Enhancing pharmaceutical potential and oral bioavailability of Allium cepa nanosuspension in male albino rats using response surface methodology

Objective: To enhance the pharmaceutical potential and oral bioavailability of quercetin contents of Allium cepa peel extract by novel nanosuspension technology. Methods: Nanoprecipitation approach was successfully used for the formulation of nanosuspension. To obtain pharmaceutical-grade nanosuspension with minimum particle size and polydispersity index, sodium lauryl sulphate was selected as a stabilizer. Important formulation parameters were statistically optimized by the response surface methodology approach. The optimized nanosuspension was subjected to stability and in vitro dissolution testing and characterized by scanning electron microscopy, atomic force microscopy, Fourier transform infrared spectroscopy, and zeta sizer. To evaluate the preeminence of nanosuspension over coarse suspension, comparative bioavailability studies were carried out in male albino rats. The pharmaceutical potential of developed nanosuspension was evaluated by antioxidant, antimicrobial, and toxicity studies. Results: The optimized nanosuspension showed an average particle size of 275.5 nm with a polydispersity index and zeta potential value of 0.415 and -48.8 mV, respectively. Atomic force microscopy revealed that the average particle size of nanosuspension was below 100 nm. The formulated nanosuspension showed better stability under refrigerated conditions. Nanosuspension showed an improved dissolution rate and a 2.14-fold greater plasma concentration of quercetin than coarse suspension. Moreover, the formulated nanosuspension exhibited enhanced antioxidant and antimicrobial potential and was non-toxic. Conclusions: Optimization of nanosuspension effectively improves the pharmaceutical potential and oral bioavailability of Allium cepa extract.

Enhancing pharmaceutical potential and oral bioavailability of Allium cepa nanosuspension in male albino rats using response surface methodology

Objective: To enhance the pharmaceutical potential and oral bioavailability of quercetin contents of Allium cepa peel extract by novel nanosuspension technology. Methods: Nanoprecipitation approach was successfully used for the formulation of nanosuspension. To obtain pharmaceutical-grade nanosuspension with minimum particle size and polydispersity index, sodium lauryl sulphate was selected as a stabilizer. Important formulation parameters were statistically optimized by the response surface methodology approach. The optimized nanosuspension was subjected to stability and in vitro dissolution testing and characterized by scanning electron microscopy, atomic force microscopy, Fourier transform infrared spectroscopy, and zeta sizer. To evaluate the preeminence of nanosuspension over coarse suspension, comparative bioavailability studies were carried out in male albino rats. The pharmaceutical potential of developed nanosuspension was evaluated by antioxidant, antimicrobial, and toxicity studies. Results: The optimized nanosuspension showed an average particle size of 275.5 nm with a polydispersity index and zeta potential value of 0.415 and -48.8 mV, respectively. Atomic force microscopy revealed that the average particle size of nanosuspension was below 100 nm. The formulated nanosuspension showed better stability under refrigerated conditions. Nanosuspension showed an improved dissolution rate and a 2.14-fold greater plasma concentration of quercetin than coarse suspension. Moreover, the formulated nanosuspension exhibited enhanced antioxidant and antimicrobial potential and was non-toxic. Conclusions: Optimization of nanosuspension effectively improves the pharmaceutical potential and oral bioavailability of Allium cepa extract.

Nanosuspension enhances dissolution rate and oral bioavailability of Terminalia arjuna bark extract in vivo and in vitro

Objective: To enhance the dissolution rate and oral bioavailability of Terminalia arjuna bark extract by formulating its nanosuspension. Methods: Nanoprecipitation approach was used for the formulation of nanosuspension using polysorbate-80 as a stabilizer. The formulated nanosuspension was assessed for particle size, polydispersity index, zeta potential value and for in vitro dissolution study. Oral bioavailability studies were carried out in Wistar male albino rats by administering a single dose (50 mg/kg. b. wt) of the formulated nanosuspension and coarse suspension. The storage stability of the formulated nanosuspension was determined after three months of storage at room temperature and under the refrigerated condition. Mutagenicity assay was carried out to evaluate the toxicity of the formulated nanosuspension using two mutant strains (Salmonella typhimurium TA100 and Salmonella typhimurium TA98). Results: The mean particle size of the formulated nanosuspension was 90.53 nm with polydispersity index and zeta potential values of 0.175 and-15.7 mV, respectively. Terminalia arjuna nanosuspension showed improved dissolution rate and 1.33 fold higher oral bioavailability than its coarse suspension. The formulated nanosuspension also showed better stability under the refrigerated condition and was non-mutagenic against both strains. Conclusions: Our study demonstrates that nanosuspension technology can effectively enhance the dissolution rate and oral bioavailability of Terminalia arjuna bark extract. Zafar Fatiqa 1 Department of Chemistry, University of Okara, Okara Jahan Nazish 2 Department of Chemistry, University of Agriculture, Faisalabad Khalil-Ur-Rahman 3 Department of Biochemistry, University of Agriculture, Faisalabad Asi Muhammad 4 Food Toxicology Lab, Plant Protection Division, Nuclear Institute for Agriculture and Biology, Faisalabad Zafar Waseeq-Ul-Islam 5 Department of Computer Science, COMSATS University of Information and Technology, Islamabad Pawar SS, Dahifale BR, Nagargoje SP, Shendge RS. Nanosuspension technologies for delivery of drugs. Nanosci Nanotech Res 2017; 4(2): 5966. Kilor V, Sapkal N, Daud A, Humne S, Gupta T. Development of stable nanosuspension loaded oral films of glimepiride with improved bioavailability. Int J Appl Pharm 2017; 9(2): 28-33. He J, Han Y, Xu G, Yin L, Neubi MN, Zhou J, et al. Preparation and evaluation of celecoxib nanosuspensions for bioavailability enhancement. RSC Adv 2017; 7: 13053-13064. 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In vitro antioxidant, hepatoprotective potential and chemical profiling of Syzygium aromaticum using HPLC and GC?MS

The objective of the present study was to evaluate the in vitro antioxidant and hepatoprotective potential of Syzygium aromaticum [clove] against CCl[4]-induced hepatotoxicity using rat liver slice culture [LSC] model. Antioxidant activity in terms of DPPH radical scavenging activity and ferric reducing antioxidant power [FRAP] of different concentrations of S. aromaticum was in the range of 41.01-90.33% and 138.15-595.63 Fe [II] mg/mL, respectively. Plasmid pBR322 DNA protection activity was observed with all three concentrations of S. aromaticum against H2O2 induced oxidative damage, as no strand breaks were observed. Chemical profiling through HPLC confirmed the presence of six major phenolic acids and 13 volatile bioactive compounds were identified though GC-MS. Significant hepatoprotection [p<0.05] was observed in liver slice culture [LSC] as liver slices treated with various concentrations of S. aromaticum extract presented very low percentage cytotoxicity [7.35-16.16%] as compared to the CCl4 treated liver slices [75.58 %]. The hepatoprotective potential of S. aromaticum may be due to the presence of bioactive components as confirmed by HPLC and GC-MS. The results of present study support the use of S. aromaticum in the formation of potential hepatoprotective drugs against various liver diseases

Synergistic interactions of polyphenols and their effect on antiradical potential

The aim of the current study was to evaluate interactions among polyphenols from different plants and their effect on antioxidant potential. Different mixtures of plant extracts of Crataegus oxyacantha [C], Elettaria cardamomum [Cr], Terminalia arjuna [T] and Rauvolfia serpentina [R] were prepared and evaluated for total phenolics, flavonoid contents, and antioxidant activity. A correlation was also established between total phenolics, flavonoids and antioxidant activity. Comparative evaluation revealed that phenolics, flavonoids and antioxidant activity were found high in plant extracts mixtures than individual plants. Highest phenolics [580+/-1.12mg GAE/g], flavonoids [67.10+/-0.11mg CE/g] and antioxidant activity [IC[50] 0.109mg/ml] was observed with ratio 1:1:1:2 of plant mixture C, Cr, T, R. A weak linear positive correlation was found between antioxidant activity, total phenolic and flavonoid contents. A negative correlation was observed among IC[50] value, total phenolics and flavonoid contents. Investigation through RP-HPLC revealed the presence of different potent phenolics in plants understudy. More antioxidant potential of extracts in combinations as compared to that of individual plants was clear corroboration of synergism. The ratio [1:1:1:2] of the studied plants in combination, that showed the highest free radical potential, was another expected better pharmacological prospect. This formulation can bring maximum relief against free radical-associated diseases

Protection of DNA during oxidative stress and cytotoxic potential of Artemisia absinthium

Medicinal plants are rich in secondary metabolites [alkaloids, glycosides, coumarins, flavonides, steroids, etc.] and considered to be more effective and a safer alternative source to manage a variety of diseases related to liver, heart and kidney disordered. This study determines in vitro antioxidant and in vivo toxicological profile including hemolytic, brine shrimp lethality and mutagenicity of aerial parts of Artemisia absinthium. DNA protection assay was performed on pUC19 plasmid vector using H2O2 as oxidative agent. Total phenolic and flavonoid content were determined using colorimetric methods. Toxicity of the plant was evaluated by brine shrimp lethality, hemolytic and mutagenic activity. DNA protection assay of the plant showed concentration dependent protective effect and at concentration 10microL/mL revealed complete protective effect against H2O2 induced DNA damage. Highest phenolic and flavonoid content was found to be 167.3 [mg GAE 100g DW-1] and 14 [mg CE 100g DW-1] respectively. Results showed that A. absinthium is potent against standard toxicological procedures, that indicates the presence of bioactive components in the plant and possess antioxidant activity that protects DNA against H2O2 induced oxidative damage. Thus the results showed/support that A. absinthium provides significant health benefits

Hepatitis C; early prediction of therapy response in patients and the benefits of treatment extension in non responders

Hepatitis C virus [HCV] has infected about 200 million individuals across the world and is known as the major cause of liver disease. Viral load measurement at early stages of the therapy in Hepatitis C patients is believed to be a more effective tool to predict the sustained virological response [SVR]. The primary aim of the present study was to evaluate whether the decline in viral load of HCV at early stages of the therapy may predict the treatment response. Another objective was to see the benefits of therapy extension in non-responders. Descriptive, analytical study. Shalamar Hospital Lahore. November 2010 to October 2013. Four hundred and thirty patients, chronically infected with different genotypes of Hepatitis C virus were treated with Interferon alpha 2b plus Ribavirin [IFN alpha-2b + RBV]. Viral load was assessed at day zero, week four, in the mid time of therapy and at the end of therapy. The treatment duration was extended 12-24 weeks [according to HCV genotypes] in non-responders. The patients with <2 MIU/ mL viral load at day zero, able to drop >/=2 log viral load at week-4 or showed no virus at the time of half therapy completion, exhibited better response. The extension of therapy was more beneficial for those non-responder who had <0.05 MIU/mL viral load at the end point of therapy than those who had >/=0.05 MIU/mL at that stage. The viral load detection at early stages of the therapy will be useful in clinical practice. Moreover, the patients with <0.05 MIU/ mL viral load at the end of therapy are suitable candidates for the therapy extension

Gemmomodification: an emerging source of natural antioxidants from Silybum marianum

Gemmomodification is a form of herbal medicine in which young freshly growing buds of plants are used. At germinating stage, plants metabolic activities are maximum and various nutrients, hormones enzymes and bioactive phytoconstituents are released and available at this stage. Plants may be promising source of natural antioxidants at growing stage. Oxidative stress leads to many chronic and degenerative diseases. Antioxidants are very essential for human body; they can protect the body from damage caused by free radical induced oxidative stress. This research project had been designed to investigate the antioxidant potential of gemmo modified and native [dry leaves] extract of Silybum marianum. Total phenolic contents was calculated by using Folin-Ciocalteu reagent and antioxidant potential was evaluated by using four radical assays [DPPH, ABTS, Super oxide and nitric oxide], reducing power assay and lipid peroxidation assay spectrophotometrically. Gemmo modified extract showed significantly higher [p<0.050] TPC [830 mg GAE/g of plant extract] as compared to native extract [800 mg GAE/g.] Results of this study revealed that gemmo modified extract demonstrated better antioxidant potential than natively used parts of Silybum marianum

Synthesis and applications of coumarin

In this work, coumarin was synthesized by Perkin reaction using salicylaldehyde, acetic acid and sodium acetate. Due to the misuse of acetic anhydride in narcotics synthesis, acetic acid was substituted for acetic anhydride in Perkin reaction. On the basis of this substitution a hypothesis was proposed that "acetic acid could be substituted as an acetylating agent in place of acetic anhydride in coumarin synthesis via Perkin reaction". In the present research project, salicylaldehyde was prepared from phenol, sodium hydroxide and chloroform for further procedure. Then four different coumarin samples were synthesized by changing the parameter of reactants proportions. From this parameter, we designed a trend of high product yield. Yields of Coumarin samples will lead towards either acception or rejection of the above proposed hypothesis. In the next step, these Coumarin samples were characterized by age yield [%], solubility and melting points. At last Antibacterial activities of all the four coumarin samples were evaluated against two bacterial strains; E.coli and S.aureus. As a consequence of all above, it was inferred that the yields of all coumarin samples obtained were low as compared to the yield obtained by the use of acetic anhydride in previous reports. This led to the rejection of proposed hypothesis. Among four Coumarin samples, sample-4 obtained by taking equal amounts of all the reactants had shown maximum yield, best characterization and excellent antibacterial activity. In spite of low yields obtained, the remarkable antibacterial activities of Coumarin samples have enabled us to suggest coumarin as a strong antibacterial agent and it must be employed for further applications