There has been a number of studies looking into an alternative mode of therapy for the treament of breast cancer via 4-hydroxytamoxifen (4-OHT) transdermal administration.This systematic review aims to compare the safety and efficacy of a transdermal 4-OHT local therapy and oral tamoxifen (oral-T) on the treatment of ductal carcinoma in situ breast cancer. Through a systematic search of health science databases, eligible trials were located and the end points assessed were Ki-67 labeling index, concentration of 4-OHT in breast adipose tissue (ng/g) and plasma (ng/ml). Revman 5.3 version was used to perfom the meta-analysis. Three trials were identified (n=103), while only two were included for meta analysis. The mean difference between the two studies included were 0.40 and -10.58. Overall the I2 value was 89.0%, (Tau2 =53.86) and the differences between the two trials were statistically significant p=0.002. The meta analysis of the randomized controlled trials showed that the use of local transdermal therapy of 4-OHT gel is more safer than oral-T. However, due to the limited number of studies, the potential use of 4-OHT topical transdermal therapy for the treatment of breast cancer could not be concluded for healthcare professionals.
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.
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.
Brewers' rice is one of abundant agricultural waste products in the rice industry. The present study is designed to investigate the potential of brewers' rice to inhibit the development of aberrant crypt foci (ACF) in colon of azoxymethane (AOM)-treated rats. The effects on the attenuation of hepatic toxicity and kidney function enzymes were also evaluated. Male Sprague-Dawley rats were randomly divided into five groups: (G1) normal; (G2) AOM alone; and (G3), (G4), and (G5), which were AOM fed with 10%, 20%, and 40% (w/w) of brewers' rice, respectively. The rats in group 2-5 were injected intraperitoneally with AOM (15 mg/kg body weight) once weekly for two weeks. After 8 weeks of treatment,the total number of ACF/colon and the number of ACF in the distal and middle colon were significantly reduced in all treatment groups compared to G2 (p<0.05). Brewers' rice decreased the number of ACF with dysplastic morphology in a dose-dependent manner. Alkaline phosphatase (ALP) level in G5 was significantly lower compared to the G2 (p<0.05). In conclusion, this study found the potential value of brewers' rice in reducing the risk of cancer susceptibility in colon.
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.
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.
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 study evaluated the synergistic antibacterial activity of Curcumin with 8 different antibiotic groups. Two reference, one clinical and ten environmental strains of Staphylococcus aureus (S. aureus) were tested. Disc diffusion assay with 25 μg/mL Curcumin demonstrated synergism in combination with a majority of tested antibiotics against S. aureus. However, checkerboard micro dilution assay only showed synergism, fractional inhibitory concentration index (FICI) <0.5 in three antibiotics i.e. Gentamicin, Amikacin, and Ciprofloxacin. Other antibiotics showed indifferent interactions but no antagonism was observed. In time-kill curve, appreciable reduction of bacterial cells was also observed in combination therapy (Curcumin + antibiotics) compared to monotherapy (Curcumin or antibiotic(s) alone). The antibiotics with higher synergistic interaction with Curcumin are arranged in a decreasing order: Amikacin > Gentamicin > Ciprofloxacin.
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.
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.
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.
Elaeocarpus floribundus is higher plant that has been used as traditional medicine for treating several diseases. There is no previous report on phytochemicals and bioactivity studies of this species. In this investigation, triterpenoids friedelin, epifriedelanol and β-sitosterol were isolated from its leaves and stem bark. Determination of total phenolic content of methanolic extract of leaves and stem bark was carried out using Folin-Ciocalteu reagent. All extracts and isolated compounds were subjected to screening of antioxidant activity using DPPH free radical scavenging method and cytotoxic activities by MTT assay towards human T4 lymphoblastoid (CEM-SS) and human cervical (HeLa) cancer cells. In the total phenolic content determination, methanolic extract of leaves gave higher value of 503.08±16.71 mg GAE/g DW than stem bark with value of 161.5±24.81 mg GAE/g DW. Polar extracts of leaves and stem bark possessed promising antioxidant activity with methanol extract of stem bark exhibited strongest activity with IC50 value of 7.36±0.01 μg/ml. In the cytotoxic activity assay, only chloroform extract of leaves showed significant activity with IC50 value of 25.6±0.06 μg/ml against CEM-SS cancer cell, while friedelin and epifriedelanol were found to be active against the two cancer cells with IC50 values ranging from 3.54 to 11.45 μg/ml.
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.
Microwave and conventional techniques were employed to synthesize a novel array of compounds 7a-g with 1,2,4-triazole and piperidine rings having great biological importance. The microwave assisted method has a better operational scope with respect to time and yield comparative to the conventional method. 1H-NMR, 13C-NMR and IR techniques were employed to justify the structure of synthesized compounds. The antioxidant, butyrylcholinesterase inhibition and urease inhibition potential of every synthesized compound was evaluated. Every member of the synthesized series was found potent against mentioned activities. Compound 7g was the most active anti-urease agent having IC50 (μM) value 16.5±0.09 even better than the thiourea with an IC50(μM) value of 24.3±0.24. The better urease inhibition potential of 7g was also elaborated and explained by docking and bovine serum albumin (BSA) binding studies.
N-(Substituted)-5-(1-(4-methoxyphenylsulfonyl)piperidin-4-yl)-4H-1,2,4-triazol-3-ylthio) acetamide were synthesized by following conventional as well as microwave assisted protocol through five consecutive steps under the impact of various reaction conditions to control the reaction time and the yield of product. Starting from 4-methoxybenzenesulfonyl chloride and ethyl isonipecotate, product 3 was obtained which was converted into product 4 by treating with hydrazine hydrate. In step 3, the product 4 was refluxed with methyl isothiocyanate and KOH to yield compound 5 which was finally treated with variety of N-substituted acetamides to yield an array of different new compounds (8a-k). These synthesized compounds were evaluated for their inhibition potential against bovine carbonic anhydrase (bCA-II), acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. Compound 8g demonstrated good activity against bCA-II, AChE and BChE with IC50 values of 8.69 ± 0.38 μM, 11.87±0.19 μM and 26.01±0.55 μM respectively. SAR studies assisted with molecular docking were carried out to explore the mode of binding of the compounds against the studied enzymes.
The drug resistance phenomenon in microbes is resulting in the ineffectiveness of available drugs to treat the infections. Thus, there is a continued need to discover new molecules to combat the drug resistance phenomenon. Norfloxacin is a fluoroquinolone antibiotic that is used for the treatment of urinary tract infections. In this research work, norfloxacin is structurally modified by hybridizing with a range of substituted acetohydrazidic moieties through a multistep reaction. The first step involves the coupling of norfloxacin 1 with methyl chloroacetate followed by the treatment with hydrazine hydrate to result in corresponding acetohydrazide 3. A range of substituted benzaldehydes were reacted with the acetohydrazide to form the targeted series of norfloxacin derivatives 4a-i. The final compounds were screened for antimicrobial activity. Among the tested compounds, 4c, 4d, 4e and 4f displayed better antifungal activity against F.avenaceum, while compound 4c and 4e were active against F. bubigeum.
α-Glucosidase inhibitors occupy a prominent position among the various treatments of type-2 diabetes mellitus (DM2). In this study, a series of new norfloxacin-acetanilide hybrid molecules were synthesized and screened for α-glucosidase inhibition activity. The synthetic methodology involves the synthesis of a series of α-bromoacetanilides by condensing bromoacetyl bromide with various substituted anilines. These α-bromoacetanilides were coupled with norfloxacin in DMF to get the titled hybrids. The structure elucidation of synthesized compounds were characterized by 1H NMR, 13C NMR and LC-MS. Finally, the compounds were screened for their α-glucosidase inhibition activity using acarbose as a reference drug (IC50 =58 μM). Among the tested compounds, 3i and 3j displayed potent α-glucosidase inhibition activity with IC50 values of 7.81±0.038 and 5.55±0.012 μM respectively. In-addition, 3m, 3f and 3k were demonstrated moderate alpha-glucosidase inhibition activities with IC50 values of 52.905±0.041, 23.79± 0.087 and 23.06±0.026 μM respectively. The structure-activity relationship was established with the help of molecular docking by using Molecular Operating Environment software (MOE 2014).
Melastoma malabathricum L. Smith (Melastomaceae) has been used in the Malay traditional culture to treat ulcer-based ailments.The objective of the present study was to investigate the potential anti-ulcer effect of aqueous extract of M. malabathricum leaves (AEMM) using ethanol- and indomethacin-induced gastric ulcer models in rats. Rats were divided into ten groups (n=6) and received DMSO (10%; negative group), ranitidine (100mg/kg; positive group) or AEMM (50, 250 and 500mg/kg) orally for 7 days and on the 8(th) day subjected to the respective gastric ulcer models. The stomachs were collected and subjected to macroscopic and microscopic analysis. At all groups tested, the AEMM exerted significant (p<0.05) anti-ulcer effect only against the ethanol-induced gastric ulcer model. The percentage of anti-ulcer for the 50-500mg/kg AEMM ranging between 50-82%, respectively. The macroscopic observations were supported by histological findings. In conclusion, AEMM exhibits potential anti-ulcer activity attributed to its previously proven high flavonoids content and antioxidant activity.
Heavy metals in cigarette tobacco such as iron may cause a serious damage on human health. Surveys showed that the accumulation of certain toxic heavy metals like cadmium, mercury, iron is very often due to the effect of smoking. This work involved 15 volunteers in two randomly divided groups having the habit of cigarette smoking over 15 cigarettes / day. Concentration level of iron in blood and urine before and after treatment using the herbal medicine, widely used in Europe, is analyzed. Determination of Iron concentration in blood and urine was calculated by Inductively Coupled Plasma-Atomic Emission Spectrometry (ICP-AES) according to the procedure DIN EN ISO 11885 ("E22" from April 1998). The analysis shows that the concentration of iron in blood and urine samples in both groups increased in some volunteers instead of decrease. The independent T-test shows that the mean of iron concentration in the group A and group B had no significant difference (p>0.05). The results suggested that the herbal medicine under test does not have significant influence on reduction of iron concentration levels.
Hypertension is one of the major causes of morbidity and mortality. Worldwide, Hypertension is estimated to cause 7.5 million deaths, about 12.8% of the total of all deaths. This accounts for 57 million disability adjusted life years (DALYS) or 3.7% of total DALYS. This led WHO to set a target of 25% reduction in prevalence by 2025. To reach that, WHO has adopted non-conventional methods for the management of hypertension? Despite worldwide popularity of such non-conventional therapies, only small volume of evidence exists that supports its effectiveness. This review attempted to make a critical appraisal of the evidence, with the aim to (1) describe the therapeutic modalities frequently used, and (2) review the current level of evidence attributable to each modality. Databases from Cochrane Library, MEDLINE, PUBMED, and EMBASE were searched from 2005-2015. A total of 23 publications have been identified and selected. Out of these, 15 systematic reviews and/or meta-analysis of RCTs, 5 RCTs, 1 non-RCT, and 2 observational studies without control. Among those 23 publications, therapeutic modalities identified are: fish oil, qigong, yoga, coenzyme Q10, melatonin, meditation, vitamin D, vitamin C, monounsaturated fatty acids, dietary amino-acids, chiropractic, osteopathy, folate, inorganic nitrate, beetroot juice, beetroot bread, magnesium, and L-arginine. The followings were found to have weak or no evidence: fish oil, yoga, vitamin D, monounsaturated fatty acid, dietary amino-acids, and osteopathy. Those found to have significant reduction in blood pressure are: magnesium, qigong, melatonin, meditation, vitamin C, chiropractic, folate, inorganic nitrate, beetroot juice and L-arginine. Coenzyme Q10on the other hand, showed contradicting results were some studies found weak or no effect on blood pressure while others showed significant blood pressure reduction effect. By virtue of the research designs and methodologies, the evidence contributed from these studies is at level 1. Results from this review suggest that certain non-conventional therapies may be effective in treating hypertension and improving cardiac function and therefore considered as part of an evidence-based approach.