Utilization of nanotechnology and experimental design in the development and optimization of a posaconazole‒calendula oil nanoemulgel for the treatment of mouth disorders.

Introduction: Essential oil‒based nanoemulsions (NEs) are the subjects of extensive investigation due to their potential to address a variety of oral health issues. NEs are delivery systems that improve lipid medicine solubility and distribution to intended sites. The goal of the current study was to create and enhance a self-nanoemulsifying drug delivery paradigm based on calendula oil (CO) and decorated with chitosan (CS) that could deliver posaconazole (PSZ) for the treatment of gingivitis. Method: Employing a response-surface Box‒Behnken design, PSZ-CO-CS NEs were created with varying amounts of PSZ (10, 15, and 20 mg), percentages of CO (6%, 12%, and 18%), and percentages of CS (0.5%, 1.5%, and 2.5%). Results and conclusion: The optimized formulation resulted in a 22-mm bacterial growth suppression zone, 25-mm fungal growth inhibition zone, droplet sizes of 110 nm, and a viscosity of 750 centipoise (cP). Using the appropriate design, the ideal formulation was produced; it contained 20 mg of PSZ, 18% of CO, and 1.35% of CS. Furthermore, the optimal formulation had a more controlled drug release, larger inhibition zones of bacterial and fungal growth, and desirable rheologic properties. Additionally, the optimized formulation substantially lowered the ulcer index in rats when tested against other formulations. Thus, this investigation showed that PSZ-CO-CS NEs could provide efficient protection against microbially induced gingivitis.

Antiulcerogenic and antioxidant activities of Plantago ovata ethanolic extract in rats / Atividade antiulcerogênica e antioxidante do extrato etanólico de Plantago ovata em ratos

This study aimed to determine the antiulcerogenic and antioxidant activities of Psyllium (Plantago ovata Forssk) seed ethanolic extract in rats. We assessed the antioxidant potential using free radical scavenging on DPPH, ß-carotene bleaching activity, ferric reducing power, and hydroxyl radical scavenging activity. In the antiulcerogenic study, pre-treatment with Plantago ovata seeds ethanolic extract (POE) (400 mg/kg b.wt) significantly protected against ethanol-induced gastric ulcer in rats by decreasing the ulcer index value and preserving the integrity of the gastric mucosa. The oxidative stress status in the stomach tissues showed a significant increase in the antioxidant enzyme levels of superoxide dismutase, catalase, and glutathione peroxidase with a significant decrease in lipid peroxidation during pre-treatment with POE. In conclusion, the POE protects against gastric ulcer due to its antioxidant potential and presence of bioactive molecules.

O presente estudo teve como objetivo determinar as atividades antiulcerogênica e antioxidante das sementes de Psyllium (Plantago ovata Forssk) em ratos. O potencial antioxidante foi avaliado utilizando o método do sequestro do radical livre DPPH, autooxidação do ß-caroteno, poder redutor de ferro e atividade de sequestro do radical hidroxila. No estudo antiulcerogênico, o pré-tratamento com o extrato etanólico das sementes de Plantago ovata (POE) (400 mg/Kg b.wt) reduziu a úlcera gástrica induzida pelo etanol em ratos, diminuindo o valor do índice de úlcera e preservando a integridade da mucosa gástrica. O estudo do estresse oxidativo nos tecidos estomacais mostrou um aumento significativo dos níveis das enzimas antioxidantes superóxido dismutase, catalase e glutationa peroxidase, com uma diminuição significativa da peroxidação lipídica enquanto pré-tratamento com POE. Em conclusão, o POE protege contra úlcera gástrica devido aos seus potenciais antioxidantes e à presença de moléculas bioativas.

Antiulcerogenic and antioxidant activities of Plantago ovata ethanolic extract in rats

Abstract This study aimed to determine the antiulcerogenic and antioxidant activities of Psyllium (Plantago ovata Forssk) seed ethanolic extract in rats. We assessed the antioxidant potential using free radical scavenging on DPPH, -carotene bleaching activity, ferric reducing power, and hydroxyl radical scavenging activity. In the antiulcerogenic study, pre-treatment with Plantago ovata seeds ethanolic extract (POE) (400 mg/kg b.wt) significantly protected against ethanol-induced gastric ulcer in rats by decreasing the ulcer index value and preserving the integrity of the gastric mucosa. The oxidative stress status in the stomach tissues showed a significant increase in the antioxidant enzyme levels of superoxide dismutase, catalase, and glutathione peroxidase with a significant decrease in lipid peroxidation during pre-treatment with POE. In conclusion, the POE protects against gastric ulcer due to its antioxidant potential and presence of bioactive molecules.

Resumo O presente estudo teve como objetivo determinar as atividades antiulcerogênica e antioxidante das sementes de Psyllium (Plantago ovata Forssk) em ratos. O potencial antioxidante foi avaliado utilizando o método do sequestro do radical livre DPPH, autooxidação do -caroteno, poder redutor de ferro e atividade de sequestro do radical hidroxila. No estudo antiulcerogênico, o pré-tratamento com o extrato etanólico das sementes de Plantago ovata (POE) (400 mg/Kg b.wt) reduziu a úlcera gástrica induzida pelo etanol em ratos, diminuindo o valor do índice de úlcera e preservando a integridade da mucosa gástrica. O estudo do estresse oxidativo nos tecidos estomacais mostrou um aumento significativo dos níveis das enzimas antioxidantes superóxido dismutase, catalase e glutationa peroxidase, com uma diminuição significativa da peroxidação lipídica enquanto pré-tratamento com POE. Em conclusão, o POE protege contra úlcera gástrica devido aos seus potenciais antioxidantes e à presença de moléculas bioativas.

The role of sodium lauryl sulfate on formulation of directly compressed tablets containing simvastatin and aspirin: Effect on drugs dissolution and gastric mucosa.

According to the American College of Cardiology/American Heart Association (ACC/AHA), both aspirin and statin are used in the primary prevention of cardiovascular diseases. Aspirin (ASA) is contraindicated if there is gastrointestinal bleeding because it will exaggerate the condition. In this study, the effect of surfactant; sodium lauryl sulfate (SLS), in enhancing the in vitro dissolution of simvastatin (SIM) and ASA, as well as gastric irritation and upset, was studied. Oral tablets containing both ASA and SIM with and without the SLS were manufactured using the direct compression technique. The prepared tablets were characterized with respect to hardness, friability, uniformity of dosage units, in vitro disintegration, and dissolution. The effect of the addition of SLS in reducing the in vivo irritation and protection of gastric mucosa were also investigated. The results showed that the compressed tablets possessed sufficient hardness, acceptable friability, and are uniform with respect to disintegration, drugs contents, and tablet weight. The results showed that SIM alone exhibited a gastroprotective effect on the induced irritation. In addition, the incorporation of the SLS in the tablets containing SIM and ASA significantly enhanced the dissolution rates of both drugs and significantly decreased the gastric irritation and the ulcer index. The ulcer index of aspirin was decreased from 2.3 for tablets manufactured without SLS to 0.8 for tablets containing SLS. In a conclusion, the addition of pH modifier surfactant; SLS could enhance the dissolution rate of poorly soluble acidic drugs, reduce gastric upset and irritation without any effect on the main characters of the tablets. Moreover, the addition of SLS is very useful in improving the therapeutic activities and reducing the side effects of ASA and SIM for patients who require long-term administration of these drugs.

Improved Image Analysis for Measuring Gastric Ulcer Index in Animal Models and Clinical Diagnostic Data.

Gastric ulcers are one of the most common gastrointestinal diseases. In this study, as an attempt to reduce the minimal error in clinical observations during the diagnosis of gastric ulcers, the applicability of improved ImageJ analysis (IA) was investigated by comparing the results of animal experiments and clinical data. As a result, IA exhibited a significantly improved potential for determining the ulcer index (UI) of clinical data sheets compared to those rated directly by conventional clinical observation (CCO). This indicated that IA enhanced the reproducibility of the measurement of gastric UI using a Bland-Altman plot, resulting in a reduced deviation of each UI value. In addition, it was confirmed that errors in gastric UI decisions can be reduced by adjusting RGB values in diagnostic clinical data (i.e., adjusting to 100 is relatively better than adjusting to 50 or 200). Together, these results suggest that the new enhanced IA could be compatible with novel applications for measuring and evaluating gastric ulcers in clinical settings, meaning that the developed method could be used not only as an auxiliary tool for CCO, but also as a pipeline for ulcer diagnosis.

Ameliorative effects of ribes rubrum oil against gastric ulcers caused by indomethacin in experimental models.

The objective of this study was to assess the anti-inflammatory effects of ribes rubrum oil at three different doses (5, 10 and 15 ml/kg b.w/day) in adult male albino rats with indomethacin-induced stomach ulcers (IND). Forty rats (135 ± 5 g) categorized into 5 groups (n = 8), for 45 days. Group (1) normal control, thirty-two rats were gavaged IND as single oral dose (30 mg/Kg b.w) resulted in gastric ulcer, then distributed to four groups, group (2) IND-intoxicated control, Groups 3, 4 and 5 were administrated ribes rubrum oil at levels of (5, 10 & 15 ml/kg b.w) respectively. Administrated levels of ribes rubrum oil found to have remarkable elevation in food conversion efficiency in experimental rats, gastric juice pH, in compared to the drunken control group, gastric prostaglandin E2 and gastric cytochrome P450 reductase levels were lower. The levels of pro-inflammatory cytokines NO, TNF-, and IL-1 were dramatically reduced, which was related with an increase in blood hemoglobin (Hb), packed cell volume (PCV), and red blood cells (RBCs)in ulcerogenic rats compared to intoxicated control. Data showed that, the main components of ribes rubrum oil are ß-Pinene, γ-linolenic and Linalool oxide levels (25.9%, 23.10% and 10.5%, respectively) for their antioxidant activity. Findings showed that administrate ribes rubrum oil at dose 15 ml/kg followed by 10 ml/kg had the best results against ulcerogenic rats. In conclusion, the outcomes are consistent with the concept that ribes rubrum oil had a gastroprotective and antisecretory effects against gastric ulcer that may be attributed to the antioxidant properties of the oil that ameliorates the damage occur in gastric of rats.

Development, optimization, and evaluation of a nanostructured lipid carrier of sesame oil loaded with miconazole for the treatment of oral candidiasis.

Candida albicans is the fungus responsible for oral candidiasis, a prevalent disease. The development of antifungal-based delivery systems has always been a major challenge for researchers. This study was designed to develop a nanostructured lipid carrier (NLC) of sesame oil (SO) loaded with miconazole (MZ) that could overcome the solubility problems of MZ and enhance its antifungal activity against oral candidiasis. In the formulation of this study, SO was used as a component of a liquid lipid that showed an improved antifungal effect of MZ. An optimized MZ-loaded NLC of SO (MZ-SO NLC) was used, based on a central composite design-based experimental design; the particle size, dissolution efficiency, and inhibition zone against oral candidiasis were chosen as dependent variables. A software analysis provided an optimized MZ-SO NLC with a particle size of 92 nm, dissolution efficiency of 88%, and inhibition zone of 29 mm. Concurrently, the ex vivo permeation rate of the sheep buccal mucosa was shown to be significantly (p < .05) higher for MZ-SO NLC (1472 µg/cm2) as compared with a marketed MZ formulation (1215 µg/cm2) and an aqueous MZ suspension (470 µg/cm2). Additionally, an in vivo efficacy study in terms of the ulcer index against C. albicans found a superior result for the optimized MZ-SO NLC (0.5 ± 0.50) in a treated group of animals. Hence, it can be concluded that MZ, through an optimized NLC of SO, can treat candidiasis effectively by inhibiting the growth of C. albicans.

Evaluation of mechanism(s) of action underlying the antioxidant and antiulcer activity of Sesamum indicum leaves extract in experimental rats.

OBJECTIVE: The current study aimed to estimate phytochemical screening, in vitro antioxidant activity, and gastroprotective activity of Sesamum indicum Linn ethanolic extract. MATERIALS AND METHODS: The current study was held out by ulceration induced by pylorus ligation and indomethacin-induced ulcer screening models in Wister albino rats. The screening of antiulcer activity of ethanolic extract of S. indicum leaves (EESIL) at the different amounts (100, 200, and 400 mg/kg; per orally for 7 days) was compared with omeprazole as a usual antiulcer drug. Additional parameters such as gastric content, pH, total acidity, pepsin activity ulcer score, free acidity, ulcer index (UI), % inhibition of ulcers, mean mucin, pepsin content, and total protein content were observed. RESULTS: In the pylorus ligation model, the pepsin activity free acidity, pepsin content, UI, total acidity, ulcer score, total protein content, and percentage ulcer inhibition were considerably decreased (P < 0.05 and P < 0.01), and mean mucin and gastric content pH extensively elevated (P < 0.05 and P < 0.01) in EESIL tested groups in the comparison of the control group. Doses (100, 200, and 400 mg/kg p.o.) of EESIL showed dose-reliant gastro protective outcomes, a considerable (P < 0.05 and P < 0.01) decrease in gastric parameters as UI and ulcer score and induction in gastric pH and percentage inhibition of ulcer compared with the control group. CONCLUSION: Antioxidant, anti-Ulcer, EESIL, and EESIL show antioxidant activity at different concentration. The fallout of the study indicated that the EESIL had improved antiulcer potential due to the decrease in offensive factors and increase in defensive factors.

Gastroprotective effect of Hyssopus officinalis L. leaves via reduction of oxidative stress in indomethacin-induced gastric ulcer in experimental rats.

Peptic ulcer disease (PUD) is an important cause of morbidity and mortality throughout the world affecting lives of millions of people. Hyssopus officinalis L. have been used as carminative and antispasmodic stomachic in Iran and Indian traditional systems of medicine. Thus, present study was aimed to evaluate gastroprotective activity of ethanolic extract of Hyssopus officinalis L. leaves (EEHO) in indomethacin-induced gastric ulcer in experimental rats. Female Sprague Dawley rats of groups I, II, III, IV, V, and VI received orally 1 mL/kg/day 1% CMC (carboxy methylcellulose), 1 mL/kg/day 1% CMC, 250 mg EEHO/kg/day, 500 mg EEHO/kg/day, 50 mg ranitidine/kg/day and 500 mg EEHO/kg/day respectively for 10 days. Then, all the groups except groups I and VI were orally administered with 20 mg indomethacin/kg b.wt on 11th day. Ulcer index and mucus barrier were determined. Antioxidant parameters thiobarbituric acid reactive substances (TBARS), glutathione-reduced (GSH), catalase and superoxide dismutase (SOD) were evaluated. Stomach was examined for histopathology also. EEHO in groups III and IV significantly (p < 0.01) increased the mucus barrier, SOD, GSH, and catalase while significantly (p < 0.01) decreased the ulcer index and TBARS as compared to ulcer control group II. Histopathological findings showed that indomethacin administration in group II caused PUD (gastric ulcer) and the gastric ulcer was protected by pretreatment with EEHO in groups III and IV. Thus, EEHO possesses gastroprotective activity where the gastroprotection is by strengthening of the gastric mucosa and reduction of oxidative stress. The gastroprotective activity of EEHO was comparable to that of standard drug ranitidine.

Formulation, Optimization, and Evaluation of Oregano Oil Nanoemulsions for the Treatment of Infections Due to Oral Microbiota.

INTRODUCTION: Natural oil-based nanoemulsions (NEs) have been widely investigated in many diseases that affect the oral cavity. NEs are delivery systems that enhance the solubility of lipid therapeutics and improve their delivery to target sites; they are known as self-nanoemulsifying drug delivery systems (SNEDDSs). The current investigation's aim was to produce an oregano essential oil-based nanoemulsion (OEO-SNEDD) that would have antibacterial and antifungal effects against oral microbiota and improve oral health. METHODS: Several OEO-SNEDDSs were developed using different percentages of OEO (10%, 14%, and 18%), percentages of a surfactant mixture Pluracare L64:Lauroglycol FCC (18%, 32%, and 36%), Smix ratios (1:2, 1:1, and 2:1), and hydrophilic-lipophilic balances (HLBs) of the surfactant mixture (8, 10, and 12) using the Box‒Behnken design. The optimized concentration of excipients was determined using a pseudoternary phase diagram to obtain the NEs. The formulations were evaluated for their droplet size, stability index, and antibacterial and antifungal activities. RESULTS: The NEs had a droplet size of 150 to 500 nm and stability index of 47% to 95%, and the produced formulation reached antibacterial and antifungal inhibition zones of up to 19 and 17 mm, respectively. The Box‒Behnken design was adopted to get the optimum formulation, which was 18% OEO, 36% Smix, 10.29 HLB of Smix, and a 1.25:1 Smix ratio. The optimized formulation had a lower ulcer index compared with various other formulations evaluated in rats. CONCLUSION: This study illustrated that OEO-SNEDDSs can provide good protection against oral microbial infections.

Efficacy of extract from Ononis spinosa L. on ethanol-induced gastric ulcer in rats.

OBJECTIVE: To investigate the efficacy of the extract from Ononis spinosa L. (O. spinosa) on ethanol-induced gastric ulcer in rats. METHODS: Phytochemical constituents of the extract from O. spinosa were analyzed using liquid chromatography-mass spectrometry. Rats were classified into 4 equal groups; ulcer control received oral vehicle; positive control was administered with 40 mg/kg esomeprazole (standard drug) and 2 groups received 0.5 and 1 g/kg of O. spinosa extract, respectively. Gastric ulcer was induced by absolute ethanol (5 mL/kg) orally to all groups. Measurement of ulcer index, cyclooxygenase-2 (COX-2) expression and determination of total glutathione level in gastric mucosa were performed. RESULTS: Oral administration of the extract from O. spinosa at doses 0.5 and 1 g/kg lowered the ulcer indices by 80.39% and 98.71% , respectively, compared to 67.89% by esomeprazole (40 mg/kg). Histologically, treatment with the extract decreased necrosis and hemorrhage in mucosa and edema and infiltration by inflammatory cells in submucosa. Using immunohistochemical technique, it was demonstrated that COX-2 expression increased in mucosa of animals treated with the extract as well as by esomeprazole. O. spinosa and esomeprazole increased total glutathione level in the stomach compared to control. Ononin was the major compound of the extract followed by trifolirhizin, myricitrin, gentisic acid, cycloartenol and quercetin. CONCLUSION: The present study demonstrated that the extract from O. spinosa was able to protect gastric mucosa from ethanol injury by at least 2 mechanisms, namely the induction of COX-2 and decreasing oxidative stress in the stomach.

Development of omega-3 loxoprofen-loaded nanoemulsion to limit the side effect associated with NSAIDs in treatment of tooth pain.

The majority of newly developed drugs need to be incorporated with delivery systems to maximize their effect and minimize side effects. Nanoemulsions (NEs) are one type of delivery system that helps to improve the solubility and dissolution of drugs, attempting to enhance their bioavailability and onset of action. The objective of this investigation was to develop an omega-3 oil-based NE loaded with loxoprofen (LXP) to enhance its dissolution, in vitro release, and mucosal penetration and decrease its mucosal ulcerative effects when applied in an oral treatment. LXP-loaded NEs were formulated with varying levels of omega-3 oil (10-30%), surfactant polyoxyethylene-C21-ethers (laureth-21) (40-60%), and co-surfactant polyethylene glycol-40 hydrogenated castor oil (HCO-40) (30-50%) using an extreme vertices mixture design. The developed NEs were characterized for globule size and drug loading capacity. The optimal formulation was tested for in vitro drug release, ex vivo permeation, and ulcer index value. The developed NE acquired a globule size ranging 71-195 nm and drug loading capacity of 43-87%. Considering the results of the in vitro release study, the optimized NE formulation achieved 2.45-fold and 2-fold increases in drug permeation across tested mucosa compared to a marketed tablet and drug aqueous dispersion, respectively. Moreover, the optimum NE exhibited the best ulcer index in comparison to drug aqueous suspension and different formulations when tested in rats. Overall, this research highlights the capacity of NEs to deliver LXP with enhanced solubility, drug release, and permeation while effectively protecting the application site from side effects of the model drug.

Pistacia atlantica Desf. roots extract: LC-ESI-MS Analysis, antioxidant activity and gastroprotective effect on experimentally-induced ultrastructural gastric ulcers in mice.

Pistacia atlantica Desf. (Atlas Pistachio) is an Anacardiaceae tree traditionally used in Tunisia for the treatment of ophthalmic, stomatitis, and digestive tract diseases. In the present study, the Pistacia atlantica Desf. roots extract (PR) was phytochemically analyzed, for the first time, by LC-ESI-MS for phenolic and flavonoid contents, in vitro tested for its potential antioxidant activity based on the 2.2-diphenyl-1-picrylhydrazyl (DPPH) and the reduced power essays (FRAP), and in vivo tested for its ability to shield against ethanol-induced gastric ulcer in mice. The LC-ESI-MS analysis proved the identification of 12 compounds, including Quinic, Gallic, and Protocatechuic, as major phenolic acids and high levels of flavonoids, such as Catechin, Epicatechin, and Cirsiliol. PR also exhibited a mild in vitro antioxidant activity when compared with ascorbic acid. In vivo pretreatment of ethanol-ulcerated mice with PR doses 50 mg/kg and 100 mg/kg body weight (b.w) significantly reduced (P< .05) gastric lesions at a rate of 20.10% and a rate of 40.90%, respectively, when compared with 60.70% rate of sucralfate (50 mg/kg b.w) evidenced by a dose-dependent manner increase in the gastric mucosa enzymatic (SOD, CAT, GPx) antioxidant levels, the decline of the lipid peroxidation, and the preservation of normal gastric superficial epithelium. The underlying mechanism of PR antiulcerogenic activity could be due to a synergistic effect of phenolic acids and flavonoid contents which enhances the gastric antioxidant defense system.Abbreviations: BHT: butylated hydroxytoluene, b.w: body weight, CAT: catalase, DPPH:1-Diphenyl-2-picrylhydrazyl, DW: dry weight, EtOH: ethanol, FRAP: Ferric reducing antioxidant power, GAE: gallic acid equivalents, GPx: Glutathione peroxidase, QE: quercetin equivalents, LC-ESI-MS: Liquid chromatography-Electrospray Ionization-Tandem Mass Spectrometry, MDA: malondialdehyde, PR: Pistacia root, TBA: thiobarbituric acid reagent, TBARS: thiobarbituric acid reactive substances, TCA: trichloroacetic acid, SOD: Superoxide dismutase.

Ameliorative activity of aqueous leaf extract from Madhuca longifolia against diclofenac-administered toxicity on rat stomach and intestine.

Madhuca longifolia, a tropical tree used as medicine and food, is known to have a beneficial effect against stomach gastric toxicity. Madhuca longifolia is used in treating cough, skin disease and nerve disorders. Diclofenac, a non-steroidal anti-inflammatory drug (NSAID), with overdosage and prolonged use, is known to cause gastric toxicity. Silymarin (SLY), a polyphenolic antioxidant flavonoid, is a derivative of Silybum marianum extracted from milk thistle seeds and fruits, has been widely used in the treatment of gastric ulcer. SLY was used as the standard drug to compare the effects with the Madhuca longifolia aqueous leaf extract treatment. The aim of the current study is to understand the effect of Madhuca longifolia aq. leaf extract on rat stomach and intestine against diclofenac-administered toxicity. Rats (n = 30) were divided into Group I normal control, Group II treated with diclofenac, Group III treated with diclofenac and Madhuca longifolia leaf extract, Group IV treated with diclofenac and silymarin, and Group V was treated with Madhuca longifolia leaf extract alone. After the study duration, rats were euthanized and tissue samples were analyzed for antioxidant, cytokine, protein expression levels and histopathological changes. Diclofenac treated rats had significant (p < 0.05) changes in levels of antioxidants, cytokines, protein expression and pathological changes as compared to rats treated with Madhuca longifolia. This study demonstrated that Madhuca longifolia leaf extract had gastroprotective activity in rats treated with diclofenac.

Oral Gel Loaded by Fluconazole‒Sesame Oil Nanotransfersomes: Development, Optimization, and Assessment of Antifungal Activity.

Candidiasis is one of the frequently encountered opportunistic infections in the oral cavity and can be found in acute and chronic presentations. The study aimed to develop fluconazole-loaded sesame oil containing nanotransfersomes (FS-NTF) by the thin-layer evaporation technique to improve the local treatment of oral candidiasis. Optimization of the formulation was performed using the Box‒Behnken statistical design to determine the variable parameters that influence the vesicle size, entrapment efficiency, zone of inhibition, and ulcer index. Finally, the formulated FS-NTF was embedded within the hyaluronic acid‒based hydrogel (HA-FS-NTF). The rheological behavior of the optimized HA-FS-NTF was assessed and the thixotropic behavior with the pseudoplastic flow was recorded; this is desirable for an oral application. An in vitro release study revealed the rapid release of fluconazole from the HA-FS-NTF. This was significantly higher when compared with the fluconazole suspension and hyaluronic acid hydrogel containing fluconazole. Correspondingly, the ex vivo permeation was also found to be higher in HA-FS-NTF in sheep buccal mucosa (400 µg/cm2) when compared with the fluconazole suspension (122 µg/cm2) and hyaluronic acid hydrogel (294 µg/cm2). The optimized formulation had an inhibition zone of 14.33 ± 0.76 mm and enhanced antifungal efficacy for the ulcer index (0.67 ± 0.29) in immunocompromised animals with Candida infection; these findings were superior to those of other tested formulations. Hence, it can be summarized that fluconazole can effectively be delivered for the treatment of oral candidiasis when it is entrapped in a nanotransfersome carrier and embedded into cross-linked hyaluronic acid hydrogel.

Ethanolic extract of okra has a potential gastroprotective effect on acute gastric lesions in Sprague Dawley rats.

Okra (Abelmoschus esculentus) has various bioactive components used for the treatment of different diseases such as gastritis and ulcers. This research aims to examine the anti-inflammatory and anti-ulcer attributes of okra extract against gastric lesions. Adult Sprague Dawley male albino rats were divided into five groups. The negative control (G1) received normal feed, positive control (G2) received ulcer-inducing drug aspirin 150 mg/kg of body weight (b.w), G3 group received reference drug omeprazole 20 mg/kg of b.w, G4 group received okra extract 250 mg/kg of b.w, and G5 group received 500 mg/kg of b.w. Acute gastric damage was induced in G1, G2, G3, and G4 using aspirin 150 mg/kg of b.w, during 14-day-long efficacy trials after that all the animals were sacrificed. Anti-ulcer parameters and histopathological analysis of stomachs were performed to evaluate the degree of recovery against tissue damage by the administration of okra extract. The obtained results indicated that the 500 mg/kg of b.w okra extract exerted a protective effect in aspirin-induced gastric ulcers by significantly (p < .05) reducing ulcer score, ulcer area, total acidity, and gastric volume, and significantly (p < .05) increasing gastric pH. Moreover, histopathological observation revealed that gastric mucosa was normal in G1, G3, G4, and G5; however, disruptions in the gastric epithelium were observed in G2. Congestion was observed in all groups except G1 and G5. Gastric pits and gastric glands were increased in size in G2 and G4. A higher concentration of okra extract (500 mg/kg of b.w) showed almost similar results when compared to the reference drug omeprazole.

Antiulcerogenic effects of Celosia trigyna plant extracts on ethanol-induced gastric ulcer in adult Wistar rats.

BACKGROUND AND AIM: Gastric ulcer is a chronic disease and serious health issue. Celosia trigyna is a medicinal plant used traditionally for wound healing. This study aimed to isolate the bioactive compounds from Celosia trigyna and to investigate the in vitro and in vivo anti-ulcerogenic effects of the extracts on ethanol-induced gastric ulcer on adult Wistar rats to determine their regenerative potential. EXPERIMENTAL PROCEDURE: Seven groups (A - negative control, B - vehicle control, C, D, E, F and G - positive control, n = 5) of five adult Wistar rats received treatment for ethanol-induced gastric ulcer. RESULTS AND CONCLUSION: Phytochemical analysis led to the isolation of chondrillasterol, lutein, pheophytin a and chondrillasterol acetate. The in vitro results showed dichloromethane and hexane extracts to have maximum chymotrypsin inhibition relative to the standard (chymostatin) while in vivo results showed a significant increase in ulcer parameters of the vehicle control relative to groups treated with plant extracts (P < 0.05). Ulcer parameters and DNA density in groups treated with dichloromethane and hexane extracts were comparable to the negative control. Gross and histopathological findings confirmed gastric mucosa lesions in the vehicle control. There were mild ulcerations in groups treated with the ethyl acetate and methanol extracts with no observable ulcerations in the groups treated with dichloromethane and hexane extracts as the histoarchitectural outlines do not show any form of necrosis, distortion or cellular vacuolation. It was concluded that non-polar, hydrophobic compounds are able to remediate the degree of ulceration but not polar compounds.

Phytochemical and Antiulcer Activity Screening of Seed Extract of Cordia africana Lam (Boraginaceae) in Pyloric Ligated Rats.

INTRODUCTION: Peptic ulcer disease represents a worldwide health problem because of its high morbidity, mortality and economic loss. It is a very prevalent condition affecting around 10%-15% of the general population worldwide. Most of the available antiulcer drugs are costly and have an incidence of relapse, drug interactions and several side effects upon chronic usage. Hence, the use of herbal medicine may be safe, economical and effective in such cases when drugs are used for long periods. Ethnobotanical reports showed traditional claims on the use of Cordia africana seeds for the treatment of gastric ulcers. However, the safety and efficacy of these remedies are not well known. The aim of this study is, therefore, to evaluate the antiulcer activity and safety of a crude extract of C. africana seeds in animal models. METHODS: Shade-dried seeds of C. africana were extracted by 80% methanol and dried by the rotator evaporator and lyophilized. The crude extract was used to evaluate antiulcer activity in vivo with pylorus ligation method, on Wistar albino rats weighing 230-250g. Preliminary phytochemical screening was performed using a standard procedure. Acute toxicity study was carried out in Swiss albino mice before antiulcer activity tests. RESULTS: No sign of toxicity was observed upon the administration of 2000 mg/kg of the crude extract to mice. Single-dose administration of 400 and 600 mg/kg extract showed a significant reduction in the volume of secretion and acidity of the stomach (p <0.01). The doses 400 and 600 mg/kg have reduced the ulcer score by 83.58% and 88%. CONCLUSION: The result of this study showed that the hydromethanolic crude extract of C. africana has strong antisecretory and ulcer protective activities against ulcers produced by pylorus ligation.

Ethanol-induced gastric ulcer in rats and intervention of tert-butylhydroquinone: Involvement of Nrf2/HO-1 signalling pathway.

Gastric ulcer (GU) is the most common health concern that occurs due to alcohol consumption, smoking and physiological stress. Ethanol-induced GU in animal model resembles the pathophysiology of human ulcer. The present study was designed to investigate the cytoprotective and anti-inflammatory properties of tert-butylhydroquinone (tBHQ), a nuclear factor erythroid 2-related factor 2 (Nrf2) activator, against gastric mucosal damage induced by acute exposure of ethanol (5 ml/kg). The intervention of tBHQ (25 and 50 mg/kg, per os (po)) and omeprazole (20 mg/kg, po) was done for 10 consecutive days. Omeprazole was chosen as a standard drug because it is prescribed for the treatment of GU. Pretreatment of tBHQ decreased gastric mucosal lesion, ulcer index, apoptotic cells and lipid peroxidation level induced by ethanol. Furthermore, the intervention of tBHQ increased gastric mucosa integrity, pH, reduced glutathione, collagen and mucus-producing goblet cells. Intervention of tBHQ increased the expression of antioxidant markers such as Nrf2, haeme oxygenase-1 and catalase and decreased the expressions of inflammatory markers such as nuclear factor kappa-light-chain-enhancer of activated B cells and cyclooxygenase-2. The cytoprotective potential of tBHQ against gastric mucosal damage might be due to its ability to enhance cellular antioxidants and anti-inflammatory responses.

New ibuprofen derivatives as H2S and NO donors as safer anti-inflammatory agents.

Aim: Nonsteroidal anti-inflammatory drugs are expansively used worldwide. However, their prolonged administration is associated with serious side effects, especially gastrointestinal ulceration. Materials & methods: New ibuprofen derivatives hybridized with H2S- or NO-donating moieties were synthesized and evaluated for their anti-inflammatory activity and ulcerogenic effect. COX-1/COX-2 isozymes selectivity test for the most promising derivatives was performed. Molecular docking studies were performed. Results: Most of the compounds showed promising anti-inflammatory activity comparable to that of ibuprofen (% edema inhibition = 76.6 and ulcer index = 21.26) with much better gastrointestinal tract tolerance (ulcer indices ranging from 0 to 14.67), especially compound 2 -H2S donor- (% edema inhibition = 75.5 and ulcer index = 11.75) and compound 16 -NO donor- (% edema inhibition = 65.4 and ulcer index = 8.66).