The COVID-19 epidemic is considered the most important health disaster of the century and the largest humanitarian crisis since World War II. In December 2019, a new respiratory disease/disorder was discovered in Wuhan, Hubei province, China and World Health Organization named it COVID-19 (coronavirus 2019). It has been diagnosed with a new class of corona virus, called SARS-CoV-2 (a serious respiratory disease). According to the history of human civilization it is affected by the incidence of disease outbreaks caused by the number of viruses. Covid-19 is rapidly spreading across the globe, due to which mankind faces major health, economic, environmental and social challenges. The outbreak of coronavirus is seriously affecting the global economy. Almost all nations have problems limiting the spread of the disease by screening and treating patients, setting up suspects by keeping in touch, blocking large gatherings, maintaining full or partial closure etc. This paper describes the impact of COVID-19 on society and the global environment, and the ways in which the disease is likely to be controlled have been discussed.
A simple and sensitive stability-indicating HPLC-UV method was developed and validated for the determination of montelukast in the development of chewable tablet formulation. Chromatographic separation was achieved using Atlantis® T3 3µm C18 (4.6mmID X 10cm) analytical column. The mobile phase was consisted of KH2PO4 (0.05mM)-ACN-TEA (450:550:1.33, v/v/v) adjusted to pH 2.0 with orthophosphoric acid. The analysis was run at a flow rate of 1.5 mL/min with detection wavelength at 255nm. Method validation was performed in accordance with ICH guideline. Stress degradation studies, comprising of acid and alkali hydrolysis (1M HCl and 1M NaOH), oxidative degradation (3% H2O2), photo degradation and heat degradation, were performed. The standard calibration curve was linear from 0.0025 - 0.375mg/mL. The LOD and LLOQ were 0.01μg/mL and 0.04μg/mL. Stress degradation result shows that montelukast sodium was sensitive to photo degradation, oxidation and acid hydrolysis. Oxidative degradation kinetic study of montelukast sodium followed first order reaction, with r2 =0.9877, apparent degradation rate constant, k= 0.1066 h-1, t1/2= 6.6151 hr and t90% = 1.0118hr. In conclusion, HPLC-UV method was successfully developed and validated for determination of montelukast sodium in chewable tablet formulation.
Empagliflozin is a selective inhibitor of sodium glucose co-transporter II, given as mono therapy or an add-on treatment to reduce the glycated hemoglobin levels in type 2 diabetes. This work deals with designing, formulating and optimizing empagliflozin (10mg) immediate release (IR) tablets by direct compression technique using different excipients. Through central composite rotatable design (CCRD), total nine formulations (EF1-EF9) were generated by changing the composition of binder avicel PH 102® (X1) and superdisintegrant acdisol⌖ (X2). Formulation runs with in suitable weight range and powder properties were subjected to compression. The influence of interaction of excipients on friability (Y1), hardness (Y2) and disintegration (Y3) were analyzed by fitting the polynomial quadratic model with response surface methodology (RSM). Trials EF2, EF7, EF8 and EF9 exhibited acceptable tablet attributes upon physico-chemical testing. Different dissolution models were applied to observe the in vitro drug release pattern in phosphate buffer of pH 6.8. The cumulative drug release of IR tablet batches followed the Weibull kinetics with regression coefficient (r2) values of 0.983-0.992. Empagliflozin trials were exposed to accelerated storage conditions (40±2°C/ 75±5% RH) for stability testing. Shelf life period of exposed formulations were computed in range of 22 to 25 months. Keeping in view of the results, it is concluded that the employed technique of preparation and optimization are observed to be excellent for developing immediate release empagliflozin (10mg) tablets.
The current research was aimed to isolate newer phyto-metabolites from rhizomes of Alpinia galanga plant. Study involved preparation of Alpinia galanga rhizome methanolic extract, followed by normal phase column chromatography assisted isolation of new phytometabolites (using different combinations of chloroform and methanol), and characterization (by UV, FTIR, 13C-NMR, 1H-NMR, COSY, DEPT and Mass spectrometry). The isolation and characterization experiment offered two phytometabolites: an ester (Ag-1) and tetrahydronapthalene type lactone (Ag-2). Present study concludes and reports the two phytometabolites, benzyl myristate (Ag-1) and 3-Methyl-6α, 8β-diol-7-carboxylic acid tetralin-11, 9β-olide (Ag-2) for the first time in Alpinia galanga rhizome. The study recommends that these phytometabolites Ag-1 and Ag-2 can be utilized as effective analytical biomarkers for identification, purity and quality control of this plant in future.
A series of new derivatives of 4-(2-chloroethyl)morpholine hydrochloride (5) were efficiently synthesized. Briefly, different aromatic organic acids (1a-f) were refluxed to acquire respective esters (2a-f) using conc. H2SO4 as catalyst. The esters were subjected to nucleophillic substitution by monohydrated hydrazine to acquire hydrazides (3a-f). The hydrazides were cyclized with CS2 in the presence of KOH to yield corresponding oxadiazoles (4a-f). Finally, the derivatives, 6a-f, were prepared by reacting oxadiazoles (4a-f) with 5 using NaH as activator. Structures of all the derivatives were elucidated through 1D-NMR EI-MS and IR spectral data. All these molecules were subjected to antibacterial and hemolytic activities and showed good antibacterial and hemolytic potential relative to the reference standards.
The current investigation is based on efficient method development for the quantification of empagliflozin in raw and pharmaceutical dosage forms, as no pharmacopoeial method for the drug is available so far. The developed analytical method was validated as per ICH guidelines. C18 column with mobile phase (pH 4.8) consisted of 0.1% trifluoroacetic acid solution and acetonitrile (70:30 v/v) was used for drug analysis. The calibration plot showed good linear regression (r2>0.999) over the concentration of 0.025-30 μg mL-1. The LOD and LOQ were found to be 0.020 μg mL-1 and 0.061 μg mL-1, respectively. The percentage recovery was estimated between 98.0 to 100.13%. Accuracy and precision data were found to be less than 2%, indicating the suitability of method for routine analysis in pharmaceutical industries. Moreover, the drug solution was found to be stable in refrigerator and ambient room temperature with mean % accuracy of >98%. Empagliflozin contents were also tested in both the raw API and marketed tablet brands using this newly developed method. The mean assay of raw empagliflozin and tablet brands were ranged from 99.29%±1.12 to 100.95%±1.69 and 97.18%±1.59 to 98.92%±1.00 respectively. Based on these findings, the present investigated approach is suitable for quantification of empagliflozin in raw and pharmaceutical dosage forms.
The undertaken research was initiated by transforming 2-(1H-Indol-3-yl)acetic acid (1) in catalytic amount of sulfuric acid and ethanol to ethyl 2-(1H-Indol-3-yl)acetate (2), which was then reacted with hydrazine monohydrate in methanol to form 2-(1H-Indol-3-yl)acetohydrazide (3). Further, The reaction scheme was designed into two pathways where, first pathway involved The reaction of 3 with substituted aromatic aldehydes (4a-o) in methanol with few drops of glacial acetic acid to generate 2-(1H-Indol-3-yl)-N'-[(un)substitutedphenylmethylidene]acetohydrazides (5a-o) and in second pathway 3 was reacted with acyl halides (6a-e) in basic aqueous medium (pH 9-10) to afford 2-(1H-Indol-3-yl)-N'-[(un)substitutedbenzoyl/2-thienylcarbonyl]acetohydrazides (7a-e). All The synthesized derivatives were characterized by IR, EI-MS and 1H-NMR spectral techniques and evaluated for their anti-bacterial potentials against Gram positive and Gram negative bacterial strains and it was found that compounds 7a-d exhibited antibacterial activities very close to standard Ciprofloxacin. The synthesized derivatives demonstrated moderate to weak anti-enzymatic potential against α-Glucosidase and Butyrylcholinesterase (BChE) where, compounds 7c and 5c exhibited comparatively better inhibition against these enzymes respectively. Compounds 7a, 7d and 7e showed excellent anti-enzymatic potentials against Lipoxygenase (LOX) and their IC50 values were much lower than the reference standard Baicalein. Enzyme inhibitory activities were also supported by computational docking results. Compounds 5c, 7a, 7b and 7c also showed low values of % hemolytic activity as well, showing that these molecules were not toxic, indicating that these molecules can be utilized as potential therapeutic agents against inflammatory ailments.
A new naturally occurring dibenzylbutyrolactone lignan named isocubebinic ether has been isolated from Knema patentinervia. The structure was established by spectroscopic methods, which include Ultraviolet, Infrared, Nuclear Magnetic Resonance and Mass Spectrometry. The compound showed activity in the stimulation of glucose uptake by 3T3-L1 adipocytes.
Drug nanosuspensions have gained tremendous attraction as a platform in drug delivery. In the present work, a nanosuspension was prepared by a wet milling approach in order to increase saturation solubility and dissolution of the water insoluble drug, hydrocortisone. Size of the generated particeles was 290 nm ± 9 nm having a zeta potential of -1.9 mV ± 0.6 mV. Nanosized particles were found to have a rod shape with a narrow particle size distribution (PDI =0.17). Results of differential scanning calorimetry and X-ray diffraction analyses revealed minor modifications of crystallinity of hydrocortisone following the milling process. Solubility of hydrocortisone was enhanced by nanonization to 875µg/ml ±2.5, an almost 2.9-fold compared to the raw hydrocortisone. Moreover, the nanosuspension formulation substabtially enhanced the dissolution rate of hydrocortisone where >97% of the hydrocortisone was dissolved within 10 minutes opposed to 22.3% for the raw 50% for the raw hydrocortisone and the commercial tablet, respectively. The bioavailability study resulted in AUC 0-9h for HC nanosuspensions (31.50±2.50), which is significantly (p<0.05) higher compared to the AUC 0-9h (14.85±3.25) resulted for HC solution. The nanosuspension was physically stable at room temperature for 24 months.
Consumption of corn oil for cooking purpose is gaining popularity. The present study examined the effect of heated corn oil on blood pressure and its possible mechanism in experimental rats. Thirty male Sprague-Dawley rats were randomly divided into 5 groups and were fed with the following diets, Group I was fed with basal diet only; whereas group II,III,IV and V were fed with basal diet fortified with 15% (w/w) either fresh, once-heated, five-times-heated or ten-times-heated corn oil, respectively for 16 weeks. Body weight, blood pressure were measured at baseline and weekly interval for 16 weeks. Inflammatory biomarkers which included soluble intracellular adhesion molecules (sICAM), soluble vascular adhesion molecules (sVCAM) and C reactive protein (CRP), were measured at baseline and the end of 16 weeks. The rats were sacrificed and thoracic aorta was taken for measurement of vascular reactivity. There was significant increase in the blood pressure in the groups fed with heated once, five-times (5HCO) and ten-times-heated corn oil (10-HCO) compared to the control. The increase in the blood pressure was associated with an increase in CRP, sICAM and sVCAM, reduction in vasodilatation response to acetylcholine and greater vasoconstriction response to phenylephrine. The results suggest that repeatedly heated corn oil causes elevation in blood pressure, vascular inflammation which impairs vascular reactivity thereby predisposing to hypertension. There is a need to educate people not to consume corn oil in a heated state.
The absence of chromophore and/or conjugated system, prerequisite for UV and florescent light detection, or absorbance at very low wavelength necessitates the development of simple and reliable methods for the determination of amikacin sulphate. Therefore, the present study describes for the first time dynamics of the drug derivatization using ninhydrin reagent and development and validation of a simple RP-HPLC method, using diode array detector (DAD). The variables such as heating time, heating type, drug-reagent ratio, reagent composition and storage temperature of the derivative were optimized. The analyte and aqueous ninhydrin solution upon heating for 2.00-5.00 min produced the colored drug-derivative which was stable for one month at refrigeration. The derivatized drug (20.00μL) was eluted through a column - Eclipse DB-C18 (5.00 µm, 4.60×150.00 mm), maintained at 25°C- using isocratic mobile phase comprising water and acetonitrile (70:30, v/v) at a flow rate of 1.00 mL/min, and detected at 400 nm. The method was found to be reliable (98.08-100.72% recovery), repeatable (98.02-100.72% intraday accuracy) and reproducible (98.47-101.27% inter day accuracy) with relative standard deviation less than 5%. The results of the present study indicate that the method is easy to perform, specific and sensitive, and suitable to be used for the determination of amikacin sulphate in bulk and pharmaceutical preparations using less expensive/laborious derivatization.
Heterocyclic molecules have been frequently investigated to possess various biological activities during the last few decades. The present work elaborates the synthesis and enzymatic inhibition potentials of a series of sulfonamides. A series of 1-arylsulfonyl-4-Phenylpiperazine (3a-n) geared up by the reaction of 1-phenylpiperazine (1) and different (un)substituted alkyl/arylsulfonyl chlorides (2a-n), under defined pH control using water as a reaction medium. The synthesized molecules were characterized by 1H-NMR, 13C-NMR, IR and EI-MS spectral data. The enzyme inhibition study was carried on α-glucosidase, lipoxygenase (LOX), acetyl cholinesterase (AChE) and butyryl cholinesterase (BChE) enzymes supported by docking simulation studies and the IC50 values rendered a few of the synthesized molecules as moderate inhibitors of these enzymes where, the compound 3e exhibited comparatively better potency against α-glucosidase enzyme. The synthesized compounds showed weak or no inhibition against LOX, AChE and BChE enzymes.
Patient adherence with a therapeutic regimen predicts successful treatment and reduces the severity of negative complications. The purpose of this work was to find the relationship between general Health Related Quality of Life (HRQoL) and compliance to the treatment among type 2 diabetes mellitus patients (T2DM) in Sargodha, Pakistan. The research was planned as a cross-sectional survey. T2DM patients attending a tertiary care institute in Sargodha, Pakistan were targeted for the study. The Urdu version of the Morisky Medication Adherence Scale (MMAS-Urdu) and EuroQol Quality of Life Scale were employed to evaluate adherence to treatment regimen and HRQoL correspondingly. Descriptive statistics were used for the elaboration of socio-demographic characteristics. The Spearman rank order test was employed to determine the relationship between medicine adherence and HRQoL. P<0.05 was considered statistically significant. A total of 392 patients were selected for the survey. Most participants were males (n=222, 56.6%) with 5.58±4.09 years of history of T2DM. Majority of respondents (n=137, 34.9%) were categorized in age group of 51 to 60 years with mean age of 50.77±9.671 years. The present study highlighted that individuals with type 2 diabetes mellitus had decreased HRQoL (0.4715±0.3360) and poor medication adherence (4.44±1.8). Significant, yet weak positive correlations were observed between medication adherence and HRQoL (r=0.217 and 0.136 for EQ-5D and EQVAS respectively). Although the association between adherence to therapeutic regimen and HRQoL in the present study cohort was significant, it was rated as weak, hence failed in producing an overall impression on quality of life. The study highlights the need of identifying other individual factors affecting HRQoL among T2DM patients in Pakistan.
Antibacterial effect is one of the major therapeutic activities of plant-derived Curcumin. This work evaluated the effect of serum albumin, human plasma, and whole blood on the in vitro activity of Curcumin against eight clinical bacterial isolates by standard broth microdilution and plate-counting methods. Toxicological effects of Curcumin towards human red blood cells (RBCs) and peripheral blood mononuclear cells (PBMCs) were also investigated. Curcumin exhibited weak activity against gram-negative bacteria, except Escherichia coli and Shigella flexneri were susceptible and was most active against gram-positive bacteria: Staphylococcus aureus, Streptococcus pyogenes and Enterococcus faecalis. The antibacterial activity was impaired in the presence of bovine serum albumin (BSA), human plasma and whole blood. Curcumin was not toxic to PBMCs and RBCs at 200μg/mL. Furthermore, Curcumin showed synergistic activity in combination with antibiotics: Ciprofloxacin, Gentamicin, Vancomycin and Amikacin against Staphylococcus aureus. This study demonstrated that the interaction of Curcumin with plasma proteins diminishes its in vitro antibacterial activity. Curcumin derivatives with reduced affinity for plasma protein may improve the bioavailability and antibacterial activities.
The aim of the study was to successfully design, formulate and evaluate self-nanoemulsifying drug delivery system (SNEDDS) of poorly aqueous soluble drug viz. flurbiprofen using long (LCT), medium (MCT) and short chain triglycerides (SCT). The SNEDDS are thermodynamically stable lipid based drug delivery systems which consist of mixture of oil, surfactant and co-surfactant. Upon aqueous dilution, this mixture produces nano-emulsion spontaneously on slight agitation. The excipients intended to be used were screened for their potential to dissolve the drug and to form clear dispersion upon aqueous dilution. Labrafil M 1944 CS, capryol-90 and triacetin were selected as long, medium and short chain triglycerides, respectively, as lipids while tween-80 and polyethylene glycol-400 (PEG-400)/ethanol (3:1 ratio) were selected as surfactant and co-surfactant, respectively. The excipients were studied at every possible combination ratios using pseudo-ternary diagram. The LCT, MCT and SCT-SNEDDS were optimized using thermodynamic studies, percentage transmittance value, viscosity, refractive index (RI), electrical conductivity, globule size analysis and in-vitro drug release studies. The drug release profiles of optimized SNEDDS were then compared with market product at different pH mediums. The LCT-SNEDDS was considered to be superior for enhancement of the drug bioavailability when compared with other SNEDDS formulations and market product.
This paper aims to observe and analyze effects of Codonopsis pilosula water extract on micro RNA (miRNA) expression profile in liver tissue of senile mice. The 110 Konminmice were randomly divided into five groups, including D-galactose-induced senile model group, normal control group, and low, middle and high dose intervention groups. Continuous modeling lasted 40 days. General symptoms and changes of body mass of the model mice were monitored and observed. The levels of serum glutamic pyruvic transaminase (ALT) and alkaline phosphatase (ALP) of mice were compared, and miRNA of differential expression during aging of D-galactose-induction and high-dose Codonopsis pilosula intervention was analyzed. The serum ALT and ALP levels in the aging model group were significantly higher than those in the normal control group (P<0.05). The serum ALT and ALP levels of Codonopsis pilosula intervention group were lower than those of aging model group, and decrease in ALP value of high dose intervention group was higher (P<0.05). The expression profile of miRNA in the aging model group was significantly different from that in normal control group and high-dose Codonopsis pilosula intervention group, and miRNA expression profile in high-dose Codonopsis pilosula intervention group was clustered with that in the normal control group. The differentially expressed miRNAs of D-galactose-induced senescence and Codonopsis pilosula anti-aging usually belong to 7 miRNA clusters. The target gene function of the differentially expressed miRNAs during senescence process was enriched in 29 signal pathways. There were 67 regulatory signal pathways in differentially expressed miRNA target genes during Codonopsis pilosula intervention. The effect of miRNA targeting may play an important role during D-galactose-induced senescence and Codonopsis pilosula anti-aging period.
Channa striatus (Haruan) is Malaysian freshwater fish that is traditionally used to treat ailments related to wound and also ulcers. The aimed of the present study was to determine the mechanisms of anti-ulcer activity of chloroform: methanol extract of C. striatus fillet (CMCS) in rats. The antiulcer profile of CMCS, given orally in the doses of 50, 250 and 500mg/kg, was assessed using the ethanol- and indomethacin-induced gastric ulcer models. The mechanisms of antiulcer of CMCS were determined as follows; i) the antisecretory activity of CMCS was measured using the pyloric ligation rat model, and; ii) the role of nitric oxide (NO) and sulfhydryl compounds in the modulation of CMCS antiulcer activity were determined by pre-treating the rats with L-NAME or NEM, respectively, followed by the pre-treatment of rats with CMCS before subjecting the animals to the ethanol-induced gastric ulcer model. From the results obtained, CMCS exerted significant (P<0.05) antiulcer activity in both models of gastric ulcer wherein the macroscopic and microscopic analysis of the stomach supported the antiulcer claim. With regard to its antisecretory effect, CMCS did not change the volume and pH, but reduce the total acidity only at the lower doses of the gastric juice. Moreover, CMCS demonstrated antiulcer activity was reversed by NEM, but not affected by L-NAME. In conclusion, CMCS shows antiulcer activity that is modulated via its cytoprotective, but not antisecretory effect, and in the presence of sulfhysryl compounds, but not NO.
This study was conducted to investigate the antifungal potential and cytotoxicity of selected medicinal plants from Malaysia. The extracts from the stem of Cissus quadrangularis and the leaves of Asplenium nidus, Pereskia bleo, Persicaria odorata and Sauropus androgynus were assayed against six fungi using p-iodonitrotetrazolium-based on colorimetric broth microdilution method. All the plant extracts were found to be fungicidal against at least one type of fungus. The strongest fungicidal activity (minimum fungicidal concentration=0.16 mg/mL) were exhibited by the hexane extract of C. quadrangularis, the hexane, chloroform, ethanol and methanol extracts of P. bleo, the hexane and ethyl acetate extracts of P. odorata, and the water extract of A. nidus. In terms of cytotoxicity on the African monkey kidney epithelial (Vero) cells, the chloroform extract of P. odorata produced the lowest 50% cytotoxic concentration (100.3 ± 4.2 μ g/mL). In contrast, none of the water extracts from the studied plants caused significant toxicity on the cells. The water extract of A. nidus warrants further investigation since it showed the strongest fungicidal activity and the highest total activity (179.22 L/g) against Issatchenkia orientalis, and did not cause any toxicity to the Vero cells.
Telfairia occidentalis possesses high antioxidant activity. However, the antioxidant components of the plant have not yet been identified. This study was undertaken to identify the phenolics in the leaf of the plant. Extract and fractions of the leaf of the plant were analysed using the HPLC and GCMS. HPLC analysis revealed the presence of gallic acid (22.19μg/mg), catechin (29.17μg/mg), caffeic acid (9.17μg/mg), ferulic acid (0.94μg/mg), sinapic acid (1.91 μg/mg) and 4-hydroxy benzoic acid (43.86 μg/mg) in the aqueous extract. Phenolics fraction contained gallic acid (0.88 μg/mg), catechin (2.70μg/mg), caffeic acid (7.92μg/mg), ferulic acid (2.72μg/mg), benzoic acid (6.36μg/mg), p-coumaric acid (1.48μg/mg), quercetin (12.00μg/mg). Only caffeic acid (2.50μg/mg), ferulic acid (0.44μg/mg) and quercetin (8.50μg/mg) were detected in the flavonoid fraction. While GCMS analysis showed the presence of methylparaben; ethylparaben; benzoic acid; 4-hydroxy-2-methoxy-3,5,6-trimethyl-, methyl ester; 4-hydroxy-3-methoxy; phenol, 5-methoxy-2-(methoxymethyl)-; phenol, 5-methoxy-2, 3- dimethyl; and phenol, 2-(2-benzothiazolyl)-. This study is the first to reveal the identity of some phenolics components of the leaf of Telfairia occidentalis.
This study aimed to determine the ability of Persea americana (Mill.) or avocado peels ethanolic extract and its fractions to cause bacterial cell leakage in Staphylococcus aureus. The interaction of antibacterial compound with bacterial cells induces several changes leading to the damage of membrane permeability, followed by intracellular bacterial cell leakage. The experiment started with the determination of minimum inhibitory concentration and minimum bactericidal concentration by micro dilution method. Following the determination of MIC and MBC values, the samples, at the concentrations of 1xMIC and 2xMIC, were tested and analyzed by UV-Vis spectrophotometer at 260 and 280 nm to determine the leakage of bacteria cells. The value of K+ ion leakage was determined using atomic absorption spectrophotometry while the value of electrical conductivity was measured by conducto meter to determine the leakage of the cell membrane. The recorded MIC and MBC values of samples were 10% w/v. At the concentrations of 10% and 20% w/v, the samples caused an increase in nucleic acid, protein and DNA levels as well as an increase in extra cellular electrical conductivity. Prolonged exposure of the extract increased the leakage of bacterial cell contents and the electrical conductivity, indicating the damage of bacterial cell membrane.