Irritation In Rats Research Articles

Inhibitory Effects of Polyphenols from Equisetum ramosissimum and Moringa peregrina Extracts on Staphylococcus aureus, Collagenase, and Tyrosinase Enzymes: In vitro Studies

Background: Skin problems caused by oxidative stress lead to the activation of collagenase and tyrosinase enzymes, contributing to skin aging, discoloration, and infections. Equisetum ramosissimum and Moringa peregrina were assessed for their potential uses in treating various skin conditions. Objective: The present research aimed to investigate the positive effects of polyphenols in Equisetum ramosissimum and Moringa peregrina extracts as potential cosmetic products for the treatment of different skin conditions. Methods: Total phenolic and flavonoid contents, antioxidants, and anti-collagenase and anti-tyrosinase activities of plant extract mixtures (PEM) at different ratios of (M. peregrina: E. ramosissimum) were determined using standard procedures. Inhibitory effects of PEM against acne-causing Staphylococcus aureus (ATCC 29213) were evaluated using the diameter (cm) of the inhibition zone method. A cream formulation containing PEM was developed and characterized for stability and potential skin irritation in rats using standard procedures. Results: The PEM at a ratio of (2:1) showed the highest total phenolic and flavonoid content (150.15 ± 2.8 mg/g, equivalent to gallic acid, and 41.5 ± 1.2 mg/g, equivalent to quercetin, respectively). Antioxidant activities for PEM (2:1) were also optimal, as determined by the DPPH and ABTS methods (IC50 = 7.06 ± 0.12 µg/mL and 53.29 ± 3.3 µg/mL, respectively). Furthermore, PEM (2:1) exhibited superior inhibitory activities against collagenase and tyrosinase enzymes (IC50 = 32.4 ± 1.19 µg/mL and 8.4 ± 1.19 µg/mL, respectively). Antimicrobial activity of PEM (2:1) tested on S. aureus showed the largest zone of growth inhibition (2.8 cm) at a concentration of 60 mg/mL. Studies on the PEM (2:1) cream formulation revealed that it remained stable under room conditions. Skin irritation tests on rats showed no signs of oedema or erythema after treatment. Conclusion: The PEM with a ratio of (2:1) demonstrated optimal activity as an oxidative stress-neutralizing agent, inhibitor of enzymes responsible for skin aging and hyperpigmentation, and antibacterial agent. The cream formulation containing PEM exhibited physical stability and no detectable risk of skin irritation throughout the research procedures.

Potentilla tormentilla Extract Loaded Gel: Formulation, In Vivo and In Silico Evaluation of Anti-Inflammatory Properties.

The objective of the study was to develop a novel topical gel by mixing Potentilla tormentilla ethanolic extract, thermosensitive poloxamer 407, and carbomer 940 and evaluating its stability and rheological behavior. The irritation potential of the gel was evaluated in accordance with the Organization for Economic Cooperation and Development Guidelines 404. The potential anti-inflammatory effects of the developed gel were evaluated in vivo in rats using the carrageenan-induced paw edema test. Moreover, the in silico binding affinity for chlorogenic and ellagic acid, as dominant components in the extract, against cyclooxygenase (COX) 1 and 2 was also determined. Our findings suggest that the gel containing Potentilla tormentilla extract remained stable throughout the observation period, exhibited pseudoplastic behavior, and caused no irritation in rats, thus being considered safe for topical treatment. Additionally, the developed gel showed the capability to reduce rat paw edema, which highlights significant anti-inflammatory potential. In silico analysis revealed that chlorogenic and ellagic acid exhibited a reduced binding affinity against COX-1 but had a similar inhibitory effect on COX-2 as flurbiprofen, which was confirmed by molecular dynamics results. The study proposes the possible application of Potentilla tormentilla ethanolic extract gel for the alleviation of localized inflammatory diseases; however, future clinical evaluation is required.

A gel plaster in the form of nipple cover: A comfortable and safe transdermal delivery method for mammary hyperplasia

Hyperplasia of mammary glands (HMG) is considered a precancerous condition with a risk of malignant transformation, highlighting the necessity of proactive treatment in the early stages. Transdermal drug delivery offers significant advantages such as painlessness, absence of first-pass effect, and good patient compliance. However, the unique structure of the breast requires transdermal formulations for treating mammary hyperplasia to exhibit higher levels of safety and comfort. We have formulated an ancient topical formula called ’Muxiang Bing,’ comprising traditional Chinese medicines Aucklandiae Radix (AR) and Rehmanniae Radix (RR), for the treatment of HMG. This formula has been transformed into a gel paster in the form of nipple cover for trans-nipple-areola delivery. In our investigations, we observed that the optimal formulation of the Muxiang gel plaster demonstrated enhanced permeation facilitated by AR’s effect on RR. Furthermore, pre-treatment with the Muxiang gel plaster improved mammary tissue morphology, hormone levels, oxidative stress, aberrant cell proliferation, and damage in rat models, thus preventing and ameliorating mammary hyperplasia. The Muxiang gel plaster exhibited low skin irritability in rats, and long-term use did not cause harm to their internal organs or blood cells, indicating its safety and efficacy.

Surface modification of medical grade biomaterials by using a low-temperature-processed dual functional Ag-TiO2 coating for preventing biofilm formation.

Biofilm development in medical devices is considered the major virulence component that leads to increased mortality and morbidity among patients. Removing a biofilm once formed is challenging and frequently results in persistent infections. Many current antibiofilm coating strategies involve harsh conditions causing damage to the surface of the medical devices. To address the issue of bacterial attachment in medical devices, we propose a novel antibacterial surface modification approach. In this paper, we developed a novel low-temperature based solution-processed approach to deposit silver nanoparticles (Ag NPs) inside a titanium oxide (TiO2) matrix to obtain a Ag-TiO2 nanoparticle coating. The low temperature (120 °C)-based UV annealed drop cast method is novel and ensures no surface damage to the medical devices. Various medical-grade biomaterials were then coated using Ag-TiO2 to modify the surface of the materials. Several studies were performed to observe the antibacterial and antibiofilm properties of Ag-TiO2-coated medical devices and biomaterials. Moreover, the Ag-TiO2 NPs did not show any skin irritation in rats and showed biocompatibility in the chicken egg model. This study indicates that Ag-TiO2 coating has promising potential for healthcare applications to combat microbial infection and biofilm formation.

Xiangshao Granules reduce the aggressive behavior and hippocampal injury of premenstrual irritability in rats by regulating JIK/JNK/p38 signal pathway

Ethnopharmacological relevanceAs a typical prescription for soothing the liver, Xiangshao granule has a good effect on the symptoms of irritability and anxiety. Clinical evidence suggests that it has significant efficacy in the treatment of Premenstrual dysphoria disorder (PMDD). However, the underlying mechanism remains unclear. Aim of the studyPMDD is a common disease in women of childbearing age, seriously affecting their family, society, and daily work life. The registered herbal medicine, Xiangshao granules, is used for relieving PMDD dysphoria and irritability symptoms with excellent efficacy in China. This study was focused on the deep intervention mechanism of Xiangshao granules in treating PMDD. Materials and methodsThe vaginal smear and open field test were used to screen rats in nonreception phase of estrus cycle with similar macroscopic behaviors and regular estrus cycle. The rat model of PMDD irritability was established through social isolation and residential invasion, with which, the irritability symptoms of PMDD patients with menstrual cycle dependence was also well simulated. Elevated plus Maze Test and Social interaction activities were used to measure the anxiety-like behavior of rats. TUNEL Staining and Hematoxylin-Eosin staining were used to measure apoptosis of hippocampal neurons. RT-PCR, Western blot and immunofluorescence were used to measure the expression of GR, JIK, p-JIK, p38, P–P38, JNK, caspase 3, and caspase 12. ResultsIn this study, Xiangshao granules showed consistent therapeutic effects similar with those in clinic, significantly reducing aggressive and anxiety-like behaviors with improved social skills in PMDD rats. In mechanism, Xiangshao granules lowered the apoptosis of hippocampal neurons and weakened the morphological damage of the hippocampal brain evidenced by the decreased mRNA and protein expression of glucocorticoid receptor, caspase-3, and caspase-12. In addition, administration of Xiangshao granules led to the decreased expression of JIK in the PMDD irritability rat model which agreed well with the previous studies. The JNK/p38 mitogen-activated protein kinases (MAPKs) signaling pathway is abnormally activated in the hippocampal brain region of PMDD rats, while treated with Xiangshao granules could increase JIK expression and inhibit the abnormal activation of the JNK/p38 MAPK signaling pathway, effectively reducing the stress damage in the hippocampus. ConclusionsXiangshao Granules Reduce the Aggressive Behavior and Hippocampal Injury of Premenstrual Irritability in Rats by Regulating JIK/JNK/p38 Signal Pathway.

Buspirone, a 5-HT1A agonist attenuates social isolation-induced behavior deficits in rats: a comparative study with fluoxetine.

Social isolation is a potent stressor in both humans and animals that results in increased anger-like emotion, (anger in humans), aggression and suicidal ideation in humans [suicidal trait-related behavior in rats (STRB)]. The study's purpose was to compare the effects of buspirone (BUS) and fluoxetine (Flx) on social isolation-induced behavior deficits in rats. The male Wistar rats were randomized into six groups and caged individually for 14 days except for the non stress control (nSC) group. They were then divided into the following groups, stress control (SC), Flx (30), BUS (10), BUS (20) and BUS (40) and treated from day 14 to day 28. On the last day of treatment behavior parameters were recorded. Serum cortisol, blood pressure (BP) measurement, magnetic resonance imaging (MRI) of the rat's brain and brain-derived neurotrophic factor (BDNF) expression were performed. SC group showed a significant increase in anger-like emotion, aggression, irritability score, learned helplessness, increased cortisol level and reduced BDNF. These behavioral deficits were attenuated by BUS and Flx, Both were found to be equally beneficial in preventing anger-like emotions and aggression. Flx, which has been found to promote suicidal thoughts in people, did not reduce irritability in rats, showing that it did not affect it. BUS significantly improved all behavioral traits also reduced cortisol levels, significantly increased BDNF and normalized BP. Neuroimaging studies in SC brains showed a reduction in amygdala size compared to nSC, BUS treatment mitigated this reduction. Buspirone is effective in preventing social isolation induced behavioural-deficits.

Aceclofenac-Loaded Microspheres Prepared by Vesicular Ionotropic Gelation to Minimize Drug-induced Gastric Ulcers in Rats.

Aceclofenac is a non-steroidal anti-inflammatory drug and a potent analgesic. However, its oral ingestion may cause gastrointestinal problems, including dyspepsia, abnormal pain, nausea, diarrhea, and ulcerative colitis. This study aimed to prepare vesicular-based enteric microspheres containing aceclofenac by ionotropic gelation technique to minimize gastric irritation in rats. The micron-size vesicles were prepared by the ionic-orifice gelation method. Three types of vesicularbased microcapsules containing aceclofenac were prepared by employing sodium alginate as the coating material in combination with Eudragit L100, Eudragit S100, and polyvinylpyrrolidone PVP K90. The drug to sodium alginate to polymer ratios were 1:0.5:0.5, 1:1:1, and 1:1.5:1.5, respectively. Gelation of sodium alginate was induced by the dropwise addition of calcium chloride solution (10 % w/v). Aceclofenac-loaded microspheres were evaluated in terms of aceclofenac content and in vitro drug release, and FTIR, DSC, and XRD were used for physicochemical evaluation of some selected formulae. The effects of microencapsulation on aceclofenac-induced ulcerative activity in male Wistar rats were also investigated. The results indicated no interaction between aceclofenac and microcapsules forming polymers. In addition, microcapsules formulations M1, M4, and M7 gave maximal protection in acidic pH and optimal release in alkaline pH. The histopathological studies revealed that the reduction of ulceration is evident from the macroscopic and microscopic studies, which showed complete protection of the tissue morphology with no ulcers, indicating the effectiveness of the microcapsules system against aceclofenac-induced gastric ulceration in rats again. Ionotropic gelation seems to be a simple, efficient technique to prepare aceclofenac-loaded microspheres with a reduced risk of gastric ulceration. It is possible to overcome the problem of gastric damage while utilizing aceclofenac by avoiding the exposure of the drug to the ulcer-prone area of the gastrointestinal tract.

A target lipidomics approach to investigate the acute inflammatory irritation induced by indolealkylamines from Chansu water fraction in rats.

Chansu has demonstrated adverse reactions in clinical settings, which is associated with its toxicity and limits its clinical applications. But there are methodological limitations for drug safety evaluation. In the current study, ultra-high performance liquid chromatography, lipidomic profiling, and molecular docking were used to systemically assess Chansu-induced acute inflammatory irritation and further identify the underlying drug targets. Compared with the EtOAc extract, Chansu water fraction containing indolealkylamines caused acute inflammatory irritation in rats, including acute pain (spontaneous raising foot reaction), and inflammation (paw edema). At the molecular level, lipids analysis revealed significantly higher levels of pro-inflammatory mediators of the COX and LOX pathways. However, anti-inflammatory mediators from the CYP 450, ALA, and DHA pathways markedly decreased after exposure to Chansu water fraction. Moreover, four indolealkylamines from Chansu showed a high theoretical affinity to a known irritation target, 5-HT2AR. These results suggest that Chansu-induced inflammatory irritation is related to the distinct dysregulation of inflammatory lipids, and peripheral 5-HT2AR is a potential target for irritation therapy. The strategy used in this study can be a crucial approach in the safety evaluation of natural medicinal substances.

In-depth investigation of analgesic activity of N-(4-methoxybenzyl)-4-methyl-2.2-dioxo-1H-2 λ6.1-benzothiazine-3-carboxamide derivate on different models of pain perception

Among N-(4-methoxybenzyl)-4-methyl-2.2-dioxo-1H-2 λ6.1-benzothiazine-3-carboxamide derivates, the compound methoxybenzyl-amide derivative 4-methyl-2.2-dioxo-1H-2λ6.1-benzothiazine-3-carboxylic acid (compound NI-9) with pronounced analgesic and anti-inflammatory activities, which was superior to those of diclofenac and lornoxicam in the model of carrageenan edema. The aim of the study was to investigate the analgesic effect of benzothiazine-3-carboxamide derivative on different models of somatic and neuropathic pain syndromes. The study was performed on 91 male Wistar rats. Compound NI-9 and reference drugs meloxicam, diclofenac and gabapentin were administered intragastrically at doses of 3, 5, 8 and 5 mg/kg, respectively, corresponding to their ED50 in analgesic activity. Acetic spasms in mice, a model of thermal irritation of the tail flick in rats, as well as adjuvant arthritis and diabetic polyneuropathy were selected as models of pain syndromes. The results were processed in the program STATISTICA 10.0 using non-parametric methods. The results showed that methoxybenzyl-amide derivative 4-methyl-2.2-dioxo-1H-2λ6.1-benzothiazine-3-carboxylic acid (compound NI-9) has a pronounced analgesic effect on various models of pain syndromes, both somatic and inflammatory. and of neurogenic origin. The analgesic activity of the compound NI-9 in the model of acetic acid cramps in mice and thermal irritation in rats was 38.09 and 49.75 %, respectively, which was higher than that of meloxicam (36.73 and 45.68 %), and inferior to diclofenac (41.95 and 55.95 %). In the model of the systemic inflammatory process (adjuvant arthritis), the analgesic effect of NI-9 was statistically superior to meloxicam and diclofenac (43.32 % vs. 26.26 and 33.69 %). In a model of neuropathic pain syndrome (diabetic neuropathy), the analgesic effect of methoxybenzyl-amide derivative 4-methyl-2.2-dioxo-1H-2λ6.1-benzothiazine-3-carboxylic acid was greater than meloxicam (18.96 vs. 13.34 %), but this figure was lower than that of gaapentin (20.83 %). Further in-depth study of its pharmacodynamics and toxicity will be the theoretical basis for the development on the basis of this biologically active compound of the original drug with analgesic and anti-inflammatory activities.

Medicinal Properties of Asparagus

Asparagus ia a vegetable and a medicinal or traditional herb. It has many health benefits because of its pharmacological properties and the active ingredients responsible for its effectiveness against various illnesses. A few medicinal Properties are discussed below:
 Anti-Inflammation Property of Asparagus
 Anti-inflammation can be defined as “It acts on body responses and reduce the inflammation, without directly counteracting the active agent such as glucocorticoids and aspirin”. One of these saponins has been of unique exuberance for relationship to amyotrophic horizontal sclerosis, otherwise called Lou Gehrig's Disease [1]. Even however amyotrophic parallel sclerosis is delegated a perpetual, neurodegenerative illness and isn't right now acknowledged as an immune system issue, over the top, undesirable irritation may assume an imperative part in the passing of certain nerve cells in amyotrophic sidelong sclerosis. In this mitigating setting, it is important that current research on the shatavarins in asparagus has uncovered another assemblage of saponins that impact aggravation through cytokine informing [2].
 Asparagus as the Best Antioxidant
 Analysts in Brazil has estimated the general reinforcement limit of asparagus. These specialists broke down twenty three ordinarily eaten vegetables in Brazil including asparagus. Their general outcomes demonstrated turmeric, watercress, lettuces, and broccoli to give the best general cancer prevention agent limit. Be that as it may, in a portion of the vegetables testing, asparagus turned out in the best ten among each of the twenty three vegetables for general cancer prevention agent limit. This finding isn't astonishing, given thenumerous customary and offbeat cell reinforcements show in asparagus. It merits recollecting here that asparagus positions as an astounding wellspring of both vitamin E and vitamin C two spotlight antioxidantas well as the mineral selenium, which assumes a key part in the capacity of glutathione peroxidase a standout amongst the most-examined cell reinforcement proteins in the body [3].The impact of methanolic concentrate of Asparagus pubescens was explored on compound, warm actuated agony and new egg whites incited aggravation. The concentrate measurement conditionally pent-up acidic corrosive incited wiggling, formalin-initiated torment licking and hot plate-actuated agony in mice. The concentrate essentially hindered the new egg whites prompted irritation in rats also. These hindrances were measurably critical [4].
 Antidepressant Activity
 The methanolic extract of asparagus demonstrated a decrease in immobility time in FST and TST in mice, which was comparable to imipramine and increase the levels of dopamine in vitro [5]. Futhermore, it was found to significantly brain monoamine oxidase levels as compared to control in a study focusing on finding the underlying mechanism of action, it was seen that methanolic extracts significantly inhibited cholinesterase and MAO activities [6]. In another study, antidepressant like activity was seen with methanolic root extract in FST and learned helplessness model [7].
 Anti Amnesic Activity
 Ethanolic root extract of asparagus was observed to produce a significant dose dependent enhancement of memory in the elevated plus maze model in mice [8]. The effect being significantly higher then the produced by piracetam [9]. Also there was an increase in the acetylcholinestrease levels in hippocampus areas associated with learning and memory [10]. In another study, methanolic exracts was found to reverse amnesia produced by scopolamine and sodium nitrate in the EPM and Morris water maze model in mice [11].
 Analgesic Action
 Aqueous and alcohalic root extracts of asparagus has been found to produce indicative analgesic action in heat conduction model. In another study, ethanolic extracts of asparagus was found to inhibit writing reflex in acetic acid induced writing model in mice [12].
 Antipyretic Action
 The ethanolic extracts of asparagus showed significant more antipyretic activity in albino Wistar rats than the aqueous extract in the yeast-derived pyrexia model, an effect comparable to normal antipyretic paracetamol [13]. Asparagus root extract which contains highest amount of flavonoids, polyphenols and vitamin-C exhibits the greatest antioxidant activity. Asparagus is likewise rich in flavonoid rutin
 REFERENCES

Safety and immunogenicity of a novel quadrivalent subunit influenza vaccine in animal models

ABSTRACT Background: Compared with trivalent influenza vaccines, quadrivalent influenza vaccines are expected to provide wider protection against influenza B virus infections. We developed a novel quadrivalent subunit influenza vaccine which was distinct from the influenza vaccines available on the market in production process. In this research, we evaluated the safety and immunogenicity of the quadrivalent subunit influenza vaccine in animal models. Methods: In toxicity assessment, 40 SD rats were randomly assigned to be intramuscularly injected with 1.0 ml of the tested vaccine (33 μg/ml) or 0.9% sodium chloride solution. In irritation assessment, eight rabbits were randomly assigned to receive 0.5 ml of tested vaccine or phosphate buffer solution intramuscularly. Thirty-two guinea pigs were randomly assigned to be intramuscularly injected with high-dose tested vaccine (0.5 ml), low-dose tested vaccine (0.05 ml), ovalbumin, or 0.9% sodium chloride solution, respectively, for sensitization assessment. In immunogenicity assessment, 50 BALB/c mice were equally randomized to receive one dose of tested vaccine, two doses of tested vaccine with an interval of 14 days, 0.5 ml of trivalent subunit influenza vaccine, 0.5 ml of monovalent subunit influenza vaccine, or 0.5 ml of phosphate buffer solution. Orbital blood was collected before and 28 and 42 days after administration of the injections for detecting influenza antibody titers. Results: No abnormal toxicity and irritation in rats and rabbits showed in the gross autopsy and histopathological examinations. The results of sensitization in guinea pigs indicated that no obvious allergic symptoms observed in the high-dose and low-dose vaccine groups within 30 min after twice provocations, and the result of sensitization evaluation was negative. Vaccine induced significant immune responses in mice with 100% seroconversion rates at 28 and 42 days after the first dose. The geometric mean titers (GMTs) of hemagglutination inhibition (HI) antibodies at day 28 in one-dose quadri–vaccine and two-dose quadri–vaccine groups were comparable to those in the tri–vaccine or mono-vaccine groups for shared influenza strains. However, the GMTs of HI antibodies against H1N1 (P = 0.025) and BV (P = 0.049) at day 42 in one-dose quadri–vaccine group were significantly lower than those in the tri–vaccine or mono-vaccine groups. The GMTs of HI antibodies against H1N1, H3N1, BY, and BV at day 28 and day 42 were comparable between one-dose quadri–vaccine and two-dose quadri–vaccine groups. Conclusions: The quadrivalent subunit influenza vaccine was safe and immunogenic in animal models. One dose of the vaccine could elicit a satisfactory antibody response in mice.

Evaluation of skin irritation in rats using simultaneous laser Doppler flowmetry and oxygenation monitoring

The possibility of assessment of skin irritation in rats with the use of simultaneous laser Doppler flowmetry (LDF) and oxygenation monitoring was investigated. The study was designed according to ISO 10993-10 using formaldehyde as a model irritant. 4-Hour application of 1 % formaldehyde induced significant local increase in skin microcirculation for the first 2 days by a factor of up to 2.4, whereas tissue oxygenation increased in much lower extent. The microcirculation was significantly inhibited by 10 % formaldehyde following treatment and then it gradually increased for 24 and 48 h of recovery period. The results correlated with visual evaluation of skin edema and erythema in treated zones. LDF/oxygenation signals provide early information on skin irritation and damage in rat model. The technique is valuable for preclinical/toxicological studies of chemical substances and medical materials.

A simple method for oral mucosal irritation test by intraoral instillation in rats.

Evaluation of oral mucosal irritation is required by regulatory agencies when the intended clinical route of the drug candidate is intraoral administration. In this study, we investigated whether it was possible to evaluate oral mucosal irritation in rats by an intraoral instillation which was thought to mimic the clinical route of gargle products. Although no oral mucosal irritation was observed in the animals instilled with 0.5% and 4% sodium dodecyl sulfate (SDS, an anionic detergent) solutions for 10 days, instillation of 15% SDS solution for 4 days induced oral mucosal irritation macro- and microscopically, and this was evaluated as moderate irritant. It was suggested that the oral mucosal irritation test by intraoral instillation in rats could be a simple and useful method mimicking the clinical route of gargle products.

Oral delivery of capsaicin using MPEG-PCL nanoparticles

To prepare a biodegradable polymeric carrier for oral delivery of a water-insoluble drug capsaicin (CAP) and evaluate its quality. CAP-loaded methoxy poly (ethylene glycol)-poly(ε-caprolactone) nanoparticles (CAP/NPs) were prepared using a modified emulsification solvent diffusion technique. The quality of CAP/NPs were evaluated using transmission electron microscopy, powder X-ray diffraction, differential scanning calorimetry and Fourier transform infrared techniques. A dialysis method was used to analyze the in vitro release profile of CAP from the CAP/NPs. Adult male rats were orally administered CAP/NPs (35 mg/kg), and the plasma concentrations of CAP were measured with a validated HPLC method. The morphology of rat gastric mucosa was studied with HE staining. CAP/NPs had an average diameter of 82.54 ± 0.51 nm, high drug-loading capacity of 14.0% ± 0.13% and high stability. CAP/NPs showed a biphasic release profile in vitro: the burst release was less than 25% of the loaded drug within 12 h followed by a more sustained release for 60 h. The pharmacokinetics study showed that the mean maximum plasma concentration was observed 4 h after oral administered of CAP/NPs, and approximately 90 ng/mL of CAP was detected in serum after 36 h. The area under the curve for the CAP/NPs group was approximately 6-fold higher than that for raw CAP suspension. Histological studies showed that CAP/NPs markedly reduced CAP-caused gastric mucosa irritation. CAP/NPs significantly enhance the bioavailability of CAP and markedly reduce gastric mucosa irritation in rats.

Spinal toll-like receptor 4-mediated signalling pathway contributes to visceral hypersensitivity induced by neonatal colonic irritation in rats.

Although visceral hypersensitivity is a major pathophysiological feature of irritable bowel syndrome (IBS), its underlying mechanisms remain elusive. Toll-like receptor 4 (TLR4) is a critical pattern recognition molecule of the innate immune system. In this study, we investigated whether the TLR4/myeloid differentiation factor 88 (MyD88)/nuclear factor-kappa B (NF-κB) signalling pathway in the spinal cord contributed to the visceral hypersensitivity induced by neonatal colonic irritation (CI) in rats. The Sprague-Dawley rat model of IBS was induced by colon irritation on post-natal day (PND) 8, PND10 and PND12. Experiments were conducted in adult rats. TLR4 mRNA and protein, and its downstream signalling molecules, MyD88, inhibitory nuclear factor-kappa B (IκB) and NF-κB protein expressions in L2-S4 spinal segments were detected by quantitative real-time reverse transcription-polymerase chain reaction as well as Western blotting. TLR4 co-localization was determined by immunohistochemistry. Levels of tumour necrosis factor-alpha (TNF-α) and interleukin 1β (IL-1β) were measured with enzyme-linked immunosorbent assay. We found that neonatal CI treatment induced long-lasting visceral hypersensitivity without identifiable structural abnormalities in descending colons of adult rats. Neonatal CI treatment evoked a significant up-regulation of the expressions of TLR4 in glia, MyD88, p-IκB-α and NF-κB in adult rats. Neonatal CI treatment also increased the levels of its downstream inflammatory agents TNF-α and IL-1β in the L2-S4 regions of the spinal cord of adult rats. These results suggest that neonatal CI stimulates the production of IL-1β and TNF-α through the TLR4/MyD88/NF-κB signalling pathway in the spinal cord, which contributed to visceral hypersensitivity induced by neonatal CI in rats.

Tu2088 Role of TRPV1 in Gastric Hypersensitivity Induced by Neonatal Irritation in Rats

Tu2088 Role of TRPV1 in Gastric Hypersensitivity Induced by Neonatal Irritation in Rats

Spinal Cord FAAH in Normal Micturition Control and Bladder Overactivity in Awake Rats

We assessed whether spinal inhibition of the cannabinoid degrading enzyme FAAH would have urodynamic effects in normal rats and rats with bladder overactivity induced by partial urethral obstruction or prostaglandin E2. We also determined the expression of FAAH, and the cannabinoid receptors CB1 and CB2 in the sacral spinal cord. We used 44 rats for functional (cystometry) and Western blot experiments. The FAAH inhibitor oleoyl ethyl amide (3 to 300 nmol) was administered intrathecally (subarachnoidally) or intravenously. The expression of FAAH and CB1/CB2 receptors was determined by Western blot. Oleoyl ethyl amide given intrathecally affected micturition in normal rats and rats with bladder overactivity but effects were more pronounced in the latter. In normal rats oleoyl ethyl amide only decreased micturition frequency, while it decreased frequency and bladder pressures in rats with bladder overactivity. Intravenous oleoyl ethyl amide (3 to 300 nmol) had no urodynamic effect. FAAH and CB1/CB2 receptors were expressed in the rat sacral spinal cord. The expression of CB1/CB2 receptors but not FAAH was higher in obstructed than in normal rats. FAAH inhibition in the sacral spinal cord by oleoyl ethyl amide resulted in urodynamic effects in normal rats and rats with bladder overactivity. The spinal endocannabinoid system may be involved in normal micturition control and it appears altered when there is bladder overactivity.

3,4-methylenedioxyamphetamine upregulates p75 neurotrophin receptor protein expression in the rat brain.

The p75 neurotrophin receptor, which is a member of the tumor necrosis factor receptor superfamily, facilitates apoptosis during development and following central nervous system injury. Previous studies have shown that programmed cell death is likely involved in the neurotoxic effects of 3, 4-methylenedioxy-N-methylamphetamine (MDMA), because MDMA induces apoptosis of immortalized neurons through regulation of proteins belonging to the Bcl-2 family. In the present study, intraperitoneal injection of different doses of MDMA (20, 50, and 100 mg/kg) induced significant behavioral changes, such as increased excitability, increased activity, and irritability in rats. Moreover, changes exhibited dose-dependent adaptation. Following MDMA injection in rat brain tissue, the number of apoptotic cells dose-dependently increased and p75 neurotrophin receptor expression significantly increased in the prefrontal cortex, cerebellum, and hippocampus. These findings confirmed that MDMA induced neuronal apoptosis, and results suggested that this effect was related by upregulated protein expression of the p75 neurotrophin receptor.

Evaluation of Anti-inflammatory and Analgesic Activity of a New Class of Biphenyl Analogs in Animal Models of Inflammation

A new class of 4'-methylbiphenyl-2-(substituted phenyl)carboxamide derivatives had been previously evaluated in vivo for their anti-inflammatory activities in animal models of inflammation. In the present study, the most active compound of that series, compound 4e (4'-methylbiphenyl-2-(4-carboxy phenyl)carboxamide), was investigated in detail for its anti-inflammatory, analgesic and ulcerogenic potential. Pretreatment of rats with 4e (100 mg/kg) reduced carrageenan induced rat paw edema at 3 h compared to control group. Dose dependent percent inhibition of granuloma formation, exudate volume, total leukocyte count was observed in 4e (25, 50 and 100 mg/kg) and celecoxib (CAS 169590-42-5; 5 mg/kg) treated groups in the cotton pellet granuloma and granuloma pouch technique, respectively, in rats. C-reactive proteins were absent in the 4e treated group. Compound 4e inhibited acetic acid induced writhing dose dependently (10, 20 and 30 mg/kg). Compound 4e was inactive in the hot plate test. Gastric toxicity screening experiments showed that compound 4e, both after single and repeated oral administration, is devoid of any gastric irritation in rats. The LD50 was found to be more than 2000 mg/kg.

A novel herbal formulation in the management of diabetes

Background and Aim:Momordica charantia Linn. is traditionally used as a medicine for diabetes. The present investigation was aimed to formulate and evaluate transdermal patchesof Momordica charantia Linn.Materials and Methods:The transdermal films containing the herbal drug component fractionated fromethanolicextract of M. charantia fruits were prepared by using hydroxy propyl methyl cellulose as a polymer. The films were evaluated for folding endurance, thickness, weight variation, drug contents and in vitro diffusion studies and in vivo parameterslike acute and sub-acute antihyperglycemic activity in diabetic rats, biochemicalstudies, skin irritation in rats and stability studies.Result and discussion:The weightof transdermal patches of M. charantia (2 cm2; 10 mg/patch) and was found to be 0.03 gm.Thickness of patches of M. charantia (2 cm2; 10 mg/patch) was found to be satisfactory. The percentage release of active constituents from transdermal patches of M.charantia (2 cm2; 10 mg/patch) was found to be 47.59% in 10% hydroalcoholic phosphate buffer pH 7.4 at the end of 6 h.The transdermal route exhibited negligible skin irritation and in vivo results revealed that the patches successfully decrease the blood glucose level.Conclusion:From the results, we concluded that the well-known herbal drug M. charantia Linn. have been found to be effective for diabetes through modern pharmaceutical formulation techniques.