Search results for: rats
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 723

Search results for: rats

213 Salmonella Spp. and Essential Oil of Laurus nobilis

Authors: Karima Oldyerou, B. Meddah, A. Tirtouil

Abstract:

The food borne infections have a significant impact on public health. Salmonella is the first bacterial cause, especially because of its general availability in the intestinal tract of poultry, pigs and cattle. This bacteria and essential oil of Laurus nobilis subject in this article. In vitro evaluation of the antibacterial activity shows a sensitivity of Salmonella spp. with a MIC of 2.5 mg.ml -1 in vivo after infection of wistar rats and administered orally this essential oil, microbiological results fecal material shows the antibacterial effect of this oil on Salmonella spp.

Keywords: Laurus nobilis, essential oil, salmonella, antibacterial activity, fecal matte

Procedia PDF Downloads 319
212 Bioavailability Enhancement of Ficus religiosa Extract by Solid Lipid Nanoparticles

Authors: Sanjay Singh, Karunanithi Priyanka, Ramoji Kosuru, Raju Prasad Sharma

Abstract:

Herbal drugs are well known for their mixed pharmacological activities with the benefit of no harmful side effects. The use of herbal drugs is limited because of their higher dose requirement, frequent drug administration, poor bioavailability of phytochemicals and delayed onset of action. Ficus religiosa, a potent anti-oxidant plant useful in the treatment of diabetes and cancer was selected for the study. Solid lipid nanoparticles (SLN) of Ficus religiosa extract was developed for the enhancement in oral bioavailability of stigmasterol and β-sitosterol-d-glucoside, principal components present in the extract. Hot homogenization followed by ultrasonication method was used to develop extract loaded SLN. Developed extract loaded SLN were characterized for particle size, PDI, zeta potential, entrapment efficiency, in vitro drug release and kinetics, fourier transform infra-red spectroscopy, differential scanning calorimetry, powder X-ray diffractrometry and stability studies. Entrapment efficiency of optimized extract loaded SLN was found to be 68.46 % (56.13 % of stigmasterol and 12.33 % of β-sitosteryl-d-glucoside, respectively). RP HPLC method development was done for simultaneous estimation of stigmasterol and β-sitosterol-d-glucoside in Ficus religiosa extract in rat plasma. Bioavailability studies were carried out for extract in suspension form and optimized extract loaded SLN. AUC of stigmasterol and β-sitosterol-d-glucoside were increased by 6.7-folds by 9.2-folds, respectively in rats treated with extract loaded SLN compared to extract suspension. Also, Cmax of stigmasterol and β-sitosterol-d-glucoside were increased by 4.3-folds by 3.9-folds, respectively in rats treated with extract loaded SLN compared to extract suspension. Mean residence times (MRT) for stigmasterol were found to be 12.3 ± 0.67 hours from extract and 7.4 ± 2.1 hours from SLN and for β-sitosterol-d-glucoside, 10.49 ± 2.9 hours from extract and 6.4 ± 0.3 hours from SLN. Hence, it was concluded that SLN enhanced the bioavailability and reduced the MRT of stigmasterol and β-sitosterol-d-glucoside in Ficus religiosa extract which in turn may lead to reduction in dose of Ficus religiosa extract, prolonged duration of action and also enhanced therapeutic efficacy.

Keywords: Ficus religiosa, phytosterolins, bioavailability, solid lipid nanoparticles, stigmasterol and β-sitosteryl-d-glucoside

Procedia PDF Downloads 442
211 Development of NO-Ergic Synaptic Transmission in Sympathetic Neurons of Mammals: Immunohistochemical Study

Authors: Konstantin Yu. Moiseev, Antonina F. Budnik, Andrey I. Emanuilov, Petr M. Masliukov

Abstract:

The vast majority of sympathetic ganglionic neurons are catecholaminergic. Some sympathetic neurons lack catecholamines and mostly use acetylcholine as their main neurotransmitter. Some cholinergic postganglionic neurons also express neuronal nitric oxide synthase (nNOS). Preganglionic sympathetic neurons are cholinergic and most of them are also nNOS-immunoreactive (IR). The purpose of this study was to gain further insight into the neuroplasticity of sympathetic neurons during postnatal ontogenesis by comparing the development of pre- and postganglionic neurons expressing nNOS in different mammals. nNOS was investigated by immunohistochemistry in the sympathetic superior cervical ganglion (SCG), stellate ganglion (SG), celiac ganglion (CG) and spinal cord from rats, mice and cats of different ages (newborn, 10-day-old, 20-day-old, 30-day-old, 2-month-old and 2-year-old). In rats and mice, nNOS-positive neurons were not found in sympathetic ganglia from birth onwards. In cats, non-catecholaminergic nNOS-IR sympathetic ganglionic neurons are present from the moment of birth. In all studied age groups, substantial populations of nNOS-IR cells (up to 8.3%) was found in the SG, with a much smaller population found in the SCG (<1%) and only few cells observed in the CG. The percentage of nNOS-IR neurons in the CG and SCG did not significantly change during development. The proportion of nNOS-IR neuron profiles in the SG increased in first 20 days of life from 2.3±0.15% to 8.3±0.56%. In the SG, percentages of nNOS-IR sympathetic neurons colocalizing vasoactive intestinal peptide increased in the first 20 days of life. Choline acetyltransferase (ChAT)-IR and calcitonin gene-related peptide-IR neurons were not observed in the sympathetic ganglia of newborn animals and did not appear until 10 days after birth. In the SG of newborn and 10-day-old kittens, the majority of NOS-IR neurons were calbindin (CB)-IR, whereas in the SCG and CG of cats of all age groups and in the SG of 30-day-old and older kittens, the vast majority of NOS-IR neurons lacked CB. In newborn mammals, the most of sympathetic preganglionic neurons in the nucleus intermediolateralis thoracolumbalis pars principalis (nucl.ILp) were nNOS-IR. The percentage of nNOS-IR neurons decreased and the same parameter of ChAT-IR neurons increased during the development. We conclude that the development of nNOS-IR preganglionic and ganglionic sympathetic neurons in different mammals has time and species differences.

Keywords: sympathetic neuron, nitric oxide synthase, immunohistochemistry, development

Procedia PDF Downloads 192
210 Metagenomic Analysis and Pharmacokinetics of Phage Therapy in the Treatment of Bovine Subclinical Mastitis

Authors: Vaibhav D. Bhatt, Anju P. Kunjadia, D. S. Nauriyal, Bhumika J. Joshi, Chaitanya G. Joshi

Abstract:

Metagenomic analysis of milk samples collected from local cattle breed, kankrej (Bos indicus), Gir (Bos indicus) and Crossbred (Bos indicus X Bos taurus) cattle harbouring subclinical mastitis was carried out by next-generation sequencing (NGS) 454 GS-FLX technology. Around 56 different species including members of Enterobacteriales, Pseudomonadales, Bacillales and Lactobacillales with varying abundance were detected in infected milk. The interesting presence of bacteriophages against Staphylococcus aureus, Escherichia coli, Enterobacter and Yersinia species were observed, especially Enterobacteria and E. coli phages (0∙32%) in Kankrej, Enterobacteria and Staphylococcus phages (1∙05%) in Gir and Staphylococcus phages (2∙32%) in crossbred cattle. NGS findings suggest that phages may be involved in imparting natural resistance of the cattle against pathogens. Further infected milk samples were subjected for bacterial isolation. Fourteen different isolates were identified, and DNA was extracted. Genes (Tet-K, Msr-A, and Mec-A) providing antibiotic resistance to the bacteria were screened by Polymerase Chain Reaction and results were validated with traditional antibiotic assay. Total 3 bacteriophages were isolated from nearby environment of the cattle farm. The efficacy of phages was checked against multi-drug resistant bacteria, identified by PCR. In-vivo study was carried out for phage therapy in mammary glands of female rats “Wister albino”. Mammary glands were infused with MDR isolates for 3 consecutive days. Recovery was observed in infected rats after intramammary infusion of sterile phage suspension. From day 4th onwards, level of C-reactive protein was significant increases up to day 12th . However, significant reduction was observed between days 12th to 18th post treatment. Bacteriophages have significant potential as antibacterial agents and their ability to replicate exponentially within their hosts and their specificity, make them ideal candidates for more sustainable mastitis control.

Keywords: bacteriophages, c-reactive protein, mastitis, metagenomic analysis

Procedia PDF Downloads 279
209 Proprotein Convertase Subtilisin/Kexin Type 9 Enhances Arterial Medial Calcification in a Uremic Rat Model of Chronic Kidney Disease

Authors: Maria Giovanna Lupo, Marina Camera, Marcello Rattazzi, Nicola Ferri

Abstract:

A complex interplay among chronic kidney disease, lipid metabolism and aortic calcification has been recognized starting from results of many clinical and experimental studies. Here we investigated the influence of kidney function on PCSK9 levels, both in uremic rats and in clinical observation study, and its potential direct action on cultured smooth muscle cells (SMCs) calcification. In a cohort of 594 subjects enrolled in a single centre, observational, cross-sectional and longitudinal study, a negative association between GFR and plasma PCSK9 was found. Atherosclerotic cardiovascular disease (ASCVD), as co-morbidity, further increased PCSK9 plasma levels. Diet-induced uremic condition in rats, induced aortic calcification and increased total cholesterol and PCSK9 levels in plasma, livers and kidneys. Immunohistochemical analysis confirmed PCSK9 expression in aortic SMCs. SMCs overexpressing PCSK9 (SMCsPCSK9), cultured for 7-days in a pro-calcification environment (2.0mM or 2.4mM inorganic phosphate, Pi) showed a significantly higher extracellular calcium (Ca2+) deposition compared to mocked SMCs. Under the same experimental conditions, the addition of exogenous recombinant PCSK9 did not increase the extracellular calcification of SMCs. By flow cytometry analysis we showed that SMCsPCSK9, in response to 2.4mM Pi, released higher number of extracellular vesicles (EVs) positive for three tetraspanin molecules, such as CD63, CD9, and CD81. EVs derived from SMCsPCSK9 tended to be more enriched in calcium and alkaline phosphatase (ALPL), compared to EVs from mocks SMCs. In conclusion, our study reveals a direct role of PCSK9 on vascular calcification induced by higher inorganic phosphate levels associated to CKD condition. This effect appears to be mediated by a positive effect of endogenous PCSK9 on the release of EVs containing Ca2+ and ALP, which facilitate the deposition inorganic calcium phosphate crystals.

Keywords: PCSK9, calcification, extracellular vesicles, chronic kidney disease

Procedia PDF Downloads 83
208 Acoustic Characteristics of Ultrasonic Vocalizations in Rat Pups Prenatally Exposed to Ethanol

Authors: Mohd. Ashik Shahrier, Hiromi Wada

Abstract:

Prenatal ethanol exposure has potential to induce difficulties in the social behavior of rats and can alter pup-dam communication suggesting that deficits in pups could result in altered dam behavior, which in turn could result in more aberrant behavior in the pup. Ultrasonic vocalization (USV) is a sensitive tool for investigating social behavior between rat pups and their dam. Rat pups produce USVs on separation from their dam. This signals the dam to locate her pups and retrieve them back to the nest. In this study, it was predicted that prenatal ethanol exposure cause alterations on the acoustic characteristics of USVs in rat pups. Thirteen pregnant rats were purchased and randomly assigned into three groups: high-ethanol (n = 4), low-ethanol (n = 5), and control (n = 4) groups. Laboratory ethanol (purity = 99.5%) was dissolved in tap water and administered to the high- and low-ethanol groups as drinking water from gestational days (GD) 8-20. Ethanol-containing water was administered to the animals in three stages by gradually increasing the concentration between GDs 8–20. From GDs 8–10, 10% and 5%, from GDs 11–13, 20% and 10%, and from GDs 14–20, 30% and 15% ethanol-containing water (v/v) was administered to the high- and low-ethanol groups, respectively. Tap water without ethanol was given to the control group throughout the experiment. The day of birth of the pups was designated as postnatal day (PND) 0. On PND 4, each litter was culled to four male and four female pups. For the present study, two male and two female pups were randomly sampled from each litter as subjects. Thus, eight male and eight female pups from the high-ethanol and control groups and another 10 male and 10 female pups from the low-ethanol group, were sampled. An ultrasonic microphone and the Sonotrack system version 2.4.0 (Metris, Hoofddorp, The Netherlands) were used to record and analyze USVs of the pups. On postnatal days 4, 8, 12 and 16, the resultant pups were individually isolated from their dams and littermates, and USVs were recorded for 5 min in a sound-proof box. Pups in the high-ethanol group produced greater number of USVs compared with that in both low-ethanol and control groups on PND 12. Rat pups in the high-ethanol group also produced higher mean, minimum, and maximum fundamental frequencies of USVs compared with that in both low-ethanol and control groups. Male pups in the high-ethanol group had higher USV amplitudes than in those in low-ethanol and control groups on PND 12. These results suggest that pups in the high-ethanol group relatively experienced more negative emotionality due to the ethanol-induced neuronal activation in the core limbic system and tegmental structures and accordingly, produced altered USVs as distress calls.

Keywords: emotionality, ethanol, maternal separation, ultrasonic vocalization

Procedia PDF Downloads 105
207 The Effect of Santolina Plant Extract on Nitro-Oxidative Stress

Authors: Sabrina Sebbane, Alina Elena Parvu

Abstract:

Introduction: Santolina rosmarinifolia is a plant of the Santolina genus, a family made of medicinal plants widely used. Some of the Santolina species have been proven to have potent anti-inflammatory and anti-oxidant effects. However, no in vivo study has been made to demonstrate this in Santolina rosmarinifolia. The aim of our study is to experimentally evaluate the potential anti-inflammatory and anti-oxidant effects of Santolina rosmarinifolia plant extracts on acute inflammation in rats. These effects are defined by measuring the modifications on nitric oxide, reactive oxygen species and anti-oxidant response in serum. Materials and Methods: Rats were divided into 5 groups (n=6). Three groups were given Santolina rosmarinifolia extract by gavage in different concentrations(100%, 50%, 25%) for a week. Inflammation was induced by i.m injection of turpentine oil on the 8th day. One group was only given turpentine oil and the fifth group acted as control and was given only saline solution. Blood was collected and serum separated. Global tests were used to measure the oxidative stress, total oxidative status (TOS), total antioxidant reactivity (TAR) and the modified method of Griess assay to measure NO synthesis. Malondilaldehyde (MDA) and thiols levels were also assessed. Results: Santolina rosmarinifolia did not significantly change the TOS levels (p > 0.05). Santolina rosmarinifolia 25% and 50% decreased significantly the TAR levels (p < 0.001). Santolina 100% didn't have a significant effect on TAR (p > 0.05). All concentrations of Santolina rosmarinifolia increased the oxidative stress index (OSI) significantly(p < 0.05). Santolina rosmarinifolia 100% significantly decreased NO synthesis (p value < 0.05). In the diluted Santolina groups, no significant effect on NO synthesis was observed. In the groups treated with Santolina 100% and Santolina rosmarinifolia 50%, thiols concentration were significantly higher compared to the inflammation group (p < 0.02). A higher stimulatory effect was found in the Santolina 25% group (p value < 0.05). MDA levels were not significantly modified by the administration of Santolina rosmarinifolia (p > 0.05). Conclusion: All three solutions of Santolina rosmarinifolia had no important effect on oxidant production. However, Santolina rosmarinifolia solutions had a positive effect by increasing the thiols concentration in the serum of the models. The sum of all the effects produced by the administration of Santolina did not show a significant decrease of nitro-oxidative stress. Further experiments including smaller concentrations of Santolina rosmarinifolia will be made. Santolina rosmarinifolia should also be tested as a curative treatment.

Keywords: inflammation, MDA, nitric oxide, santolina rosmarinifolia, thiols, TAR, TOS

Procedia PDF Downloads 236
206 Development of 90y-Chitosan Complex for Radiosynovectomy

Authors: A. Mirzaei, S. Zolghadri, M. Athari-Allaf, H. Yousefnia, A. R. Jalilian

Abstract:

Rheumatoid arthritis is the most common autoimmune disease, leading to the destruction of the joints. The aim of this study was the preparation of 90Y-chitosan complex as a novel agent for radiosynovectomy. The complex was prepared in the diluted acetic acid solution. At the optimized condition, the radiochemical purity of higher than 99% was obtained by ITLC method on Whatman No. 1 and by using a mixture of methanol/water/acetic acid (4:4:2) as the mobile phase. The complex was stable in acidic media (pH=3) and its radiochemical purity was above 98% even after 48 hours. The biodistribution data in rats showed that there was no significant leakage of the injected activity even after 48 h. Considering all of the excellent features of the complex, 90Y-chitosan can be used to manipulate synovial inflammation effectively.

Keywords: chitosan, Y-90, radiosynovectomy, biodistribution

Procedia PDF Downloads 454
205 Phytochemical Screening and Toxicological Studies of Aqueous Stem Bark Extract of Boswellia papyrifera (DEL) in Rats

Authors: Y. Abdulmumin, K. I. Matazu, A. M. Wudil, A. J. Alhassan, A. A. Imam

Abstract:

Phytochemical analysis of Boswellia papryfera confirms the presence of various phytochemicals such as alkaloids, flavonoids, tannins, saponins and cardiac glycosides in its aqueous stem bark extract at different concentration, with tannins being the highest (0.611 ± 0.002 g %). Acute toxicity test (LD50, oral, rat) of the extract showed no mortality at up to 5000 mg/kg and the animals were found active and healthy. The extract was declared as practically non-toxic, this suggest the safety of the extract in traditional medicine.

Keywords: acute toxicity, aqueous extract, boswellia papryfera, phytochemicals and stem bark

Procedia PDF Downloads 427
204 Phytochemical Screening and Toxicological Studies of Aqueous Stem Bark Extract of Boswellia papyrifera (DEL) in Albino Rats

Authors: Y. Abdulmumin, K. I. Matazu, A. M. Wudil, A. J. Alhassan, A. A. Imam

Abstract:

Phytochemical analysis of Boswellia papryfera confirms the presence of various phytochemicals such as alkaloids, flavonoids, tannins, saponins and cardiac glycosides in its aqueous stem bark extract at different concentration, with tannins being the highest (0.611 ± 0.002 g %). Acute toxicity test (LD50,oral, rat) of the extract showed no mortality at up to 5000 mg/kg and the animals were found active and healthy. The extract was declared as practically non-toxic, this suggest the safety of the extract in traditional medicine.

Keywords: acute toxicity, aqueous extract, boswellia papryfera, phytochemicals, stem bark extract

Procedia PDF Downloads 400
203 Evaluation of Neuroprotective Potential of Olea europaea and Malus domestica in Experimentally Induced Stroke Rat Model

Authors: Humaira M. Khan, Kanwal Asif

Abstract:

Ischemic stroke is a neurological disorder with a complex pathophysiology associated with motor, sensory and cognitive deficits. Major approaches developed to treat acute ischemic stroke fall into two categories, thrombolysis and neuroprotection. The objectives of this study were to evaluate the neuroprotective and anti-thrombolytic effects of Olea europaea (olive oil) and Malus domestica (apple cider vinegar) and their combination in rat stroke model. Furthermore, histopathological analysis was also performed to assess the severity of ischemia among treated and reference groups. Male albino rats (12 months age) weighing 300- 350gm were acclimatized and subjected to middle cerebral artery occlusion method for stroke induction. Olea europaea and Malus domestica was administered orally in dose of 0.75ml/kg and 3ml/kg and combination was administered at dose of 0.375ml/kg and 1.5ml/kg prophylactically for consecutive 21 days. Negative control group was dosed with normal saline whereas piracetam (250mg/kg) was administered as reference. Neuroprotective activity of standard piracetam, Olea europaea, Malus domestica and their combination was evaluated by performing functional outcome tests i.e. Cylinder, pasta, ladder run, pole and water maize tests. Rats were subjected to surgery after 21 days of treatment for analysis from stroke recovery. Olea europaea and Malus domestica in individual doses of 0.75ml/kg and 3ml/kg respectively showed neuroprotection by significant improvement in ladder run test (121.6± 0.92;128.2 ± 0.73) as compare to reference (125.4 ± 0.74). Both test doses showed significant neuroprotection as compare to reference (9.60 ± 0.50) in pasta test (8.40 ± 0.24;9.80 ± 0.37) whereas with cylinder test, experimental groups showed significant increase in movements (6.60 ± 0.24; 8.40 ± 0.24) in contrast to reference (7.80 ± 0.37).There was a decrease in percentage time taken f to reach the hidden maize in water maize test (56.80 ± 0.58;61.80 ± 0.66) at doses 0.75ml/kg and 3ml/kg respectively as compare to piracetam (59.40 ± 1.07). Olea europaea and Malus domestica individually showed significant reduction in duration of mobility (127.0 ± 0.44; 123.0 ± 0.44) in pole test as compare to piracetam (124.0 ± 0.70). Histopathological analysis revealed the significant extent of protection from ischemia after prophylactic treatments. Hence it is concluded that Olea europaea and Malus domestica are effective neuroprotective agents alone as compare to their combination.

Keywords: ischemia, Malus domestica, neuroprotection, Olea europaea

Procedia PDF Downloads 107
202 Microorganism and Laurus nobilis from Mascara - Algeria

Authors: Karima Oldyerou, B. Meddah, A. Tirtouil

Abstract:

Laurusnobilis is an aromatic plant, common in Algeria and widely used by local people as a source of spice and for medicinal purposes. The essential oil of this plant is the subject of this work in a physicochemical and microbiological study. The extraction of the essential oil was carried by steam distillation and the highest yield (1.5%) was determined in May. The organoleptic and physico-chemical characters are consistent with those obtained in the literature with some differences that can be attributed to certain factors. Evaluation of antibacterial activity showed a sensitivity of Salmonella spp. with an MIC of 2,5 mg.ml-1, and other bacteria of the intestinal flora of Wistar rats: E. coli and Lactobacillus sp. have a high potential for resistance with MICs respectively equal to 10 and 20 mg.ml-1.

Keywords: laurus nobilis, essential oil, physicochemical character, MIC, intestinal flora, antibacterial activity

Procedia PDF Downloads 299
201 Bioactivities and Phytochemical Studies of Acrocarpus fraxinifolius Bark Wight and Arn

Authors: H. M. El-Rafie, A. H. Abou Zeid, R. S. Mohammed, A. A. Sleem

Abstract:

Acrocarpus is a genus of flowering plants in the legume family Fabaceae which considered as a large and economically important family. This study aimed to investigate the phytoconstituents of the petroleum ether extract (PEE) of Acrocarpus fraxinofolius bark by Gas chromatography coupled with mass spectrometry (GC/MS) analysis of its fractions (fatty acid and unsaponifiable matter). Concerning this, identification of 52 compounds constituting 97.03 % of the total composition of the unsaponifiable matter fraction. Cycloeucalenol was found to be the major compound representing 32.52% followed by 4a, 14a-dimethyl-A8~24(28)-ergostadien (26.50%) and ß-sitosterol(13.74%), furthermore Gas liquid chromatography (GLC) analysis of the sterol fraction revealed the identification of cholesterol (7.22 %), campesterol (13.30 %), stigmasterol (10.00 %) and β - sitosterol (69.48 %). Meanwhile, the identification of 33 fatty acids representing 90.71% of the total fatty acid constituents. Methyl-9,12-octadecadienoate (40.39%) followed by methyl hexadecanoate (23.64%) were found to be the major compounds. On the other hand, column chromatography and Thin layer chromatography (TLC) fractionation of PEE separate the triterpenoid: 21β-hydroxylup-20(29)-en-3-one and β- amyrin which were structurally identified by spectroscopic analysis (NMR, MS and IR). PEE has been biologically evaluated for 1: management of diabetes in alloxan induced diabetic rats 2: cytotoxic activity against four human tumor cell lines (Cervix carcinoma cell line[HELA], Breast carcinoma cell line [MCF7], Liver carcinoma cell line[HEPG2] and Colon carcinoma cell line[HCT-116] 3: hepatoprotective activity against CCl4-induced hepatotoxicity in rats and the activity was studied by assaying the serum marker enzymes like AST, ALT, and ALP. Concerning this, the anti-diabetic activity exhibited by 100mg of PEE extract was 74.38% relative to metformin (100% potency). It also showed a significant anti-proliferative activity against MCF-7 (IC50= 2.35µg), Hela(IC50=3.85µg) and HEPG-2 (IC50= 9.54µg) compared with Doxorubicin as reference drug. The hepatoprotective activity was evidenced by significant decrease in liver function enzymes, i.e. AST, ALT and ALP by (29.18%, 28.26%, and 34.11%, respectively using silymarin as the reference drug, compared to their concentration levels in an untreated group with liver damage induced by CCl₄. This study was performed for the first time on the bark of this species.

Keywords: Acrocarpus fraxinofolius, antidiabetic, cytotoxic, hepatoprotective

Procedia PDF Downloads 174
200 Biochemical and Cellular Correlates of Essential Oil of Pistacia Integerrima against in vitro and Murine Models of Bronchial Asthma

Authors: R. L. Shirole, N. L. Shirole, R. B. Patil, M. N. Saraf

Abstract:

The present investigation aimed to elucidate the probable mechanism of antiasthmatic action of essential oil of Pistacia integerrima J.L. Stewart ex Brandis galls (EOPI). EOPI was investigated for its potential antiasthmatic action using in vitro antiallergic assays mast cell degranulation and soyabean lipoxidase enzyme activit, and spasmolytic action using isolated guinea pig ileum preparation. In vivo studies included lipopolysaccharide-induced bronchial inflammation in rats and airway hyperresponsiveness in ovalbumin in sensitized guinea pigs using spirometry. Data was analysed by GraphPad Prism 5.01 and results were expressed as means ± SEM. P < 0.05 was considered to be significant. EOPI inhibits 5-lipoxidase enzyme activity, DPPH scavenging activity and erythropoietin- induced angiogenesis. It showed dose dependent anti-allergic activity by inhibiting compound 48/80 induced mast cell degranulation. The finding that essential oil induced inhibition of transient contraction of acetylcholine in calcium free medium, and relaxation of S-(-)-Bay 8644-precontracted isolated guinea pig ileum jointly suggest that suggesting that the L-subtype Cav channel is involved in spasmolytic action of EOPI. Treatment with EOPI dose dependently (7.5, 15 and 30 mg/kg i.p.) inhibited lipopolysaccharide- induced increased in total cell count, neutrophil count, nitrate-nitrite, total protein, albumin levels in bronchoalveolar fluid and myeloperoxidase levels in lung homogenates. Mild diffused lesions involving focal interalveolar septal, intraluminal infiltration of neutrophils were observed in EOPI (7.5 &15 mg/kg) pretreated while no abnormality was detected in EOPI (30 mg/kg) and roflumilast (1mg/kg) pretreated rats. Roflumilast was used as standard. EOPI reduced the respiratory flow due to gasping in ovalbumin sensitized guinea pigs. The study demonstrates the effectiveness of EOPI in bronchial asthma possibly related to its ability to inhibit L-subtype Cav channel, mast cell stabilization, antioxidant, angiostatic and through inhibition of 5-lipoxygenase enzyme.

Keywords: asthma, lipopolysaccharide, spirometry, Pistacia integerrima J.L. Stewart ex Brandis, essential oil

Procedia PDF Downloads 262
199 Intrathecal: Not Intravenous Administration of Evans Blue Reduces Pain Behavior in Neuropathic Rats

Authors: Kun Hua O., Dong Woon Kim, Won Hyung Lee

Abstract:

Introduction: Neuropathic pain induced by spinal or peripheral nerve injury is highly resistant to common painkillers, nerve blocks, and other pain management approaches. Recently, several new therapeutic drug candidates have been developed to control neuropathic pain. In this study, we used the spinal nerve L5 ligation (SNL) model to investigate the ability of intrathecal or intravenous Evans blue to decrease pain behavior and to study the relationship between Evans blue and the neural structure of pain transmission. Method: Neuropathic pain (allodynia) of the left hind paw was induced by unilateral SNL in Sprague-Dawley rats(n=10) in each group. Evans blue (5, 15, 50μg/10μl) or phosphate buffer saline(PBS,10μl) was injected intrathecally at 3days post-ligation or intravenously(1mg/200 μl) 3days and 5days post-ligation . Mechanical sensitivity was assessed using Von Frey filaments at 3 days post-ligation and at 2 hours, days 1, 2, 3, 5,7 after intrathecal Evans blue injection, and on days 2, 4, 7, and 11 at 14 days after intravenous injection. In the intrathecal group, microglia and glutaminergic neurons in the dorsal horn and VNUT(vesicular nucleotide transporter) in the dorsal root ganglia were tested to evaluate co-staining with Evans blue. The experimental procedures were performed in accordance with the animal care guideline of the Korean Academy of Medical Science(Animal ethic committee of Chungnam National University Hospital: CNUH-014-A0005-1). Results: Tight ligation of the L5 spinal nerve induced allodynia in the left hind paw 3 days post-ligation. Intrathecal Evans blue most significantly(P<0.001) alleviated allodynia at 2 days after intrathecal, but not an intravenous injection. Glutaminergic neurons in the dorsal horn and VNUT in the dorsal root ganglia were co-stained with Evans blue. On the other hand, microglia in the dorsal horn were partially co-stained with Evans blue. Conclusion: We confirmed that Evans blue might have an analgesic effect through the central nervous system, not another system in neuropathic pain of the SNL animal model. These results suggest Evans blue may be a potential new drug for the treatment of chronic pain. This research was supported by the National Research Foundation of Korea (NRF-2020R1A2C100757512), funded by the Ministry of Education.

Keywords: neuropathic pain, Evas blue, intrathecal, intravenous

Procedia PDF Downloads 67
198 Determination of Myocardial Function Using Heart Accumulated Radiopharmaceuticals

Authors: C. C .D. Kulathilake, M. Jayatilake, T. Takahashi

Abstract:

The myocardium is composed of specialized muscle which relies mainly on fatty acid and sugar metabolism and it is widely contribute to the heart functioning. The changes of the cardiac energy-producing system during heart failure have been proved using autoradiography techniques. This study focused on evaluating sugar and fatty acid metabolism in myocardium as cardiac energy getting system using heart-accumulated radiopharmaceuticals. Two sets of autoradiographs of heart cross sections of Lewis male rats were analyzed and the time- accumulation curve obtained with use of the MATLAB image processing software to evaluate fatty acid and sugar metabolic functions.

Keywords: autoradiographs, fatty acid, radiopharmaceuticals, sugar

Procedia PDF Downloads 422
197 Innovative Preparation Techniques: Boosting Oral Bioavailability of Phenylbutyric Acid Through Choline Salt-Based API-Ionic Liquids and Therapeutic Deep Eutectic Systems

Authors: Lin Po-Hsi, Sheu Ming-Thau

Abstract:

Urea cycle disorders (UCD) are rare genetic metabolic disorders that compromise the body's urea cycle. Sodium phenylbutyrate (SPB) is a medication commonly administered in tablet or powder form to lower ammonia levels. Nonetheless, its high sodium content poses risks to sodium-sensitive UCD patients. This necessitates the creation of an alternative drug formulation to mitigate sodium load and optimize drug delivery for UCD patients. This study focused on crafting a novel oral drug formulation for UCD, leveraging choline bicarbonate and phenylbutyric acid. The active pharmaceutical ingredient-ionic liquids (API-ILs) and therapeutic deep eutectic systems (THEDES) were formed by combining these with choline chloride. These systems display characteristics like maintaining a liquid state at room temperature and exhibiting enhanced solubility. This in turn amplifies drug dissolution rate, permeability, and ultimately oral bioavailability. Incorporating choline-based phenylbutyric acid as a substitute for traditional SPB can effectively curtail the sodium load in UCD patients. Our in vitro dissolution experiments revealed that the ILs and DESs, synthesized using choline bicarbonate and choline chloride with phenylbutyric acid, surpassed commercial tablets in dissolution speed. Pharmacokinetic evaluations in SD rats indicated a notable uptick in the oral bioavailability of phenylbutyric acid, underscoring the efficacy of choline salt ILs in augmenting its bioavailability. Additional in vitro intestinal permeability tests on SD rats authenticated that the ILs, formulated with choline bicarbonate and phenylbutyric acid, demonstrate superior permeability compared to their sodium and acid counterparts. To conclude, choline salt ILs developed from choline bicarbonate and phenylbutyric acid present a promising avenue for UCD treatment, with the added benefit of reduced sodium load. They also hold merit in formulation engineering. The sustained-release capabilities of DESs position them favorably for drug delivery, while the low toxicity and cost-effectiveness of choline chloride signal potential in formulation engineering. Overall, this drug formulation heralds a prospective therapeutic avenue for UCD patients.

Keywords: phenylbutyric acid, sodium phenylbutyrate, choline salt, ionic liquids, deep eutectic systems, oral bioavailability

Procedia PDF Downloads 75
196 Biological Studies on Producing Samoli Bread Supplement with Irradiated Sunflower Flour by Gamma Rays

Authors: Amal. N. Al-Kuraieef

Abstract:

Smoli bread was made by supplementation sunflower flour which was prepared from sunflower (Dahr-EL-Haea) gray after hilling and milling, flour was irradiated by two doses (5 and 10 kGy). After that, the ratios of irradiated sunflower flour were 5 and 10%. All samples of samoli bread were examined for organoleptic and biological evaluation. Biological assay (PER, NPU, FE, DC and BV) was carried out on rats fed 5 and 10% irradiated and non-irradiated sunflower Samoli bread. Results obtained showed that, total lipids, cholesterol and triglycerides were reduced comparable, to that of casein. Also, figures of the biological evaluations were higher than those of the control samoli bread and improved its nutritive values.

Keywords: gamma rays, sunflower, samoli bread, cholesterol, lipids, triglycerides

Procedia PDF Downloads 132
195 Microglia Activation in Animal Model of Schizophrenia

Authors: Esshili Awatef, Manitz Marie-Pierre, Eßlinger Manuela, Gerhardt Alexandra, Plümper Jennifer, Wachholz Simone, Friebe Astrid, Juckel Georg

Abstract:

Maternal immune activation (MIA) resulting from maternal viral infection during pregnancy is a known risk factor for schizophrenia. The neural mechanisms by which maternal infections increase the risk for schizophrenia remain unknown, although the prevailing hypothesis argues that an activation of the maternal immune system induces changes in the maternal-fetal environment that might interact with fetal brain development. It may lead to an activation of fetal microglia inducing long-lasting functional changes of these cells. Based on post-mortem analysis showing an increased number of activated microglial cells in patients with schizophrenia, it can be hypothesized that these cells contribute to disease pathogenesis and may actively be involved in gray matter loss observed in such patients. In the present study, we hypothesize that prenatal treatment with the inflammatory agent Poly(I:C) during embryogenesis at contributes to microglial activation in the offspring, which may, therefore, represent a contributing factor to the pathogenesis of schizophrenia and underlines the need for new pharmacological treatment options. Pregnant rats were treated with intraperitoneal injections a single dose of Poly(I:C) or saline on gestation day 17. Brains of control and Poly(I:C) offspring, were removed and into 20-μm-thick coronal sections were cut by using a Cryostat. Brain slices were fixed and immunostained with ba1 antibody. Subsequently, Iba1-immunoreactivity was detected using a secondary antibody, goat anti-rabbit. The sections were viewed and photographed under microscope. The immunohistochemical analysis revealed increases in microglia cell number in the prefrontal cortex, in offspring of poly(I:C) treated-rats as compared to the controls injected with NaCl. However, no significant differences were observed in microglia activation in the cerebellum among the groups. Prenatal immune challenge with Poly(I:C) was able to induce long-lasting changes in the offspring brains. This lead to a higher activation of microglia cells in the prefrontal cortex, a brain region critical for many higher brain functions, including working memory and cognitive flexibility. which might be implicated in possible changes in cortical neuropil architecture in schizophrenia. Further studies will be needed to clarify the association between microglial cells activation and schizophrenia-related behavioral alterations.

Keywords: Microglia, neuroinflammation, PolyI:C, schizophrenia

Procedia PDF Downloads 395
194 Evaluation of the Anti Ulcer Activity of Ethyl Acetate Fraction of Methanol Leaf Extract of Clerodendrum Capitatum

Authors: M. N. Ofokansi, Onyemelukwe Chisom, Amauche Chukwuemeka, Ezema Onyinye

Abstract:

The leaves of Clerodendrumcapitatum(Lamiaceae) is mostly used in the treatment of gastric ulcer in Nigerian folk medicine. The aim of this study was to evaluate the antiulcer activity of its crude methanol leaf extract and its ethyl acetate fraction in white albino rats. The effect of crude methanol leaf extract and its ethyl acetate fraction(250mg/kg, 500mg/kg) was evaluated using an absolute ethanol induced ulcer model. Crude methanol leaf extract and the ethyl acetate fraction was treated with distilled water and 6% Tween 80, respectively. crude methanol leaf extract was further investigated using a pylorus ligation induced ulcer model. Omeprazole was used as the standard treatment. Four groups of five albino rats of either sex were used. Parameters such as mean ulcer index and percentage ulcer protection were assessed in the ethanol-induced ulcer model, while the gastric volume, pH, and total acidity were assessed in the pyloric ligation induced ulcer model. Crude methanol leaf extract of Clerodendrumcapitatum(500mg/kg) showed a very highly significant reduction in mean ulcer index(p<0.001) in the absolute ethanol-induced model. ethyl acetate fraction of crude methanol leaf extract of Clerodendrumcapitatum(250mg/kg,500mg/kg) showed a very highly significant dose-dependent reduction in mean ulcer indices (p<0.001) in the absolute ethanol-induced model. The mean ulcer indices (1.6,2.2) with dose concentration (250mg/kg, 500mg/kg) of ethyl acetate fraction increased with ulcer protection (82.85%,76.42%) respectively when compared to the control group in the absolute ethanol-induced ulcer model. Crude methanol leaf extract of Clerodendrumcapitatum(250mg/kg, 500mg/kg) treated animals showed a highly significant dose-dependent reduction in mean ulcer index(p<0.01) with an increase in ulcer protection (56.77%,63.22%) respectively in pyloric ligated induced, ulcer model. Gastric parameters such as volume of gastric juice, pH, and total acidity were of no significance in the different doses of the crude methanol leaf extract when compared to the control group. The phytochemical investigation showed that the crude methanol leaf extracts Possess Saponins and Flavonoids while its ethyl acetate fraction possess only Flavonoids. The results of the study indicate that the crude methanol leaf extract and its ethyl acetate fraction is effective and has gastro protective and ulcer healing capacity. Ethyl acetate fraction is more potent than crude methanol leaf extract against ethanol-induced This result provides scientific evidence as a validation for its folkloric use in the treatment of gastric ulcer.

Keywords: gastroprotective, herbal medicine, anti-ulcer, pharmacology

Procedia PDF Downloads 137
193 Cardiolipin-Incorporated Liposomes Carrying Curcumin and Nerve Growth Factor to Rescue Neurons from Apoptosis for Alzheimer’s Disease Treatment

Authors: Yung-Chih Kuo, Che-Yu Lin, Jay-Shake Li, Yung-I Lou

Abstract:

Curcumin (CRM) and nerve growth factor (NGF) were entrapped in liposomes (LIP) with cardiolipin (CL) to downregulate the phosphorylation of mitogen-activated protein kinases for Alzheimer’s disease (AD) management. AD belongs to neurodegenerative disorder with a gradual loss of memory, yielding irreversible dementia. CL-conjugated LIP loaded with CRM (CRM-CL/LIP) and that with NGF (NGF-CL/LIP) were applied to AD models of SK-N-MC cells and Wistar rats with an insult of β-amyloid peptide (Aβ). Lipids comprising 1,2-dipalmitoyl-sn-glycero-3- phosphocholine (Avanti Polar Lipids, Alabaster, AL), 1',3'-bis[1,2- dimyristoyl-sn-glycero-3-phospho]-sn-glycerol (CL; Avanti Polar Lipids), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N- [methoxy(polyethylene glycol)-2000] (Avanti Polar Lipids), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethylene glycol)-2000] (Avanti Polar Lipids) and CRM (Sigma–Aldrich, St. Louis, MO) were dissolved in chloroform (J. T. Baker, Phillipsburg, NJ) and condensed using a rotary evaporator (Panchum, Kaohsiung, Taiwan). Human β-NGF (Alomone Lab, Jerusalem, Israel) was added in the aqueous phase. Wheat germ agglutinin (WGA; Medicago AB, Uppsala, Sweden) was grafted on LIP loaded with CRM for (WGA-CRM-LIP) and CL-conjugated LIP loaded with CRM (WGA-CRM-CL/LIP) using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (Sigma–Aldrich) and N-hydroxysuccinimide (Alfa Aesar, Ward Hill, MA). The protein samples of SK-N-MC cells (American Type Tissue Collection, Rockville, MD) were used for sodium dodecyl sulfate (Sigma–Aldrich) polyacrylamide gel (Sigma–Aldrich) electrophoresis. In animal study, the LIP formulations were administered by intravenous injection via a tail vein of male Wistar rats (250–280 g, 8 weeks, BioLasco, Taipei, Taiwan), which were housed in the Animal Laboratory of National Chung Cheng University in accordance with the institutional guidelines and the guidelines of Animal Protection Committee under the Council of Agriculture of the Republic of China. We found that CRM-CL/LIP could inhibit the expressions of phosphorylated p38 (p-p38), p-Jun N-terminal kinase (p-JNK), and p-tau protein at serine 202 (p-Ser202) to retard the neuronal apoptosis. Free CRM and released CRM from CRM-LIP and CRM-CL/LIP were not in a straightforward manner to effectively inhibit the expression of p-p38 and p-JNK in the cytoplasm. In addition, NGF-CL/LIP enhanced the quantities of p-neurotrophic tyrosine kinase receptor type 1 (p-TrkA) and p-extracellular-signal-regulated kinase 5 (p-ERK5), preventing the Aβ-induced degeneration of neurons. The membrane fusion of NGF-LIP activated the ERK5 pathway and the targeting capacity of NGF-CL/LIP enhanced the possibility of released NGF to affect the TrkA level. Moreover, WGA-CRM-LIP improved the permeation of CRM across the blood–brain barrier (BBB) and significantly reduced the Aβ plaque deposition and malondialdehyde level and increased the percentage of normal neurons and cholinergic function in the hippocampus of AD rats. This was mainly because the encapsulated CRM was protected by LIP against a rapid degradation in the blood. Furthermore, WGA on LIP could target N-acetylglucosamine on endothelia and increased the quantity of CRM transported across the BBB. In addition, WGA-CRM-CL/LIP could be effective in suppressing the synthesis of acetylcholinesterase and reduced the decomposition of acetylcholine for better neurotransmission. Based on the in vitro and in vivo evidences, WGA-CRM-CL/LIP can rescue neurons from apoptosis in the brain and can be a promising drug delivery system for clinical AD therapy.

Keywords: Alzheimer’s disease, β-amyloid, liposome, mitogen-activated protein kinase

Procedia PDF Downloads 309
192 Evaluation of the Analgesic Activity of Defatted Methanol Extract of Capparis spinosa L. Root Barks

Authors: Asma Meddour, Mouloud Yahia, Afaf Benhouda, Souhila Benbia, Hachani Khadhraoui

Abstract:

Peripheral analgesic activity of defatted methanol extract of root barks of Capparis spinosa was tested orally at the dose of 100 and 200 mg/kg against pain induced by acetic acid in rats. The dose of 200 mg/kg presents significant analgesic effect with a percentage of inhibition of torsions of 88.51% compared to the positive control which is the acetylsalicylic acid which represents a percentage of inhibition of 92.55%. The dose of 100 mg/kg presents a percentage of inhibition of 81.68%.

Keywords: peripheral analgesic activity, Capparis spinosa, percentage of inhibition of torsions, chemical sciences

Procedia PDF Downloads 269
191 Synthesis and Anticholinesterase Activity of Carvacrol Derivatives

Authors: Fatih Sonmez

Abstract:

Alzheimer’s disease (AD) is a progressive neurodegenerative disease and it is the most common form of dementia that affects aged people. Acetylcholinesterase is a hydrolase involved in the termination of impulse transmission at cholinergic synapses by rapid hydrolysis of the neurotransmitter ACh in the central and peripheral nervous system. Carvacrol (5-iso-propyl-2-methyl-phenol) is a main bioactive monoterpene isolated from many medicinal herbs, such as Thymus vulgaris, Monarda punctate and Origanum vulgare spp. It is known that carvacrol has been widely used as an active anti-inflammatory ingredient, which can inhibit the isoproterenol induced inflammation in myocardial infarcted rats. In this paper, a series of 12 carvacrol substituted carbamate derivatives (2a-l) was synthesized and their inhibitory activities on AChE and BuChE were evaluated. Among them, 2d exhibited the strongest inhibition against AChE with an IC50 value of 2.22 µM, which was 130-fold more than that of carvacrol (IC50 = 288.26 µM).

Keywords: Acetylcholinesterase, Butyrylcholinesterase, Carbamate, Carvacrol

Procedia PDF Downloads 330
190 Comparative Histological, Immunohistochemical and Biochemical Study on the Effect of Vit. C, Vit. E, Gallic Acid and Silymarin on Carbon Tetrachloride Model of Liver Fibrosis in Rats

Authors: Safaa S. Hassan, Mohammed H. Elbakry, Safwat A. Mangoura, Zainab M. Omar

Abstract:

Background: Liver fibrosis is the main reason for increased mortality in chronic liver disease. It has no standard treatment. Antioxidants from a variety of sources are capable of slowing or preventing oxidation of other molecules. Aim: to evaluate the hepatoprotective effect of vit. C, vit. E and gallic acid in comparison to silymarin in the rat model of carbon tetrachloride induced liver fibrosis and their possible mechanisms of action. Material& Methods: A total number of 60 adult male albino rats 160-200gm were divided into six equal groups; received subcutaneous (s.c) injection for 8 weeks. Group I: as control. Group II: received 1.5 mL/kg of CCL4 .Group III: CCL4 and co- treatment with silymarin 100mg/kg p.o. daily. Group IV: CCL4 and co-treatment with vit. C 50mg/kg p.o. daily. Group V: CCL4 and co-treatment with vit. E 200mg/kg. p.o. Group VI: CCL4 and co-treatment with Gallic acid 100mg/kg. p.o. daily. Liver was processed for histological and immunohistochemical examination. Levels of AST, ALT, ALP, reduced GSH, MDA, SOD and hydroxyproline concentration were measured and evaluated statistically. Results: Light and electron microscopic examination of liver of group II exhibited foci of altered cells with dense nuclei and vacuolated, granular cytoplasm, mononuclear cell infiltration in portal areas, profuse collagen fiber deposits were found around portal tract, more intense staining α-SMA-positive cells occupied most of the liver fibrosis tissue, electron lucent areas in the cytoplasm of the hepatocytes, margination of nuclear chromatin. Treatment by any of the antioxidants variably reduced the hepatic structural changes induced by CCL4. Biochemical analysis showed that carbon tetrachloride significantly increased the levels of serum AST, ALT, ALP, hepatic malondialdehyde and hydroxyproline content. Moreover, it decreased the activities of superoxide dismutase and glutathione. Treatment with silymarin, gallic acid, vit. C and vit. E decreased significantly the AST, ALT, and ALP levels in plasma, MDA and hydroxyproline and increased the activities of SOD and glutathione in liver tissue. The effect of administration of CCl4 was improved with the used antioxidants in variable degrees. The most efficient antioxidant was silymarin followed by gallic acid and vit. C then vit. E. It is possibly due to their antioxidant effect, free radical scavenging properties and the reduction of oxidant dependent activation and proliferation of HSCs. Conclusion: So these antioxidants can be a promising drugs candidate for ameliorating liver fibrosis better than the use of the drugs and their side effects.

Keywords: antioxidant, ccl4, gallic acid, liver fibrosis

Procedia PDF Downloads 244
189 Wet Polymeric Precipitation Synthesis for Monophasic Tricalcium Phosphate

Authors: I. Grigoraviciute-Puroniene, K. Tsuru, E. Garskaite, Z. Stankeviciute, A. Beganskiene, K. Ishikawa, A. Kareiva

Abstract:

Tricalcium phosphate (β-Ca3(PO4)2, β-TCP) powders were synthesized using wet polymeric precipitation method for the first time to our best knowledge. The results of X-ray diffraction analysis showed the formation of almost single a Ca-deficient hydroxyapatite (CDHA) phase of a poor crystallinity already at room temperature. With continuously increasing the calcination temperature up to 800 °C, the crystalline β-TCP was obtained as the main phase. It was demonstrated that infrared spectroscopy is very effective method to characterize the formation of β-TCP. The SEM results showed that β-TCP solids were homogeneous having a small particle size distribution. The β-TCP powders consisted of spherical particles varying in size from 100 to 300 nm. Fabricated β-TCP specimens were placed to the bones of the rats and maintained for 1-2 months.

Keywords: Tricalcium phosphate (β-Ca3(PO4)2, bone regeneration, wet chemical processing, polymeric precipitation

Procedia PDF Downloads 273
188 Systematic Formulation Development and Evaluation of Self-Nanoemulsifying Systems of Rosuvastatin Employing QbD Approach and Chemometric Techniques

Authors: Sarwar Beg, Gajanand Sharma, O. P. Katare, Bhupinder Singh

Abstract:

The current studies entail development of self-nano emulsifying drug delivery systems (SNEDDS) of rosuvastatin, employing rational QbD-based approach for enhancing its oral bioavailability. SNEDDS were prepared using the blend of lipidic and emulsifying excipients, i.e., Peceol, Tween 80, and Transcutol HP. The prepared formulations evaluated for in vitro drug release, ex vivo permeation, in situ perfusion studies and in vivo pharmacokinetic studies in rats, which demonstrated 3-4 fold improvement in biopharmaceutical performance of the developed formulations. Cytotoxicity studies using MTT assay and histopathological studies in intestinal cells revealed the lack of cytotoxicity and thereby safety and efficacy of the developed formulations.

Keywords: SNEDDS, bioavailability, solubility, Quality by Design (QbD)

Procedia PDF Downloads 482
187 Biocompatibility Tests for Chronic Application of Sieve-Type Neural Electrodes in Rats

Authors: Jeong-Hyun Hong, Wonsuk Choi, Hyungdal Park, Jinseok Kim, Junesun Kim

Abstract:

Identifying the chronic functions of an implanted neural electrode is an important factor in acquiring neural signals through the electrode or restoring the nerve functions after peripheral nerve injury. The purpose of this study was to investigate the biocompatibility of the chronic implanted neural electrode into the sciatic nerve. To do this, a sieve-type neural electrode was implanted at proximal and distal ends of a transected sciatic nerve as an experimental group (Sieve group, n=6), and the end-to-end epineural repair was operated with the cut sciatic nerve as a control group (reconstruction group, n=6). All surgeries were performed on the sciatic nerve of the right leg in Sprague Dawley rats. Behavioral tests were performed before and 1, 4, 7, 10, 14, and weekly days until 5 months following surgery. Changes in sensory function were assessed by measuring paw withdrawal responses to mechanical and cold stimuli. Motor function was assessed by motion analysis using a Qualisys program, which showed a range of motion (ROM) related to the joints. Neurofilament-heavy chain and fibronectin expression were detected 5 months after surgery. In both groups, the paw withdrawal response to mechanical stimuli was slightly decreased from 3 weeks after surgery and then significantly decreased at 6 weeks after surgery. The paw withdrawal response to cold stimuli was increased from 4 days following surgery in both groups and began to decrease from 6 weeks after surgery. The ROM of the ankle joint was showed a similar pattern in both groups. There was significantly increased from 1 day after surgery and then decreased from 4 days after surgery. Neurofilament-heavy chain expression was observed throughout the entire sciatic nerve tissues in both groups. Especially, the sieve group was showed several neurofilaments that passed through the channels of the sieve-type neural electrode. In the reconstruction group, however, a suture line was seen through neurofilament-heavy chain expression up to 5 months following surgery. In the reconstruction group, fibronectin was detected throughout the sciatic nerve. However, in the sieve group, the fibronectin was observed only in the surrounding nervous tissues of an implanted neural electrode. The present results demonstrated that the implanted sieve-type neural electrode induced a focal inflammatory response. However, the chronic implanted sieve-type neural electrodes did not cause any further inflammatory response following peripheral nerve injury, suggesting the possibility of the chronic application of the sieve-type neural electrodes. This work was supported by the Basic Science Research Program funded by the Ministry of Science (2016R1D1A1B03933986), and by the convergence technology development program for bionic arm (2017M3C1B2085303).

Keywords: biocompatibility, motor functions, neural electrodes, peripheral nerve injury, sensory functions

Procedia PDF Downloads 115
186 Design and Development of Small Peptides as Anti-inflammatory Agents

Authors: Palwinder Singh

Abstract:

Beyond the conventional mode of working with anti-inflammatory agents through enzyme inhibition, herein, an alternate substrate of cyclooxygenase-2 was developed. Proline centered pentapeptide iso-conformational to arachidonic acid exhibited appreciable selectivity for COX-2 overcoming acetic acid and formalin induced pain in rats to almost 80% and was treated as a substrate by the enzyme. Remarkably, COX-2 metabolized the pentapeptide into small fragments consisting mainly of di- and tri-peptides that ensured the safe breakdown of the peptide under in-vivo conditions. The kinetic parameter Kcat/Km for COX-2 mediated metabolism of peptide 6.3 x 105 M-1 s-1 was quite similar to 9.5 x 105 M-1 s-1 for arachidonic acid. Evidenced by the dynamic molecular studies and the use of Y385F COX-2, it was observed that the breakage of the pentapeptide has probably taken place through H-bond activation of the peptide bond by the side chains of Y385 and S530.

Keywords: small peptides, anti-inflammatory agents, cyclooxygenase-2, unnatural substrates

Procedia PDF Downloads 48
185 Synthesis of Metal Curcumin Complexes with Iron(III) and Manganese(II): The Effects on Alzheimer's Disease

Authors: Emel Yildiz, Nurcan Biçer, Fazilet Aksu, Arash Alizadeh Yegani

Abstract:

Plants provide the wealth of bioactive compounds, which exert a substantial strategy for the treatment of neurological disorders such as Alzheimer's disease. Recently, a lot of studies have explored the medicinal properties of curcumin, including antitumoral, antimicrobial, anti-inflammatory, antioxidant, antiviral, and anti-Alzheimer's disease effects. Metal complexes of curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) were synthesized with Mn(II) and Fe(III). The structures of synthesized metal complexes have been characterized by using spectroscopic and analytic methods such as elemental analysis, magnetic susceptibility, FT-IR, AAS, TG and argentometric titration. It was determined that the complexes have octahedral geometry. The effects of the metal complexes on the disorder of memory, which is an important symptom of Alzheimer's Disease were studied on lab rats with Plus-Maze Tests at Behavioral Pharmacology Laboratory.

Keywords: curcumin, Mn(II), Fe(III), Alzheimer disease, beta amyloid 25-35

Procedia PDF Downloads 278
184 Effect of High Dose of Black Tea Extract on Physiological Parameters of Mother and Pups in Experimental Albino Rats

Authors: Avijit Dey, Antony Gomes, Subir Chandra Dasgupta

Abstract:

Tea (Camellia sinensis) is the most popular beverages in the world and is ranked second after the water. Tea has been considered as a health promoting beverage since ancient times due to its health-promoting activity. Recently, immunomodulatory, anti-arthritic, antioxidant, anticancer and cardioprotective activity of tea has been established. Very few studies have demonstrated the effect of high dose of black tea on health. The aim of the present study was to evaluate the role of low & high dose of Black Tea Extract (BTE) on the different physiological parameters of mother and pups during prenatal and postnatal developmental period in the experimental rodent. BTE was orally administered in LD (50mg BTE/kg/day) and HD (100mg BTE/kg/day) except control groups of rats (n=6/group) throughout the prenatal (day 0-21) and postnatal (day 21-42) periods. During prenatal period (0, 7th, 14th, 20th days) body weight, urinary calcium, magnesium, urea and creatinine was measured. In postnatal period physical (0, 10th, 21th days) parameters of pups like body weight, cranial length, cranial diameter, neck width, tail length, craniosacral length of pups were analyzed. Liver and lungs from pups and kidney spleen, etc. from mothers were collected on day 42 for histopathological studies. The comparative urine strip and morphology of RBC was also analyzed by SEM from mothers of different groups on day 42. The level of cytokines like IL-1alpha, IL-1beta, IL-6, IL-10, TNF-alpha were analysed by enzyme-linked immunosorbent assay (ELISA) on day 0, day 20 and day 42. The body weight of LD and HD mothers were also significantly (P<0.05) less than control mothers at 20th day of pregnancy and there was also significant changes in urinary calcium, urea, creatinine. The bio morphometric analysis of pups showed significant alteration (P<0.05) in HD groups relative to control. Some histological alterations were also observed in pups and mothers. Comparative urine strip analysis and morphology of RBC showed significant changes in treated groups. LD and HD treated mothers showed an increase in proinflammatory cytokines like IL-1beta, TNF-alpha and decrease in anti-inflammatory cytokine-like IL-10 on day 20 compared to PC mothers. This study clearly indicated that high dose of BTE possesses detrimental effect on pregnant mother and the pup. Further studies are in progress to elucidate the molecular mechanism of actions. This project work has been sponsored by National Tea Research Foundation vide Project Sanction No.: 17 (305)/2013/4423 dated 11th March, 2014. All experimental protocols described in the study were approved by animal ethics committee.

Keywords: black tea extract, pregnancy, prenatal and postnatal development, inflammation

Procedia PDF Downloads 251