Permender Rathee

Mechanism of Action of Flavonoids as Anti-inflammatory Agents: A Review

Flavonoids are polyphenolic compounds that occur ubiquitously in plants having a variety of biological effects both in vitro and in vivo. They have been found to have antimicrobial, antiviral, anti-ulcerogenic, cytotoxic, anti-neoplastic, mutagenic, antioxidant, antihepatotoxic, antihypertensive, hypolipidemic, antiplatelet and anti-inflammatory activities. Flavonoids also have biochemical effects, which inhibit a number of enzymes such as aldose reductase, xanthine oxidase, phosphodiesterase, Ca(+2)-ATPase, lipoxygenase, cycloxygenase, etc. They also have a regulatory role on different hormones like estrogens, androgens and thyroid hormone. They have been found to have anti-inflammatory activity in both proliferative and exudative phases of inflammation. Several mechanisms of action have been proposed to explain anti-inflammatory action of flavonoids. The aim of the present review is to give an overview of the mechanism of action of potential anti-inflammatory flavonoids.

Optimization and Formulation Design of Gels of Diclofenac and Curcumin for Transdermal Drug Delivery by Box-Behnken Statistical Design

The aim of this study was to develop and optimize a transdermal gel formulation for Diclofenac diethylamine (DDEA) and Curcumin (CRM). A 3-factor, 3-level Box-Behnken design was used to derive a second-order polynomial equation to construct contour plots for prediction of responses. Independent variables studied were the polymer concentration (X(1)), ethanol (X(2)) and propylene glycol (X(3)) and the levels of each factor were low, medium, and high. The dependent variables studied were the skin permeation rate of DDEA (Y(1)), skin permeation rate of CRM (Y(2)), and viscosity of the gels (Y(3)). Response surface plots were drawn, statistical validity of the polynomials was established to find the compositions of optimized formulation which was evaluated using the Franz-type diffusion cell. The permeation rate of DDEA increased proportionally with ethanol concentration but decreased with polymer concentration, whereas the permeation rate of CRM increased proportionally with polymer concentration. Gels showed a non-Fickian super case II (typical zero order) and non-Fickian diffusion release mechanism for DDEA and CRM, respectively. The design demonstrated the role of the derived polynomial equation and contour plots in predicting the values of dependent variables for the preparation and optimization of gel formulation for transdermal drug release.

Mushrooms as therapeutic agents

Mushrooms have been known for their nutritional and culinary values and used as medicines and tonics by humans for ages. In modern terms, they can be considered as functional foods which can provide health benefits beyond the traditional nutrients. There are monographs that cover the medicinal and healing properties of some individual traditional mushrooms. There has been a recent upsurge of interest in mushrooms not only as a health food which is rich in protein but also as a source of biologically active compounds of medicinal value which include complementary medicine/dietary supplements for anticancer, antiviral, hepatoprotective, immunopotentiating and hypocholesterolemic agents. However the mechanisms of the various health benefits of mushrooms to humans still require intensive investigation, especially given the emergence of new evidence of their health benefits. In the present paper the medicinal potential of mushrooms is being discussed.

Optimization and formulation design of carbopol loaded Piroxicam gel using novel penetration enhancers

The aim of the study was to develop and optimize Piroxicam transdermal gel formulation using three-factor, three-level Box-Behnken design by deriving a second-order polynomial equation to construct contour plots for prediction of responses as three selected independent variables with ratio of carbopol 974 (X1), ratio of propylene glycol (PG) (X2) and ratio of ethanol (X3). The dependent variables studied were the skin permeation rate of piroxicam (Y1), viscosity of the gel (Y2) and pH of the gel (Y3). Response surface plots were drawn, statistical validity of the polynomials was established to find the compositions of optimized formulation which was evaluated using the vertical Franz-type diffusion cell. The permeation rate of piroxicam increased proportionally with ethanol concentration but decreased with polymer concentration. The design demonstrated the role of the derived polynomial equation and contour plots in predicting the values of dependent variables for the preparation and optimization of gel formulation.

Optimization and evaluation of gastroretentive ranitidine HCl microspheres by using design expert software

The current study involves the development and optimization of their drug entrapment and ex vivo bioadhesion of multiunit chitosan based floating system containing Ranitidine HCl by ionotropic gelation method for gastroretentive delivery. Chitosan being cationic, non-toxic, biocompatible, biodegradable and bioadhesive is frequently used as a material for drug delivery systems and used to transport a drug to an acidic environment where it enhances the transport of polar drugs across epithelial surfaces. The effect of various process variables like drug polymer ratio, concentration of sodium tripolyphosphate and stirring speed on various physiochemical properties like drug entrapment efficiency, particle size and bioadhesion was optimized using central composite design and analyzed using response surface methodology. The observed responses were coincided well with the predicted values given by the optimization technique. The optimized microspheres showed drug entrapment efficiency of 74.73%, particle size 707.26 μm and bioadhesion 71.68% in simulated gastric fluid (pH 1.2) after 8 h with floating lag time 40s. The average size of all the dried microspheres ranged from 608.24 to 720.80 μm. The drug entrapment efficiency of microspheres ranged from 41.67% to 87.58% and bioadhesion ranged from 62% to 86%. Accelerated stability study was performed on optimized formulation as per ICH guidelines and no significant change was found in drug content on storage.

Immuno-modulation effect of sulphated polysaccharide (porphyran) from Porphyra vietnamensis.

Our investigation explores the immuno-efficiency of sulphated polysaccharides enriched Porphyra vietnamenis. Isolated polysaccharide fraction (17.1-25.8%) was characterized by FTIR and NMR spectroscopy which showed the presence of typical linear backbone structure called as porphyran. Oral administration of porphyran (200-500 mg/kg) evoked a significant (P ≤ 0.05) increase in weight of the thymus, spleen and lymphoid organ cellularity. The total leucocyte and lymphocyte count was increased significantly (P<0.005). The increase in the percent neutrophil adhesion to nylon fibres as well as a dose-dependent increase in antibody titre values was observed. A decreased response to DTH reaction induced by SRBC was recorded. A potential phagocytic response was seen and significant changes were observed in the formation of formazone crystals. It also prevented myelosuppression in cyclophosphamide drug treated rats. The results indicated that P. vietnamenis possesses potential immunomodulatory activity and has therapeutic potential for the prevention of autoimmune diseases.

In vitro anticancer activity of stachydrine isolated from Capparis decidua on prostate cancer cell lines

In this article we report our work on the isolation, characterisation and evaluation of in vitro anticancer activity of stachydrine on solid tumour cells. The in vitro activity was assessed by MTT assay and propidium iodide (PI) staining. Further, an attempt was also made to check the effect of stachydrine on the invasion and metastasis of cancer cells by inhibiting the expression of chemokine receptors (CXCR3 and CXCR4). The influence of stachydrine on the gene expression of CXCR3 and CXCR4 at mRNA and protein levels was examined. Studies revealed a dose dependent decrease in expression of mRNA, and protein levels were observed in stachydrine-treated human prostate cancer cells (PC-3 and LNcaP) as detected by reverse transcriptase-polymerase chain reaction (RT-PCR). The data therefore provides direct evidence for the role of stachydrine as a potent anti-metastatic agent, which can markedly inhibit the malignancy and invasive capacity of malignant cancer cells.

In-vitro cytotoxic activity of β-Sitosterol triacontenate isolated from Capparis decidua(Forsk.) Edgew

OBJECTIVE To study the isolation and characterization of the constituent responsible for the cytotoxic activity of the ethanolic extract of stem of Capparis decidua (C. decidua). METHODS The preliminary cytotoxic effect of isolated compound (β-Sitosterol triacontenate) was investigated by MTT assay on A549 solid tumor cells. RESULTS IC(50) value of the β-Sitosterol triacontenate was found to be 1 μM. The cytotoxic activity increased in a dose dependent manner in case of β-Sitosterol triacontenate. CONCLUSIONS The data therefore provide direct evidence for the role of β-Sitosterol triacontenate as a potent antimetastatic agent, which can markedly inhibit the metastatic and invasive capacity of malignant cells.

DEVELOPMENT AND VALIDATION OF RP-HPLC METHOD FOR SIMULTANEOUS ESTIMATION OF DICLOFENAC DIETHYLAMINE AND CURCUMIN IN TRANSDERMAL GELS

A reversed phase high performance liquid chromatographic (RP-HPLC) method using Symmetry C18, 5.0-µm column was developed for simultaneous determination of Diclofenac diethylamine (DDEA) and Curcumin (CRM). Mobile phase consisted of orthophosphoric acid 0.1% and acetonitrile (65:35), and the flow rate was 1.5 mL/min and elution was monitored initially at 425 nm for CRM, after 14.7 min wavelength was changed to 275 nm for detection of DDEA. Response was a linear function of concentration over the range 0.245–1.96 µg/mL (R2 = 0.9998) for DDEA and 55–445 ng/mL (R2 = 0.9992) for CRM and the limits of detection were 245.5 ng/mL for DDEA and 55.30 ng/mL for CRM. The limit of quantitation was 491.1 ng mL − 1 for DDEA and 165.87 ng mL − 1 for CRM. The method was validated in accordance with ICH guidelines. The method was used for simultaneous quantification of DDEA and CRM in transdermal gel formulations and to check content uniformity. The excipients present in the formulation did not interfere with the assay. The method is suitable for application in quality-control laboratories, because it is simple and rapid with good accuracy and precision.

Statistical Design for Optimization and Determination of Tizanidine Hclusing Folin-Ciocalteu (Fc) as Chromogenic Reagent

A simple, sensitive spectrophotometric method has been developed for quantitative determination of Tizanidine Hydrochloride in bulk and pharmaceutical formulations with application of factorial design. In this method, Tizanidine Hydrochloride is made to react with Folin-Ciocalteu (FC) reagent under alkaline conditions forming a blue chromogen having absorption maximum at 663 nm. Beer’s law was obeyed in the concentration range of 4-36 μg/ml. Results of the analysis were validated as per ICH guidelines and by recovery studies. A 3-factor, 3-level statistical design (Box-Behnken) was used to derive a second-order polynomial equation to construct contour plots for prediction of response. Independent variables studied were the FC-reagent (X1), sodium carbonate (X2) and drug concentration (X3) and the levels of each factor were low, medium, and high. The dependent variable studied was absorbance (Y1). The aims of this study to determination and optimize the Tizanidine HCl using FC as Chromogenic reagent; the design demonstrated the role of the derived equation (polynomial) and two dimensional plots in predicting the values of dependent variable for optimization.