An alkaloid from Maclurodendron porteri has been isolated and characterized. Extraction process was conducted by acid-base extraction method followed by column chromatography. The structure was established by nuclear magnetic resonance spectroscopy and mass spectrometry. The compound was identified as haplophytin B which occurs commonly in the Rutaceae family. However, this is the first time this alkaloid was isolated and reported from the species. The compound showed no inhibition against Staphylococus aureus, Pseudomonas aeruginosa, Bacillus cereus and Escherichia coli and no cytotoxic activity against H199 and A549 cell lines.
Imatinib inhibits Bcr-Abl, c-KIT and PDGFR kinases. It is approved for the treatment of chronic myeloid leukemia (CML), gastrointestinal stromal tumors (GIST) and has further therapeutic potential. Male ICR mice were given imatinib PO (50 or 25 mg/kg, 5 doses every 2 h); euthanized 2 h after the last dose administration; plasma, liver, brain, spleen and kidney were collected and imatinib concentration measured by an optimized HPLC method for quantification in tissues. Methanol (1:1 v/v plasma) and pH 4, 40:30:30 (v/v/v) water-methanol-acetonitrile at 5 ml/g (brain) and 10 ml/g (spleen, kidney, liver) ratio was added to the samples, homogenized, sonicated, centrifuged (15,000 rpm, 5 min, 2 degrees C) and the supernatant injected into an Inertsil CN-3 column (4.6 mm x 150 mm, 5 microm) using 64:35:1 (v/v/v) water-methanol-triethylamine (pH 4.8), flow rate 1 ml/min, 25 degrees C. Imatinib eluted at 7.5 min (268 nm). Linearity: 0.1-50 microg/ml; precision, accuracy, inter- and intra-day variability was within 15%. Recovery was above 95% (plasma), 80% (brain) and 90% (kidney, liver, spleen). Imatinib tissue concentrations were 6-8 folds higher than plasma except brain, where the ratio decreased from 0.24 to 0.08 suggesting limited brain penetration, likely due to blood brain barrier efflux transporters. The extensive distribution supports the expansion of therapeutic applications.
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.
In this phyto-pharmacological screening of Pistia stratiotes L leaf and root extracts each separately in two different solvents demonstrated its potential medicinal value. Apparent antioxidant value is demonstrated by DPPH, Nitric oxide scavenging and Ferric ion reducing method. Additionally, total flavonoid and phenolic compounds were measured. The leaf methanolic extract scavenged both nitric oxide (NO) and DPPH radical with a dose dependent manner. But the pet ether fraction of root was found to have highest efficacy in Fe(3±) reducing power assay. Flavonoid was found to contain highest in the pet ether fraction of root (411.35mg/g) in terms of quercetin equivalent, similarly highest amount (34.96mg/g) of total phenolic compounds (assayed as gallic acid equivalents) were found to contain in the same fraction. The methanolic fractions appeared less cytotoxic compared to pet ether extracts. The plant extracts caused a dose dependent decrease in faecal droppings in both castor oil and magnesium sulphate induced diarrhea, where as leaf extracts in each solvent appeared most effective. Also, the plant extracts showed anthelmintic activity in earthworm by inducing paralysis and death in a dose dependent manner. At highest doses (50 mg/ml) all fractions were almost effective as the positive control piperazine citrate (10 mg/ml). Thus, besides this cytotoxic effect it's traditional claim for therapeutic use can never be overlooked.
The present work investigates the formulation and biopharmaceutical estimation of gastric floating drug delivery system (GFDDS) of propranolol HCl using semi-synthetic polymer carboxymethyl ethyl cellulose (CMEC) and a synthetic polymer polyethylene oxide (PEO). A central composite design was applied for optimization of polymer quantity (CMEC or PEO) and sodium bicarbonate concentration as independent variables. The dependent variables evaluated were: % of drug release at 1 hr (D1hr), % drug release at 3 hr (D3hr) and time taken for 95% of drug release (t95). Numerical optimization and graphical optimization were conducted to optimize the response variables. All observed responses of statistically optimized formulations were in high treaty with predicted values. Accelerated stability studies were conducted on the optimized formulations at 40 ± 2°C/75% ± 5% RH and confirm that formulations were stable. Optimized formulations were evaluated for in vivo buoyancy characterization in human volunteers and were found buoyant in gastric fluid. Gastric residence time was enhanced in the fed but not the fasted state. The optimized formulations and marketed formulation were administered to healthy human volunteers and evaluated for pharmacokinetic parameters. Mean residence time (MRT) was prolonged and AUC levels were increased for both optimized floating tablets when compared with marketed product. High relative bioavailability obtained with optimized gastric floating tablets compared to commercial formulation, indicated the improvement of bioavailability.
The main objective of the present study was to explore the potential of matrix tablets as extended release dosage form of tianeptine, using HMPC K100 as a polymer. HPMC K100 extended the release of the drug from formulation due to the gel-like structure. Direct compression method was adopted to compress the tablets using different concentrations of polymer. Tablets were evaluated for pre-compression and post-compression parameters. Drug release study showed that tablet extends the release of drug with the increasing concentration of polymer. Drug, polymers and tablets were analyzed and/or characterized for compatibility, degradation, thermal stability, amorphous or crystalline nature via FTIR, DSC, TGA, XRD studies. SEM study predicted that tablets had a uniform structure. HPMC K100 based tablets were similar to that of the reference product. Acute toxicity study conducted on Swiss albino mice showed that matrix tablets were safe and non-toxic, as no changes in physical activity and functions of organs were observed. Biochemical and histopathological study revealed lack of any kind of abnormality in liver and renal function. Moreover, necrotic changes were absent at organ level.
The objective of present study was to explore the hepatoprotective and antioxidant profile of Citrullus colocynthis fruits. Hepatoprotective profile of methanolic extract of Citrullus colocynthis fruits (MECCF) was investigated on rats, which were made hepatotoxic using paracetamol. The antioxidant profile of MECCF was evaluated by conducting Catalase, Super oxide Dismutase, Lipid Peroxidation and Diphenyl Picryl Hydrazyl tests. During hepatoprotective investigation, the Paracetamol treated group II showed significant increase in total bilirubin (TB), serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) and alkaline phosphatase (ALP) level. The results so obtained showed that pretreatment of rats with MECCF 300mg/kg p.o. decreases the elevated TB, SGOT, SGPT and ALP serum levels. Also, MECCF inhibitory profile was found comparable with toxicant group (Paracetamol 2g/kg, p.o.). The present study concludes that MECCF fruit possess significant hepatoprotective and antioxidant activity.
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.
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.
Phytochemicals investigation on rhizomes of Alpinia mutica has afforded five compounds namely 5,6-dehydrokawain (1), flavokawin B (2), pinostrobin (3) and pinocembrin (4) together with β-sitosterol (5). All crude extracts of the plant demonstrated strong cytotoxicity against CEMss (human T4 lymphoblastoid) cancer cells with IC50 values less than 19 μg/mL, while flavokawin B (2) was the most cytotoxic isolate with IC50 value 1.86±0.37 μg/mL. Most of the crude extracts and isolated compounds showed weak activity in antimicrobial and diphenylpicrylhydrazyl (DPPH) radical scavenging activity tests.
Parkia speciosa Hassk is a traditional medicinal plant with strong antioxidant and hypoglycemic properties. This study aims to investigate the total phenolic content, antioxidant, cytotoxic and antiangiogenic effect of eight extracts from P. speciosa empty pods. The extracts were found to contain high levels of total phenols and demonstrated strong antioxidant effect in DPPH scavenging test. In rat aortic rings, P. speciosa extracts significantly inhibited the microvessel outgrowth from aortic tissue explants by more than 50%. The antiangiogenic activity was further confirmed by tube formation on matrigel matrix involving human endothelial cells. Cytotoxic effect was evaluated by XTT test on endothelial cells as a model of angiogenesis versus a panel of human cancer and normal cell lines. Basically the extracts did not show acute cytotoxicity. Morphology examination of endothelial cells indicated induction of autophagy characterized by formation of plenty of cytoplasmic vacuoles. The extracts were found to work by decreasing expression of vascular endothelial growth factor in endothelial cells.
Acanthaster planci, the crown-of-thorns starfish, naturally endowed with the numerous toxic spines around the dorsal area of its body. Scientific investigations demonstrated several toxico-pharmacological efficacies of A. planci such as, myonecrotic activity, hemorrhagic activity, hemolytic activity, mouse lethality, phospholipase A2 (PLA2) activity, capillary permeability-increasing activity, edema-forming activity, anticoagulant activity and histamine-releasing activity from mast cells. The present study was performed to evaluate the cytotoxic activity of A. planci extracts obtained by different methods of extraction on MCF-7 and HCT-116, human breast and colon cancer cell lines, respectively. Results of the cell proliferation assay showed that PBS extract exhibited very potent cytotoxic activity against both MCF-7 and HCT-116 cell lines with IC(50) of 13.48 μg/mL and 28.78 μg/mL, respectively, while the extracts prepared by Bligh and Dyer method showed moderate cytotoxicity effect against MCF-7 and HCT-116 cell lines, for chloroform extract, IC(50) = 121.37 μg/mL (MCF-7) and 77.65 μg/mL (HCT-116), and for methanol extract, IC(50) = 46.11 μg/mL (MCF-7) and 59.29 μg/mL (HCT-116). However, the extracts prepared by sequential extraction procedure from dried starfish found to be ineffective. This study paves the way for further investigation on the peptide composition in the PBS extract of the starfish to discover potential chemotherapeutic agents.
Tack is a concept that is widely used to describe the forces or energies involved in the separation of two parallel surfaces initially in contact through an intervening thin liquid film. The tackiness may cause tablets to stick with each other or to the walls of the coating apparatus. In this study, the HPMC coating solutions were evaluated for their tackiness and the effects of interactions between the polymer and plasticizers on the tack behavior of HPMC film-forming coating solutions were investigated, using type TA-XT2 texture analyzer. It was found that experimental factors such as the contact time, rate of separation and volume of the film-forming test solution could effectively influence the magnitude of tack behavior. Moreover, up to certain levels, the addition of plasticizers such as PEG 400 & 1000 and of triacetin caused a reduction in the tack value of the polymer solutions. It was concluded that in general, the tackiness depended upon the molecular weight and/or type and concentration of a plasticizer. The efficiency of plasticizers used to reduce the tackiness of HPMC solutions ranked as PEG1000 > triacetin > PEG400.
Out-of-pocket (OOP) payments may burden Methadone Maintenance Clinic patients. Since treatment is fully subsidized by the government, financial constraint might lead to patients being made to pay or be given incentive for inconvenience of therapy. This study thus evaluates the characteristic and commitment of methadone therapy patient's in terms of OOP cost, Willingness-To-Pay (WTP) and Willingness-To-Accept (WTA) concept. This survey utilizes the questionnaire by Boris ova & Goodman (2003) on the OOP, WTP and WTA. The forty adult patient's selected medical records from year 2009-2011 were from an urban government methadone clinic. Subject's selection was by convenient sampling based on the predetermined criteria. Most were male (95%) and Malay (60%) was the predominant group. Patients were group into three income groups; ≤ RM1000, ≥ RM1000 -≤ RM2000 and ≥ RM3000. The average OOP cost per month was RM391.30 (s.d RM337.50), which is about 35% of employed patient's monthly income. The wide variation could be attributed by high inter-individual and significant differences between patients in terms of transport, times taken to clinic, cost per trip and weekly household income (p=<0.05). Patients with income of less than RM1000 showed the highest tendency to pay for treatment, asked for the least money for inconvenience and many are unwilling to accept any payments. These findings showed that WTP and WTA is less of a concern for patients in the low-income group. To conclude, OOP payment is not a treatment barrier for most of the urban MMT patients.
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.
Indiscriminate application of organophosphate (OP) pesticides has led to environmental pollution and severe health problems. The aim of the present study was to evaluate the effect of palm oil tocotrienol-rich fraction (TRF) on biochemical and morphological changes of the liver in rats treated with fenitrothion (FNT), a type of OP pesticide. A total of 28 male Sprague-Dawley rats were divided into four groups; control group, TRF-supplemented group, FNT-treated group and TRF+FNT group. TRF (200 mg/kg) was supplemented 30 minutes prior to FNT (20 mg/kg) administration, both orally for 28 consecutive days. Following 28 days of treatment, plasma biochemical changes and liver morphology were evaluated. The body and absolute liver weights were significantly elevated in TRF+FNT group compared to FNT group. TRF administration significantly decreased the total protein level and restored the activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in TRF + FNT group. In contrast, total bilirubin level, γ-glutamyltranferase (GGT) and cholinesterase activity in TRF + FNT group did not significantly differ from FNT group. Administration of TRF also prevented FNT-induced morphological changes of liver as observed by electron microscope. In conclusion, TRF supplementation showed potential protective effect towards biochemical and ultrastructural changes in liver induced by FNT.
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.
Anticoagulant responses to warfarin vary among patients, based on genetic factors, diet, concomitant medications, and disease state. We evaluated the effectiveness and safety of a 10mg warfarin initiation nomogram in an Asian population. Retrospective cross-sectional audit studies were conducted from March 2009 to March 2010. The use of a 10mg-loading dose to initiate warfarin treatment resulted in 33(84.6%) patients attaining a therapeutic INR within four days (mean time, 2.6 days). There was no significant correlation between age, gender, race, and serum albumin for the time to reach a therapeutic INR. A significant correlation was noted for patient's baseline INR and time to reach a therapeutic INR (P<0.05). No significant differences were observed in time to reach a therapeutic INR in patients treated with specific class of concomitant drugs or patients with specific disease states. The overall incidence of over-anticoagulation was 35.9%; however, no bleeding episodes were encountered. In conclusion, the use of a 10mg warfarin nomogram was effective in rapidly achieving a therapeutic INR. However, the nomogram's safety is debatable owing to the high over-anticoagulation rate warfarin-administered patients. Caution is recommended in the initiation of warfarin treatment using the 10mg nomogram.
To investigate the physiological indices such as body weight, food and fluid drinking concern to antidiabetic properties of syringin and its useful outcome on hematological parameters in streptozotocin stimulated diabetic rats. Six normal and 18 diabetic rats totally 24 rats have been used for the present investigation. Streptozotocin was injected in male Wistar rats to induce diabetes through intraperitoneal route. After the confirmation of diabetes, the test animals were treated with distilled water through oral route or syringin 5 mg/kg body weight/ rat /day for 10 days. The diabetic treated groups compared with the controls were evaluated based on their hematological parameters such as red blood cells, white blood cells and its functional indices. The blood glucose levels significantly decreased in syringin injected rats. The intake of water and feed in diabetic rats were significantly decreased, whereas after syringin administration the weight loss was minimized. Congruently, the level of red blood cells, white blood cells and their functional key characters were also considerably enhanced. It can be conjectured that syringin has antihyperglycemic properties. In addition, it can positively amend some hematological parameters.
Orally disintegrating tablet (ODT) is a friendly dosage form that requires no access to water and serves as a solution to non-compliance. There are many co-processed adjuvants available in the market. However, there is no single product possesses all the ideal characteristics such as good compressibility, fast disintegration and good palatability for ODT application. The aim of this research was to produce a xylitol-starch base co-processed adjuvant which is suitable for ODT application. Two processing methods namely wet granulation and freeze drying were used to compare the characteristics of co-processed adjuvant comprising of xylitol, starch and crospovidone XL-10 mixed at various ratios. The co-processed excipients were compressed into ODT and physically characterized for powder flow, particle size, hardness, thickness, weight, friability, in-vitro disintegration time and in-situ disintegration time, lubricant sensitivity, dilution potential, Fourier transform infrared spectroscopy, scanning electronic microscopy and x-ray diffraction analysis. Formulation F6 was selected as the optimum formulation due to the fastest in-vitro (135.33±11.52 s) and in-situ disintegration time (88.67±13.56s) among all the formulations (p<0.05). Increase in starch component decreases disintegration time of ODT. The powder flow fell under the category of fair flow. Generally, it was observed that freeze drying method produced smaller particle size granules compared to wet granulation method. ODT produced from freeze drying method had shorter disintegration time compared to ODT from wet granulation batch. In conclusion, a novel co-processed excipient comprised of xylitol, starch and crospovidone XL-10, produced using freeze drying method with fast disintegration time, good compressibility and palatability was developed and characterized. The co-processed excipient is suitable for ODT application.