System Biology Investigation Revealed Lipopolysaccharide and Alcohol-Induced Hepatocellular Carcinoma Resembled Hepatitis B Virus Immunobiology and Pathogenesis.

Hepatitis B infection caused by the hepatitis B virus is a life-threatening cause of liver fibrosis, cirrhosis, and hepatocellular carcinoma. Researchers have produced multiple in vivo models for hepatitis B virus (HBV) and, currently, there are no specific laboratory animal models available to study HBV pathogenesis or immune response; nonetheless, their limitations prevent them from being used to study HBV pathogenesis, immune response, or therapeutic methods because HBV can only infect humans and chimpanzees. The current study is the first of its kind to identify a suitable chemically induced liver cirrhosis/HCC model that parallels HBV pathophysiology. Initially, data from the peer-reviewed literature and the GeneCards database were compiled to identify the genes that HBV and seven drugs (acetaminophen, isoniazid, alcohol, D-galactosamine, lipopolysaccharide, thioacetamide, and rifampicin) regulate. Functional enrichment analysis was performed in the STRING server. The network HBV/Chemical, genes, and pathways were constructed by Cytoscape 3.6.1. About 1546 genes were modulated by HBV, of which 25.2% and 17.6% of the genes were common for alcohol and lipopolysaccharide-induced hepatitis. In accordance with the enrichment analysis, HBV activates the signaling pathways for apoptosis, cell cycle, PI3K-Akt, TNF, JAK-STAT, MAPK, chemokines, NF-kappa B, and TGF-beta. In addition, alcohol and lipopolysaccharide significantly activated these pathways more than other chemicals, with higher gene counts and lower FDR scores. In conclusion, alcohol-induced hepatitis could be a suitable model to study chronic HBV infection and lipopolysaccharide-induced hepatitis for an acute inflammatory response to HBV.

One pot synthesis, in silico study and evaluation of some novel flavonoids as potent topoisomerase II inhibitors.

A library of novel flavonoid derivatives with diverse heterocyclic groups was designed and efficiently synthesized. Structures of the newly synthesized compounds 4a-i and 8a-l have been characterized by 1H NMR, 13C NMR, MS and elemental analysis. Anticancer activities were evaluated against MCF-7, A549, HepG2 and MCF-10A by MTT based assay. Compared with the positive control Adriamycin, compounds 4a, 4b, 4c, 4d, 8d, 8e and 8j were found to be most active anti-proliferative compounds against human cancer cell line. We found that compounds 4a and 4c exhibited inhibition of enzyme topoisomerase II with IC50 values 10.28 and 12.38 µM, respectively. In silico docking study of synthesized compounds showed that compounds 4a and 4c have good binding affinity toward topoisomerase IIα enzyme and have placed in between DNA base pair at active site of enzyme. In silico ADME prediction results that flavonoid coumarin analogues 4a-i could be exploited as an oral drug candidate.

Design, synthesis, and molecular docking study of some 2-((7-chloroquinolin-4-yl) amino) benzohydrazide Schiff bases as potential Eg5 inhibitory agents.

In Search of new microtubule-targeting compounds and to identify a promising Eg5 inhibitory agents, a series of 2-((7-chloroquinolin-4-yl) amino) benzohydrazide Schiff bases molecules (6 a-r) were synthesized using appropriate synthetic method. The synthesized compounds were characterized by using FTIR, Proton NMR, Carbon NMR and mass spectral analysis. All eighteen compounds were evaluated for their Eg5 inhibitory activity. Among the evaluated compounds, only seven compounds are shown inhibitory activity. The results of Steady state ATPase reveled that compounds 6b, 6l and 6p exhibited promising inhibitory activity with IC50 Values of 2.720 ± 0.69, 2.676 ± 0.53 and 2.408 ± 0.46 respectively. Malachite Green Assay results reveled that 6q compound showed better inhibitory activity with IC50 Value of 0.095 ± 0.27. In vitro antioxidant capacity of the synthesized compounds was investigated. A molecular docking studies were performed to evaluate interaction in to binding site of kinesin spindle protein, these interaction influencing may support Eg5 inhibitory activity. The drug like parameters of the eighteen synthesized compounds were also computed using Qikprop software. In conclusion, some of 2-((7-chloroquinolin-4-yl) amino) benzohydrazide Schiff base compounds represent promising drug like agents for discovery of effective anticancer molecules.

Ultrasound assisted synthesis of tetrazole based pyrazolines and isoxazolines as potent anticancer agents via inhibition of tubulin polymerization.

In search of new active molecules against MCF-7, A549 and HepG2, tetrazole based pyrazoline and isoxazoline derivatives under both conventional and ultrasonic irradiation method were designed and efficiently synthesized. Structures of newly synthesized compounds 5a-h and 6a-h were characterized by 1H NMR, 13C NMR, MS and elemental analysis. Several derivatives were found to be excellent cytotoxic against MCF-7, A549 and HepG2 cell lines characterized by lower IC50 values (0.78-3.12 µg/mL). Compounds 5b and 5c demonstrated an antiproliferative effect comparable to that of CA-4. Western blot analysis revealed that, reported compounds accumulate more tubulin in the soluble fraction. Docking studies suggested that, binding of these compounds mimics at the colchicine site of tubulin. In vitro study revealed that the tetrazole based pyrazolines and isoxazolines may possess ideal structural requirements for further development of novel therapeutic agents.

Factorial design based curcumin ethosomal nanocarriers for the skin cancer delivery: in vitro evaluation.

Melanoma is the most deadly and life-threatening form of skin cancer with progressively higher rates of incidence worldwide. The objective of the present investigation is to develop and to statistically optimize and characterize curcumin (CUR) loaded ethosomes for treatment of melanoma. A two factor, three level (32) factorial design approach was employed for the optimization of ethosomes. The prepared ethosomes were evaluated for size, zeta potential, entrapment efficiency, in vitro skin permeation and deposition ability. The optimized ethosomal formulation was evaluated for in vitro cytotoxicity and cellular uptake studies using A375 human melanoma cells. The optimized formulation has imperfect round shaped unilamellar structures with a mean vesicle size of 247 ± 5.25 nm and an entrapment efficiency of 92.24 ± 0.20%. The in vitro skin permeation studies proved the superiority of ethosomes over the traditional liposomes in terms of the amount of drug permeated and deposited in skin layers. Fluorescence microscopy showed the enhanced penetration of ethosomes into the deeper layers of the skin. In vitro cytotoxicity and cellular uptake studies revealed that curcumin ethosomes have significantly improved cytotoxicity and cellular uptake in A375 human melanoma cell lines. The colony formation assay results showed that curcumin ethosomes have a superior antiproliferative effect as they effectively inhibit the clonogenic ability of A375 cells. The flow cytometry results indicate that curcumin ethosomes induce cell death in A375 cells by apoptosis mechanism. The present study provides a strong rationale and motivation for further investigation of newly developed curcumin ethosomes as a potential therapeutic strategy for melanoma treatment.

Preparation, Optimization, and In Vivo Evaluation of Nanoparticle-Based Formulation for Pulmonary Delivery of Anticancer Drug.

Background and Oobjectives: Lung cancer, a pressing issue in present-day society due to its high prevalence and mortality rate, can be managed effectively by long-term delivery of anticancer agents encapsulated in nanoparticles in the form of inhalable dry powder. This approach is expected to be of strategic importance in the management of lung cancer and is a developing area in current research. In the present investigation, we report on the formulation and characterization of docetaxel inhalable nanoparticles as a viable alternative for effective treatment of non-small cell lung cancer as a long-term delivery choice. Materials and Methods: Poloxamer (PLX-188) coated poly (lactic-co-glycolic acid) (PLGA) nanoparticles containing docetaxel (DTX-NPs) were prepared by simple oil in water (o/w) single emulsification-solvent evaporation process. The nanoparticles were collected as pellet by centrifugation, dispersed in mannitol solution, and lyophilized to get dry powder. Results: Optimized DTX-NPs were smooth and spherical in morphology, had particle size around 200 nm, zeta potential around -36 mV, and entrapment efficiency of around 60%. The invitro anticancer assay was assessed and it was observed that nanoparticle-based formulation exhibited enhanced cytotoxicity when compared to the free form of the drug post 48 h. On examining for invitro drug release, slow but continuous release was seen until 96 h following Higuchi release kinetics. DTX-NPs were able to maintain their desired characteristics when studied at accelerated conditions of stability. Conclusions: In-vivo study indicated that the optimized nanoparticles were well retained in lungs and that the drug level could be maintained for a longer duration if given in the form of DTX-NPs by the pulmonary route. Thus, the non-invasive nature and target specificity of DTX-NPs paves the way for its future use as a pulmonary delivery for treating non-small cell lung cancer (NSCLC).

Doxorubicin loaded gold nanoparticles: Implication of passive targeting on anticancer efficacy.

The present work aims to investigate targeting potential of doxorubicin (Dox) functionalized gold nanoparticles (D-GNPs) for treatment of chemically induced fibrosarcoma in mice. Carrier GNPs were synthesised by green chemistry method and loaded with doxorubicin by incubation method. D-GNPs were studied for its biocompatibility using normal mouse fibroblasts (L929) and found to be cell compatible and non-toxic. D-GNPs (at a dose of 2.5, 2 and 1.5mg/kg equivalent to Dox) demonstrated passive targeting measured as function of antitumor efficacy against chemical induced fibrosarcoma which showed higher latency to the tumour growth as compared to free Dox (2.5mg/kg). D-GNPs exhibited significantly higher therapeutic anticancer efficacy (∼81% tumour suppression at dose of 2.5mg/kg equivalent to Dox) in the same model as compared to that of free doxorubicin (∼48% tumour suppression at dose of 2.5mg/kg). Safety profile and targeting efficiency of developed formulation was established by assessing cardiac and blood markers.

Poloxamer 407-based intranasal thermoreversible gel of zolmitriptan-loaded nanoethosomes: formulation, optimization, evaluation and permeation studies.

Zolmitriptan is the drug of choice for migraine, but low oral bioavailability (<50%) and recurrence of migraine lead to frequent dosing and increase in associated side effects. Increase in the residence time of drug at the site of drug absorption along with direct nose to brain targeting of zolmitriptan can be a solution to the existing problems. Hence, in the present investigation, thermoreversible intranasal gel of zolmitriptan-loaded nanoethosomes was formulated by using mucoadhesive polymers to increase the residence of the drug into the nasal cavity. The preparation of ethosomes was optimized by using 3(2) factorial design for percent drug entrapment efficiency, vesicle size, zeta potential, and polydispersity index. Optimized formulation E6 showed the vesicle size (171.67 nm) and entrapment efficiency (66%) when compared with the other formulations. Thermoreversible gels prepared by using poloxamer 407 showed the phase transition temperature at 32-33 °C which was in line with the nasal physiological temperature. The optimized ethosomes were loaded into the thermoreversible mucoadhesive gel optimized by varying concentrations of poloxamer 407, carbopol 934, HPMC K100, and evaluated for gel strength, gelation temperature, mucoadhesive strength, in vitro drug release, and ex vivo drug permeation, where G3 and G6 were found to be optimized formulations. In vitro drug release was studied by different kinetic models suggested that G3 (n = 0.582) and G6 (n = 0.648) showed Korsemeyer-Peppas (KKP) model indicating non-Fickian release profiles. A permeation coefficient of 5.92 and 5.9 µg/cm(2) for G3 and G6, respectively, revealed very little difference in release rate after 24 h between both the formulations. Non-toxic nature of the gels on columnar epithelial cells was confirmed by histopathological evaluation.

Cubosomal nanoformulation increase invitro dissolution and anticancer activity of Fisetin in A549 lung cancer cells.

Aim: To prepare fisetin (FIS) cubosomal nanoformulation to increase aqueous solubility and anticancer activity. Methods: Top-down method using glyceryl monooleate (GMO) and Pluronic F-127. Results: Optimized using 2% GMO and 1% Pluronic F-127, reported 93.07 nm particle size, 80.10% drug entrapment, and reports more than 50% enhanced in vitro drug release than native FIS. MTT assay reports IC50 Values of FIS 16.59 µg/ml and optimized cubosomal FIS nanoformulation (FISCUB) 12.18 µg/ml. The colony numbers observed in clonogenic assay for FISCUB were 8.33 ± 0.58 and FIS 11.67 ± 1.15. In flow cytometry study, apoptotic cells in FISCUB and FIS-treated A549 cells were found to be 33.4 and 6.83% respectively. Conclusion: A stable cubosomal nanoformulation of FIS showed enhanced aqueous solubility and anticancer activity.

Molecular detection of Listeria monocytogenes from different dairy and street food sources in North Karnataka, India.

BACKGROUND: Food-borne pathogen Listeria monocytogenes is abundantly present in nature and accountable for sporadic and epidemic cases of listeriosis in humans. The objective of this study was to screen common food sources for L. monocytogenes using biochemical and molecular methods to detect and characterise its toxin genes as well as for biofilm formation. METHODS: A total of 92 samples, comprising dairy and street food products, were randomly collected from various sources for this investigation. The collected samples were processed for biochemical and molecular methods to detect L. monocytogenes. Additionally, virulence factors associated genes, antibiogram profiles and biofilm formation related assays were determined. RESULTS: L. monocytogenes presence was confirmed using molecular detection methods targeting prs and lmo1030 genes, along with MALDI-TOF MS. Following 16 S rRNA sequencing, the identified Listeria species were further categorised into two groups. L. monocytogenes was detected in two (2.17%) food samples tested (L-23 and L-74). Multiplex PCR indicated the presence of seven virulence-related genes in L. monocytogenes isolates, i.e., inlA, inlB, prfA, iap, actA, plcB, and hlyA. In addition, 17 antibiotics were tested, whereby two isolates showed resistance to clindamycin and azithromycin, while one isolate (L-74) was also resistant to nalidixic acid, co-trimoxazole, ampicillin, norfloxacin, and cefotaxime. L-23 and L-74 isolates showed biofilm formation, especially at pH 8.6 and 37°C. CONCLUSIONS: Besides the demonstration of the presence of L. monocytogenes in some dairy and street food products, this study underscores the need to increase the standards of hygiene on the one hand and the importance of the surveillance of food-borne pathogens on the other.

Neuroprotective effects of photobiomodulation by hormesis on scopolamine induced neurodegenerative diseases of memory disorders in rats a paradigm shift.

The loss and progressive dysfunction of neurons are hallmarks of neurodegenerative diseases. The aim of the current study is to explore the effects of photobiomodulation at 460-660 nm (100-1000 lux units) on the progression of scopolamine-induced cognitive dysfunctions in Wistar male rats. Photobiomodulation (PBM) is defined as "the use of monochromatic or quasi-monochromatic light from a low-power laser or light-emitting diode (LED) source to modify or modulate biological functions." Neuroprotective activity was assessed by in vivo models such as the Morris water maze, the elevated plus maze (EPM), and the T-maze. After using scopolamine (1 mg/kg/day) as a dementia induction model for 21 days, the induction was primarily due to impairments in cholinergic transmission, oxidative stress, and inflammation. The in vitro determinations, including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), reduced glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor-alpha (TNF-α), Interleukin 1 beta (IL-1ß), and alkaline phosphatase (ALP), were assessed biochemicals and biomarkers. The structural and morphological integrity of the cortex and hippocampus was investigated through histopathology. In vivo studies of exteroceptive behavior models such as the Morris water maze, the EPM, and the T-maze revealed that administration of scopolamine resulted in enhanced escape latency time (ELT), transfer latency (TL), and decreased percentage alternation, respectively. The levels of AChE, BChE, reduced, GSH, SOD, TNF-α, IL-1ß and ALP were increased, while MDA level was decreased. In contrast to normal and control groups with treatment groups, histopathology of the cortex and hippocampus examination revealed the maintenance of structural integrity and densities of CA1 and CA3 neuronal cells. However, network pharmacology predicted Ca+2 modulation of various pathways, among the treatments with red LED light showed highly significant amelioration compared with normal and control groups. Photobiomodulation by hormesis, chromophores in cells, and tissues excitation can influence neuroprotective effect mainly by scavenging of ROS, variation in the level of GSH MDA and SOD mitochondrial electron transfer, the improved abscopal effects on improved in gut microbiome by resembles the of fecal ALP level correlation of intestinal microbiome, cholinergic neurotransmissions, anti-inflammatory, and antioxidant activities.

Structural insights into modeling of hepatitis B virus reverse transcriptase and identification of its inhibitors from potential medicinal plants of Western Ghats: an in silico and in vitro study.

The present study was proposed to model full-length HBV-RT and investigate the intermolecular interactions of known inhibitor and libraries of phytocompounds to probe the potential natural leads by in silico and in vitro studies. Homology modeling of RT was performed by Phyre2 and Modeller and virtual screening of ligands implemented through POAP pipeline. Molecular dynamics (MD) simulation (100 ns) and MM-GBSA calculations were performed using Schrodinger Desmond and Prime, respectively. Phytocompounds probable host protein targets gene set pathway enrichment and network analysis were executed by KEGG database and Cytoscape software. Prioritized plant extracts/enriched fraction LC-MS analysis was performed and along with pure compound, RT inhibitory activity, time-dependent HBsAg and HBeAg secretion, and intracellular HBV DNA, and pgRNA by qRT-PCR was performed in HepG2.2.15 cell line. Among the screened chemical library of 268 phytocompounds from 18 medicinal plants, 15 molecules from Terminalia chebula (6), Bidens pilosa (5), and Centella asiatica (4)) were identified as potential inhibitors of YMDD and RT1 motif of HBV-RT. MD simulation demonstrated stable interactions of 15 phytocompounds with HBV-RT, of which 1,2,3,4,6-Pentagalloyl Glucose (PGG) was identified as lead molecule. Out of 15 compounds, 11 were predicted to modulate 39 proteins and 15 molecular pathways associated with HBV infection. TCN and TCW (500 µg/mL) showed potent RT inhibition, decreased intracellular HBV DNA, and pgRNA, and time-dependent inhibition of HBsAg and HBeAg levels compared to PGG and Tenofovir Disoproxil Fumarate. We propose that the identified lead molecules from T. chebula as promising and cost-effective moieties for the management of HBV infection.Communicated by Ramaswamy H. Sarma.

Design, synthesis, molecular dynamics simulation, MM/GBSA studies and kinesin spindle protein inhibitory evaluation of some 4-aminoquinoline hybrids.

The discovery of novel chemotherapeutic agents is always challenging for researchers in industry and academia. Among the recent promising anticancer therapeutic targets, an important modulatory factor in mitosis is the expression of the kinesin family motor protein (Eg5). In terms of chemotherapy treatment, mitosis has gained significant attention due to its role as one of the biological processes that can be intervened in it. This study was undertaken to design, synthesise and evaluation of 4-aminoquinoline hybrid compounds as potential Eg5 inhibitors. Based on data collected from Malachite green and steady state ATPase assays, it has been determined that compounds such as 6c, 6d, 6g, and 6h are sensitive to Eg5 inhibition. In special mention, compounds 4 and 6c showed promising inhibitory activity in Malachite green assay with IC50 values of 2.32 ± 0.23 µM and 1.97 ± 0.23 µM respectively. Compound 4 showed favourable inhibitory potential Steady state ATPase Assay with IC50 value of 5.39 ± 1.39 µM. We performed molecular docking, MM/GBSA calculations, and molecular dynamic simulations to evaluate the interactions between ligands and the binding site of the kinesin spindle protein to evaluate the functional consequences of these interactions. As a result of these findings, it can be concluded that these 4-amioquinoline Schiff's base hybrids may prove to be promising candidates for development as novel inhibitors of Eg5. Further in-vivo research in this area is required.

Decipher the inhibitory potential of phytocompounds from Leptadenia reticulata on dopamine D2 receptor to enhance prolactin secretion.

Dopamine is secreted by the hypothalamus, which inhibits the proliferation and effectiveness of lactotroph cells that release prolactin via dopamine D2 receptor (D2R). D2R activation inhibits lactotroph cell prolactin synthesis and regulates prolactin gene expression. Although, commercial medications are available for hypogalactia and agalactia, various plant sources significantly alleviate these problems. Leptadenia reticulata (Jivanti) is one of the important medicinal plants often consumed by nursing mothers to improve breast milk production. However, mechanism and chemical constituents involved in the inhibition of D2R by Jivanti is unclear. Therefore, in this study the phytocompounds reported from Jivanti were used for in-silico analysis to predict D2R inhibitory potential. The binding affinity value of campesterol and ß-sitosterol (- 10.1 and -10.0 kcal/mol) with D2R has high revealed by molecular docking and stable interaction reveled by molecular dynamics simulation. Thus, these lead compounds could exert more D2R inhibitory activity resulting into prolactin release, which may lead to an increase in breast milk production. Although all selected compounds had fine permeation, non-toxic, and non-carcinogenic characteristics predicted by ADMET, campesterol had good solubility, absorption characteristics compared to other. Therefore, Jivanti, which is traditionally known medicinal plant, could be explored as a medication candidate to boost breast milk production.

Synthesis, molecular docking and ADME studies of thiazole-thiazolidinedione hybrids as antimicrobial agents.

New thiazole-thiazolidinedione hybrids (5a-k) were efficiently synthesized and evaluated for their in-vitro antimicrobial activity against four fungal and bacterial strains. The chemical structures of the compounds were elucidated by FTIR, 1H NMR, and 13C NMR spectral data. Most of the synthesized compounds were sensitive against gram positive, gram negative bacterial and fungal strains. Among the synthesized molecules, compounds 5h, and 5i exhibited promising inhibitory activity against all selected fungal strains and gram positive bacteria namely, Staphylococcus aureus, and Enterococcus faecalis. The molecular docking results predicted that the thiazole-thiazolidinedione derivatives bind to the active site protein ATP-binding pocket from E. coli, S. aureus and C. albicans with good interaction energy scores. Ct-DNA was used to evaluate the binding interactions of the selected compounds by means of absorption spectroscopy. To further characterize the drug-likeness and ADME properties were calculated using the Qikprop, the result of present study suggests that thiazole-thiazolidinedione hybrid could be an interesting approach for the design of new antimicrobial agents.Communicated by Ramaswamy H. Sarma.

Formulation and Evaluation of Resveratrol Loaded Cubosomal Nanoformulation for Topical Delivery.

AIM: The aim of the study was to formulate, characterize, and evaluate the Resveratrol- loaded Cubosomes (RC) for topical application. BACKGROUND: Resveratrol (RV) is a nutraceutical compound with exciting pharmacological potential in different diseases, including cancers. Many studies on resveratrol have been reported for anti- melanoma activity. Due to its low bioavailability, the therapeutic activities of resveratrol are strongly limited. Hence, an approach with nanotechnology has been made to increase its activity through transdermal drug delivery. OBJECTIVE: To formulate, characterize, and evaluate the resveratrol-loaded cubosomes (RC). To evaluate Resveratrol-loaded Cubosomal Gel (RC-Gel) for its topical application. METHODS: RC was formulated by homogenization technique and optimized using a 2-factor 3-level factorial design. Formulated RCs were characterized for particle size, zeta potential, and entrapment efficiency. Optimized RC was evaluated for in vitro release and stability study. Optimized RC was further formulated into cubosomal gel (RC-Gel) using carbopol and evaluated for drug permeation and deposition. Furthermore, developed RC-Gel was evaluated for its topical application using skin irritancy, toxicity, and in vivo local bioavailability studies. RESULTS: The optimized RC indicated cubic-shaped structure with mean particle size, entrapment efficiency, and zeta potential were 113±2.36 nm, 85.07 ± 0.91%, and -27.40 ± 1.40 mV, respectively. In vitro drug release of optimized RC demonstrated biphasic drug release with the diffusion-controlled release of resveratrol (RV) (87.20 ± 3.91%). The RC-Gel demonstrated better drug permeation and deposition in mice skin layers. The composition of RC-Gel has been proved non-irritant to mice skin. In vivo local bioavailability study depicted the good potential of RC-Gel for skin localization. CONCLUSION: The RC nanoformulation proposes a promising drug delivery system for melanoma treatment simply through topical application.

Antidiabetic activity of aqueous bark extract of Cassia glauca in streptozotocin-induced diabetic rats.

The leaves and bark of Cassia glauca Lam., a glabrous tree in the family Fabaceae, are used in folk medicine for the treatment of diabetes. The aim of this study was to investigate the antidiabetic activity of the aqueous extract of C. glauca bark. The various parameters that were studied in treated or untreated normoglycemic and STZ-induced diabetic rats included the effect of the aqueous extract on oral glucose tolerance, fasting blood glucose, body weight, serum lipids, liver glycogen, serum insulin, and glycosylated haemoglobin. Oral administration of the aqueous extract of C. glauca bark at a dose of 500 mg/kg significantly reduced the effect of external glucose load. In a chronic treatment model, aqueous extract and glibenclamide (0.25 mg/kg) were administered for 21 days. At the end of the treatment, there was a significant increase in liver glycogen, serum insulin, and HDL cholesterol for both treatments. A significant decrease in fasting blood glucose, glycosylated haemoglobin, total cholesterol, and serum triglycerides was also observed. The body weights of the animals were observed to be consistent throughout the study. The findings showed the significant antidiabetic potential of the extract in ameliorating the diabetic condition in the diabetic rats. No significant activity was found in the normoglycemic rats.

Pharmacokinetic and Pharmacodynamic Evaluation of Resveratrol Loaded Cationic Liposomes for Targeting Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. The destructive nature of the disease makes it difficult for clinicians to manage the condition. Hence, there is an urgent need to find new alternatives for HCC, as the role of conventional cytotoxic drugs has reached a plateau to control HCC associated mortality. Antioxidant compounds of plant origin with potential anti-tumor effect have been recognized as alternate modes in cancer treatment and chemoprevention. Resveratrol (RS) is a model natural nonflavonoid drug known for its anti-cancer activity. However, its clinical application is limited due to its poor bioavailability. The current research work aims to formulate, optimize, and characterize RS loaded cationic liposomes (RLs) for specific delivery in HCC. The optimized liposomes formulation (RL5) was spherical with a vesicle size (VS) of 145.78 ± 9.9 nm, ζ potential (ZP) of 38.03 ± 9.12 mV, and encapsulation efficiency (EE) of 78.14 ± 8.04%. In vitro cytotoxicity studies in HepG2 cells demonstrated an improved anti-cancer activity of RL5 in comparison with free RS. These outcomes were supported by a cell uptake study in HepG2 cells, in which RL5 exhibited a higher uptake than free RS. Furthermore, confocal images of HepG2 cells after 3 and 5 h of incubation showed higher internalization of coumarin 6 (C6) loaded liposomes (CL) as compared to those of the free C6. Pharmacokinetic and pharmacodynamic (prophylactic and therapeutic treatment modalities) studies were performed in N-nitrosodiethylamine (NDEA-carcinogen) induced HCC in rats. Pharmacokinetic evaluation of RL5 demonstrated increased localization of RS in cancerous liver tissues by 3.2- and 2.2-fold increase in AUC and Cmax, respectively, when compared to those of the free RS group. A pharmacodynamic investigation revealed a significant reduction in hepatocyte nodules in RL5 treated animals when compared to those of free RS. Further, on treatment with RL5, HCC-bearing rats showed a significant decrease in the liver marker enzymes (alanine transaminase, alkaline phosphatase, aspartate transaminase, total bilirubin levels, γ-glutamyl transpeptidase, and α-fetoprotein), in comparison with that of the disease control group. Our findings were supported by histopathological analysis, and we were first to demonstrate that NDEA induced detrimental effect on rat livers was successfully reversed with the treatment of RL5 formulation. These results implied that delivery of RS loaded cationic liposomes substantially controlled the severity of HCC and that they can be considered as a promising nanocarrier in the management of HCC.

A validated stability-indicating HPLC method for simultaneous estimation of resveratrol and piperine in cubosome and human plasma.

Resveratrol and piperine are proven for their therapeutic benefits to treat various diseases. Due to their synergistic actions and combined drug delivery application, a rapid and specific RP-HPLC method was developed and validated as per ICH guidelines, by using an isosbestic point. The chromatographic separation was performed with Luna 5 µ 100 ŠC-18(2) HPLC column by using acetonitrile (ACN): phosphate buffer (0.01% orthophosphoric acid) (55:45) as mobile phase, at 1 mL/min of flow rate and 330 nm. The developed method was found to be linear over the concentration range of 0.25-8 µg/mL with correlation coefficient value >0.999. The developed method was accurate (percent recovery 98.06-101.74%), precise (percent relative standard deviation <2.0%), and robust. The limit of detection and limit of quantification for resveratrol were found to be 0.02 and 0.08 µg/mL, respectively and 0.04 and 0.11 µg/mL, for piperine, respectively. The developed method was also validated in human plasma as per ICH guidelines. Moreover, stress degradation studies of both phytoconstituents were studied and the relevancy of the developed method was analyzed on cubosome nanoformulation. A good separation of drug peaks was observed in the presence of the degradation products. This method could thus be used for regular in vitro and in vivo estimation of piperine and resveratrol.

Local drug delivery systems in the management of periodontitis: A scientific review.

Periodontitis (PD) is a microbial disease of tooth supporting tissues that results in progressive destruction of surrounding soft and hard tissues with eventual tooth mobility and exfoliation. Perioceutics, which includes the delivery of therapeutic agents via systemic and local means as an adjunct to mechanical therapy has revolutionized the arena of periodontal therapy. Selection of a right antimicrobial agent with appropriate route of drug administration is the key to successful periodontal therapy. Irrigating systems, fibers, gels, strips, films, microparticles, nanoparticles and low dose antimicrobial agents are some of the local drug delivery systems (LDDS) available in the field, which aims to deliver antimicrobial agents to sub-gingival diseased sites with minimal or no side-effects on other body sites. The present review aim to summarize the current state-of-the-art technology on LDDS in periodontal therapy ensuring the the practitioners are able to choose LDD agents which are custom made for a specific clinical condition.