Kaliappan Ilango

Anticancer activity of Moringa oleifera mediated silver nanoparticles on human cervical carcinoma cells by apoptosis induction

Silver nanomaterial plays a crucial role in the growing field of nanotechnology as there is an increasing commercial demand for silver nanoparticles (AgNPs) owing to their wide biological applications. The present investigation aims at developing anti-cancerous colloidal silver using Moringa olifera stem bark extract. Electron and atomic force microscopic images were taken to analyze the surface morphology of the synthesized AgNPs. The effects of synthesized AgNPs were tested against human cervical carcinoma cells (HeLa) and cell morphology was further evaluated using 4,6-diamidino-2-phenylindole (DAPI) staining. The efficiency of green synthesized AgNPs was studied with the help of fluorescence activated cell sorting (FACS) and was shown to induce apoptosis through reactive oxygen species (ROS) generation in HeLa cells.

Comparative inhibitory potential of selected dietary bioactive polyphenols, phytosterols on CYP3A4 and CYP2D6 with fluorometric high-throughput screening.

Cytochrome P450 (CYP450) inhibition by the bioactive molecules of dietary supplements or herbal products leading to greater potential for toxicity of co-administered drugs. The present study was aimed to compare the inhibitory potential of selected common dietary bioactive molecules (Gallic acid, Ellagic acid, β-Sitosterol, Stigmasterol, Quercetin and Rutin) on CYP3A4 and CYP2D6 to assess safety through its inhibitory potency and to predict interaction potential with co-administered drugs. CYP450-CO complex assay was carried out for all the selected dietary bioactive molecules in isolated rat microsomes. CYP450 concentration of the rat liver microsome was found to be 0.474xa0nmol/mg protein, quercetin in DMSO has shown maximum inhibition on CYP450 (51.02u2009±u20091.24xa0%) but less when compared with positive control (79.02u2009±u20091.61xa0%). In high throughput fluorometric assay, IC50 value of quercetin (49.08u2009±u20091.02–54.36u2009±u20090.85xa0μg/ml) and gallic acid (78.46u2009±u20091.32–83.84u2009±u20091.06xa0μg/ml) was lower than other bioactive compounds on CYP3A4 and CYP2D6 respectively but it was higher than positive controls (06.28u2009±u20091.76–07.74u2009±u20091.32xa0μg/ml). In comparison of in vitro inhibitory potential on CYP3A4 and CYP2D6, consumption of food or herbal or dietary supplements containing quercetin and gallic acid without any limitation should be carefully considered when narrow therapeutic drugs are administered together.

Pulmonary function assessment in mild to moderate persistent asthma patients receiving montelukast, doxofylline, and tiotropium with budesonide: a randomized controlled study.

BACKGROUNDnThere is no comparative study among asthma patients receiving first-line versus various second-line treatment regimens for mild to moderate persistent asthma.nnnOBJECTIVEnWe assessed the pulmonary function in asthma patients receiving montelukast, doxofylline, and tiotropium with budesonide in a pilot group.nnnMETHODSnPatients were recruited as per the study criteria and randomly allocated to 4 groups to receive budesonide (400 µg) with formoterol (12 µg), doxofylline (400 mg), montelukast (10 mg), or tiotropium (18 µg) for a period of 3 months. Outcomes included forced expiratory volume in 1 second (FEV1) and rescue medication use.nnnRESULTSnA total of 167 patients were recruited; among them, 123 patients completed the study. At baseline, no significant difference (P > 0.05) was observed in any of the outcome measures. Significant within-group improvement in FEV1 was observed in all the groups. At day 90, between-group difference revealed that improvement in FEV1 was significantly (P < 0.05) high for budesonide plus formoterol followed by budesonide plus doxofylline, budesonide plus montelukast, and, lastly, budesonide plus tiotropium. Similarly, within-group comparison revealed a significant (P < 0.05) reduction in rescue medication use in all the groups. The intensity in decrease was more in budesonide plus formoterol group followed by budesonide plus doxofylline, budesonide plus montelukast, and budesonide plus tiotropium groups.nnnCONCLUSIONnOn the basis of our findings, among the second-line treatment regimens, budesonide plus doxofylline and budesonide plus montelukast was found to be better than budesonide plus tiotropium in patients with mild to moderate persistent asthma. Further studies with a larger sample size are likely to be useful.

Assessment of montelukast, doxofylline, and tiotropium with budesonide for the treatment of asthma: which is the best among the second-line treatment? A randomized trial.

PURPOSEnData comparing various second-line treatments for asthma with subjective and objective assessment are lacking. This study aimed to compare the efficacy and safety of montelukast, doxofylline, and tiotropium with a low-dose budesonide in patients with mild to moderate persistent asthma.nnnMETHODSnPatients, all of whom were concurrently using inhaled budesonide (400 µg), were treated for 6 months with formoterol (12 µg), montelukast (10 mg), doxofylline (400 mg), or tiotropium (18 µg). Outcomes included forced expiratory volume in 1 second (FEV1), Saint George Respiratory Questionnaire (SGRQ) scores, asthma symptom scores (daytime and nighttime), and assessment of tolerability and rescue medication use.nnnFINDINGSnA total of 297 patients completed the study. In all 4 groups, significant improvements were observed in all the outcome measures, with formoterol treatment having greater and earlier improvements than the other 3 second-line controller medications with budesonide. Among the second-line treatments, monteradlukast improved the FEV1 from day 45 (P < 0.01), SGRQ scores from day 30 (P < 0.0001), daytime scores from day 30 (P < 0.05), nighttime scores from day 30 (P < 0.0001), and rescue medication use from day 15 (P < .0001) at a faster rate than doxofylline or tiotropium with budesonide. No patients discontinued the treatment because of adverse reactions.nnnIMPLICATIONSnAmong the tested second-line treatment regimens, the budesonide/montelukast combination was found to be superior to either the budesonide/doxofylline or budesonide/tiotropium combination in all the outcome measures without adversely affecting the tolerability of the patients. Further clinical studies with blinding techniques are likely to be useful.

Age dependent levels of plasma homocysteine and cognitive performance.

Elevated plasma homocysteine (hcy) levels, also known as hyperhomocysteinemia (hhcy), have been associated with cognitive impairment and neurodegenerative disorders. Hhcy has been attributed to deficiency of B vitamins which can adversely affect the brain and result in memory loss and poor attention power. Monitoring hcy levels and the use of vitamin supplementation to treat hhcy may therefore prove advantageous for the prevention and management of cognitive impairment. With this in consideration, we measured plasma hcy, folate and vitamin B12 levels in 639 subjects from different age groups in two sub-regions of India. Cognitive function was also measured using attention span and immediate and delayed memory recall tests. Depression scores were obtained using the Beck Depression Inventory-II and functional impairment was assessed using the functional activities questionnaire (FAQ) score. As hhcy has also been linked to inflammation, plasma levels of high sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) were also measured. The results demonstrated significant negative correlations between hcy levels and folic acid levels, vitamin B12 levels and cognitive performance (attention span and delayed but not immediate memory recall) along with significant positive correlations between hcy levels and depression scores and hsCRP (but not IL-6) levels. A positive correlation was also observed between hcy levels and FAQ scores, however this was not found to be significant. Based on these results, folic acid and vitamin B12 intervention in people with elevated hcy levels in India could prove to be effective in lowering hcy levels and help maintain or improve cognitive function.

Structural Elucidation of Possible Metabolic Profile of Mangiferin by Oral and Intraperitoneal Administration

Structural Elucidation of Possible Metabolic Profile of Mangiferin by Oral and Intraperitoneal Administration nThe natural bioactive xanthone glycoside compound originated from Mangifera indica was Mangiferin. The metabolic fate of the mangiferin through oral and intraperitoneal route is of great significance for its pharmacological mechanisms and discovering drugs from metabolites. In the present study, a systematic and comparative investigation of the metabolism and pharmacokinetics of mangiferin was studied in Wistar rats through intraperitoneal and oral route of administration by sensitive and specific LC-ESI-MS. The structures of the metabolites were unambiguously identified or tentatively proposed by comparing their fragmentation patterns with that of standards, basis of their precursor ions, product ions, and HPLC retention time. The relative bioavailability of the mangiferin after oral administration at a dose of 30 mg/kg of mangiferin is 1.15%. When mangiferin was administered intraperitoneal route, it shows greater extent of absorption and it undergoes methylation, glycosylation and glucuronidation. The aglycone of the mangiferin, Norathyriol is a major metabolite formed oral and i.p route and it also undergoes methylation and glucuronidation. Therefore to increase the bioavailability of the mangiferin from the different extracts and to enhance its pharmacological activity, effective routes of administration in the effective dosage forms should be adopted.

Quantitative analysis of heavy metals in medicinal plants collected from environmentally diverse locations in India for use in a novel phytopharmaceutical product

It is important to monitor the quality of the phytopharmaceutical product as its therapeutic potential depends on standardized delivery of active ingredients present in the botanical source. Minimal presence of toxic impurities like heavy metals (HMs) is warranted to ensure product safety and prevent hazardous health impacts. In the present study, conducted as part of the development of a novel phytopharmaceutical product, the chemical profile of 13 heavy metals (Fe, Cu, Mn, Zn, Ni, Co, Mo, V, Cr, As, Pb, Hg, and Cd) was studied in the whole plant, fruit, and rhizome of Bacopa monnieri, Hippophae rhamnoides, and Dioscorea bulbifera, respectively, from environmentally diverse regions in India. Most samples had HM profiles within permissible limits as established by regulatory authorities, with the exception of Cd and Hg in low-altitude regions. This study indicates geographical regions in India suitable for procuring raw materials to develop and manufacture phytopharmaceutical products.

Inhibitory Potency of Selected Therapeutic Bioactive Molecules of Standardized Terminalia arjuna (Roxb.) Extract on CYP3A4 and CYP2D6: Exploring Possible Herb-Drug Interactions

A number of significant herbal drug interactions have their origins in the alteration of cytochrome P450 (CYP) activity by various phytochemicals. In the present study, inhibition potential of Terminalia arjuna extracts and its constituent gallic acid (GA) and ellagic acid (EA) to cause herb-drug interactions through rat liver cytochrome enzymes, CYP3A4, and CYP2D6 was evaluated, a rapid RP-HPLC method was developed for quantitative estimation of GA and EA in the extract. In vitro safety of the extract and active components were evaluated through CYP450 inhibition method using pooled rat microsomes and high throughput fluorometric assay with CYP3A4 and CYP2D6. The binding mode and the molecular interaction of GA and EA within the CYP3A4 and CYP2D6 active site were demonstrated using an in-silico docking studies. From CYP450-CO Complex assay, the inhibitory potential of T. arjuna standardized extract (31.02 ± 2.24%), was found to be less than positive control. In high throughput i¬x82uorometric assay, T. arjuna extracts exhibited higher IC50 values (48.06 ± 1.14-57.89 ± 2.15 μg/mL) compared to positive inhibitors and lower than GA (66.54 ± 1.04-83.84 ± 1.06 μg/mL), EA (69.47 ± 1.18-102.69 ± 2.87 μg/mL) on CYP3A4 and CYP2D6. Based on the inhibitory potential of test samples, it can be concluded that T. arjuna and its standardized bioactive molecules could produce weak interaction potential when co-administered with conventional medicines.

Effect of Dioscorea bulbifera and its Major Bioactive Compound, Diosgenin on CYP450 Mediated Drug Metabolism

Cytochrome P450 (CYP450) inhibition by the bioactive molecules of herbs leading to greater potential for toxicity of co-administered drugs. Diosgenin is an important bioactive steroidal sapogenin from Dioscorea bulbifera belonging to the triterpene group and is of great interest to the pharmaceutical industry. The purpose of this study was, to find whether D. bulbifera and Diosgenin influences the effect on rat CYP450 enzymes and its important isoforms (CYP3A4, CYP2D6) by using high through put screening. CYP450-CO Complex assay was performed in rat pooled liver microsomes to calculate percentage inhibition of test samples on CYP450. IC values were determined by fluorometric assays of CYP3A4 and CYP2D6. Mode of inhibition of Diosgenin on these CYPs were further assessed by molecular docking studies with the Glide (Schrodinger Inc. U.S.A.). In CYP450 inhibition assay, the inhibitory potential of herb extract (40.44±1.28 %) was found to be less than positive control (72.08±1.96 %). In fluorometric assay, herb extract exhibited higher IC values (96.21 ± 1.32 to 180.42±0.12u2005µg/ml) when compared to positive inhibitors and lower than Diosgenin (172.54±0.52 to 201.86±1.49u2005µg/ml) on CYP3A4 and CYP2D6. Based on the inhibitory potential, test substances exhibited very less interaction capacity, thereby leading to less significant herb-drug interaction with co-administered drugs.Further clinical studies are required to fully assess the safety of Diosgenin in terms of CYP450.

Evaluation of plant based formulation on adolescent obesity and its associated bio-markers: A randomized, double blind, placebo controlled study

OBJECTIVEnObesity and overweight are the fifth most fatal diseases leading to an increased rate of morbidity and mortality in global population, with its incidence increasing drastically. Taking this into consideration we have conducted the present study in order to explore the efficacy of plant based formulation in the management of adolescent obesity and its associated biomarkers.nnnDESIGNnRandomized, double blind, placebo controlled trial was conducted in 130 obese adolescent of both sexes, with BMI above 25kg/m(2). The subjects were randomly assigned into test formulation group (TFG) and placebo group (PG). TFG received two 500mg capsule containing test formulation whereas, the PG received two 500mg of cellulose powder containing capsule daily for 3 months. The parameters such as blood pressure, inflammatory cytokines, adipokines and lipid profile were assessed in all subjects pre and post treatment.nnnRESULTSnThere was a considerable improvement in the levels of lipid profile, inflammatory cytokines, adipokines and blood pressure after treatment in TFG compared to PG. The statistical difference obtained between the groups after three months of treatment for the various biomarkers are given as mean with 95% CI for BMI (-1.4±0.6 (-2.5 to -0.7)), total cholesterol mg/dl (-20.9±5.0 (-30.8 to -11.0)), triglyceride mg/dl (-12.9±5.7 (-23.9 to -1.2)), HDL-c mg/dl (7.2±0.8 (5.6-8.8)), IL-6 (-0.7±0.1 (-0.9 to -0.6)), hs C-reactive protein (CRP) mg/l(-1.0±0.01 (-1.2 to -0.8)), adiponectin µg/ml(4.9±0.4 (4.2-5.7)), leptin ng/ml (-8.0±1.4 (-10.7 to -5.3)), diastolic blood pressure (DBP) mmHg (-10.4±0.8 (-12.0 to -8.7)) and systolic blood pressure (SBP) mmHg (-6.7±0.7 (-8.1 to -5.3)). Also, there was a statistical significance within group TFG.nnnCONCLUSIONnThe study concludes that the test formulation may prevent the future cardio vascular risk incidence in obese adolescents by reducing inflammation, overweight, lipid profile and by regulating adipokines. Thus it may help to improve the health pattern in obese patients with least side effects.