BIOFLAVONOIDS WITH ANTICANCER ACTIVITY AND THEIR NOVEL FORMULATIONS

Context: Nature blesses human with a lot of natural products with a wide range of medicinal properties from plants, animals, marine animals, and microorganisms. Among these natural sources, plant origin drugs constitute around 25% which includes various secondary metabolites such as alkaloids, bioflavonoids, terpenes, saponins, glucosides, and lignans. The bioflavonoids belonging to the polyphenol group possess various therapeutic activities such as antioxidant, hepatoprotective, antibacterial, anti-inflammatory, anticancer, and antiviral.Objectives: The main objective of this article is to collectively present the research data published worldwide about the anticancer activity of bioflavonoids by loading them in novel formulations. Thus, the present review explored the novel formulations of the bioflavonoids with improved pharmacokinetic properties along with the enhanced anticancer activity.Methods: A systematic scientific review was made across the peer-reviewed scientific journals and books to collect the data pertaining to areas research related to the application of bioflavonoids for treatment of cancer using novel pharmaceutical formulations.Results: The major drawback with bioflavonoids is its poor solubility and bioavailability, which restricts the usage of bioflavonoids in the treatment of cancer in the market worldwide. Novel drug delivery system seems to possess many benefits like site-specific drug delivery along with minimal side effects and improving its pharmaceutical and therapeutic properties of drugs compared to a conventional dosage form of bioflavonoids.Conclusion: The scope for improvement of anticancer activity of bioflavonoids by incorporating in novel pharmaceutical formulations like nanoparticles is very high, and it has to be considered as a potential area of research

FORMULATION AND EVALUATION OF FLOATING ORAL IN SITU GEL OF DILTIAZEM HYDROCHLORIDE

Objective: The objective of the present study was to formulate and evaluate the floating in-situ gelling system of diltiazem hydrochloride.Methods: Sodium alginate based diltiazem hydrochloride floating in situ gelling systems were prepared by dissolving hydroxyl propyl methyl cellulose (HPMC) in 25% of water, to which calcium carbonate and diltiazem hydrochloride were added with stirring to form, a proper and a homogenous dispersion of diltiazem hydrochloride. Meanwhile, 30% of water was heated to 60 ËšC on a hot plate to dissolve sodium alginate and cooled to 40 ËšC. The resulting solution was added to HPMC solution and mixed well. To 5% of water at 60 ËšC, sodium methyl paraben was added and dissolved and cooled to 40 ËšC and was added to the above mixture and mixed well. The volume was adjusted finally to 100% with distilled water. Prepared formulae were evaluated for physicochemical properties, drug content, pH, in vitro gelling capacity, in vitro buoyancy, viscosity, water uptake and in vitro drug release.Results: Formulation variables such as type and concentration of viscosity enhancing polymer (sodium alginate) and HPMC affected the formulation viscosity, gelling properties, floating behavior, and in vitro drug release. Formulation F5 and F6 showed the floating time of 5 min and more than 20 h respectively. A significant decrease in the rate and extent of the drug release was observed with the increase in polymer concentration in in-situ gelling preparation. Formulation F4, F5, F6 were shown to have extended drug release until the end of 7 h.Conclusion: The prepared in situ gelling formulations of diltiazem hydrochloride could float in the gastric conditions and released the drug in a sustained manner. The present formulation was non-irritant, easy to administer along with good retention properties, better patient compliant and with greater efficacy of the drug

Molecular docking study of ferulic acid

The main purpose of this study is the molecular docking of Ferulic acid with various enzymes such as 2PRG, 6COX, 1HD2, 2HCK, 2IOK, 2Y6W, 2YXJ, 4IEH, 5FDO, 3MWD, 3QNT. A molecular docking study was carried out by AutoDock 4. The results of the molecular docking study revealed that ferulic acid binds to the different enzymes. The results show the high affinity of ferulic acid with 2PRG, 6COX, 1HD2, 2HCK, 2IOK, 2Y6W, 2YXJ, 4IEH, 5FDO, 3MWD, 3QNT. The binding energy of the ferulic acid was compared with the known Anti-diabetic, anti-inflammatory, anticancer, antioxidant, Anti-apoptotic and Antihyperlipidemic standard drugs that inhibits 2PRG, 6COX, 1HD2, 2HCK, 2IOK, 2Y6W, 2YXJ, 4IEH, 5FDO, 3MWD, 3QNT enzyme. This study has tremendous scope in the pharmaceutical industry and biology for designing novel formulations for inhibiting different enzymes responsible for various diseases

NANOPARTICLE FORMULATION OF BIOFLAVONOIDS FOR ENHANCED ANTI-CANCER ACTIVITY

Among the natural sources, plant origin drugs constitute around 25% which includes various secondary metabolites such as bioflavonoids, alkaloids, terpenes, saponins, glucosides, and lignans. The bioflavonoids belonging to the polyphenol group shows many beneficial effects like hepatoprotective, antioxidant, antibacterial, anticancer, anti-inflammatory and antiviral. The main objective of this article is to collectively present the research data published worldwide about the anticancer activity of bioflavonoids by loading them in novel formulations. Thus, the present review explored the novel formulations of the bioflavonoids with improved pharmacokinetic properties along with the enhanced anticancer activity. The major drawback with bioflavonoids is its poor solubility and bioavailability, which restricts the usage of bioflavonoids in the treatment of cancer in the market worldwide. Novel drug delivery system seems to possess many benefits like site-specific drug delivery along with minimal side effects and improves pharmaceutical and therapeutic properties of drugs compared to a conventional dosage form of bioflavonoids. The scope for improvement of anticancer activity of bioflavonoids by incorporating in novel pharmaceutical formulations like nanoparticles is very high, and it has to be considered as a potential area of research

Zinc oxide nanoparticle-coated films: fabrication, characterization, and antibacterial properties

In this article, novel antibacterial PVC-based films coated with ZnO nanoparticles (NPs) were fabricated, characterized, and studied for their antibacterial properties. It was shown that the ZnO NPs were coated on the surface of the PVC films uniformly and that the coating process did not affect the size and shape of the NPs on the surface of PVC films. Films coated with concentrations of either 0.2 or 0.075 g/L of ZnO NPs exhibited antibacterial activity against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria, but exhibited no antifungal activity against Aspergillus flavus and Penicillium citrinum. Smaller particles (100 nm) exhibited more potent antibacterial activity than larger particles (1000 nm). All ZnO-coated films maintained antibacterial activity after 30 days in water

Cleanup of industrial effluents containing heavy metals : a new opportunity of valorising the biomass produced by brewing industry

Heavy metal pollution is a matter of concern in industrialised countries. Contrary to organic pollutants, heavy metals are not metabolically degraded. This fact has two main consequences: its bioremediation requires another strategy and heavy metals can be indefinitely recycled. Yeast cells of Saccharomyces cerevisiae are produced at high amounts as a by-product of brewing industry constituting a cheap raw material. In the present work, the possibility of valorising this type of biomass in the bioremediation of real industrial effluents containing heavy metals is reviewed. Given the auto-aggregation capacity (flocculation) of brewing yeast cells, a fast and off-cost yeast separation is achieved after the treatment of metal-laden effluent, which reduces the costs associated with the process. This is a critical issue when we are looking for an effective, eco-friendly, and low-cost technology. The possibility of the bioremediation of industrial effluents linked with the selective recovery of metals, in a strategy of simultaneous minimisation of environmental hazard of industrial wastes with financial benefits from reselling or recycling the metals, is discussed

3D Hepatic Cultures Simultaneously Maintain Primary Hepatocyte and Liver Sinusoidal Endothelial Cell Phenotypes

Developing in vitro engineered hepatic tissues that exhibit stable phenotype is a major challenge in the field of hepatic tissue engineering. However, the rapid dedifferentiation of hepatic parenchymal (hepatocytes) and non-parenchymal (liver sinusoidal endothelial, LSEC) cell types when removed from their natural environment in vivo remains a major obstacle. The primary goal of this study was to demonstrate that hepatic cells cultured in layered architectures could preserve or potentially enhance liver-specific behavior of both cell types. Primary rat hepatocytes and rat LSECs (rLSECs) were cultured in a layered three-dimensional (3D) configuration. The cell layers were separated by a chitosan-hyaluronic acid polyelectrolyte multilayer (PEM), which served to mimic the Space of Disse. Hepatocytes and rLSECs exhibited several key phenotypic characteristics over a twelve day culture period. Immunostaining for the sinusoidal endothelial 1 antibody (SE-1) demonstrated that rLSECs cultured in the 3D hepatic model maintained this unique feature over twelve days. In contrast, rLSECs cultured in monolayers lost their phenotype within three days. The unique stratified structure of the 3D culture resulted in enhanced heterotypic cell-cell interactions, which led to improvements in hepatocyte functions. Albumin production increased three to six fold in the rLSEC-PEM-Hepatocyte cultures. Only rLSEC-PEM-Hepatocyte cultures exhibited increasing CYP1A1/2 and CYP3A activity. Well-defined bile canaliculi were observed only in the rLSEC-PEM-Hepatocyte cultures. Together, these data suggest that rLSEC-PEM-Hepatocyte cultures are highly suitable models to monitor the transformation of toxins in the liver and their transport out of this organ. In summary, these results indicate that the layered rLSEC-PEM-hepatocyte model, which recapitulates key features of hepatic sinusoids, is a potentially powerful medium for obtaining comprehensive knowledge on liver metabolism, detoxification and signaling pathways in vitro

Decompressive surgery in cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia

Background and purpose: Cerebral venous sinus thrombosis due to vaccine-induced im-mune thrombotic thrombocytopenia (CVST-VITT) is an adverse drug reaction occurring after severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) vaccination. CVST-VITT patients often present with large intracerebral haemorrhages and a high proportion undergoes decompressive surgery. Clinical characteristics, therapeutic management and outcomes of CVST-VITT patients who underwent decompressive surgery are described and predictors of in- hospital mortality in these patients are explored.Methods: Data from an ongoing international registry of patients who developed CVST within 28 days of SARS-CoV- 2 vaccination, reported between 29 March 2021 and 10 May 2022, were used. Definite, probable and possible VITT cases, as defined by Pavord et al. (N Engl J Med 2021; 385: 1680–1689), were included. Results: Decompressive surgery was performed in 34/128 (27%) patients with CVST- VITT. In- hospital mortality was 22/34 (65%) in the surgical and 27/94 (29%) in the non- surgical group (p< 0.001). In all surgical cases, the cause of death was brain herniation. The highest mortality rates were found amongst patients with preoperative coma (17/18, 94% vs. 4/14, 29% in the non-comatose; p< 0.001) and bilaterally absent pupillary re-flexes (7/7, 100% vs. 6/9, 67% with unilaterally reactive pupil, and 4/11, 36% with bi-laterally reactive pupils; p= 0.023). Postoperative imaging revealed worsening of index haemorrhagic lesion in 19 (70%) patients and new haemorrhagic lesions in 16 (59%) pa-tients. At a median follow-up of 6 months, 8/10 of surgical CVST-VITT who survived ad-mission were functionally independent.Conclusions: Almost two-thirds of surgical CVST-VITT patients died during hospital ad-mission. Preoperative coma and bilateral absence of pupillary responses were associated with higher mortality rates. Survivors often achieved functional independence.Peer reviewe

Discovering Networks of Perturbed Biological Processes in Hepatocyte Cultures

The liver plays a vital role in glucose homeostasis, the synthesis of bile acids and the detoxification of foreign substances. Liver culture systems are widely used to test adverse effects of drugs and environmental toxicants. The two most prevalent liver culture systems are hepatocyte monolayers (HMs) and collagen sandwiches (CS). Despite their wide use, comprehensive transcriptional programs and interaction networks in these culture systems have not been systematically investigated. We integrated an existing temporal transcriptional dataset for HM and CS cultures of rat hepatocytes with a functional interaction network of rat genes. We aimed to exploit the functional interactions to identify statistically significant linkages between perturbed biological processes. To this end, we developed a novel approach to compute Contextual Biological Process Linkage Networks (CBPLNs). CBPLNs revealed numerous meaningful connections between different biological processes and gene sets, which we were successful in interpreting within the context of liver metabolism. Multiple phenomena captured by CBPLNs at the process level such as regulation, downstream effects, and feedback loops have well described counterparts at the gene and protein level. CBPLNs reveal high-level linkages between pathways and processes, making the identification of important biological trends more tractable than through interactions between individual genes and molecules alone. Our approach may provide a new route to explore, analyze, and understand cellular responses to internal and external cues within the context of the intricate networks of molecular interactions that control cellular behavior