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.
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.
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.
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.
This study evaluated the impact of pH (7.4 and 6.5), bovine serum albumin (BSA), and human serum albumin (HSA) on Curcumin activity against 2 reference, 1 clinical, and 10 environmental strains of Staphylococcus aureus (S. aureus). Minimal inhibitory concentrations (MICs) of Curcumin against S. aureus were statistically indifferent (p>0.05) at pH7.4 and pH6.5. Activity of Curcumin against S. aureus was reduced by two folds in the presence of 1.25-5% BSA/HSA.
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.
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.
Inhibition of intestinal α-amylase and α-glucosidase is an important strategy to regulate diabetes mellitus (DM). Antioxidants from plants are widely regarded in the prevention of diabetes. Fruits of Elettaria cardamomum (L.) Maton (Zingiberaceae) and Piper cubeba L. f. (Piperaceae) and flowers of Plumeria rubra L. (Apocynaceae) are traditionally used to cure DM in different countries. However, the role of these plants has been grossly under reported and is yet to receive proper scientific evaluation with respect to understand their traditional role in the management of diabetes especially as digestive enzymes inhibitors. Hence, methanol and aqueous extracts of the aforementioned plants were evaluated for their in vitro α-glucosidase and α-amylase inhibition at 1 mg/mL and quantification of their antioxidant properties (DPPH, FRAP tests, total phenolic and total flavonoids contents). In vitro optimization studies for the extracts were also performed to enhance in vitro biological activities. The % inhibition of α-glucosidase by the aqueous extracts of the fruits of E. cardamomum, P. cubeba and flowers of P. rubra were 10.41 (0.03), 95.19 (0.01), and -2.92 (0.03), while the methanol extracts exhibited % inhibition 13.73 (0.02), 92.77 (0.01), and -0.98 (0.01), respectively. The % inhibition of α-amylase by the aqueous extracts were 82.99 (0.01), 64.35 (0.01), and 20.28 (0.02), while the methanol extracts displayed % inhibition 39.93 (0.01), 31.06 (0.02), and 39.40 (0.01), respectively. Aqueous extracts displayed good in vitro antidiabetic and antioxidant activities. Moreover, in vitro optimization experiments helped to increase the α-glucosidase inhibitory activity of E. cardamomum. Our findings further justify the traditional claims of these plants as folk medicines to manage diabetes, however, through digestive enzymes inhibition effect.
180 million people are affected by chronic Hepatitis C Virus infection globally and more than 50 million in South East Asia. Combination of Interferon and Ribavirin is the current anti-HCV therapy in practice and is associated with certain hematologic adverse effects. In this concurrent observational study the incidence rate of major hematologic adverse effects and efficacy outcomes of Interferon and Ribavirin combination therapy was evaluated in 288 chronic hepatitis C patients at Lahore General Hospital. Levels of Hb, TLC, and Platelets counts were monitored for hematologic adverse effects monitoring, whereas, ALT, AST and bilirubin levels were monitored for efficacy. PCR was done at week 4, 12 &36 for therapeutic success evaluation. A significant reduction in Hb levels (p<0.05) was observed after week 4, 8 and 12 of therapy. Frequency of anemia increased in both genders with body weight <65kg and platelet count <150,000/mm(3). End Treatment Response (ETR) was achieved in 64.5%. Anemia was the major side effect of the combination therapy particularly in the males. Higher ETR was observed in patients who achieved RVR and were <50 years of age.
To explore in vitro release rules of isoniazid (INH) when Isoniazid Super paramagnetic Iron Oxide Microspheres (ISPIOM) are subject to no external magnetic field, applied mechanical magnetic field and scillating magnetic field. ISPIOM was prepared by using the spray drying method; Isoniazid contented in the microspheres was determined, the drug loading capacity and encapsulation efficiency were calculated. Release of isoniazid in the microspheres was determined respectively under the effect of no external magnetic field, applied mechanical magnetic field and oscillating magnetic field, to explore the release rules. In solution with pH=7.4 PBS, microspheres featured 8-hour sustained release under the effect of magnetic field, the released rate of the microspheres is accelerated,. In solution with pH=3 PBS, microspheres release faster and could realize the fastest completion of release in 2 hours under the effect of oscillating magnetic field. To join the external magnetic field in different point time to can't affect the release, under pH=3 of medium, ISPIOM release faster; under the effect of magnetic field, the released rate of the microspheres is accelerated, and the longer effect of magnetic field, the faster release. Oscillating magnetic field can make ISPIOM within a certain period of time, get ideal release curve, so as to achieve good control release effect.
To compare the value of light-cured composite resin with that of nano-composite resin in dental caries repair. 88 patients taking dental caries repair in our hospital from May 2014 to April 2015 were selected, and divided into observation group and control group by coin method with 44 patients in each group. Nano-composite resin was used in observation group, while light-cured composite resin in control group. Then, the occurrence rates of odontohyperesthesia, aesthetic satisfaction with dental caries repair and complications were compared between two groups by visual analogue scale (VAS). The occurrence rate of odontohyperesthesia in observation group is significantly lower than that in control group (9.09% (4/44) vs 31.82% (14/44), 6.82% (3/44) vs 22.73% (10/44), 2.27% (1/44) vs 13.64% (6/44)) with difference of statistical significance (P<0.05) 1 week, 4 weeks, and 8 weeks after repair. VAS score of patients in observation is significantly lower than that in control group ((2.78±0.56) scores vs (5.22±0.76) scores, (2.02±0.35) scores vs (4.32±0.57) scores, (1.12±0.14) scores vs (2.41±0.43) scores) 1 week, 4 weeks, and 8 weeks after repair. Moreover, the difference in comparison of interactive effects between two groups, between different time points, and between groups at different time points has statistical significance (P<0.05). Nano-composite resin can lower the occurrence rate of odontohyperesthesia in dental caries repair, reduce the pain of patients, and improve the satisfaction of patients with tooth appearance.
The leaves of Gynotroches axillaris were chemically and biologically studied. Sequential extraction of the leaves using petroleum ether, chloroform, and methanol afforded three extracts. Purification of pet. ether extract yielded, squalene and β-amyrin palmitate as the major compounds, together with palmitic acid and myristic acid as the minor components. The methanol extract yielded two flavonoids, quercitrin and epicatechin. The isolated compounds were characterized by MS, IR and NMR (1D and 2D). Anti-acetyl cholinesterase screening using TLC bio-autography assay showed that palmitic acid and myristic acid were the strongest inhibition with detection limit 1.14 and 1.28 μ/g/ 5 μL respectively. Antibacterial against Gram-positive and negative and antifungal activities exhibited that β-amyrin palmitate was the strongest (450-225 μ/mL) against all the tested microbes. The tyrosinase inhibition assay of extracts and the pure compounds were screened against tyrosinase enzyme. The inhibition percentage (I%) of methanol extract against tyrosinase enzyme was stronger than the other extracts with value 68.4%. Quercitrin (59%) was found to be the highest in the tyrosinase inhibition activity amongst the pure compounds. To the best of our knowledge, this is first report on the phytochemicals, tyrosinase inhibition, anti-acetycholinesterase and antimicrobial activities of the leaves of G. axillaris.
Peptides derived from HIV-1 transmembrane proteins have been extensively studied for antimicrobial activities, and they are known as antimicrobial peptides (AMPs). These AMPs have also been reported to potently combat the drug-resistant microbes. In this study, we demonstrated that peptide #6383 originated from HIV-1 MN strain membrane-spanning domain of gp41 was active (2-log reductions) at 100βg/mL (56.5βM) against methicillin-resistant Staphylococcus aureus (MRSA) in 10% and 50% human plasma-supplemented phosphate buffered saline (PBS). The activity was further enhanced (3-log reductions) in the presence of 5% human serum albumin (HSA) alone. All bactericidal activities were achieved within 6 hours. At 100μg/mL, the peptide showed only 13% toxicity against human erythrocytes. This peptide can serve as an attractive template for a design of a novel peptide antibiotic against drug-resistant bacteria. By sequence-specific engineering or modifications, we anticipated that the bactericidal activity and the reduced toxicity against human erythrocytes will be improved.
New potent organic compounds were synthesized with an aim of good biological activities such as antibacterial and anti-enzymatic. Three series of sulfonamide derivatives were synthesized by treating N-alkyl/aryl substituted amines (2a-f) with 4-chlorobenzensulfonyl chloride (1) to yield N-alkyl/aryl-4-chlorobenzenesulfonamide(3af) that was then derivatized by gearing up with ethyl iodide (4), benzyl chloride (5) and 4-chlorobenzyl chloride (6) using sodium hydride as base to initialize the reaction in a polar aprotic solvent (DMF) to synthesize the derivatives, 7a-f, 8af and 9a-f respectively. Structure elucidation was brought about by IR, 1H-NMR and EIMS spectra for all the synthesized molecules which were evaluated for their antibacterial activities and inhibitory potentials for certain enzymes.