Search

Background: Type 2 diabetes mellitus (T2DM) is defined by a wide variety of metabolic abnormalities, persistent hyperglycemia, and a slew of other complications. Catharanthus roseus L. (apocyanaceae), remarkably notable as Vinca Rosea, appears to be the source of the active component hirsutidin, which is reported in various diseases. Objective: The study intended to appraise the antidiabetic capability of hirsutidin in a high-fat diet (HFD) and streptozotocin (STZ) induced diabetes in experimental rats. Materials and methods: An experimental rodent T2DM model was elicited by consuming an HFD regimen with STZ 50 mg/kg, i.p. dose formulated in a 0.1 M cold citrate buffer (pH 4.5). The test drug hirsutidin (10 and 20 mg/kg) and the standard drug glimeclamide (5 mg/kg) were administered daily for six weeks. The efficacy of hirsutidin was observed on several diabetes parameters. The average body weight and an array of biochemical markers were determined, including blood glucose, insulin, dyslipidemia (lipid profile), total protein (TP), liver injury [aspartate aminotransferase (AST), alanine aminotransferase (ALT)], inflammation [IL-6, IL-1β, tumor necrosis factor-α (TNF-α)], oxidative stress [malondialdehyde (MDA)] and antioxidant status [catalase (CAT), glutathione (GSH), and superoxide dismutase (SOD)]. In addition, the concentrations of leptin, adiponectin, and resistin were also assessed. Also, molecular docking studies were undertaken to investigate critical targets associated with diabetes, including TNF-α, insulin, adiponectin, and leptin. Results: Diabetes induction with HFD/STZ resulted in hyperglycemia (significantly reduced blood glucose and increased insulin level), dyslipidemia (significantly reduced TC, TG and increased HDL), total protein (significantly reduced), oxidative stress and antioxidant status (significantly reduced MDA and increased CAT, SOD and GSH levels), inflammation (significantly decreased IL-6, IL-1β, TNF-α), liver damage (significantly reduced AST, ALT), and specific hormones such as adiponectin, leptin significantly improved and resistin significantly reduced as evidenced by biochemical data in this study. Intermolecular interactions of ligands and docking score, hirsutidin proteins TNF-α (2AZ5), Insulin (4IBM), Adiponectin (6KS1), Leptin (7Z3Q) with binding energy of -6.708, -7.674, -7.2 and -7.547 Kcal/mol. Conclusion: Hirsutidin may have an evidential hypoglycemic outcome and may exhibit potent antidiabetic activity in HFD/STZ-induced T2DM in rats. Treatment with hirsutidin significantly improved glycemic control, lipid metabolism, oxidative stress, inflammation, and liver function. Additionally, it normalized dysregulated levels of adiponectin, leptin, and resistin. Molecular docking confirmed its strong binding affinity to key diabetic targets.

Background and Objectives: Rosiridin is a monoterpene with outstanding monoamine inhibitory activity that is useful to treat depressive episodes and rapid-onset dementia. The current investigation aims to evaluate the neurologically protective impact of rosiridin, which opposes aluminum chloride (AlCl3) and causes memory dysfunction in rats. Materials and Methods: Memory impairment was developed in Wistar rats by administering AlCl3 (100 mg/kg p.o.) orally for 42 days and then supplemented with rosiridin at 10 and 20 mg/kg/p.o. Upon completion of the investigation, the behavior factor was performed utilizing the Y-maze, Morris Water Maze, and open field tests. Estimating numerous biological factors, such as nitric oxide (NO), oxidative stress (malondialdehyde MDA), acetylcholinesterase (AChE), butyrylcholinesterase levels (BuChE), antioxidants (glutathione GSH, catalase CAT, and superoxide dismutases SODs) and neurotransmitter (serotonin-5HT, dopamine-DA, acetylcholine-Ach) in the brain. Furthermore, interleukin-6 (IL-6), IL-1β, tumor necrosis factor (TNF-α), brain-derived neurotrophic factor (BNDF), nuclear factor kappa B (NFᴋB), phosphatidylinositol 3-kinase (PI3K), and pAkt were assessed in the diffused brain cells. Results: The rosiridin-treated group significantly improved in terms of behavioral parameters, including in the Y-maze, Morris Water Maze, and open field tests. Further, rosiridin restored biochemical parameters, including NO, oxidative stress AChE, BuChE, antioxidants, neurotransmitters, IL-6, IL-1β, TNF-α, BNDF, NFᴋB, PI3K, and pAkt compared to AlCl3. Conclusions: The current investigation reveals that rosiridin could ameliorate the impairment of memory that AlCl3 causes in rats via improvements in behavioral and restored biochemical parameters.

The purpose of this study was to determine the improvement of learning outcomes of students in class X MIPA 1 in Integrated Islamic High School of Nurhidayah Sukoharjo by applying the Discovery Learning “TERPADU” model in online learning. This research is a classroom action research model of Kemmis and Taggart which consists of four stages in each action, namely planning, implementation and observation, evaluation, and reflection. The research was conducted in two cycles of action. The subjects of this research were students of class X MIPA 1 with a total of 34 students. This research instrument is in the form of tests and non-tests. The results of this study indicate the achievement of student learning outcomes that have increased from pre-action to cycle I to cycle II, namely: (1) the student's average score of 66.68 (pre-action) increased to 82.72 (cycle I) then increased again to 89.11 (cycle II), (2) the percentage of classical completeness of 51.67% (pre-action) increased to 82.33% (cycle I) then increased again to 100% (cycle II), (3) N-gain of 0.31 in the “medium” category (cycle I) increased to 0.58 or stayed in the “medium” category (cycle II). Based on these results, it can be concluded that the application of the Discovery Learning “TERPADU” model can improve Biology learning outcomes. Based on this study, the researcher provides suggestions: (1) this Discovery Learning “TERPADU” model also needs to be tested in other class action research either conducted in online mode or offline mode (in the classroom) and (2) this research needs to be developed by using information technology and computer-based learning media in offline mode learning.

Memory loss or dementia is a progressive disorder, and one of its common forms is Alzheimer’s disease (AD), effecting mostly middle aged and older adults. In the present study, we developed Rivastigmine (RIV) nanoparticles using poly(lactic-co-glycolic acid) (RIV-loaded PLGA NPs) and polyvinyl alcohol (PVA). The prepared RIV-PLGA nanoparticles was evaluated for the management of Alzheimer's disease (AD). The nanoparticles were prepared by the slightly modified nano-precipitation technique. The developed formulations were evaluated for particle size, zeta potential (ZP), polydispersibility index (PDI) and surface morphology and drug content. The experimental result revealed that prepared RIV-loaded PLGA NPs (F1) was optimized having particle size (61.2 ± 4.6 nm), PDI (0.292), ZP (−11.2 ± 1.2). SEM study confirms the prepared nanoparticles depicted non-aggregated as well smooth surface particles without any fracture. This formulation (F1) was further assessed for in vivo studies on animal model. A pharmacological screening on an animal model of Alzheimer's disease revealed that RIV-loaded PLGA NPs formulations treat CNS disorders like Alzheimer's effectively. In addition to that, an in-vivo brain cholinesterase estimation study found that, animals treated with optimized formulation significantly (p

Background/Objectives: 6-Shogaol is a comparatively innovative anti-Parkinson’s remedy with antioxidant and anti-inflammatory characteristics. This investigation intended to determine the role of 6-shogaol in the Parkinson’s disease (PD) paradigm in rotenone-induced rats. Methods: Thirty male Wistar rats (10–12 weeks old; 180 ± 20 g) were divided into five groups. Animals with rotenone-induced experimental PD were subsequently treated with 6-shogaol-10 at 20 mg/kg for 28 days. After the experimental duration, behavioural investigations were performed, i.e., open field test, forced swim test, rotarod test, and catalepsy test. Biochemical assessments like AChE, GSH, CAT, SOD, MDA, nitrite, ceruloplasmin, proinflammatory markers such as IL-1β, NF-κB, TNF-α, and catecholamines markers (DA, GABA, and MAO-B) were determined. The docking procedure was conducted using the AutoDock Vina docking protocol. Furthermore, histopathology was performed. Results: Rotenone significantly increased the level of MAO-B, oxidative, nitrative, and pro-inflammatory markers. However, there was a decline in ceruloplasmin, dopamine, and endogenous antioxidants. Treatment with 6-shogaol (10 and 20 mg/kg) considerably sustained the elevation of oxidative stress and inflammatory indicators and decreased AChE activity and dopamine levels. In the histology of the brain, 6-shogaol improved the neuronal structure and reduced the degeneration of neurons. Based on the binding energy values, compound 6-shogaol demonstrates a favourable binding affinity to AChE, MAO-B, DA, and GABA with respective binding energies of −8.214, −8.133, −7.396 and −6.189 kcal/mol. Conclusions: In this study, 6-shogaol exhibited neuroprotective properties against PD, which could be employed as a prospective medication for PD.

Lipopolysaccharides (LPS), the lipid component of gram-negative bacterial cell wall, is recognized as the key factor in acute lung inflammation and is found to exhibit severe immunologic reactions. Phosphodiesterase-4 (PDE-4) inhibitor: “apremilast (AP)” is an immune suppressant and anti-inflammatory drug which introduced to treat psoriatic arthritis. The contemporary experiment designed to study the protective influences of AP against LPS induced lung injury in rodents. Twenty-four (24) male experimental Wistar rats selected, acclimatized, and administered with normal saline, LPS, or AP + LPS respectively from 1 to 4 groups. The lung tissues were evaluated for biochemical parameters (MPO), Enzyme Linked Immunosorbent Assay (ELISA), flowcytometry assay, gene expressions, proteins expression and histopathological examination. AP ameliorates the lung injuries by attenuating immunomodulation and inflammation. LPS exposure upregulated IL-6, TNF-α, and MPO while downregulating IL-4 which were restored in AP pretreated rats. The changes in immunomodulation markers by LPS were reduced by AP treatment. Furthermore, results from the qPCR analysis represented an upregulation in IL-1β, MPO, TNF-α, and p38 whereas downregulated in IL-10 and p53 gene expressions in disease control animals while AP pretreated rats exhibited significant reversal in these expressions. Western blot analysis suggested an upregulation of MCP-1, and NOS-2, whereas HO-1, and Nrf-2 expression were suppressed in LPS exposed animals, while pretreatment with AP showed down regulation in the expression MCP-1, NOS-2, and upregulation of HO-1, and Nrf-2 expression of the mentioned intracellular proteins. Histological studies further affirmed the toxic influences of LPS on the pulmonary tissues. It is concluded that, LPS exposure causes pulmonary toxicities via up regulation of oxidative stress, inflammatory cytokines and stimulation of IL-1β, MPO, TNF-α, p38, MCP-1, and NOS-2 while downregulation of IL-4, IL-10, p53, HO-1, and Nrf-2 at different expression level. Pretreatment with AP controlled the toxic influences of LPS by modulating these signaling pathways.

Carfilzomib (CFZ), a chemotherapeutic agent used for multiple myeloma treatments reported to cause high incidence of cardiac events either new onset and/or exacerbate formerly diagnosed heart failure with ventricular and myocardial dysfunction.Purpose: Current research designed to explore and examine the preventive effect of oxyphenbutazone in the CFZ -instigated cardiotoxicity. Methodology: Female Wistar Rats weighing 200–250 g selected randomly and grouped as follows: Group 1 designated as the Normal control and receive normal saline only. Group 2 served toxic control and exposed to CFZ (4 mg/kg, intraperitoneally [i.p.]). Group 3 & 4 served as treatment groups and administered with CFZ concomitantly orally fed with oxyphenbutazone at doses of 35 and 70 mg/kg/three times a week, respectively. The total duration of experimental protocol was of 21 days. After completion of the experiments animals subjected to blood collection using light ether anesthesia and serum was separated for biochemical analysis further. The serum levels of Mg+2, Ca+2 and cardiac enzymes (aspartate transaminase (AST), lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase-MB (CK-MB) levels were estimated. Later animals sacrificed and heart tissue isolated for further examinations. Intracellular proteins NFkB and IkBα were estimated by western blot. Results: The serum analysis revealed that CFZ administration significantly elevated the levels of LDH, CK and CKMB in CFZ exposed animals when compared to normal animals while administration of oxyphenbutazone significantly reduced these biochemical changes, Intracellular antioxidant enzymes and NF-kB in treatment groups as compared to disease control animals. Conclusion: Findings of the research protocol suggests significant injuries to cardiac tissues when animals exposed to CFZ and Oxyphenbutazone protected the cardiac tissues.

The complicated multiple sclerosis (MS) can exhibit subacute sight deterioration and can lead to total deprivation of vision. In the current work, we explored the therapeutic outcome of Cathepsin B inhibitor (CA-074) against retinopathy and optic neuritis (ON) caused by experimental autoimmune encephalomyelitis (EAE) induced by proteolipid protein peptide (PLP) in female SJL/J mice. A daily dose of 10 mg/kg CA-074 was administered to the EAE mice intraperitoneally for 14 days from day 14 post-immunization until day 28. The Western blot and immunofluorescence analyses show inflammation in the optic nerve through the elevation of iNOS and NFkB markers in EAE mice. Optic neuritis was reported which is a consequence of demyelination and axon injury, estimated with the reduction in myelin basic protein (MBP). The glial fibrillary acidic protein (GFAP) expression level was found to be elevated in the retina of EAE mice which confirmed the retinopathy. The administration of CA-074 ameliorated optic neuritis and retinopathy by reducing inflammation. The treatment with CA-074 also reduced the demyelination and axonal injuries in the EAE mice. The findings of this study have shown the protective effect of CA-074 in the case of retinopathy and ON inflicted by EAE in SJL/J mice.

Objective: To investigate the effect of Nigella sativa oil on cardiomyopathy and neurobehavioral changes induced by doxorubicin in mice. Methods: Swiss strain of albino female mice were divided into 6 groups of 5 animals in each: Group I (control group), group II (doxorubicin, 10 mg/kg, i.v.), group III, IV, and V (Nigella sativa oil; 1.5, 3, and 6 mL/kg, respectively), group Ή (Nigella sativa oil per se; 6 mL/kg, p.o.). The duration of treatment was 15 d (10 days’ pre-treatment and 5 days’ post-treatment) and doxorubicin was administered on day 11th of the treatment schedule. Following Nigella sativa oil treatment, neurobehavioral tests, cardiac hypertrophy tests, and biochemical tests in serum and tissues were performed. Neurological tests included assessment of anxiety-like behavior in the elevated plus maze, spontaneous alternation behavior in the cross maze, and depression-like behavior in modified forced swim tests. Biochemical tests included serum lactate dehydrogenase and creatinine kinase-MB, malondialdehyde and reduced glutathione in tissues. Lastly, molecular docking was used to estimate the affinity of the phytoconstituents of Nigella sativa oil with histone deacetylases. Results: Nigella sativa oil treatment significantly (P

Umifenovir is one of the most often prescribed antiviral medications for the prevention and treatment of COVID-19 and other viral infections. Herein, a UPLC-MS/MS method is developed through using ibrutinib as an internal standard (IS) for quantifying umifenovir in plasma samples. Both umifenovir and the IS were analytically separated on an Acquity BEH C18 column with a total run time of only 2.5 min. At a flow rate of 0.3 mLmin−1, acetonitrile:15 mM ammonium acetate (80:20) was employed as the mobile phase composition. Electrospray ionization in positive mode was used for ionization of the samples. Detection and quantification were performed in multiple reaction monitoring mode with parent-to-daughter ionization of 477.05 → 279.02 and 441.16 → 84.4 for umifenovir and the IS, respectively. The method was validated through following international guidelines for bioanalytical method validation, and all parameters were within the acceptable limits. Moreover, the eco-scale method using AGREE software was used for the evaluation of greenness, and results showed that the method is very environmentally friendly. The validated assay was successfully employed in the bioavailability assessment of a newly developed formulation of kneaded ternary umifenovir/β-cyclodextrin with 1% poloxamer 188 (KDB).

Isoniazid is the most commonly used drug for treatment of tuberculosis, and is administered individually or in combination with other drugs as standard first line therapy. Offsetting its efficacy, severe adverse effects, especially peripheral neuropathy and hepatotoxicity, are associated with isoniazid therapy, limiting its use in tuberculosis. Isoniazid is acetylated in vivo producing hydrazine and acetyl hydrazine, which are responsible for hepatotoxicity. Marked pharmacogenetic differences in acetylation have been reported among different population across the globe. This study evaluates isoniazid acetylation patterns in tuberculosis patients receiving DOT therapy under the Revised National Tuberculosis Control Program (RNTCP) in a specialized tuberculosis hospital in north India. Of 351 patients from whom samples were taken for biochemical analysis of adverse events, 36 were assessed for acetylation patterns. Blood samples were taken 1 h after administration of a 600 mg dose of isoniazid, and plasma concentrations of isoniazid were determined using a validated HPLC method. Of these 36 patients, 20 (55.56%) were slow acetylators and 16 (44.44%) were fast acetylators. Our results are consistent with those of an earlier study conducted in a different region of India. Most biochemical changes produced during long-term isoniazid therapy resolve after therapy is terminated.

The bronchodilator effects of Roflumilast “a selective phosphodiesterase type-4 (PDE4)” inhibitor studied in this experimental protocol. The spiral strips of isolated guinea-pig tracheal chains mounted in organ bath and maintained in Krebs solution ventilated with carbogen at 32 °C and in Ca++ restricted krebs solution. PDE inhibitory activity was evaluated by recording dose response curves using inhibitory effect of isoprenaline on CCh induced contractions. For confirmation of PDE inhibition the intracellular cAMP levels were also estimated. Roflumilast resulted a sharp inhibition in contractile responses of carbachol (CCh, 1 µM) and K+ (80 mM) and the results were almost similar to verapamil. In Ca++ restricted Krebs solution, a rightward shift in the Ca++ response curves observed in the tracheal chain strips which were pretreated with Roflumilast (0.001–0.003 mg/mL) and the maximum response was suppressed, similarly as with verapamil. PDE inhibitory effect of Roflumilast evaluated by recording dose-dependent (0.03–0.1 mg/mL) responses, the isoprenaline-induced inhibitory dose response curves shifted leftward similar to papaverine (PDE inhibitor). Pretreatment with Roflumilast exhibited elevated intracellular cAMP levels in tracheal strips. Findings of the experiment conclude bronchodilatory influence of Roflumilast via PDE and Ca++ channel inhibition. Results of current experiment offers comprehensive mechanistic background of Roflumilast in future as therapeutic bronchodilator for hyperactive bronchial airway diseases.

Otostegia fruticosa, a plant belonging to the family Lamiaceae, is endemic to Ethiopia. In Ethiopian traditional medicine, O. fruticosa has been used for the treatment of several respiratory-related disorders. The present study was designed to evaluate the bronchodilatory and antimicrobial activities of O. fruticosa leaves crude extract (Of.Cr). Ex-vivo experiments were conducted on guinea-pig trachea provided with physiological oxygenated buffer solution using emkaBath setup. The crude extract was analyzed by gas chromatography-mass spectrometry. Of.Cr, showed the presence of terpenes, fragrance components, saponins, and higher fatty acids. Of.Cr when tested on contracted tracheal chains with carbamylcholine (CCh, 1 µM) and high K+ (80 mM) produced relaxation by showing higher potency against CCh with incomplete inhibition of high K+. Dicyclomine, used as a positive control, also showed selectively higher potency to inhibit CCh when compared with its effect against K+. In the anticholinergic curves, Of.Cr at 1 mg/mL deflected CCh-induced concentration–response curves (CRCs) competitively to the right like dicyclomine (0.03 µM) and atropine whereas a higher dose of Of.Cr (3 mg/mL) produced a non-parallel shift in the CCh curves like a higher dose of dicyclomine (0.1 µM). In the calcium channel inhibitory assay, Of.Cr at 3 & 5 mg/mL, deflected CRCs of Ca++ to the right like verapamil, used as positive control. Of.Cr, at concentrations (1–3 mg/mL) increases cAMP levels in isolated tracheal homogenates, similar to positive control phosphodiesterase inhibitor (papaverine). When tested for antibacterial activity against standard and clinical strains, Of.Cr was found more active (MIC 475 µg/ml) against S. aureus (NCTC 6571), while the maximum inhibition (MIC 625 µg/ml) was observed by the extract when tested against MRSA. These results determine the mechanistic pathways of the observed bronchodilatory effect of Otostegia fruticosa with a combination of anticholinergic and dual inhibition of phosphodiesterase and voltage-gated Ca++ channels. Keywords: Antimicrobial, Antimuscarinic, Asthma, Bronchodilatation, Ca++ channel blocker, Otostegia fruticosa, Phosphodiesterase inhibitor

Purpose: Understanding the appearance of anti-tubercular drug-related adverse drug reactions (ADRs) in patients receiving tuberculosis (TB) treatment is important, and may be related to morbidity and mortality if not recognized early. Here, we aimed to characterize the mechanisms underlying adverse drug reactions due to combination anti-tuberculosis therapy of the Revised National Tuberculosis Control Program (RNTCP). Methods: This was a prospective observational study conducted in 9 DOTS centers of New Delhi, India. All enrolled TB patients receiving first-line tuberculosis treatment as per RNTCP guidelines were monitored for ADRs. All ADRs that appeared during the treatment were recorded and analyzed. Results: The study included 1011 TB patients on anti-TB treatment under DOTS. According to Naranjo’s probability scale, of a total 351 (34.72%) reported adverse events, 102 (10.09%) were definite, 59 (5.83%) probable, 123 (12.17%) possible, and 67 (6.63%) doubtful. On the Hartwig severity scale, of the 351 adverse drug events, 225 (22.26%) were mild, 105 (10.38%) were moderate, and 21 (2.08%) were severe. Out of 102 reported adverse drug reactions, 81 (79.41%) were moderate and 21 (20.59%), while 65.28% did not experience any ADRs. Conclusions: Directly Observed Treatment (DOT) is effective and safe compared to daily treatment regimens. Patients receiving DOTS therapy needed close monitoring for adverse events. Therefore, a pharmacovigilance program should be added at the National level to accesses the adverse event incidence.

Recent research has shown that phytocomponents may be useful in the treatment of renal toxicity. This study was conducted to evaluate the renal disease hirsutidin in the paradigm of renal toxicity induced by cisplatin. Male Wistar rats were given cisplatin (3 mg/kg body weight/day, for 25 days, i.p.) to induce renal toxicity. Experimental rats were randomly allocated to four different groups: group I received saline, group II received cisplatin, group III received cisplatin + hirsutidin (10 mg/kg) and group IV (per se) received hirsutidin (10 m/kg) for 25 days. Various biochemical parameters were assessed, oxidative stress (superoxide dismutase (SOD), glutathione transferase (GSH), malonaldehyde (MDA) and catalase (CAT)), blood-chemistry parameters (blood urea nitrogen (BUN) and cholesterol), non-protein-nitrogenous components (uric acid, urea, and creatinine), and anti-inflammatory-tumor necrosis factor-α (TNF-α), interleukin-1β(IL-1β). IL-6 and nuclear factor-kB (NFκB) were evaluated and histopathology was conducted. Hirsutidin alleviated renal injury which was manifested by significantly diminished uric acid, urea, urine volume, creatinine, and BUN, compared to the cisplatin group. Hirsutidin restored the activities of several antioxidant enzyme parameters—MDA, CAT, GSH, and SOD. Additionally, there was a decline in the levels of inflammatory markers—TNF-α, IL-1β, IL-6, and NFκB—compared to the cisplatin group. The current research study shows that hirsutidin may act as a therapeutic agent for the treatment of nephrotoxicity induced by cisplatin.

Lemborexant (LEM) is a novel dual orexin receptor antagonist (DORA), recently approved for the treatment of insomnia. As with other DORAs, LEM has potential of abuse and therefore placed in Schedule IV class by the United States Drug Enforcement Administration (USDEA). In this study, a sensitive and accurate UPLC-MS/MS assay was developed for the quantification of LEM in human plasma sample using losartan as an internal standard (IS). The chromatographic separation was performed by using gradient elution of mobile phase, comprising of 10 mM ammonium acetate and acetonitrile with a flow rate of 0.3 mL/min. An Acquity UPLC BEH C18 (1.7 μm, 2.1 × 50 mm) column was used for separation of LEM and IS by maintaining the oven temperature of 40 °C. The electrospray ionization in positive mode was used for sample ionization. The precursor to product ion transition of 411.12 > 175.09 (qualifier) and 411.1 > 287.14 (quantifier) was used for detection and quantification of LEM, respectively, in multiple reaction monitoring mode. Being a drug of abuse, the assay was validated according to “Scientific Working Group for Toxicology” (SWGTOX) guidelines, including limit of detection (LOD), limit of quantification (LOQ), precision and bias, calibration model, interferences, carry-over effects, matrix effects, and stability parameters. The LOD and LOQ of the assay were 0.35 and 1.0 ng/mL, respectively. The linear range was between 1–300 ng/mL with correlation coefficient of ≥0.995. The method was also cross validated in rat plasma samples with acceptable ranges of precision and accuracy before its application for pharmacokinetic study in rats.

Cadmium (Cd), a potent cardiotoxic environmental heavy metal, induces oxidative stress and membrane disturbances in cardiac myocytes. Phosphodiesterase (PDEs) retards the positive inotropic effects of β-adrenoceptor activation by decreasing levels of cAMP via degradation. Hence, PDE inhibitors sensitize the heart to catecholamine and are therefore, used as positive inotropic agents. The present study was designed to probe the potential attenuating effects of the selective PDE4 inhibitor (Roflumilast, ROF), on cardiac biomarkers, lipid profile, lipid peroxidation products, antioxidant status and histology of cardiac tissues against Cd-induced cardiotoxicity in rats. Rats were randomly distributed into four different groups: group 1, served as the normal control group. Group 2, served as the toxic control group and were administered Cd (3 mg/kg, i.p.) for next 7 days. Groups 3 and 4, served as treatment groups that received Cd with concomitant oral administration of ROF doses (0.5 and 1.5 mg/kg), respectively for 7 days. Serum samples of toxic control group rats resulted in significant (P

The genus Thymus is traditionally used for the treatment of hyperactive airways complaints. The purpose of the current study is to investigate the potential tracheal relaxant effect and possible mechanism(s) of the essential oil of Thymus serrulatus (TS Oil) in isolated guinea pig tracheal tissues. The essential oil was obtained from the fresh erial parts of Thymus serrulatus, and its phyto-components were identified by GC-MS analysis. Guinea pig tracheal preparations were used for testing the tracheal relaxant effect of TS Oil with the determination of the mechanism(s) involved in this relaxation. GC-MS findings reveal that terpenes, fragrance constituents, saponins, and higher fatty acids are present in TS Oil. In isolated guinea pig trachea, TS Oil inhibited carbachol (CCh, 1 µM) and K+ (80 mM)-induced contractions in a pattern similar to that of dicyclomine. TS Oil, at 0.3 mg/ml, shifted parallel CCh-curves towards the right, followed by a non-parallel shift at higher concentration (1 mg/ml), thus suppressing maximum response in the same manner as produced by dicyclomine. Pretreatment of tissues with TS Oil (1 and 3 mg/ml) also produced a rightward shift of Ca++ concentration-response curves (CRCs) in the same manner as caused by verapamil. Further, TS Oil at low concentrations (0.3 and 1 mg/ml) shifted isoprenaline-induced inhibitory CRCs towards the left and increased cAMP levels in isolated tracheal homogenates similar to papaverine, a phosphodiesterase (PDE) inhibitor. In the antimicrobial assay performed by the agar well diffusion method, TS Oil was found most active against Candida albicans and Staphylococcus aureus where the zone of inhibition measured was 28 mm. Additionally, there was little difference between standard strains of gram-positive and gram-negative bacteria. However, methicillin-resistant S. aureus (MRSA) showed a small zone of inhibition as compared to standard strains (22 mm). From these results, it can be concluded that the essential oil of T. serrulatus has the potential to produce antimicrobial effects while causing tracheal relaxation mediated possibly by anticholinergic effects, Ca++ channel blockade, and PDE inhibition whereas additional mechanism(s) cannot be ruled out.

A novel UPLC-MS/MS assay was developed for rapid quantification of delafloxacin (a novel fluoroquinolone antibiotic in plasma samples by one step sample cleanup procedure. Delafloxacin (DFX) and internal standard (losartan) were separated on a UPLC BEH C18 column (50 × 2.1 mm; 1.7 μm) by using gradient programing of a mobile phase containing 0.1% formic acid in acetonitrile and 0.1% formic acid in water. The quantification was performed by a using triple-quadrupole mass detector at an electrospray ionization interface in positive mode. The precursor to the product ion transition of 441.1 → 379.1 for the qualifier and 441.1 → 423.1 for the quantifier was used for DFX monitoring, whereas 423.1 → 207.1 was used for the internal standard. The validation was performed as per guidelines of bioanalytical method validation, and the evaluated parameters were within the acceptable range. The greenness assessment of the method was evaluated by using AGREE software covering all 12 principles of green analytical chemistry. The final score obtained was 0.78, suggesting excellent greenness of the method. Moreover, Deming regression analysis showed an excellent linear relationship between this method and our previously reported method, and it is suitable for high-throughput analysis for routine application. The proposed method was effectively applied in a pharmacokinetic study of novel formulation (self-nanoemulsifying drug delivery systems) of DFX in rats.

The purpose of the research was to examine the protective effect of essential oil from Thymus serrulatus Hochst. ex Benth. (TSA oil) against cadmium (Cd)-induced renal toxicity. The experimental protocol was designed using 30 healthy adult Wistar albino rats allocated into five groups containing six animals in each group. Group 1 was treated as normal control and groups 2, 3, 4, and 5 were treated with cadmium chloride (CdCl2, 3 mg/kg, IP) for 7 days. Group 3 was also treated with silymarin (100 mg/kg, PO) as a standard group, while groups 4 and 5 were administered with TSA oil at doses of 100 and 200 mg/kg PO, respectively. The nephrotoxicity was measured with various parameters such as kidney function markers, oxidative stress markers (glutathione (GSH) and malondialdehyde (MDA)), and messenger ribonucleic acid (mRNA) expression levels of inflammatory factors. The histological studies were also evaluated in the experimental protocol. The CdCl2-treated groups showed a significant increase in the levels of serum kidney function markers along with MDA levels in kidney homogenate. However, renal GSH level was found to be reduced significantly. It was found that CdCl2 significantly upregulated the nuclear factor levels of kappaB (NF-κB p65), inducible nitric oxide synthase (iNOS), and small mothers against decapentaplegic (Smad2) as compared to the normal control group. On the other hand, TSA oil significantly improved the increased levels of serum kidney function markers, non-enzymatic antioxidants, and lipid peroxidation. In addition, TSA oil significantly downregulated the increased expression of NF-κB p65, iNOS, and Smad2 in Cd-intoxicated rats. Moreover, the histological changes in the tissue samples of the kidney of Cd-treated groups were significantly ameliorated in the silymarin- and TSA-oil-treated groups. The present study reveals that TSA oil ameliorates Cd-induced renal injury, and it is also proposed that the observed nephroprotective effect could be due to the antioxidant potential of TSA oil and healing due to its anti-inflammatory action.

Delafloxacin (DFL) is a novel potent and broad-spectrum fluoroquinolone group of antibiotics effective against both Gram-positive and negative aerobic and anaerobic bacteria. In this study, DFL-loaded stearic acid (lipid) chitosan (polymer) hybrid nanoparticles (L-P-NPs) have been developed by single-emulsion-solvent evaporation technique. The mean particle size and polydispersity index (PDI) of optimized DFL-loaded L-P-NPs (F1-F3) were measured in the range of 299−368 nm and 0.215−0.269, respectively. The drug encapsulation efficiency (EE%) and loading capacity (LC%) of DFL-loaded L-P-NPs (F1-F3) were measured in the range of 64.9−80.4% and 1.7−3.8%, respectively. A sustained release of DFL was observed from optimized DFL-loaded L-P-NPs (F3). Minimum inhibitory concentration (MIC) values of the DFL-loaded L-P-NPs (F3) appeared typically to be four-fold lower than those of delafloxacin in the case of Gram-positive strains and was 2-4-fold more potent than those of delafloxacin against Gram-negative strains. The pharmacokinetic study in rats confirmed that the bioavailability (both rate and extent of absorption) of DFL-loaded L-P-NPs was significantly higher (2.3-fold) than the delafloxacin normal suspension. These results concluded that the newly optimized DFL-loaded L-P-NPs were more potent against both Gram-positive and negative strains of bacteria and highly bioavailable in comparison to delafloxacin normal suspension.