ABSTRACT
The capsule is a major virulence factor for Streptococcus pneumoniae which causes global morbidity and mortality. It is already known that there are few conserved genes in the capsular biosynthesis pathway, which are common among all known serotypes, called CpsA, CpsB, CpsC and CpsD. Inhibiting capsular synthesis can render S. pneumoniae defenseless and vulnerable to phagocytosis. The Inhibitory potential of active Zingiber officinale compounds was investigated against the 3D (3-dimensional) structural products of Cps genes using in silico techniques. A 3D compound repository was created and screened for drug-likeness and the qualified compounds were used for molecular docking and dynamic simulation-based experiments using gallic acid for outcome comparison. Cavity-based docking revealed five different cavities in the CpsA, CpsB and CpsD proteins, with gallic acid and selected compounds of Zingiber in a binding affinity range of -6.8 to -8.8 kcal/mol. Gingerenone A, gingerenone B, isogingerenone B and gingerenone C showed the highest binding affinities for CpsA, CpsB and CpsD, respectively. Through the Molegro Virtual Docker re-docking strategy, the highest binding energies (-126.5 kcal/mol) were computed for CpsB with gingerenone A and CpsD with gingerenone B. These findings suggest that gingerenone A, B and C are potential inhibitors of S. pneumoniae-conserved capsule-synthesizing proteins.
Subject(s)
Bacterial Proteins , Molecular Docking Simulation , Streptococcus pneumoniae , Zingiber officinale , Zingiber officinale/chemistry , Streptococcus pneumoniae/drug effects , Streptococcus pneumoniae/metabolism , Bacterial Proteins/metabolism , Bacterial Proteins/antagonists & inhibitors , Computer Simulation , Bacterial Capsules/metabolism , Bacterial Capsules/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Molecular Dynamics Simulation , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/biosynthesis , Gallic Acid/pharmacology , Gallic Acid/chemistryABSTRACT
Present work investigates the effects of hydro-methanolic roots extract (HyMREt) of Rauwolfia serpentina in type 1 diabetic mice. Mice were divided into normal, diabetic, negative and positive controls (I-IV) and three test (HyMREt doses) groups (V-VII - 50, 100, &150mg/kg). Allocated treatment of each group was given orally for 14 days in overnight fasted state. Percent change in fasting blood glucose (FBG), body weights, body tissue weights, hepatic glycogen, total lipids, glycosylated hemoglobin (HbA1c), complete blood profile and antioxidant enzymes including catalase (CAT) and superoxide dismutase (SOD) were estimated. HyMREt doses produced meaningful (p<0.0001) reduction (-39 to -53%) in FBG. Hemoglobin (Hb) levels were raised, HbA1c were considerably decreased (4.5-3.77%) and glycosylation (HbA1c to Hb) ratio was expressively (p<0.0001) improved in test groups. Dose-wise improvement (p< 0.05) in total glycogen and decrement (p<0.05) in lipids were observed in livers of test groups. HyMREt significantly decreased (p<0.05) percent inhibition of SOD and CAT. HyMREt doses progressively (p<0.05) improved RBC and other hematological parameters while decrement was only noticed in leucocyte counts. Administration of test doses of HyMREt were significantly reduced the glycosylation, oxidative stress and anemia caused by alloxan intoxication in mice.
Subject(s)
Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/drug therapy , Plant Extracts/therapeutic use , Rauwolfia , Alloxan/toxicity , Animals , Biomarkers/blood , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Type 1/chemically induced , Glycosylation/drug effects , Male , Mice , Plant Extracts/isolation & purification , Plant Extracts/pharmacologyABSTRACT
OBJECTIVE: To investigate the relationship of seminal free L-carnitine with functional spermatozoal characteristics. METHODS: This observational study was conducted at the Jinnah Postgraduate Medical Centre, Karachi, from August 2009 to June 2013, and comprised fertile and infertile subjects. Semen analysis was performed and reported for its volume, sperm count, motility and morphology according to the World Health Organisation's guidelines. Seminal free L-carnitine was estimated by high-performance liquid chromatography. Mean values of demographic characteristics, semen analysis and seminal free L-carnitine were compared, and possible relation of seminal free L-carnitine with functional spermatozoal characteristics was explored. RESULTS: Of the 61 participants, 19(31.1%) were fertile controls, while 42(68.9%) were infertile men. The mean age of controls was 32.7±1.44 years and that of infertile patients was 33.4±0.75 years (p=0.655). The mean seminal free L-carnitine was 447.6±23.86mmol/L among controls and 154.6±12.99 among patients (p=0.001). There was a strong positive correlation of seminal free L-carnitine with sperm count, total motility and normal morphology (p<0.01 each). CONCLUSIONS: The role of seminal free L-carnitine in the maintenance of normal functional spermatozoal characteristics was validated.