Standard Indomethacin Research Articles

Feasibility of a High-Dose Inhaled Indomethacin Dry Powder with Dual Deposition for Pulmonary and Oral Delivery

In this study we have developed a high-dose dry powder inhaler formulation of indomethacin using a novel approach to carrier-based formulations. Specifically, larger drug particles serve as the carrier for the smaller micronized drug particles, such that an inhaled dose is combined with an oral dose. To study this system, the aerosol performance of a standard indomethacin–lactose formulation was compared to carrier-free micronized indomethacin and a drug-as-carrier formulation (a micronized indomethacin–coarse indomethacin blend). Indomethacin with lactose showed a very poor aerosol performance, indicating high adhesion between the drug and carrier. The performance of the carrier-free micronized drug was significantly better, indicating low cohesion. Coarse drug particles as a carrier allowed improved powder flow and aerosol performance while also providing a potential secondary route of absorption of indomethacin, namely oral. An optimal formulation ratio of 1:1 (w/w) fine indomethacin–coarse indomethacin was developed in this study.

Anti-inflammatory compounds and a new sesquiterpene lactone from Centaurea gabrieljanae Greuter

The traditional use of Centaurea spp. for anti-inflammatory purposes is widespread among the people in Turkiye. For this, the methanol extract of Centaurea gabrieljanae and sub-fractions of the methanol extract were tested for anti-inflammatory activity using 5-LOX, while their antioxidant activities, total phenol, and total flavonoid contents were also examined. The ethyl acetate fraction exhibited potent anti-inflammatory activity (IC50 = 3.864 ± 0.9 µg/ml), from which five known compounds (astragalin, picein, p-hydroxy benzoic acid, 3,4-dimethoxy-cinnamic acid, 4-hydroxybenzoic acid 4-O-β-glucopyranoside) and a new sesquiterpene lactone named Pterochlorin were obtained. Pterochlorin showed potent anti-inflammatory activity with a value of IC50 12.71 ± 0.7 µg/ml compared to standard indomethacin. Similarly, astragalin was found to be strong (IC50 = 18.23 µg/ml). In addition, 4-hydroxybenzoic acid 4-O-β-glucopyranoside was isolated for the first time in Centaurea species, and its anti-inflammatory activity was tested. This study may be a guide for the discovery of a new anti-inflammatory drug derived from natural sources.

Molecular level interaction, HOMO-LUMO, MEP, UV–Vis, Hirshfeld, topological analysis, and in-vitro of isoflavones from Eremostachys Vicaryi Benth. Ex Hook. f.

Eremostachys vicaryi Benth. Ex Hook. f. (Labiatae), a Pakistani (Baluchistan) herbal medicinal plant commonly known as “Stagh,” which has a sharp taste and smell. It acts as an antiseptic and antimicrobial agent and is used for fish poisoning, treating skin diseases, and holding a cooling effect. Following the assessment of the plant extract's cytotoxic and phytotoxic assays using phytochemical screening, the antioxidant and anti-inflammatory properties of the pure ingredients that were separated from the ethyl acetate soluble fractions have been evaluated. The bioassay-guided fractionation and purification of E. vicaryi B. crude methanol extract yielded two isoflavones (1–2) that showed promising antioxidative activities with DPPH and cytochrome-c-reduction assays. Compounds 1 and 2 have shown considerable anti-inflammatory efficacy, 1 being a good inhibitor of the superoxide within the living system. Initial assumptions on the one-electron transfer process indicated that Compound 1 has a smaller ionization potential value compared to Compound 2 and so has greater antioxidant potential than its predecessor, isoflavone. Moreover, the anti-inflammatory and antioxidant activity of isoflavones was also probed by first-principles calculations. Based on the findings, it has been concluded that the crude extract of E. vicaryi B. and its organic components exhibit noteworthy phytotoxic and cytotoxic properties. The isolated pure isoflavones 1 and 2 showed significant antioxidant and anti-inflammatory activities. Solute-solvent interactions were studied and reported for both compounds. An analysis was conducted on the UV–Vis electronic transition for different solvents. Using a Multiwave function analyzer the topological findings such as ELF, LOL, and RDG were done to comprehend the surface electron density, delocalization, localized orbital, and weak interaction in the compounds. The antioxidant activity is evaluated by radical methods using DPPH, and cytochrome-c-reduction assays using ascorbic acid as a standard. Through cell-based respiratory burst testing, the anti-inflammatory activity of standard indomethacin was examined. The ground state geometries of isoflavones and reference compounds were optimized by Density Functional Theory- (DFT) by computing various electronic properties. In-vitro bioassay results were validated by first-principles calculations.

Design, synthesis, and evaluation of benzhydrylpiperazine-based novel dual COX-2/5-LOX inhibitors with anti-inflammatory and anti-cancer activity.

Piperazine derivatives were screened using the ChEMBL database, paving the way for the design, synthesis, and evaluation of a novel series of dual COX-2/5-LOX inhibitors and identifying their role in mitigating cancer cell proliferation. Compound 9d with 4-Cl substitution at the terminal phenyl ring showed promising inhibition of COX-2 (IC50 = 0.25 ± 0.03 μM) and 5-LOX (IC50 = 7.87 ± 0.33 μM), outperforming the standards celecoxib (IC50 = 0.36 ± 0.023 μM) and zileuton (IC50 = 14.29 ± 0.173 μM), respectively. The two most active derivatives 9d and 9g indicated a significant anti-inflammatory response in a paw edema model by inhibiting PGE2, IL-6, and TNF-α and an increase in IL-10 concentrations. Interestingly, 9d effectively reduced pain by 55.78%, closely comparable to the 59.09% exhibited by the standard indomethacin, and was also devoid of GI, liver, kidney, and cardiac toxicity. Furthermore, 9d demonstrated anti-cancer potential against in vitro A549, COLO-205, and MIA-PA-CA-2 human cancer cell lines and an in vivo Drosophila cancer model. The pharmacokinetic investigations revealed that 9d has good oral absorption characteristics.

Synthesis, docking and biological evaluation of purine-5-N-isosteresas anti-inflammatory agents.

An operationally simple one-pot three-component and convenient synthesis method for a series of diverse purine analogues of 5-amino-7-(substituted)-N-(4-sulfamoylphenyl)-4,7-dihydro-[1,2,4]-triazolo[1,5-a][1,3,5]triazine-2-carboxamide derivatives generated in situ via the reaction of 2-hydrazinyl-N-(4-sulfamoylphenyl)-2-thioxoacetamide, cyanoguanidine and a variety of aldehydes was achieved under green conditions. This experiment was conducted to evaluate the anti-inflammatory effect of the newly synthesized compounds using indomethacin as a reference medication; all compounds were tested for in vitro anti-inflammatory activity using the inhibition of albumin denaturation, RBC hemolysis technique and COX inhibition assay. The results showed that all evaluated compounds exhibited significant in vitro anti-inflammatory efficacy leading to excellently effective RBC membrane stabilization, inhibition of protein denaturation, and inhibition of COX enzymes when compared to those of indomethacin. At concentrations of 50, 100, 200, and 300 μg ml-1, these compounds decreased COX-1 and COX-2 activities more than indomethacin and have IC50 values in the range of 40.04-87.29 μg ml-1 for COX-1 and 27.76-42.3 μg ml-1 for COX-2 while indomethacin showed IC50 = 91.57 for COX-1 and 42.66 μg ml-1 for COX-2. The anti-inflammatory findings show the need for more investigation to define the properties underlying the evaluated compounds' anti-inflammatory abilities. The enzyme cyclooxygenase-2 (COX 2) (PDB ID: 5IKT) was docked with ten synthetic substances. With docking scores (S) of -8.82, -7.82, and -7.76 kcal mol-1, 7-furan triazolo-triazine (4), 7-(2-hydroxy phenyl) triazolo-triazine (11), and 7-(4-dimethylamino phenyl) triazolo-triazine (12) had the greatest binding affinities, respectively. Therefore, these substances have COX-2 (PDB ID: 5IKT) inhibitory capabilities and hence may be investigated for COX 2 targeting development. Furthermore, both the top-ranked compounds (4 and 11) and the standard indomethacin were subjected to DFT analysis. The HOMO - LUMO energy difference (ΔE) of the mentioned compounds was found to be less than that of indomethacin.

Green approach for the synthesis of ZnO nanoparticles using Cymbopogon citratus aqueous leaf extract: characterization and evaluation of their biological activities

BackgroundThe green synthesis of metal and metal oxide nanoparticles (NPs), notably from plants, has attracted increasing attention in recent years. Although the increased popularity use of Cymbopogon citratus as a therapeutic substance, to date, there has not been any research on the chemistry of C. citratus aqueous leaf extract (ALE) or synthesis of ZnO NPs utilizing an extract from it. The ecologically safe ALE of C. citratus was employed in this study as a bio-reducing and capping agent to synthesize ZnO NPs.ResultsThe novelty of the current study is the investigation of the antioxidant, anti-inflammatory, anti-microbial, and cytotoxic potencies of biosynthesized ZnO NPs utilizing C. citratus ALE. Zinc acetate dihydrate was used as the precursor and the leaf extract serves as the reducing agent. ZnO NPs from ALE of C. citratus were characterized by the spherical in form by using high-resolution transmission electron microscopy (HR-TEM) and the Scherrer formula was used to calculate the size of the crystalline structure. The presence of numerous functional groups in both the ALE and the NPs is confirmed by FTIR analysis. The highest absorption peak is observed at 370 nm. The stability and particle size of the biosynthesized ZnO NPs are demonstrated by dynamic light scattering (DLS) analysis. The biosynthesized ZnO NPs exhibited excellent antioxidant activity with an IC50 value of 45.67 ± 0.1 μg/mL and exerted interesting anti-inflammatory activity (98.1% ± 0.04) when compared to the standard indomethacin (92.1% ± 0.07) at 1 mg/mL. They also showed anti-microbial activity for both bacterial and fungal which growth rates for both significantly decreased with the increase in ZnO NPs concentration compared to the control. The anticancer activity of biosynthesized ZnO NPs and C. citratus ALE was in vitro tested against seven human cancer cell lines (HCCL) (i.e. H1299, MDA-MB-468, HNO97, HEK, HCT116, HuH7, and HEPG2) compared to normal cells (HSF) using the sulforhodamine-B (SRB) assay. More interestingly, the biosynthesized ZnO NPs displayed remarkable selective cytotoxicity against all tested cancer cell lines without any effect on normal cells. In contrast, the cancer cell lines were not affected by the ALE of C. citratus at any concentrations tested.ConclusionsAll the findings confirm that the ZnO NPs biosynthesized in the current work are promising candidates for a variety of biological activities, and as a result, they can be helpful to the medical sector, environmental and agricultural applications.Graphical

Evaluation of the anti-inflammatory potential of Solanum pubescens fruit extract

Introduction and Aim: Solanum pubescens is one of the very well-known traditional medicinal plants it has been widely used in the treatment of many inflammatory conditions. This study aimed to evaluate the anti-inflammatory property of S. pubescens fruit. Materials and Methods: Anti-inflammatory activities of S. pubescens fruit extracts at different concentrations (100-200 mg/kg) were carried out using carrageenan-induced and cotton implant-induced granuloma methods. Results: The results of the carrageenan-induced paw edema study reveals the highest activity of fruit upper ethanolic (FUEE) extract at 200 mg/kg, with 64.84% followed by water (FEW), and fruit lower ethanolic extracts (FLEE). The protein and IL-6 evaluation in this experiment showed very promising results. Whereas the cellular toxicity was evaluated in terms of LPO, MPO and nitric oxide analysis which in turn showed harmless nature of extracts. Furthermore, assessment of proliferative phase of inflammation was done in rats using a cotton pellet-induced granuloma model, where FUEE at 100 mg/kg showed 32.5±2.73 mg, 200 mg/kg 25.3±2.36 mg of dry weight of granuloma, compared to the standard indomethacin activity 1.4±3.45 mg. Moreover, the hematological parameters of treated animals reveals that the erythrocyte sedimentation rate (ESR) of FUEE 4.88± 0.18 mm/hr at 200 mg/kg was the least and almost equal to the standard. Conclusion: It can be said that S. pubescens is no doubt a very good source of phytomedicine for the treatment of inflammatory diseases, with most of the valuable phytoconstituents concerned with the anti-inflammation assembled in the fruit upper ethanolic extracts as this extract showed excellent activity in both the carrageenan and cotton pellet models.

EVALUATION OF ANTI-INFLAMMATORY ACTIVITY OF SIDDHA HERBO-MINERAL FORMULATION: SURANGUSA PARPAM

Introduction: Medicinal plants, minerals and some marine products can potentially treat medical conditions in the long term based on error and trial methods. Surangusa parpam, one of the Siddha herbo-mineral formulations, is mentioned in the classical Siddha text and indicated for respiratory illnesses like cough, cold, fever, bronchial asthma and intestinal tuberculosis. Objectives: This study was designed to evaluate the anti-inflammatory activity of the trial drug Surangusa parpam. Materials and Methods: The trial drug Surangusa parpam is prepared as per literature and inflammation is induced in the experimental animal’s carrageenan-induced paw oedema model. The trial drug Surangusa parpam and standard indomethacin are given orally for the anti-inflammatory effects. The anti-inflammatory effects were measured at regular intervals, and the percentage of the inhibition of paw oedema was to compare the effect of the trial medicine with the control and standard. Results: The trial drug showed significant improvement in the percentage inhibition of paw oedema in graded doses compared to control in the carrageenan-induced paw oedema model. 15 and 35 mg/kg of the trial drug showed significant inhibition of paw oedema at 55.9 % and 58.9 % compared with the control. Conclusion: Anti-inflammatory activity is seen with the graded dose of the trial drug. It can be concluded that the herbo-mineral formulation showed significant anti-inflammatory activity.

Integrating in vivo and in silico approaches to investigate the potential of Zingiber roseum rhizome extract against pyrexia, inflammation and pain

Zingiber roseum is a perennial herb in the Zingiberaceae family. The plant is native to Bangladesh, and rhizomes are frequently used in traditional medicine to cure gastric ulcers, asthma, wounds, and rheumatic disorders. Therefore, the present study aimed to analyse the antipyretic, anti-inflammatory, and analgesic properties of Z. roseum rhizome to confirm its efficacy in traditional applications. After 24 h of treatment, ZrrME (400 mg/kg) showed a considerable drop in rectal temperature (3.42°F) compared to standard paracetamol (5.26°F). At both doses (200 and 400 mg/kg), ZrrME showed a substantial dose-dependent decrease in paw oedema. However, after 2, 3 and 4 h of testing, the extract (200 mg/kg) had a lower anti-inflammatory response than standard indomethacin, whereas the higher dose (400 mg/kg) of rhizome extract had a more robust response compared to standard. ZrrME also showed substantial analgesic activity against all in vivo analgesic test models. The in vivo findings were further evaluated by in silico study of our previously identified compounds of ZrrME with the cyclooxygenase-2 enzyme (3LN1). The substantial binding energy (ranges from-6.2 to-7.7 Kcal/mol) of the polyphenols (excluding catechin hydrate) to the COX-2 enzyme affirm the in vivo test results of the present studies. In addition, the compounds were found effective as antipyretic, anti-inflammatory, and analgesic agents, according to the biological activity prediction software. Both in vivo and in silico results demonstrated promising antipyretic, anti-inflammatory, and pain-relieving effects of Z. roseum rhizome extract, which corroborate the claim of its traditional uses.

Analgesic and anti-inflammatory activity of quinoxaline derivatives: Design synthesis and characterization

Medicinal chemistry is a basic science that involves identification, synthesis and development of new drugs for therapeutic use. Biological importance of heterocycles makes them more crucial in pharmaceutical industries.In this work heterocyclics like quinoxaline and its derivatives were prepared. Different quinoxalines such as biphenyl quinoxaline, quinoxaline dione and quinoxaline-2-one were synthesized by different synthetic routes. All the quinoxaline derivatives were obtained with better yields and high purity. Substituted quinoxaline derivatives were subjected to biological evaluation which include analgesic and invitro anti inflammatory activity. The progress of the reaction was monitored by physical constants such as TLC, melting point and Rf values were determined. The structural elucidation is done by IR, Mass and 1H NMR spectral data. Among all quinoxalines 2, 5, 9, 14f and 17c revealed significant analgesic activity with percentage protection of 56.90, 68.68, 67.70, 66.33 and 68.79 respectively. The standard drug aspirin exhibited 70.50 % with 30 mg/kg body weight. Among the synthesized quinoxalines, 3, 11, 14d and 17e were found to bring about a decrease in oedema such as 53. 91, 48.72, 46.77 and 46.85 percentage reduction in oedema comparable to that of standard Indomethacin 10 mg/kg bodyweight 49.00 % reduction in oedema. All the quinoxaline derivatives were screened for different activities like analgesic activity by acetic acid induced writhing method in mice and anti inflammatory activity by using the ‘carrageenan induced paw oedema method’ in rats. The search of more suitable anti inflammatory agent and acute pain is well accounted in terms of nociception.

Screening of aqueous extract of fenugreek seeds for its anti-inflammatory potential in albino rats

Background: Inflammation is a common defense mechanism that involves a complicated network of cell-cell, cell-mediator, and tissue interaction. Fenugreek (Trigonella foenumgraecum L.) seeds are used for the treatment of many inflammatory conditions. Aims and Objectives: The aim of the study was to analyze the anti-inflammatory properties of aqueous extracts of fenugreek seeds in albino rats and compare it to control and standard anti-inflammatory treatments in animal models of acute and chronic inflammation. Materials and Methods: The methods employed to study the anti-inflammatory activity are carrageenan-induced rat paw edema and turpentine induced arthritis model in rats for acute inflammatory model and cotton wool pellet granuloma in rats for chronic inflammatory modelfollowing acquisition of the Institutional Ethics Committee approval. The control group was given 1% gum acacia, standard group was given 10 mg/kg Indomethacin dissolved in distilled water and test group was given 200 mg/kg of aqueous extract of fenugreek seeds suspended in 1% gum acacia orally. Results: The test group displayed almost equal increase in paw volume edema as that of the standard group under experimental conditions. In Carrageenan-induced rat paw edema model and turpentine induced arthritis model, aqueous extract of fenugreek seeds and indomethacin had comparable anti-inflammatory effect. The anti-granuloma effect of aqueous extract of fenugreek seeds was of moderate degree compared to the standard under the present experimental conditions. Conclusion: When compared to standard indomethacin, the aqueous extract of fenugreek seeds demonstrated significant anti-inflammatory activity in acute models of inflammation and moderate activity in chronic models of inflammation.

Development of Oral Microemulsion Spray Containing Pentacyclic Triterpenes-Rich Centella asiatica (L.) Urb. Extract for Healing Mouth Ulcers.

Several publications have shown that Centella asiatica (L.) Urb. and its active constituents (pentacyclic triterpenes) are effective in wound healing. The pentacyclic triterpenes-rich C. asiatica extract (PRE) was prepared following a previous study by microwave-assisted extraction (MAE) and fractionation with macroporous resin. This method provided the pentacyclic triterpene content in the extract up to 59.60% w/w. The PRE showed potent anti-inflammatory activity by inhibiting nitric oxide (NO) production with an IC50 value of 20.59 ± 3.48 μg/mL and a potent fibroblast proliferative effect (165.67%) at concentrations of 10 μg/mL. The prepared microemulsion consisted of a water: oil: surfactant mixture of 2: 2: 6, using coconut oil: clove oil (1:1) as the oil phase and Tween 20: Span 20 (2:1) as the surfactant mixture and 1.0, 2.5, and 5.0% PRE. Cell proliferation, migration, and collagen production of the microemulsion base and microemulsions containing 1.0%, 2.5%, and 5.0% PRE were evaluated. The results revealed that the microemulsion containing 1% PRE had the highest proliferation effect (136.30 ± 3.93% to 152.65 ± 3.48% at concentrations of 10 μg/mL), migration activities (100.00 ± 0.0% at 24 h), and collagen production in human dermal fibroblast (HDF) and human gingival fibroblast (HGF) cells when compared with other formulations or blank. Moreover, the anti-inflammatory activity of microemulsions containing 1% PRE was slightly lower than standard indomethacin. Anti-inflammation of the microemulsion containing PRE exhibited a dose-dependent trend, while 5% PRE was more potent than the standard drug. Considering the potent wound-healing activities and the good anti-inflammatory activity of the microemulsion containing PRE, the microemulsion with 1% PRE was identified as the most suitable oral spray formulation for oral ulcer treatment.

Highly potent anti-inflammatory, analgesic and antioxidant activities of 3,5-disubstituted tetrahydro-2H-1,3,5-thiadiazine thiones

Four series of tetrahydro-2H-1,3,5-thiadiazine-2-thiones (series A and B including two novel enantiopure isomers), tetrahydro-2H-1,3,5-thiadiazine-6-thiones (series C) and N-3 ester derivatives of tetrahydro-2H-1,3,5-thiadiazine-6-thiones (series D) were synthesized and evaluated for their anti-inflammatory, analgesic and anti-oxidant activities. These THTT analogues specially series D were first time examined for their in vitro anti-inflammatory, in vivo analgesic and anti-oxidant activities. Among them lipophilic compounds (series B and D) were found to be highly active for anti-inflammatory evaluation with IC50 values between 5.1–16.9 and 4.1–32.4 μM, respectively when compared with the standard drug ibuprofen IC50 = 11.2 μM. The structure–activity relationship exposed the importance of lipophilic substituents especially ester and n-propyl group for inhibition of inflammation. The molecular docking studies demonstrated that all the active analogues of THTT have notable binding relations with Arg120 of the active sites of COX-1 enzyme either through CS moiety of the THTT nucleus or with COO attached at N-3 of THTT nucleus. In vivo analgesic activity of the selected THTT compounds 14, 17, 18, 19 (series B) and 28 (series D) were also carried out by acetic acid-induced writhing procedure. The compound 28 showed significant anti-nociceptive/analgesic activity at the oral dose of 5 mg/kg body weight with the percent protection (32.05 %) when compared with standard indomethacin at 10 mg/kg (48.83 %). Additionally, these compounds demonstrated the moderate level of antioxidant potential with IC50 values in the range of 60.9 to 93.6 μM (standard butylated hyroxyanisole; IC50 = 44.2 μM). These results indicated that this class of heterocyclic compounds may be a template specially to design better anti-inflammatory and analgesic agents.

IN VITRO AND IN VIVO SCREENING OF ANTI-INFLAMMATORY ACTIVITY OF METHANOLIC AND AQUEOUS EXTRACTS OF ANOGEISSUS LATIFOLIA LEAVES

Objective: To evaluate and compare anti-oxidant and anti-inflammatory activity of methanolic and aqueous extract of Anogeissus latifolia leaves Methods: The in vitro antioxidant activity was investigated using nitric oxide radical inhibition activity assay, hydroxyl radical scavenging activity assay, DPPH free radical scavenging assay, and reducing power assay. The in vitro anti-inflammatory activity was investigated using erythrocyte membrane stabilization, inhibition of protein denaturation, and proteinase inhibitory activity the in vivo anti-inflammatory activity was investigated using carrageenan-induced rat paw edema. The biochemical parameters were evaluated in the blood, which included the determination of serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase values and in the liver, which includes the estimation of lipid peroxidation, reduced glutathione, and superoxide dismutase. Results: The methanolic extract caused a significant dose depended on the reduction of inflammation when compared with the aqueous extract of Anogeissus latifolia. The anti-inflammatory activity of all groups was found to be comparable to the standard indomethacin group. The maximum percent inhibition in paw edema was found in methanolic extract of Anogeisuss latifolia at a dose of 500 mg/kg was 53.33%, with significant anti-inflammatory activity p<0.001. Conclusion: The leaf extract of Anogeissus latifolia possesses anti-oxidant and anti-inflammatory activity. The therapeutic effect of Anogeisuss latifolia extracts will encourage its use in the treatment of inflammation.

Exploration of anti-inflammatory activity of extract and isolated compounds obtained from the aerial root of Ficus benghalensis Linn.

Ficus benghalensis L. is a traditional heritage tree available in Indian subcontinent and used traditionally for ailment of several diseases. Present study designed to purify and characterize the bioactive moiety (s) from the aerial root part of the plant, and assessment of the role of extract as well as purified molecules in the prevention of inflammation. Aerial root portion of the plant was first extracted using methanol as solvent, and further fractionated with n-hexane and ethyl acetate. α amyrin acetate (S1) was purified from the n-hexane and ethyl acetate fraction, and stigmasterol (S2), first time purified from the plant using from the ethyl acetate fraction using column chromatography. Extract, purified α-amyrin acetate and stigmasterol were checked for their anti-inflammatory property using Carrageenan induced paw oedema model on rat. Extract at a dose 400 mg/kg, α-amyrin acetate and stigmasterol both at 100 mg /kg dose significantly reduce the inflammation near to normal. After 3 hrs the paw volume was inhibited 25%, 47.5%, 42.5%, 45%, 62.5% by EA extract of 200 mg/kg, 400 mg/kg, stigmasterol 100mg/kg, α- amyrin acetate 100 mg/kg and standard Indomethacin, respectively. The finding of present study revealed the prospective anti-inflammatory property of α-amyrin acetate, stigmasterol and extract of aerial root of Ficus benghalensis L.

Computational Studies and Biological Evaluation on Synthesized Lead 1,3- diphenyl-4,5-dihydro-1H-pyrazole Moiety as Anti-Infective Agents

Background: Chronic non communicable diseases were interlinked with inflammation and infections should response to starting core of major diseases in both acute and chronic conditions. In drug discovery, development of a drug which acts as anti-infective agents (anti-microbial and anti-inflammatory) must be ideal and challenging for management of many chronic diseases. Objective: In this study, six lead pyrazoline hybrids were synthesized by cyclization of chalcones and characterized by various spectroscopic and elemental analysis. All synthesized compounds were screened for anti-inflammatory and anti-microbial activity by computational tools and biological evaluation. Methods: Synthesized pyrazoline analogues were characterized by various spectroscopic techniques and evaluated for prediction of pharmacokinetics, physicochemical properties and Molecular docking studies of various targeted enzymes on microbial and inflammatory mediators. Those compounds were screened by anti-microbial and anti-inflammatory activities by several in-vitro and in-vivo methods. Results: The synthesized compounds (A1-A6) were screened for anti-inflammatory activity in which compound A2 produced effective percentage inhibition (45.8 %) potent activity compared with that of standard indomethacin (49.7 %) in carrageenan paw edema method were observed. The anti-microbial activity was screened on synthesized compounds, among which A3 [2-(1,3-diphenyl-4,5-dihydro-1H-pyrazol-5-yl) phenol, A2 [5-(4-chlorophenyl)-1,3-diphenyl-4,5-dihydro-1H-pyrazole] produced potential percentage zone of inhibition between 80 - 70 % for bacterial strains and 94 - 89 % for fungal strains were observed. The minimum inhibitory concentration values of those compounds were 1.56 to 6.25 µg/ml for bacterial strains and 1.56 to 12.5 µg/ml for fungal strains were noted compared with the standard gatifloxacin and clotrimazole, respectively. The molecular docking, pharmacokinetics and toxicity predictions on those compounds were supported further for the development of potent anti-infective agents. Conclusion: The hypothesis of this research was correlated with the results of anti-inflammatory and anti-microbial activity. The binding interactions of respective enzymes were coincided with reduction of paw edema in anti-inflammatory model and zone of inhibition in anti-microbial activity were observed.

Variation in Phenolic Profile, Antioxidant, and Anti-Inflammatory Activities of Salvadora oleoides Decene. and Salvadora persica L. Fruits and Aerial Part Extracts.

(1) Background: The objective of this study was to investigate the potential of Salvadora oleoides (S. oleoides) and Salvadora persica (S. persica) polyphenols as antioxidant and anti-inflammatory agents. (2) Methods: Aerial parts and fruits of S. oleoides and S. persica were collected from the periphery of District Bhakkar, Punjab, Pakistan. Methanol extracts were prepared using the Soxhlet extraction technique. Extract yield varied from 8.15 to 19.6 g/100 g dry plant material. RP-HPLC revealed the detection of thirteen phenolic aids and five flavonoids. Gallic acid, hydroxy benzoic acid, chlorogenic acid, and cinamic acid were the major phenolic acids, whereas catechin, rutin, and myricetin were the flavonoids detected. (3) Results: Maximum total phenolic contents (TPCs) (22.2 mg/g of dry plant material) and total flavonoid contents (TFCs) (6.17 mg/g of dry plant material) were found in the fruit extract of S. persica, and the minimum TPC (11.9 mg/g) and TFC (1.72 mg/g) were found in the aerial part of S. oleoides. The fruit extract of S. persica showed the highest DPPH radical scavenging activity. In vivo anti-inflammatory activity of all the extracts was performed on albumin-induced rat paw edema that was comparable with the standard indomethacin; S. persica fruit extract showed remarkable anti-inflammatory activity. Analgesic activity of aerial part and fruit extracts of S. oleoides and S. persica was investigated using a mouse model, and the results showed that maximum possible analgesia of fruit extracts of S. persica was 53.44%, which is better than the PC group (52.98%). (4) Conclusions: The variations in the antioxidant, anti-inflammatory, and analgesic activities of methanolic extracts of S. oleoides and S. persica were found to be significant, and they have therapeutic potential as antioxidant, analgesic, and anti-inflammatory agents.

Green Synthesis and Characterization of ZnO Nanoparticles Using Pelargonium odoratissimum (L.) Aqueous Leaf Extract and Their Antioxidant, Antibacterial and Anti-inflammatory Activities.

Nanoparticles (NPs) exhibit distinct features compared to traditional physico-chemical synthesis and they have many applications in a wide range of fields of life sciences such as surface coating agents, catalysts, food packaging, corrosion protection, environmental remediation, electronics, biomedical and antimicrobial. Green-synthesized metal NPs, mainly from plant sources, have gained a lot of attention due to their intrinsic characteristics like eco-friendliness, rapidity and cost-effectiveness. In this study, zinc oxide (ZnO) NPs have been synthesized employing an aqueous leaf extract of Pelargonium odoratissimum (L.) as a reducing agent; subsequently, the biosynthesized ZnO NPs were characterized by ultraviolet-visible spectroscopy (UV-Vis), dynamic light scattering (DLS), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM) and energy-dispersive X-ray spectroscopy (EDX), high-resolution transmission electron microscopy (HRTEM) and selected area electron diffraction (SAED). Moreover, aqueous plant leaf extract was subjected to both qualitative and quantitative analysis. Antioxidant activity of ZnO NPs was assessed by DPPH assay, with varying concentrations of ZnO NPs, which revealed scavenging activity with IC50 = 28.11 μg mL−1. Furthermore, the anti-bacterial efficacy of the green synthesized ZnO NPs against four foodborne pathogenic bacterial strains was examined using the disk diffusion assay, and Staphylococcus aureus (ATCC 8095), Pseudomonas aeruginosa (ATCC10662) and Escherichia coli (ATCC 25922) were found to be the most sensitive against biosynthesized ZnO NPs, whereas the least sensitivity was shown by Bacillus cereus (ATCC 13753). The anti-inflammatory effect was also evaluated for both ZnO NPs and the aqueous leaf extract of P. odoratissimum through the human red blood cells (HRBC) membrane stabilization method (MSM) in vitro models which includes hypotonicity-induced hemolysis. A maximum membrane stabilization of ZnO NPs was found to be 95.6% at a dose of 1000 μg mL−1 compared with the standard indomethacin. The results demonstrated that leaf extract of P. odoratissimum is suitable for synthesizing ZnO NPs, with antioxidant, antibacterial as well as superior anti-inflammatory activity by improving the membrane stability of lysosome cells, which have physiological properties similar to erythrocyte membrane cells and have no hemolytic activity. Overall, this study provides biosynthesized ZnO NPs that can be used as a safe alternative to synthetic substances as well as a potential candidate for antioxidants, antibacterial and anti-inflammatory uses in the biomedical and pharmaceutical industries.

Development, optimization, and validation of Inflammatory Bowel Disease rat model using isotretinoin

Backgroundand Purpose: Inflammatory Bowel Disease (IBD) is a persistent bio-psychological disorder with the absence of actual pathological reason. Association between IBD and isotretinoin has been reported by many human and in vitro studies. However, in this study, our focus is on finding the causal relationship between IBD and isotretinoin for the development of a new animal model. MethodsTwenty-eight Sprague Dawley rats were taken for this study and divided into five groups (i.e. Group 1: Normal control, Group 2: Standard IBD Model Group (Indomethacin treated), Group 3: Isotretinoin low dose (7 mg/kg), Group 4: Isotretinoin medium dose (35 mg/kg), Group 5: Isotretinoin high dose (70 mg/kg). The rats were treated according to assigned treatment and observed on different days to evaluate the severity of IBD with the help of symptomatical (nausea, diarrhea, stool consistency, etc.) activity, biochemical parameters, macroscopy, and histological analyses. Key resultsDuring the entire study period, body weight, stool consistency and frequency of the animals had been observed daily. No significant reduction in body weight was observed between the disease induced and normal control animals; however, it was observed that the stool consistency of the animals became less (mucus in stool) day by day and stool frequency increased (frequent defecation) in the different isotretinoin groups compared to the control group. There was statistically significant increase in TBARS levels of isotretinoin low (p < 0.05), medium (p < 0.001) and high dose (p < 0.01) treated group was observed, as compared to control group. Similarly, statistically significant effects of isotretinoin on GSH level (p < 0.01), CAT activity (p < 0.01), and SOD (p < 0.01) were also observed. Increase in TNF-α levels found significantly higher in isotretinoin medium dose (35 mg/kg) treated group (p < 0.001) as compared with control group as well as standard IBD model group. All the three-isotretinoin treated groups (Isotretinoin low dose: p < 0.001; Isotretinoin medium dose: p < 0.001; Isotretinoin high dose: p < 0.001) depicted significant difference in macroscopic scores as compared with control group; these results are comparable with standard IBD model group. Histological analyses revealed that, among three-dose groups of isotretinoin, there was excessive amount of crypt abscesses, infiltration of inflammatory cells, and formation of ulceration observed in isotretinoin medium dose treated group. ConclusionAs standard indomethacin treated group, isotretinoin also caused significant damage to intestinal mucosa, and form ulceration in gastrointestinal tract. Compared to control group, isotretinoin significantly worsens the disease condition, which were comparable to the indomethacin-treated group; however, isotretinoin at the dose of 35 mg/kg caused maximum severe damage to the intestinal mucosa.

Evaluation of Anti-Inflammatory and Antipyretic Activities of The Aqueous Stem Bark Extract of Lophira Lanceolata Van Tiegh. Ex Keay

The bark of Lophira lanceolata (Ochnaceae) has been used traditionally for the treatment of many disease conditions such as dysentery, headaches, diarrhoea, cough, abdominal pains, fungal infections, nociception and cardiovascular diseases. However, no specific work on its anti-inflammatory or antipyretic effect has been reported which forms the basis of this study. This study evaluates the in-vivo anti-inflammatory and antipyretic activities of the aqueous extract of the stem bark of Lophira lanceolata using laboratory animal model. The methods adopted for this study were formalin induced inflammation and yeast induced hyperpyrexia in rats. All the results were expressed as mean ± S.E. The data were statistically analysed by one way analysis of variance (ANOVA) followed by Dunnett's multiple comparison and p-values 0.05 were considered as significant. The result of this study showed a significant anti-inflammatory effect different from the control (distilled water) at p 0.05 characterized by oedema formation, change in temperature, redness, and itching in the paw of the rats which is comparable with the standard indomethacin. The inhibition of oedema was statistically dose dependent as the group 4 rats which received 400 mg/kg body weight demonstrated more effect than the group 1 rats which received 100 mg/kg body weight of the aqueous extract of the stem bark of Lophira lanceolata. The aqueous at the dose of 400 mg/kg body weight showed the highest antipyretic effect. Hence the antipyretic activity was also dose- dependent. The study demonstrated that the aqueous Lophira lanceolata stem bark extract possesses anti-inflammatory and antipyretic activities.