
Yutian Li ◽  
Lu Wang ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Bacterial Load ◽  
Organ Damage ◽  
Dependent Manner ◽  
Phagocytic Cells ◽  
Beneficial Effects ◽  
Macrophage Phagocytosis ◽  
Cytokine Levels ◽  
Liver X Receptor Α

The defective eradication of invading pathogens is a major cause of death in sepsis. As professional phagocytic cells, macrophages actively engulf/kill microorganisms and play essential roles in innate immune response against pathogens. Growth differentiation factor 3 (GDF3) was previously implicated as an important modulator of inflammatory response upon acute sterile injury. In this study, administration of recombinant GDF3 protein (rGDF3) either before or after CLP surgery remarkably improved mouse survival, along with significant reductions in bacterial load, plasma pro-inflammatory cytokine levels, and organ damage. Notably, our in vitro experiments revealed that rGDF3 treatment substantially promoted macrophage phagocytosis and intracellular killing of bacteria in a dose-dependent manner. Mechanistically, RNA-seq analysis results showed that CD5L, known to be regulated by liver X receptor α (LXRα), was the most significantly upregulated gene in rGDF3-treated macrophages. Furthermore, we observed that rGDF3 could promote LXRα nuclear translocation and thereby, augmented phagocytosis activity in macrophages, which was similar as LXRα agonist GW3965 did. By contrast, pre-treating macrophages with LXRα antagonist GSK2033 abolished beneficial effects of rGDF3 in macrophages. In addition, rGDF3 treatment failed to enhance bacteria uptake and killing in LXRα-knockout (KO) macrophages. Taken together, these results uncover that GDF3 may represent a novel mediator for controlling bacterial infection.

Screening, Fabrication and Evaluation of Pharmaceutical Dosage Forms using P-Glycoprotein Modulators

2017 ◽  
Vol 10 (2) ◽  
pp. 3688-3699
Author(s):  
Joshi Vedamurthy ◽  
Shivakumar Inamdar ◽  
Ankit Acharya ◽  
Rajesh Kowti
Keyword(s):  
Cell Lines ◽  
Tinospora Cordifolia ◽  
Absorption Enhancement ◽  
Synergistic Activity ◽  
Capsicum Frutescens ◽  
Plumbago Zeylanica ◽  
Pharmaceutical Dosage Forms ◽  
Holarrhena Antidysenterica ◽  
Trachyspermum Ammi

In this project, in vitro absorption enhancement activity of P-gp substrates Fexofenadine (Fx) and Ciprofloxacin (Cp) were evaluated in everted rat gut sac model and Caco-2 cell lines. Verapamil was used as P-gp inhibitor. Piper betel, Trachyspermum ammi, Plumbago zeylanica, Trikatu, Moringaoleifera, Murraya koenigii,  Ferulafoitida  Zingiber officinale, Cheilocostus speciosus, Capsicum frutescens Operculina turpethum Holarrhena antidysenterica Mesuaferrea, Tinospora cordifolia,  and Picrorhiza kurroa, were selected and extracted with 99% alcohol and fresh juices of Citrus limon, Punica granatum seeds were also studied. In-vitro studies depicted that Fexofenadine and Ciprofloxacin absorption was increased greater than 20% in the presence of Operculinaturpethum, Capsicum frutescens, Holarrhena Antidysenterica, Tinospora cordifolia, Trikatu, Trachyspermum ammi, Plumbago zeylanica. The flux of the ciprofloxacin transport was in the range of 9-23 mcg/min and Papp         2.6 × 10-5 cm/sec to 4.1 × 10-5  cm/sec whereas Fexofenadine flux was in the range of 2-7.7 mcg/min and Papp 4.16 × 10–6 cm/sec to 1.62 ×       10-5 cm/sec.  In vitro antimicrobial activity of ciprofloxacin on selected microbes in presence of extracts also depicted synergistic activity. Histological studies revealed that there is no significant variation observed in the isolated sac in presence of the extracts. CaCo2 cell lines studies showed that, formulation enhanced the absorption of fexofenadine greater than 50%. Tablets were prepared and evaluated using the plant extracts which yielded >20% absorption enhancement of the substrates. In conclusion, tablet formulation containing the alcoholic extracts of Trachyspermum ammi, Plumbago zylanicum, Capsicum frutescens, Operculina turpethum, Holarrhena Antidysenterica, Tinospora cordifolia and Trikatu can act as an absorption enhancer for fexofenadine and ciprofloxacin. The mechanism of action of these herbs could be due to    P-gp inhibition. Further clinical studies are needed to prove its efficacy in humans.     

scholarly journals Bactericidal activity of three different antiseptic ophthalmic preparations as surgical prophylaxis

2021 ◽  
Author(s):  
Daniele Tognetto ◽  
Marco R. Pastore ◽  
Gian Marco Guerin ◽  
Giuliana Decorti ◽  
Martina Franzin ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Povidone Iodine ◽  
Bacterial Load ◽  
Viable Cells ◽  
Polyethylene Glycol 1000 ◽  
Oil Concentration ◽  
Short Time ◽  
First Time ◽  
Antiseptic Solutions

Abstract Purpose In the era of antibiotic resistance, there is an increased interest in antiseptic solutions that might represent a reliable option for ocular surface disinfection. The objective of this study is to compare for the first time three different antiseptic ophthalmic preparations to assess their in vitro antimicrobial activity. Methods The antiseptic activity of three commercial ophthalmic solutions, IODIM (povidone-iodine 0.6% in hyaluronic acid vehicle—Medivis, Catania, Italy), OZODROP (nanoemulsion with ozonated oil—concentration not specified—FBVision, Ophthalmic Pharmaceuticals, Rome, Italy), and DROPSEPT (chlorhexidine 0.02% and vitamin E 0.5% Tocopherol Polyethylene Glycol 1000 Succinate—TPGS, Sooft Italia, Montegiorgio, Italy), was tested in vitro on six reference strains by time-killing assays. Viable cells were evaluated after 1, 15, 30 min; 2, 6, and 24 h exposure by seeding 100 µl of the suspension (or appropriate dilutions) on LB agar or Sabouraud-dextrose agar. All plates were incubated at 37 °C for 24 h and evaluated by manually counting the colonies. Results IODIM solution showed a very rapid microbicidal activity: the number of viable cells for all the tested strains was under the detection limit (less than 10 CFU/ml) already after 1 min exposure, and this result was maintained at every incubation time. The rapid antimicrobial activity of povidone-iodine was not replicated when testing the other two antiseptics. Conclusions The study reports the great efficacy in reducing bacterial load in a very short time of povidone-iodine 0.6% compared with other antiseptic preparations.

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