Antihyperglycemic, Antioxidant and Hepatoprotective Properties of Smilax wightii A.DC. : an Endemic Plant of Western Ghats

Phytotherapy is an inevitable companion of human civilization. Smilax wightii is an ethnomedicinal plant in Smilacaceae, with unexplored scientifically therapeutic potential. The antihyperglycemic, antioxidant and hepatoprotective capabilities of the methanolic extract of leaf, stem, rhizome and root of S. wightii were inspected in the present study. Hyperglycemia is a manifestation of the prevalent metabolic disorder, Type 2 Diabetes mellitus. Inhibitors of α –glucosidase and α – amylase could be efficiently employed in diabetes mellitus therapy as hypoglycemic agents. In the α –glucosidase and α – amylase inhibitory assays, root and rhizome extracts recorded better antihyperglycemic activity. DPPH radical scavenging activity and total antioxidant capacity were the parameters employed to determine the antioxidant activity. Hepatoprotectivity determines the capability of samples to safeguard the hepatocytes from damage. Novel hepatoprotective agents are in demand since the incidence of liver impairment is on a high among global population. The rhizome extract showed comparatively superior hepatoprotectivity followed by the leaf, stem and root extracts. Rhizome, at 100μg/ml guaranteed a cell viability percentage of 77.43 in the Chang liver cell line treated with Carbon tetrachloride. So the root and rhizome of S. wightii are the therapeutically significant plant parts with hypoglycemic, free radical scavenging and hepatoprotective potentialities.

Production of value added Oyster mushrooms

Mushrooms are ironic in nutrimental resources and have converted into one of the common foods in the previous twenty years globally. The types of edible mushrooms are button, milky and oyster mushrooms. The research aimed at value addition of Oyster mushrooms by rising on paddy substrate complemented with two concentrations of four different medicinal plants. The plant parts selected were flowers of Butea monosperma, leaves of Moringa olifera, bark of Cinnamonom zeylianicum, fruits of Corindraum sativum at 5% and 10% concentration. Different species of oyster mushrooms are available. In the present study Pleurotus florida was selected for value addition. Maximum mycelium running rate was detected in Cinnamon bark (5%) and paddy straw (95%) accompanied group and lowermost running rate of mycelium was observed in Moringa leaf (5%) and paddy straw (95%). The primordial arrival was fast with Cinnamon bark (5%) supplemented group and slowest in Moringa leaf (5%) supplemented group. The mushrooms grownup on Coriander fruit (5%) produced more but the growth was slow. Mushrooms supplemented with Butea flower (5%) exhibited slow growth and yield was next to coriander fruit supplemented mushrooms. The produced mushrooms were subjected to physical evaluation, preliminary phytochemical testing and also tested for estimation of total flavonoids, total phenols, total tannins and total cinnamaldehyde contents. Value addition of Oyster mushrooms was successful with cinnamon bark as cinnamaldehyde was noticed in the Cinnamon bark supplemented group, and also with Moringa leaves as flavonoids was observed in more concentration in Moringa leaf supplemented mushroom group.

Selection the Drug Efficacy of Oroidin Derivatives as Hsp90 Inhibitors by Computer Aided Drug Design Method

Heat shock protein 90 (Hsp90) is a conserved molecular chaperone associated with regulation of hundreds of client proteins that are key drivers, regulators and promoters of numerous refractory diseases including cancer. Consequently, Hsp90 is a significant target for the development of harmless anticancer therapies. Marine organisms are the rich source of pharmacological important compounds, especially oroidin. Oroidin, a pyrrole-2-aminoimidazole alkaloid, isolated from the marine sponge Agelas oroides, binds ATP pocket of Hsp90 and suppresses the ATPase activity of the protein. Natural product oroidin was selected as potent inhibitor of Hsp90 and its drug candidature was accordingly improved by substituting various functional groups. Virtual screenings were done through in silico studies, carried out on thirty nine derivatives of oroidin. DFT study was performed with Gaussian16, UB3LYP/6-311G++ (d, p) basis set to investigate the quantum mechanical parameters such as HOMO-LUMO energies, dipole moments. Derived parameters like ionization potential, electron affinity, softness-hardness, chemical potential and electrophilicity index were also calculated. Using AutoDock 4.0 programme, we studied docking of the thirty-nine designed derivatives with macromolecule Hsp90 and recorded the binding energy values of the best conformation out of nine in each docked compound. ADME predictions, molecular descriptor properties, and theoretical toxicity tests were evaluated using preADMET, molinspiration, and OSIRIS property explorer web tools respectively. We found twenty eight derived compounds, each docked at the same region of Hsp90, possessing higher binding energies compare to the precursor oroidin. Seven of them qualified all the rules of drug candidature and could be safe in using as effective drugs for cancer treatment. This study suggests that these compounds could be synthesized for in vitro test and may leads to a novel anticancer therapeutics.

Formulation and Evaluation of Gliclazide Solid Dispersions Incorporated Tablets for Controlled Drug Release

The current study deals with formulation and evaluation of gliclazide solid dispersion with HP β Cyclodextrin to enhance solubility and incorporate into tablet formulation for controlled release of gliclazide. Gliclazide solid dispersion (SD) prepared using varying ratios of HP β Cyclodextrin and evaluated. The optimized SD formulation incorporated into tablet by using hydroxypropyl cellulose, HPMC K 100M. The drug dissolution from tablet formulation analyzed and characterize. The formulation SD3 comprising of drug and polymer in 1:3 ratio displayed 43-fold increase in solubility when compared to pure drug. The formulation SD13 displayed maximum yield of 98.96% and maximum drug content of 99% chosen optimal for tablet formulation. FTIR studies revealed that there is no incompatibility between drug and polymers found. XRD studies revealed that the optimized solid dispersion formulation was found to be in amorphous state. Around 15 formulations of controlled release tablet blends evaluated for micrometric properties show that all the formulations posses’ good flow properties. Formulation F15 with maximum drug content of 99.99% and drug release of 99.96 % over 16h was chosen optimal and characterized. The release kinetics suggest that drug release followed zero order and release from tablets was anomalous non- fickian diffusion super case II transport. The results show that combination of solid dispersion and application of hydrophilic and hydrophobic polymers in matrix formation can facilitate better dissolution and absorption profile with greater patient compliance.

Development and Validation of Stability Indicating RP-HPLC Method for the Simultaneous Estimation of Dapagliflozin Propanediol and Metformin Hydrochloride in Tablet Dosage Form

A rapid, precise, accurate, specific and simple stability indicating RP-HPLC method was developed for simultaneous estimation of Dapagliflozin Propanediol (DAPA) and Metformin Hydrochloride (MET) in its tablet dosage form. Method was performed on a column C8 Thermoquest, hypersil division of dimension 250 mm × 4.60 mm having particle size 5 micron. The mobile phase used in the method was 10 mM Ammonium Acetate buffer (pH- 4), Methanol and Acetonitrile in proportion of 30:65:05 respectively. The drug was subjected to acid and alkali hydrolysis, oxidation, photolysis and heat as stress conditions. The method was validated for specificity, linearity, range, precision, accuracy, robustness, LOD, LOQ and system suitability. The flow rate was maintained at 0.8 ml/ min and effluent was monitored at 227 nm. The retention time were observed 5.988 min and 4.661 min for DAPA and MET respectively. The standard curve was found linear over range of 60-140 μg/ml for DAPA and 300-700 μg/ml for MET with correlation coefficient of 0.9996 for DAPA and 0.9994 for MET. The limit of Detection (LOD) of this method was 1.121 μg/ml for DAPA and 6.162 μg/ml for MET. The limit of Quantitation (LOQ) of this method was 3.396 μg/ml for DAPA and 18.674 μg/ml for MET. The percentage recovery was found to be in the range of 98-102% at three different levels of a standard addition. The precision (repeatability, intra-day and inter-day) of the method was within the limit (RSD<2%). Degradation products produced because of stress studies did not interfere with the detection of DAPA and MET and the assay can thus be considered stability-indicating. Combination tablet was successfully analysed using the developed method.

Synthesis and Oral Hypoglycemic Activity of Some New Sulphonyl Linkage Thiazolidine-2,4-diones

Type 2 diabetes mellitus and its complications, decreases the quality of life in diabetic patients. Thiazolidine-2,4-diones are found to be better insulin sensitizing agents, acting on peroxisome proliferator activated receptor-γ (PPAR-γ) and decrease blood glucose level in diabetic patient. Therefore, in the present work, we synthesized 5-[4-(substituted) sulphonylbenzylidene]thiazolidine-2,4-diones and evaluated for their oral hypoglycemic activity. The synthesized compounds were further studied for their find out interactions with 2PRG protein with the help of docking score and also find out their predicated ED25 values. The results of synthesized compounds were showed significant decrease in blood glucose level as compared to positive control group. All synthesized compounds have shown good hydrogen bond interactions with 2PRG protein, docking score and predicted ED25 value as compared with reference drug, pioglitazone and rosiglitazone, respectively. Thus, sulphonyl linked thiazolidine-2,4-diones may be used as promising oral hypoglycemic agent.

Determination of Spray Pattern and Plume Geometry of Combined Budesonide and Formoterol Fumarate pressurized Metered Dose Inhalation Aerosol

Budesonide and formoterol fumarate pressurized metered-dose inhaler (pMDI) is combined aerosol dosage form. The label claim of this combined dosage form is 100 mcg of Budesonide and 6 mcg of Formoterol Fumarate per actuation. It is prescribed for the treatment of asthma and chronic obstructive pulmonary disease (COPD). Formoterol fumarate is an anti-asthmatic drug (Bronchodilator), and Budesonide is Anti Inflammatory drug (Glucocortico steroid).The objective of plume geometry and spray pattern study is to monitor the consistency and quality of a device when actuated. The plume and pattern study aims to develop a formulation with robust device which can deliver an accurate amount of drug directly to the lungs of a patient. The chemistry manufacturing and controls (CMC) guideline outlined the basic data required for spray pattern and plume geometry measurement for different pMDI devices. In 2013, draft guidance on bioavailability and bioequivalence (BABE) of pMDI published, which provides details on plume geometry and spray pattern, image collection and evaluation.In the present study, the spray patterns were collected at 2 distances 3 and 6 cm from the actuator device's exit. The spray pattern Ovality results at 3 cm show 2.52% variation and at 6 cm results show 4.31% variation. Method precision, ruggedness and robustness study for Spray pattern also performed at 6 cm distance from actuator orifice. The plume geometry was collected at 6 cm distance from the exit of an actuator device. Plume geometry results show that Plume height is found in the range 16.20 cm to 18.98 cm, Plume angle is found from 17.7–24.9°, and Plume width is found between 3.68 to 4.57 cm.

Formulation and Evaluation of Flurbiprofen Solid Dispersions Incorporated Buccal Patches

Flurbiprofen is an anti-inflammatory drug used in treating rheumatoid arthritis and ankylosing spondylitis. The present work is aimed at overcoming the deprived solubility of flurbiprofen by solid dispersion (SD) technique. The current paper is the continuance of the published solid dispersion by considering the best final optimized formulation containing flurbiprofen drug: AQOAT AS: SLS as drug: polymer: surfactant in 1:5:2 ratios, and incorporating it into buccal patches to overcome the gastric side effect and attaining sustained drug release. In this study 15 buccal patches were formulated by adopting solvent casting technique using polymers like polyvinyl hydroxyethylcellulose (HEC), hydroxypropryl methyl cellulose E15 (HPMC E15), polyvinyl pyrrolidone (PVP), carbopol and analyzed for the drug content, drug diffusion, in-vivo dissolution and stability studies. All SD loaded patches displayed superior drug release (95% to 99.96%) over 12 h. The formulation BP14 showed excellent drug release extended over 12 h with drug release of 99.96% whereas marketed formulation which is sustained release Tablet showed 96.86% drug release within 6 h. The drug release kinetics show that the buccal patches follow zero order release kinetics with correlation coefficient (R2) ranging between 0.905-0.971 and BP14 formulation shown best R2 value. All the formulations exhibited best fit to Higuchi model with R2 ranging between 0.9911 – 0.9962 indicating drug release by diffusion process. The results conclude that buccal patches are superior alternatives for flurbiprofen that facilitates enhanced drug release for prolonged period of time in the effective management of rheumatoid arthritis.

GC-MS Profiling, Invitro Antidiabetic, Antioxidant and Antimicrobial Activities of a Novel Polyherbal Formulation

In the present study the methanol extract of a novel polyherbal formulation (PHF) was studied for alpha (α)- amylase and alpha (α)-glucosidase inhibition using an in vitro antidiabetic model. The polyherbal extract were also examined for its antioxidant activity by using free radical 1,1-diphenyl-2-picryl hydrazyl (DPPH) scavenging method. The study revealed that the polyherbal formulation exhibit potent radical scavenging activity using DPPH as substrate. The methanol extract exhibited significant α-amylase and α-glucosidase inhibitory activities with an IC50 value 31.52±0.74µg and 53.13±0.97µg respectively and well compared with standard acarbose drug. Further, antibacterial activity of methanol extract of PHF valuated against standard strains, the tested extract showed more potent inhibitory effects on both Gram (+) bacteria and Gram (-) bacteria. Thus, it could be concluded that due the presence of antioxidant components the plant extract have well prospective for the management of diabetes and the related condition of oxidative stress. This knowledge will be useful in finding more potent antidiabetic principle from the natural resources for the clinical development of antidiabetic therapeutics.

Phytochemical, antioxidant and antidiabetic analysis of leaf and stem extracts of Memecylon malabaricum(C.B.Clarke)Cogn.

Memecylon malabaricum (C.B.Clarke) Cogn. belongs to the family Melastomataceae is one of the important medicinal plants in traditional system of medicine. It has been used to treat diabetes, bacterial infections, and skin disorders including Herpes. Hence, the present study deals with the analysis of stem and leaf extracts through GC-MS to identify the bioactive compounds. 29 in stem and 25 phytochemicals in leaf extract were identified. Based on the results of GC-MS analysis further studies were carried out to estimate phenols, flavonoids and total antioxidant activity. It was found that stem methanolic extract has slightly more quantity of phenolics than the leaf extract. However, leaf extract has shown a considerable amount of flavonoids and better antioxidant activity than stem extract as revealed by DPPH, ABTS and reducing power assay. Further, inhibition of the activity of α-amylase by leaf extract was detected through preliminary studies thereby supporting its traditional use to treat diabetes.