SUSTAINED RELEASE TABLETS OF SORAFENIB-SILIBININ COMBINATIONS FOR THE TREATMENT OF HEPATOCELLULAR CARCINOMA

Objective: The aim of this study was to develop polymer coated sustained release tablet using sorafenib and silibinin combination for the treatment of hepatocellular carcinoma. Methods: The qualitative analysis such as weight variation, friability, hardness, interaction studies, disintegration and in vitro release were performed to validate formulated tablets. We have maintained the acceptable official limits for weight variation, friability, hardness and disintegration time according to prescribed pharmacopoeial recommendation. In vitro drug release studies were performed using USP-II (paddle type) dissolution apparatus. The MTT assay was performed for assessment of Cell viability of drug combination for tablet formulation. Molecular docking studies have been performed to determine the combinatorial mode of action for the tablet formulation. Results: Friability and weight variation were less than 1% for each formulation, which were within range of prescribed pharmacopoeial recommendation. The hardness of 20 tablets showed 5-6.5Kg/cm2 for all formulations 5-6.5Kg/cm2. The optimized formulation resulted in 98% drug release after 28 h. The present study reports the synergistic effects of drug combination to inhibit cell growth in HepG2 cell line. Molecular docking studies showed that sorafenib has high binding affinity for B-Raf vascular endothelial growth factor receptor β and protein kinase B. Silibinin showed binding affinity with MAP kinase-11, protein phosphatase 2 A and tankyrase. Conclusion: The present study reports for the first time a novel formulation for sustained release and reduced toxicity of sorafenib with enhanced inhibitory effect of the drug combination on cancerous hepatic cell line as well collaborative mechanism of action for the formulation

Cocos nucifera L. inflorescence extract: An effective hepatoprotective agent

128-136The flowering inflorescence of Cocos nucifera, a main constituent of several traditional drug formulations was investigated with a view to study the effect of the acetone extract of C. nucifera inflorescence (CnAE) on acetaminophen-induced hepatotoxicity. The total phenol and flavonoid contents of the extract are found to be 222.6 µg gallic acid equivalent/g and 120.8 µg quercetin equivalent/g, respectively. The LD50 value was >5000 mg/kg b.w. The antioxidant activity was assessed using three methods, namely, 2,2’- diphenyl-1-picryl hydrazyl assay, 2,2’-azinobis (3-ethylbenzthiazoline-6-sulphonic acid) assay and ferric reducing antioxidant power assay and the IC50 values were found to be 65.72, 66.94 and 89.84 μg/mL, respectively. Effect of CnAE (100, 200 and 400 mg/kg b.w.) and silymarin (100 mg/kg b.w.) against acetaminophen-induced liver toxicity was evaluated in Wistar rats. The study showed that CnAE pre-treated groups remarkably prevented the increase in serum alanine amino transferase, aspartate amino transferase and alkaline phosphatase level and decrease in the level of liver superoxide dismutase, reduced glutathione, glutathione-S-transferase and glutathione peroxidise. The extract also suppressed the elevated level of malondialdehyde. The biochemical determinations supported the histopathological examination and blood parameter findings. The findings of our study indicated that the phenolic-rich CnAE could be an interesting alternative candidate against acetaminophen-induced hepato-toxicity and associated oxidative stress

Cocos nucifera L. inflorescence extract: An effective hepatoprotective agent

The flowering inflorescence of Cocos nucifera, a main constituent of several traditional drug formulations was investigated with a view to study the effect of the acetone extract of C. nucifera inflorescence (CnAE) on acetaminophen-induced hepatotoxicity. The total phenol and flavonoid contents of the extract are found to be 222.6 µg gallic acid equivalent/g and 120.8 µg quercetin equivalent/g, respectively. The LD50 value was >5000 mg/kg b.w. The antioxidant activity was assessed using three methods, namely, 2,2’- diphenyl-1-picryl hydrazyl assay, 2,2’-azinobis (3-ethylbenzthiazoline-6-sulphonic acid) assay and ferric reducing antioxidant power assay and the IC50 values were found to be 65.72, 66.94 and 89.84 μg/mL, respectively. Effect of CnAE (100, 200 and 400 mg/kg b.w.) and silymarin (100 mg/kg b.w.) against acetaminophen-induced liver toxicity was evaluated in Wistar rats. The study showed that CnAE pre-treated groups remarkably prevented the increase in serum alanine amino transferase, aspartate amino transferase and alkaline phosphatase level and decrease in the level of liver superoxide dismutase, reduced glutathione, glutathione-S-transferase and glutathione peroxidise. The extract also suppressed the elevated level of malondialdehyde. The biochemical determinations supported the histopathological examination and blood parameter findings. The findings of our study indicated that the phenolic-rich CnAE could be an interesting alternative candidate against acetaminophen-induced hepato-toxicity and associated oxidative stress

Potential inhibitory activity of phytoconstituents against black fungus: in silico admet, molecular docking and MD simulation studies

Mucormycosis or “black fungus” has been currently observed in India, as a secondary infection in COVID-19 infected patients in the post-COVID-stage. Fungus is an uncommon opportunistic infection that affects people who have a weak immune system. In this study, 158 antifungal phytochemicals were screened using molecular docking against glucoamylase enzyme of Rhizopus oryzae to identify potential inhibitors. The docking scores of the selected phytochemicals were compared with Isomaltotriose as a positive control. Most of the compounds showed lower binding energy values than Isomaltotriose (-6.4 kcal/mol). Computational studies also revealed the strongest binding affinity of the screened phytochemicals was Dioscin (-9.4 kcal/mol). Furthermore, the binding interactions of the top ten potential phytochemicals were elucidated and further analyzed. In-silico ADME and toxicity prediction were also evaluated using SwissADME and admetSAR online servers. Compounds Piscisoflavone C, 8-O-methylaverufin and Punicalagin exhibited positive results with the Lipinski filter and drug-likeness and showed mild to moderate of toxicity. Molecular dynamics (MD) simulation (at 300 K for 100 ns) was also employed to the docked ligand-target complex to explore the stability of ligand-target complex, improve docking results, and analyze the molecular mechanisms of protein-target interactions

Natural Polymers for Drug Deliver

Natural polymers have been utilized extensively in food, pharmaceuticals, cosmetics, textiles, oil drilling and paint industries. Their non-toxic and inexpensive attributes readily enhance their commercial acceptability and make them potent agents in lieu of synthetic polymers.This book explores the opportunistic utility of natural polymers in developing effective drug delivery systems and provides a comprehensive and up-to-date analysis of their source, chemical structure and mechanism of action. Covering novel polymers for drug delivery--in particular extracts from plants, microorganisms and proteins, as well as water soluble and water insoluble biodegradable polymers--it presents an encyclopedic overview of natural polymers:* quintessential roles in binding drugs towards enhancing bio-availability* modification and derivatization for targeted delivery* role as active drugsNatural Polymers for Drug Delivery is an invaluable resource for researchers, students and industrial scientists in the fields of biochemistry, chemistry, pharmacology and food science.https://openprairie.sdstate.edu/dairy_book/1000/thumbnail.jp

NATURAL POLYMER BASED CLING FILMS FOR FOOD PACKAGING

In the last decades, there has been a marked increase in the use of natural polymer based film materials in packaging, which prevents food from external contamination, retardation of deterioration by extension of its shelf life and maintenance of its quality and safety. Natural polymer based cling films for food packaging can replace the non-biodegradable petroleum-based synthetic polymers at a low cost, thereby producing a positive effect both environmentally and economically. This review aims to obtain a better understanding of use of natural polymers based cling films available for food packaging which include: protein based edible films and films from cellulose and its derivatives. Protein-based edible films offer alternative packaging sources that can be used for versatile food products to reduce loss of moisture from food, can restrict the absorption of oxygen, lessen the migration of lipids, improving mechanical handling properties, and can provide physical protection to food. Cellulose derivatives are a class of natural polymers in which cellulose is swollen to form films with higher tensile strength and improved water vapor properties. However, currently research is focusing on the blending, layering, and filling cellulose derivatives with different biopolymers or synthetic polymers to enhance the mechanical and barrier properties, therefore strengthening their position in competition with other packaging materials available for food packaging. Cling films are synthesized involving biopolymers and the preparation of their modified derivatives to develop a class of natural packaging films which will revolutionize the food packaging industry using various different formulations. The aim in future is to come up with best films for the food industry by increasing their shelf lives and by validating the films according to ASTM standards for food packaging

Synthesis, Characterization and Evaluation of Antibacterial Efficacy, Antioxidant Potential of Silver nanoparticle using Myrica nagi leaf extract

In the present work, we report an environment friendly biosynthesis of silver nanoparticles using   ethanolic extract of Myrica nagi leaves. This endangered tree with wide medicinal applications has rich amount of anti-oxidants along with other classes of chemicals. Various therapeutic compounds such as myricanol, myricanone, myricetrin, sitosterol, taraxerol are isolated from the various parts of the plant. In this process, reduction of Silver ions to silver nanoparticles was achieved by a bioactive compound from Myrica Nagi plant. The synthesized nanoparticles were characterized using UV-visible spectrophotometer, Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM) and FTIR. The formation, stability and particle size of Ag nanoparticles was characterized using UV-Vis spectrophotometer and Dynamic Light Scattering. Scanning Electron Microscopy (SEM) micrograph shows a uniform distribution of the particles with an average size of 50-60nm. FTIR analysis confirms the presence of hydroxyl, carboxyl and phenolic functional groups. Further, the antimicrobial activity of silver nanoparticles shows that these nanoparticles can be used as effective growth inhibitors against E. coli, S.aureus and S. pyogenes with zone of inhibition of 1.2, 1.3 and 0.8 cm respectively. The synthesized silver nanoparticle have a potential application in targeted drug delivery, wound healing and other medical applications. The antioxidant activity of AgNPs imparted by plant components was evaluated using DPPH assay and found to be comparable to standard ascorbic acid

In silico approach to evaluate the efficacy of dietary flavonoids and their role in Alzheimer\u27s disease

© 2015, Global Research Online. All rights reserved. Alzheimer’s disease is recognized as fatal neurological disorder that leads to constant degeneration of neurons in later stage of life. Etiology of disease progression is characterized by accumulation of amyloid beta and tau protein that contributes in the formation of senile plaques and tangles. It was also observed that nutritional status of AD patients was low and often not considered in research studies. Here we emphasize on the intake of those dietary items which are good source of natural antioxidants and hence can protect the brain from oxidative and inflammatory damage. We have compared twenty seven secondary metabolites from 5 different classes of Flavonoids found in 506 dietary items (Source: USDA Database for Flavonoid Content of Selected foods, Release 3.1(2013)) along with marketed drugs for Alzheimer’s disease to AChE receptor. Our study indicates that Flavan-3-ol family of flavonoids are the best dietary supplements for improving brain health. Theaflavin-3’-gallate is the best binding ligand to AChE receptor. Pharmacophoric studies were conducted to see the potential of respective compounds as drug candidate. Since pharmaceutical industries have always shown interest in compounds from natural sources, a little intervention of these compounds with the synthetic drugs will guarantee lesser side effects with maximum efficacy. Hence the food items like hazelnuts, Green Tea, Black Tea, Pistachio nuts, walnuts, Cocoa mix, Coffee etc. should be incorporated more in the diet of healthy people as well as in AD patients to protect brain from damage and improve the cognitive abilities

Search for new therapeutics against HIV-1 via dual inhibition of RNase H and integrase: Current status and future challenges

Reverse transcriptase and integrase are key enzymes that play a pivotal role in HIV-1 viral maturation and replication. Reverse transcriptase consists of two active sites: RNA-dependent DNA polymerase and RNase H. The catalytic domains of integrase and RNase H share striking similarity, comprising two aspartates and one glutamate residue, also known as the catalytic DDE triad, and a Mg2+ pair. The simultaneous inhibition of reverse transcriptase and integrase can be a rational drug discovery approach for combating the emerging drug resistance problem. In the present review, the dual inhibition of RNase H and integrase is systematically discussed, including rationality of design, journey of development, advancement and future perspective