Carrageenan-induced Paw Edema Test Research Articles

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.

Formulation and Evaluation of Meloxicam Hybrid nano Particles.

The goal of the present study was to prepare meloxicam (MX) entrapped hybrid particles (HPs) to enhance intestinal permeation and anti-inflammatory activity. MX-HPs were prepared by nanoprecipitation method using lipid, chitosan, poloxamer, and TPGS. The formulations (MX-HPs1, MX-HPs2, MX-HPs3) were evaluated for particle size, entrapment efficiency, and drug release to select the optimized composition and further evaluated for permeation study, stability study, morphology, interaction study, and anti-inflammatory activity by carrageenan-induced rat paw edema test. The prepared MX-HPs showed nano sized particles (198.5 ± 3.7 to 223.8 ± 2.1nm) and PDI (<0.3), zeta potential (16.5 ± 2.7 to 29.1 ± 3.6 mV), and high entrapment efficiency (75.1 ± 4.7 to 88.5 ± 3.9%). The surface morphology was assessed by transmission electron microscopy and showed non-aggregated particles. Infra-red (IR) spectroscopy of pure MX as well as formulation revealed no drug-polymer interaction and X-ray diffraction confirmed the conversion of crystalline MX into amorphous form. The release study data revealed prolonged MX release for 24h. The selected optimized hybrid particles (MX-HPs2) revealed a 2.3-fold improved enhancement ratio than free MX. The storage stability and gastrointestinal stability data demonstrated a stable formulation in SIF as well as SGF. The anti-inflammatory activity showed better therapeutic action than pure MX dispersion. From the study, it can be concluded that the prepared MX-HPs may be a promising delivery system for MX in treating inflammatory disorders.

Improved Anti-nociceptive, Anti-pyretic and Anti-inflammatory Effects of Orally Administered Liposome-encapsulated Piroxicam

Piroxicam, a nonsteroidal anti-inflammatory drug, has been shown with low oral bioavailability and delayed onset of its therapeutic effects. In this work, a promising nano/liposomal drug delivery system was exploited to improve the in vivo therapeutic efficacies of piroxicam. The current liposome-encapsulated piroxicam formulation effectively boosted and prolonged peripherally mediated anti-nociceptive activities in tests for abdominal writhing induced by acetic acid (inhibition of pain 70.19% was in mice treated with 30 mg/kg liposome-encapsulated piroxicam), paw licking induced by formalin (81.36% inhibition when compared to free unencapsulated piroxicam), and hyperalgesia induced by carrageenan (55.8% inhibition when compared to free unencapsulated piroxicam). Even lower dose of liposomes-encapsulated piroxicam was also significantly inhibit Brewer’s yeast-induced hyperthermia. Carrageenan-induced paw-edema test and cotton pellet-induced granuloma test revealed that liposomes-encapsulated piroxicam had significantly more potent acute and chronic anti-inflammatory effects than piroxicam, even if lower drug dosages were used to treat animals. A better modulation in the generation of inflammatory mediators (nitric oxide, tumour necrosis factor-α, interleukin-1β, and interleukin-10) at 18.02% (TNFa), 23.97% (IL-1β) and 10.27% (IL-10) inhibition when compared to 30mg/kg free piroxicam group respectively. was ascribed to the higher in vivo therapeutic actions. Present nano-encapsulated piroxicam also significantly enhanced the inhibition of cyclooxgenase-2 (total percentage inhibition was increased by 18.25% and 19.22% at drug dosage of 3 and 30 mg/kg, respectively), but not cyclooxgenase-1 enzyme. In conclusion, present study showed that liposomal drug formulation was able to improve the in vivo therapeutic effects of orally administered piroxicam.

Multiple drug-delivery strategies to enhance the pharmacological and toxicological properties of Mefenamic acid

ObjectiveTo improve the biological and toxicological properties of Mefenamic acid (MA), the galactosylated prodrug of MA named MefeGAL was included in polymeric solid dispersions (PSs) composed of poly(glycerol adipate) (PGA) and Pluronic® F68 (MefeGAL-PS). MefeGAL-PS was compared with polymeric solid formulations of MA (MA-PS) or a mixture of equal ratio of MefeGAL/MA (Mix-PS). MethodsThe in vitro and in vivo pharmacological and toxicological profiles of PSs have been investigated. In detail, we evaluated the anti-inflammatory (carrageenan-induced paw edema test), analgesic (acetic acid-induced writhing test) and ulcerogenic activity in mice after oral treatment. Additionally, the antiproliferative activity of PSs was assessed on in vitro models of colorectal and non-small cell lung cancer. ResultsWhen the PSs were resuspended in water, MefeGAL’s, MA’s and their mixture’s apparent solubilities improved due to the interaction with the polymeric formulation. By comparing the in-vivo biological performance of MefeGAL-PS with that of MA, MefeGAL and MA-PS, it was seen that MefeGAL-PS exhibited the same sustained and delayed analgesic and anti-inflammatory profile as MefeGAL but did not cause gastrointestinal irritation. The pharmacological effect of Mix-PS was present from the first hours after administration, lasting about 44 hours with only slight gastric mucosa irritation. In-vitro evaluation indicated that Mix-PS had statistically significant higher cytotoxicity than MA-PS and MefeGAL-PS. ConclusionsThese preliminary data are promising evidence that the galactosylated prodrug approach in tandem with a polymer-drug solid dispersion formulation strategy could represent a new drug delivery route to improve the solubility and biological activity of NSAIDs.

Acute Toxicity, Analgesic, and Anti-inflammatory Activities of Folk Thai Herbal Medicine: Yafon Formula

Yafon (YF), a formula composed of 14 herbal constituents, has been used in folk Thai herbal medicine to treat various indications, including pain relief, antipyretics, and anti-inflammatory properties. Nevertheless, this formula lacks adequate toxicological and efficacy data. Hence, this study aims to assess the safety and efficacy of YF in animal models. The study on acute oral toxicity was conducted by the Organization for Economic Co-operation and Development (OECD) number 420 guidelines. The results demonstrated that the administration of YF at a high dose of 2000 mg/kg did not result in fatality or exhibit any toxicity. The analgesic effect of YF in mice was investigated using the acetic acid-induced writhing test and the formalin test. The anti-inflammatory activity of YF was assessed in rats using the carrageenan-induced paw edema test. This investigation employed YF doses of 200, 400, and 800 mg/kg/day. The study found that all YF doses reduced writhing in the acetic acid, and YF doses of 400 and 800 mg/kg/day reduced the licking time in the late phase of the formalin test. In addition, all YF doses effectively suppressed paw edema in the carrageenan-induced paw edema test. This study demonstrated that the YF formula showed no acute toxicity and possessed acute anti-inflammatory and analgesic effects by blocking pain signals originating from the peripheral nervous system. These findings provided empirical evidence supporting the use of YF formula as an analgesic and anti-inflammatory agent.

Evaluation of Habenaria aitchisonii Reichb. for antioxidant, anti-inflammatory, and antinociceptive effects with in vivo and in silico approaches.

Habenaria aitchisonii Reichb was analyzed in this research, including its chemical composition and its in vitro antioxidant, anti-inflammatory, acute oral toxicity, and antinociceptive activity. The chloroform and ethyl acetate fractions were found to be the most powerful based on in vitro antioxidant, anti-inflammatory, and analgesic assays. The acute oral toxicity of the crude methanolic extract was determined before in vivo studies. The acetic acid and formalin tests were used to measure the antinociceptive effect, and the potential mechanisms involved in antinociception were explored. The carrageenan-induced paw edema test was used to examine the immediate anti-inflammatory effect, and many phlogistic agents were used to determine the specific mechanism. Furthermore, for ex vivo activities, the mice were sacrificed, the forebrain was isolated, and the antioxidant levels of glutathione (GSH), superoxide dismutase (SOD), thiobarbituric acid reactive substances (TBARS) and catalase (CAT) were estimated using a UV spectrophotometer. No toxicity was seen at oral dosages up to 3,000mg/kg. The antinociceptive impact was much higher than the standard drug. Both the inflammatory and neurogenic phases of the formalin experiment revealed an analgesic effect in the chloroform and ethyl acetate fractions. In carrageenan anti-inflammatory assays, the chloroform fraction (Ha.Chf) was the most potent fraction. We further studied the GC-MS of crude plant extract and found a total of 18 compounds. In the anti-inflammatory mechanism, it was observed that the Ha.Chf inhibits the COX-2 as well as 5-LOX pathways. The results exhibited that this species is a good source of phytocomponents like germacrone, which can be employed as a sustainable and natural therapeutic agent, supporting its traditional use in folk medicine for inflammatory conditions and pain.

Phytochemical characterization and biological activities evaluation of Opuntia sp. cladodes

The prickly pear is a plant belonging to the Cactaceae family, and it is the best-known species that has gained significant recognition in recent years. Opuntia sp. cladodes have been traditionally utilized as a functional food and in traditional medicine for treating chronic diseases. Therefore, this study aims to evaluate the antioxidant, antimicrobial, and pharmacological activities of cladode extracts from Opuntia microdasys (Cl1) and Opuntia macrorhiza (Cl2), as well as to identify their phytochemical compounds. The chemical composition of the cladode extracts was analyzed using spectrophotometric methods, while the antioxidant activity was determined through DNA nicking assays. Microdilution assays were employed to assess the antimicrobial activity. Analgesic and anti-inflammatory activities were determined using the acetic acid writhing test in mice and the carrageenan-induced Wistar rat paw edema test. The results revealed that the two extracts of cladodes from Cl1 and Cl2 were characterized by a high phenolic content (58.13 and 44.58 GAE/g of extract, respectively). All the tested extracts exhibited antimicrobial activity against the strains tested, with Minimum Inhibitory Concentration (MIC) values ranging from 0.312 to 5 mg/mL and Minimum Bactericidal Concentration (MBC) values ranging from 1.25 to 10 mg/mL. The cladode extracts of Cl1 and Cl2 at a dose of 300 mg/kg showed a dose-dependent inhibition of acetic acid-induced writhing in mice, with respective values of 64.76 % and 61.91 %. The maximum anti-inflammatory activity of all doses of cladode extracts was observed 5 h after carrageenan-induced paw edema, and all tested doses significantly inhibited the induced inflammation.

Tailored quinoline hybrids as promising COX-2/15-LOX dual inhibitors endowed with diverse safety profile: Design, synthesis, SAR, and histopathological study

Complications of the worldwide use of non-steroidal anti-inflammatory drugs (NSAIDs) sparked scientists to design novel harmless alternatives as an urgent need. So, a unique hybridization tactic of quinoline/pyrazole/thioamide (4a-c) has been rationalized and synthesized as potential COX-2/15-LOX dual inhibitors, utilizing relevant reported studies on these pharmacophores. Moreover, we extended these preceding hybrids into more varied functionality, bearing crucial thiazole scaffolds(5a-l). All the synthesized hybrids were evaluatedin vitroas COX-2/15-LOX dual inhibitors. Initially, series4a-cexhibited significant potency towards 15-LOX inhibition (IC50 = 5.454–4.509 μM) compared to meclofenamate sodium (IC50 = 3.837 μM). Moreover, they revealed reasonable inhibitory activities against the COX-2 enzyme in comparison to celecoxib.Otherwise, conjugates 5a-ldisclosed marked inhibitory activity against 15-LOX and strong inhibitory to COX-2. In particular, hybrids5d(IC50 = 0.239 μM, SI = 8.95), 5h(IC50 = 0.234 μM, SI = 20.35) and 5l (IC50 = 0.201 μM, SI = 14.42) revealed more potency and selectivity outperforming celecoxib (IC50 = 0.512 μM, SI = 4.28). In addition, the most potentcompounds, 4a, 5d, 5h, and 5l have been elected for further in vivoevaluation and displayed potent inhibition of edema in the carrageenan-induced rat paw edema test that surpassed indomethacin. Further, compounds5d, 5h, and 5l decreased serum inflammatory markers including oxidative biomarkersiNO, and pro-inflammatory mediators cytokines like TNF-α, IL-6, and PGE. Ulcerogenic liability for tested compounds demonstrated obvious gastric mucosal safety. Furthermore, a histopathological study for compound 5l suggested a confirmatory comprehensive safety profile for stomach, kidney, and heart tissues. Docking and drug-likeness studies offered a good convention with the obtained biological investigation.

Antinociceptive effect and anti-inflammatory activity of 1,4-naphthoquinones in mice

Aim: The ability of synthetic 1,4-naphthoquinones (1,4-NQs) to prevent adenosine triphosphate (ATP)-induced and purinergic P2X7 receptor (P2X7R) mediated inflammation in macrophage and neurodegeneration of neuronal cells in vitro was previously established. The aim of the present study was to investigate analgesic-like and anti-inflammatory activity of 1,4-NQs thioglucoside derivatives, compounds U-286 and U-548, in in vivo experiments. Methods: Spectrofluorimetry approach and YO-PRO-1 fluorescent dye uptake determination were applied to study the effect of 1,4-NQs upon ATP-induced P2X7R mediated macropore formation in mouse neuroblastoma Neuro-2a cells and macrophages RAW 264.7 cells. An acetic acid-induced writhing test, hot plate test, and carrageenan-induced paw edema test were used as an in vivo mouse models to study the ability of 1,4-NQs to inhibit pain and inflammation. In the in vivo experiments, compounds were administered to mice intraperitoneally at dosages of 0.1 mg/kg, 1.0 mg/kg and 10.0 mg/kg. A group of animals that received injections of sterile water was used as a control. Each dosage group and the control group consisted of 6 mice. Results: In the present work the analgesic-like and anti-inflammatory activity of 1,4-NQs, U-286 and U-548, was demonstrated. Compound U-548 showed a significant inhibitory effect in antinociceptive tests reducing the number of mouse writhings and eliminating the latent time of mouse hind paw licking, correspondingly. Selected compounds were able to almost completely reduce the size of carrageenan-induced paw edema 24 h after injection and had a potent anti-inflammatory activity. Observed effects were accompanied with aptitude of studied 1,4-NQs to inhibit the formation of purinergic P2X7R macropore associated with inflammation and nociceptive pain. Conclusions: The results obtained allow to consider compounds U-286 and U-548 and as a pharmacological basis for the development of new analgesic-like and anti-inflammatory drugs.

Polyphenols and extracts from Zingiber roseum (Roxb.) Roscoe leaf mitigate pain, inflammation and pyrexia by inhibiting cyclooxygenase-2: an in vivo and in silico studies.

Zingiber roseum (Roxb.) Roscoe, a perennial herb from the Zingiberaceae family, has a long history of traditional use in the treatment of several ailments including pain, inflammation, fever, cough, arthritis, skin diseases, and liver infections. This study sought to confirm the efficacy of Zingiber roseum (Roxb.) Roscoe leaves methanol extract (ZrlME) as reported in traditional usage by evaluating its analgesic, anti-inflammatory, and antipyretic capabilities. In addition, in silico molecular docking of the metabolites identified in ZrlME was studied to verify the experimental outcomes. ZrlME demonstrated strong dose-dependent analgesic efficacy against all analgesic tests. ZrlME (400mg/kg) showed higher anti-inflammatory activity than the standard in the carrageenan-induced paw edema test model. A significant reduction of rectal temperature (3.97°F↓) was also recorded at the same dose of ZrLME after 24h of treatment. Seven polyphenolic metabolites were identified and quantified by HPLC-DAD analysis, including 3, 4- dihydroxy benzoic acid, (-) epicatechin, rutin hydrate, p-coumaric acid, trans-ferulic acid, rosmarinic acid, and myricetin. Strong binding affinities (ranges from -5.8 to -8.5Kcal/mol) between the aforesaid polyphenols and cyclooxygenase-2 were discovered. Moreover, molecular dynamics simulations (MDS) demonstrated that these polyphenols exhibit significant COX-2 inhibitory activity due to their high stability in the COX-2 active site. In computational prediction, the polyphenols were also found to be nontoxic, and a variety of biological activities, such as antioxidant, analgesic, anti-inflammatory, antipyretic, and hepatoprotective, were observed. The results of this study revealed that ZrlME possesses notable analgesic, anti-inflammatory, and antipyretic properties.

Isolation, Formulation and Assessment of Anti-inflammatory Properties of Ursolic Acid from&lt;i&gt; Nerium oleander&lt;/i&gt;

Purpose: The purpose of the research work was the extraction and isolation of Ursolic Acid (URA) from the leaves of Nerium oleander (N. oleander) and the assessment of its anti-inflammatory activity using an in-vitro model. Methods: Ursolic Acid (URA) is a bioactive molecule. It is a key component of N. oleander. The hydroalcoholic maceration method was used for extract preparation and was used to isolate the bioactive components of URA. The prepared extract, isolated URA were characterize and analyse by using pharmacognostic parameters, Fourier Transform Infrared (FTIR) and Thin Layer Chromatography (TLC) method. The carrageenan-induced inflammation rat paw oedema test in-vitro model was used for the assessment of anti-inflammatory properties of isolated bioactive compound URA. Results: The results of evaluation and characterization indicated that the extract’s ash value and extractive values were within the parameters specified in the Indian Ayurvedic Pharmacopoeia. The prepared hydroalcohalic extract has potential bioactive components such as flavonoids, saponins, and triterpinoids. The isolated compound was URA. The extract may be able to alleviate inflammation, according to the percentage inhibition. Conclusion: The URA was successfully removed from the leaves of N. oleander. The examination criteria revealed that the extract contained certain small contaminants, which may have anti-inflammatory effects.

Antioxidative and anti-inflammatory activities of Erica spiculifolia extracts and fractions

There is little data on the phytochemical/pharmacological properties of Erica spiculifolia Salisb. (syn. Bruckentalia spiculifolia (Salisb.) Rchb.). This study examines the antioxidative and anti-inflammatory activities of different extracts and fractions of E. spiculifolia in vitro on isolated rat peritoneal macrophages, in the carrageenan-induced rat paw oedema test, BSA test, and two complementary antioxidant assays. Ethanolic extracts of leaves, flowers, and aboveground parts, and petroleum ether, ether, ethyl acetate, and water fractionations of the ethanol extract of E. spiculifolia applied at doses of 50–200 mg/kg p.o. exhibited dose-dependent anti-inflammatory activity comparable with indomethacin. All tested samples, except for the petroleum ether fraction, exerted excellent in vitro antioxidant activity, and all of them exhibited significant and similar inhibition of BSA denaturation comparable with diclofenac. Ethanolic extract of the aboveground parts obtained by percolation, ethyl acetate and water fractions had the highest efficiency, attenuating inflammation by more than 50% in the lowest applied concentration alongside exceptional radical scavenging activity.

Ionomic analysis, polyphenols characterization, analgesic, antiinflammatory and antioxidant capacities of Cistus laurifolius leaves: in vitro, in vivo, and in silico investigations

This study aims to investigate the chemical and mineral composition, antioxidant, analgesic, and anti-inflammatory effects of the aqueous extract of Cistus laurifolius var. atlanticus Pit. (Cistaceae). Additionally, molecular docking interactions of various ligands with antioxidant protein target urate oxidase (1R4U) and anti-inflammatory protein target cyclooxygenase-2 (3LN1), revealing potential dual activities and highlighting specific residue interactions. The chemical characterization focused at first glance on the mineral composition which showed that C. laurifolius extract is a mineral-rich source of potassium (K), magnesium (Mg), manganese (Mn), sodium (Na), phosphorus (P), and zinc (Zn). We next performed, ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis, the latter showed various polyphenols in C. laurifolius extract including Gallic acid as the predominant polyphenol. Isoquercetin, Taxifolin and Astragalin were also among the major flavonoids detected. The antioxidant capacity of C. laurifolius leaves was tested using 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1- picrylhydrazyl (DPPH) and reducing power (RP) assays. In vitro analysis of the anti-inflammatory property of C. laurifolius leaves was conducted by the albumin denaturation test and the in vivo was assessed in the sequel by carrageenan-induced paw edema test. The analgesic activity was evaluated in vivo using tail flick, acetic acid-induced contortion, and plantar tests. The findings showed that the leave extract had a powerful antioxidant activity with an IC50 values of 2.92 ± 0.03 µg/mL (DPPH) and 2.59 ± 0.09 µg/mL (in RP test). The studied extract strongly abolished the induced inflammation (82%). Albumin denaturation test recorded an IC50 value of 210 µg/mL. Importantly, the oral administration of C. laurifolius extract considerably reduced the nociceptive effect of acetic acid in rats, showing a significant analgesic effect in a dose-related manner. Altogether, our results showed that C. laurifolius can be a promising source of phytochemicals for drug development potential.

Evaluation of Anti-Inflammatory and Analgesic Property of Methanolic Extract of Momordica Dioica in Wistar Rat Model

Background: Since current medications frequently cause potentially serious side effects, countless individuals continued to have pain and inflammation despite the accessibility of treatments. Ancient practitioners have used a variety of herbal remedies with analgesic and anti-inflammatory properties extensively. Momordica Dioica is one of them, but no experimental research has been done in support of this traditional use. Objective: The purpose of the research was to assess the analgesic and anti-inflammatory properties of methanolic Momordica Dioica fruit extracts. Methods: Dryed by air According to OECD guideline the version eighteen, the fruit of Momordica Dioica is extracted with the solvent methanol as well as an acute oral toxicity study was done for the methanol-based extract of Momordica Dioica. The Active Constituent responsible for the Activity was confirmed by HPTLC method. The hot plate method was employed to assess the analgesic efficacy of centrally mediated analgesia.The ability to reduce inflammation was assessed using a carrageenan-induced paw oedema test. Results: Momordica dioica's methanolic extract inhibits the ceiling result during activity. The Methanolic Extract of Momordica dioica (MEMD) extract demonstrated a significant (p 0.0001) analgesic effect in the hot plate method at doses of 100mg/kg and in all combinations with standard. Maximum anti-inflammatory effects were seen in carrageenan-induced paw edema starting 2-4 hours after induction, and all tested doses of the extract significantly inhibited the carrageenan-induced inflammation (p 0.0001, p 0.001). The presence of a pentacyclic terpenoid i.e Ursolic acid present in the extract had potential analgesic and anti-inflammatory activity which supports the traditional claim.

Standardized seed extract of Cajanus cajan (L) Millsp. produced antinociceptive and anti-inflammatory actions through inhibition of inflammatory mediators and activation of opioidergic signaling

Background and PurposePeripheral tissue damage and diseases could lead to persistent pain beyond possible resolution suggestive of disease-promoting condition which gives rise to chronic pain. The inability of current medications to manage some chronic inflammatory and painful conditions necessitate the need for better treatment options. Natural products have been a veritable source for the discovery of more efficacious and safer therapeutics. Cajanus cajan (L) Millsp, (Fabaceae) is used in traditional African medicines for the treatment of painful, gut disturbance and inflammatory conditions. Hence, the current study aims to investigate the anti-inflammatory and antinociceptive actions of the ethanol seed extract of Cajanus cajan (CC) in rodents and possible mechanisms of action. MethodsHigh performance liquid chromatography coupled with diode-array detection (HPLC-DAD) was used to identify 8 major flavonoids in CC. Antinociceptive activity was investigated using the acetic acid-induced writhing reflex, biphasic formalin-induced flinching behaviour and supraspinal hot plate-evoked nociception in mice. Carrageenan-induced rat paw oedema test was used to evaluate the anti-inflammatory action of CC in rats. Possible mechanism of antinociception and anti-inflammatory actions were examined using both in vivo model and molecular docking procedures against µ-opioid receptor (MOR), cyclooxygenase-2 (COX-2) and phospholipase A2 (PLA2) proteins, respectively. ResultsThe chromatographic procedure qualitatively and quantitatively confirmed the presence of rutin, quercetin, gallic acid, luteolin, pinostrobin, BiochaninA, formononetin and apigenin in CC. The in vivo nociceptive assay, showed that CC (50, 100, or 200 mg/kg, p.o.) significantly decreased mean number of writhing reflex with peak effect at 50 mg/kg (72% inhibition) when compared with vehicle control in mouse writhing test. Similarly, the biphasic formalin-induced nociception was significantly reduced by CC (50 mg/kg) with 24.61 and 66.73% inhibition of nociceptive reactions in both the early and late phases of formalin-induced inflammatory pain, respectively. In addition, CC significantly increased supraspinal thermally mediated pain threshold with maximum possible effects of 42.25 and 52.16% at CC 50 and 100 mg/kg, respectively, in hot-plate test. Similarly, CC100mg/kg caused time course inhibition of carrageenan-induced paw oedema in rat with peak effect (65.78%, CC 100 mg/kg; 6 h). Interestingly, the antinociceptive action of CC was blocked by the pre-treatment of mice with l-NG-nitro arginine methyl ester (L-NAME) or naloxone. The molecular docking analysis revealed prominent interactions of pinostrobin, physcion and lupeol with MOR, COX-2, and PLA2, respectively. ConclusionFindings from this study showed that Cajanus cajan seeds extract possesses anti-nociceptive and anti-inflammatory through inhibition of inflammatory mediators (PLA2/COX-2) and activation of opioidergic signalling.

Comparative study of the antibacterial and anti-inflammatory activities of the seed coat vs. seed kernel extracts from the plant Mangifera indica L. in inflammatory acne treatment

Introduction: The present study was developed to investigate and compare the extraction yield, the contents of polyphenols and mangiferin, the activities against Propionibacterium acnes, Staphylococcus aureus, and Escherichia coli bacteria, and the anti-inflammatory activities of ethanol extracts of mango seed kernels vs. seed coats. Methods: Mango seed kernels and seed coats were extracted using ethanol as the solvent and tested against microorganisms using the disc diffusion method. The minimum inhibitory concentration (MIC) levels of extracts were determined by the agar dilution method. The anti-inflammatory activities were assessed both in vitro and in vivo by albumin denaturation method and carrageenan-induced paw edema test, respectively. Results: Both extracts yielded high contents of mangiferin and phenolic compounds. The antibacterial activities of both extracts showed inhibition of the tested microorganisms Propionibacterium acnes and Staphylococcus aureus but not Escherichia coli. Seed kernel extract (0.2 g/kg) reduced paw edema by 44.8% at 3 hours after λ-carrageenan administration. Meanwhile, 0.5 g/kg seed coat extract reduced paw edema less than the seed kernel extract (23.1% vs. 44.8%). Mango seed kernel extract, mango seed coat extract, and diclofenac sodium displayed concentration-dependent inhibition of heat-induced protein denaturation with IC50 values of 137.23 μg/mL, 292.12 μg/mL, and 6.64 μg/mL, respectively. Conclusion: The obtained results confirmed the antibacterial and anti-inflammatory potential of mango seed kernel and seed coat extracts. The mango seed kernel extract was proven to be more effective than the mango seed coat extract and thus can be used in cosmetics as an anti-inflammatory and antibacterial agent.

Phytochemical Screening, Analgesic and Anti-Inflammatory Activity of the Ethanol Extract of the Cnidoscolus Phyllacanthus Leaves

Objective: The present study aimed to investigate the analgesic and anti-inflammatory activity of the Cnidoscolus phyllacanthus (family Euphorbiaceae) ethanolic leaves extract in the laboratory using in vivo methods to justify its traditional use in the above-mentioned pathological conditions. Methods: Phytochemical screening was done to find the presence of various secondary metabolites of the plant. In vivo, analgesic activity was performed employing the acetic acid-induced writhing test and tail immersion test on Swiss albino mice at doses of 50, 100 and 200 mg/kg body weight. An anti-inflammatory activity test was done on Wistar rats at three doses (50, 100 and 200 mg/kg body weight) using a carrageenan-induced paw oedema test. Data were analyzed by one-way analysis of variance (ANOVA), and Dunnett's t-test was used as the significance test. P value was considered as the minimum level of significance. Results: Phytochemical screening revealed the presence of coumarin, flavonoids, monoterpenes, diterpenes and naphthoquinones in the extract. In the acetic acid-induced writhing test, the per cent inhibition of writhing response by the extract was 12.82%, 25.64% and 76.67% at 50, 100 and 200 mg/kg doses, respectively (p &lt; 0.01) and showed an increase in pain threshold in tail immersion method. The extract significantly (p &lt; 0.05 and p &lt; 0.01) inhibited carrageenan-induced inflammatory response in rats in a dose-related manner. Per cent, inhibition in paw oedema was 16.39 %, 29.50 % and 52.45 % at 50, 100 and 200 mg/kg doses, respectively. Conclusion: The results obtained from the tests indicate that the plant might have one or more secondary metabolite(s) having central and peripheral analgesic and anti-inflammatory activity.

One Pot Synthesis, Biological Efficacy of AuNPs and Au-Amoxicillin Conjugates Functionalized with Crude Flavonoids Extract of Micromeria biflora.

Amoxicillin is the most widely used antibiotic in human medicine for treating bacterial infections. However, in the present research, Micromeria biflora's flavonoids extract mediated gold nanoparticles (AuNPs) were conjugated with amoxicillin (Au-amoxi) to study their efficacy against the inflammation and pain caused by bacterial infections. The formation of AuNPs and Au-amoxi conjugates were confirmed by UV-visible surface plasmon peaks at 535 nm and 545 nm, respectively. The scanning electron microscopy (SEM), zeta potential (ZP), and X-ray diffraction (XRD) studies reveal that the size of AuNPs and Au-amoxi are found to be 42 nm and 45 nm, respectively. Fourier-transform infrared spectroscopy (FT-IR) absorption bands at 3200 cm-1, 1000 cm-1, 1500 cm-1, and 1650 cm-1 reveal the possible involvement of different moieties for the formation of AuNPs and Au-amoxi. The pH studies show that AuNPs and Au-amoxi conjugates are stable at lower pH. The carrageenan-induced paw edema test, writhing test, and hot plate test were used to conduct in vivo anti-inflammatory and antinociceptive studies, respectively. According to in vivo anti-inflammatory activity, Au-amoxi compounds have higher efficiency (70%) after 3 h at a dose of 10 mg/kg body weight as compared to standard diclofenac (60%) at 20 mg/kg, amoxicillin (30%) at 100 mg/kg, and flavonoids extract (35%) at 100 mg/kg. Similarly, for antinociceptive activities, writhing test results show that Au-amoxi conjugates produced the same number of writhes (15) but at a lower dose (10 mg/kg) compared to standard diclofenac (20 mg/kg). The hot plate test results demonstrate that the Au-amoxi has a better latency time of 25 s at 10 mg/kg dose when compared to standard Tramadol of 22 s at 30 mg/ kg, amoxicillin of 14 s at 100 mg/kg, and extract of 14 s at 100 mg/kg after placing the mice on the hot plate for 30, 60, and 90 min with a significance of (p ≤ 0.001). These findings show that the conjugation of AuNPs with amoxicillin to form Au-amoxi can boost its anti-inflammatory and antinociceptive potential caused by bacterial infections.

Toxicity and Anti-Inflammatory Effects of Agave sisalana Extract Derived from Agroindustrial Residue.

In several countries, the leaf juice of Agave sisalana (also known as sisal) is widely used topically, especially as an antiseptic, and orally for the treatment of different pathologies. However, in Brazil, which is the largest producer of Agave sisalana, its residue, which represents the majority of its weight, has been thrown away. For this reason, the determination of the pharmacological and toxicological potentials of sisal residue and its possible therapeutic use is seen as a way to contribute to the sustainable development and social promotion of the largest producer of sisal in Brazil, the interior of Bahia State, which is among the poorest areas in the country. Given the scarcity of available scientific studies on the pharmacological and toxicological properties of sisal residue juice, this study aimed to promote the acid hydrolysis of this juice to potentiate the anti-inflammatory effect already described in the literature. Furthermore, it aimed to evaluate the toxicological profile of the hydrolyzed extract (EAH) and to determine its acute toxicity, as well as its side effects on the reproductive aspects of rats. The anti-inflammatory effect of EAH was evaluated in vitro using the induction of hemolysis by hypotonic solution and in vivo in rats using the carrageenan-induced paw edema test and the xylene-induced ear edema test. The acute toxicity, resulting from a single-dose administration, was investigated for some manifestation of toxic symptoms related to motor control and consciousness in rats. At a concentration of 100 mg/kg, by repeated doses, the reproductive toxicity effects of EAH in rats were assessed. In vitro anti-inflammatory activity was positive using the human red blood cell membrane stabilization method. In both in vivo tests used to assess the anti-inflammatory activity, EAH (at three doses) significantly inhibited edema when compared to the control group. At a dose of 50 mg/kg, EAH exhibited a greater effect than indomethacin, a nonsteroidal anti-inflammatory drug with known activity. In vivo toxicological studies have shown that EAH does not present toxic effects when administered orally in a single dose, up to 1000 mg/kg. Finally, EAH promoted a gonadotoxic effect and increased the embryonic mortality rate after implantation. It is suggested that the anti-edematogenic effect of the acid hydrolysis extract from sisal juice is due to the high concentration of steroidal sapogenins. Therefore, this extract can be considered a potential new anti-inflammatory or even an important sapogenin source for the development of steroidal glucocorticoids. However, further studies are needed to elucidate the chemical composition of sisal juice. Regarding toxicology studies, EAH did not show cytotoxic and clastogenic potentials, but it presented a powerful reproductive toxic effect in rats.

Synthesis and Biological Evaluation of Hydroxypropyl Ester of Mefenamic Acid as a Promising Prodrug

Background: The free carboxylic acid group in the mefenamic acid (MFA) structure plays a potential role in developing various neuromuscular side effects after MFA administration. In this study, the hydroxypropyl promoiety was added to the carboxylic acid group of MFA in an attempt to reduce the neuromuscular side effects of MFA and improve its therapeutic effects. Methods: Hydroxypropylester of MFA (HPEMA) was synthesized and subjected to various in vivo investigations compared to MFA. The neuromuscular toxicity was conducted following high doses administration in mice and was evaluated at various measuring parameters, such as the percentage of catalepsy, clonic-tonic seizure, and death. In addition, the anti-inflammatory and anti-nociceptive effects of HPEMA were evaluated in the carrageenan-induced paw edema test and acetic acid-induced writhing test, respectively. Results: The findings of this study reveal that the percentage of catalepsy, clonic-tonic seizure, and death is significantly lower in mice treated with HPEMA than in those treated with equimolar doses of MFA. In addition, treatment with HPEMA caused a comparable anti-inflammatory activity in the carrageenaninduced paw edema test and a significantly higher anti-nociceptive effect in the acetic acid-induced writhing test than the MFA treatment. Conclusion: This study’s findings suggest that HPEMA is a promising prodrug for MFA.