Carrageenan-induced Paw Edema Model Research Articles

Anti-inflammatory Activity and Cyclooxygenase-2 Inhibitory effect of Peperomia pellucida (L.) Kunth Extract

Inflammation is an adaptive response underlying a wide variety of physiological and pathological processes mediated by the Cyclooxygenase (COX) enzyme. Cyclooxygenase-2 (COX-2) is an important enzyme that catalyzes the production of prostaglandins from arachidonic acid and has a crucial role in various pathologies including inflammation, neurological disorders, and cancer. The selective suppression of COX-2 over COX-1 is thought to be a useful approach for treating inflammation. Peperomia pellucida (L.)Kunth has been traditionally used as an anti-inflammatory and antioxidant, thus giving scope for anti-inflammatory studies. Since the action of Ethanol extract of Peperomia pellucida (EEPp) on COX-2 has not been previously described, in this study, we further investigated the effect of Cyclooxygenase-2 inhibitory effects spectrophotometrically in ELISA readers and evaluated of anti-inflammatory activity in the carrageenan-induced rat paw edema model. The edema volume was measured using a plethysmometer. The results showed that the EEPp (100, 200, and 400mg/kg BW) had significant anti-inflammatory activity and the EEPp demonstrated a COX-2 Inhibitory effect. The percentage of COX-2 inhibition was 10.87%, 47.04%, 56%, and the percentage of inhibition of paw edema was 34.93%, 46.61%, and 64.04%, respectively. These findings suggest that Peperomia pellucida extracts possess promising and remarkable anti-inflammatory activity, which is directed against the enzymatic activity of COX-2.

Synthesis and Evaluation of Amide Codrug of Ibuprofen and Amlodipine for Dual Inhibition of Inflammation and Hypertension

The codrugs approach showed as an effective strategy for targeting diseases synergistically, hence improving the quality of life of patients. The main goal is to address comorbid conditions of hypertension and osteoarthritic pain and inflammation in geriatric patients, eliminate the adverse gastrointestinal adverse effects of the drug, reducing dose with significant reduction of polypharmacy and improve patient compliance. The present study aimed to synthesize amide linked codrugs of Ibuprofen (nonsteroidal anti-inflammatory drug) and Amlodipine (Calcium channel Blocker), its biopharmaceutical study and evaluation of anti-inflammatory and antihypertensive activity. Codrug conjugates were synthesized by a one-pot amidation reaction of Amlodipine with Ibuprofen using DCC as coupling agent and DMAP as catalyst. The obtained compound Ibuprofen-Amlodipine amide linked codrug (IBAM) was characterized by determination of melting point, TLC, DSC, FT-IR, NMR, and mass spectroscopy. The solubility, partition coefficient, plasma protein binding and in vitro hydrolysis study in SGF and SIF were studied to determine biopharmaceutical properties.The anti-inflammatory and antihypertensive activity of synthesized compounds were tested in a carrageenan-induced rat paw oedema model and Fructose induced diabetic hypertensive model and it was discovered that the codrugs underwent significant hydrolysis in SIF (pH 7.4) and IBAM showed effective reduction in hypertension, inflammation in comparison to parent drug. Finally, it is concluded that the codrug approach could be successfully used in drug design and development for overcoming undesirable difficulties without losing the desired activities of the parent drugs.

Isolation of indole alkaloids and a new norneolignan of hydroethanol extract from the stem barks of Aspidosperma nitidum Benth: Preclinical evaluation of safety and anti-inflammatory and healing properties

Ethnopharmacological relevanceAspidosperma nitidum Benth (Apocynaceae) is a tree found in Brazil especially in the Amazonia region, known as “carapanaúba”, being used by indigenous and cabloco population in folk medicine in the treatment of malaria, leprosy, rheumatism, cancer, diabetes and inflammatory disorders. However, there are no scientific reports, up to now, to evidence its popular use as anti-inflammatory and healing agent. Aim of the studyThis study aimed to isolate indole alkaloids, as well as investigate the safety, anti-inflammatory and healing properties of hydroethanol extract from the stem barks of Aspidosperma nitidum Benth (An). Material and methodsThe compounds were isolated using diverse chromatographic methodologies and the structures were determined by extensive spectroscopic analyses. The safety was evaluated in vitro through 3-methyl-[4-5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay using murine fibroblast (3T3) and monkey kidney (Vero E6) cell lines and by the hemolytic assay, as well as, in vivo, through acute toxicity model, which the mice received a single dose of 2000 mg/kg of An, by intra-gastric (i.g.) route, and behavioral, hematological and biochemical parameters were evaluated. The anti-edematogenic effect was monitored through carrageenan-induced paw edema model, in which the rodents were treated with 50, 100 and 200 mg/kg of An by i. g., the percentage of edema (0–4 h), myeloperoxidase (MPO) and pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) levels were quantified. The anti-inflammatory activity was demonstrated through the zymosan-air-pouch model, in which the animals were treated with 50, 100 and 200 mg/kg of An by i. g, and the leukocytes number, MPO, total protein and cytokines levels were determined. In addition, the healing potential was evaluated through a skin wound model, in which the mice received 50, 100 and 200 mg/mL of An in wound area, and the wound skins were photographed and the area calculated. ResultsIn total, five compounds were isolated in the An, being a new 8,9-dinorneolignan glucoside and four known indole alkaloids. The MTT and hemolytic assays, in all concentrations of the extract, demonstrated not be cytotoxic. Acute toxicity model also evidenced no sign of toxicity or significant changes on the behavior, biochemical and hematological parameters after use of the extract. In the edematogenic model, the An reduced significantly the percentage of edema, as well as, the MPO and pro-inflammatory cytokines levels. The same form, An revealed to be efficient in decreasing the leukocytes migration (mainly polymorphonuclears), total proteins, MPO and cytokines concentrations in the zymosan-air-pouch assay. Moreover, the An revealed a healing effect, reducing the area of the skin wound. ConclusionOurs results evidence in the first time, the anti-inflammatory and healing property of An, justifying its use in traditional medicine. Moreover, include cytotoxicity in vitro and acute toxicity in vivo tests, which indicate the safety of use of the extract.

Blocking the major inflammatory pathways by newly synthesized thiadiazine derivatives via in-vivo, in-vitro and in-silico mechanism

A series of new thiadiazine derivatives including 2-(5-alkyl/aryl-6-thioxo-1,3,5-thiadiazinan-3-yl) propanoic acids (a) and 4-methyl-2-(5-alkyl/aryl-6-thioxo-1,3,5-thiadiazinan-3-yl) pentanoic acids (b) were synthesized by reacting primary alkyl/aryl amines with CS2, followed by reaction with formaldehyde and amino acids. The chemical structures of synthesized compounds were confirmed by 13C- NMR and 1H- NMR techniques. The inhibitory potential of major inflammatory enzymes, COX-2 and 5-LOX was examined. Moreover, anti-nociceptive and anti-inflammatory activities were evaluated in the in vivo thermally induced nociceptive, and carrageenan induced paw edema models in mice. The in-vitro results reflect that these compounds exhibited concentration dependent inhibition of COX-2 and 5-LOX. The tested compounds at 50 mg/kg showed significant effect on thermally induced pain, and reduced latency time (seconds) as compared to the vehicle treated animals. Moreover, tested compounds exhibited percent inhibition of paw edema in the carrageenan induced paw edema model in mice. Furthermore, the binding modes of the most active COX-2 and 5-LOX inhibitors were determined through computational methods. The computational study reflects that the docked compounds have high binding affinities for COX-2 and 5-LOX enzymes, which leads to inhibition of these enzymes.

Quercus floribunda Lindl. Ex A. Camus; a tremendous remedy against inflammation and associated symptoms

Crude extracts prepared from aerial parts and nut galls of Quercus floribunda Lindl. Ex. A. Camus were evaluated for phytochemical screening, in vitro antioxidant, and in vivo analgesic, anti-inflammatory and antipyretic activities. Various solvents including methanol (M), acetone (A), distilled water (DW), distilled water + methanol (DWM) were used for extraction. Highest total phenolic (66.9 ± 0.05 μg GAE/mgE) and flavonoid content (38.4 ± 0.72 μg QE/mgE) were measured in QFAA extract by colorimetric methods. Cumulative maximum concentrations of polyphenols were quantified in QFMG, QFAA, and QFMA extracts i.e. 19.036, 15. 574 and 11.647 μg/mg of extract by RP-HPLC analysis. From aerial parts extracts, apentacyclic tritepenoid, glutinol was isolated using column chromatography techniques and structure was elucidated using spectroscopic techniques. QFDWMA (205.5 ± 0.56 μg AAE/mg of extract) showed highest total reducing power while highest total antioxidant capacity (207.1 ± 0.49 AAE/mg of extract) and free radical scavenging potential (96.1 ± 0.42%) were observed in QFAA extract. QFAA extract showed significant (p ≤ 0.001) analgesic potential in different pain models i.e. hot plate method, cold plate method, Haffner's tail clip method and acetic acid induced writhing assay having 50.20%, 62.07%, 57.26% and 70.49% analgesia respectively at 300 mg/kg. QFAA extract showed maximum anti-inflammatory activity in croton oil induced edema (68.83%) and in carrageenan induced paw edema models (72.32%) at 300 mg/kg concentration. QFAA extract markedly reduced the rectal temperature at 300 mg/kg concentration, in brewer's yeast induced pyrexia model. Detailed investigations can be executed in future to determine the molecular mechanisms of these pharmacological attributes.

Anthocleista vogelii (Planch) stem bark ethanol extract prevents inflammatory and pain phenotypes in experimental rodent models by modulating oxido-inflammatory mediators

Ethnopharmacological relevanceThe Anthocleista species are used to treat pain, inflammation, and stomach disorders, but the mechanism by which Anthocleista vogelii Planch stem bark ethanol extract (AVSBE) elicits its anti-pain activity is not fully understood. AimThis study elucidates the phytochemical signatures of AVSBE along with its anti-nociceptive, anti-inflammatory, and antioxidant activities in animal models of pain and inflammation. MethodsThe Gas Chromatography and Mass Spectrometry (GC-MS) and Lorke's methods were used for the phytochemical characterization and LD50 determination of AVSBE. Male and female Wistar rats and Swiss mice were given oral pre-treatment of AVSBE (100, 200, and 400 mg/kg), indomethacin (10 mg/kg), morphine (10 mg/kg), and vehicle (10 mL/kg). Subsequently, various models were employed to evaluate AVSBE's anti-nociceptive and anti-inflammatory effects. Specifically, the acetic acid-induced mice writhing, formalin-induced paw licking, and hot plate models were used to assess AVSBE's anti-nociceptive activity, while the carrageenan-induced paw edema and air pouch models were used to evaluate AVSBE's anti-inflammatory activity. ResultsAVSBE (100, 200, and 400 mg/kg) reduced writhes, paw licking, and pain reaction time. It also decreased rat paw size and inflammatory exudate volume. AVSBE (200 and 400 mg/kg) lowered oxido-nitrosative stress, inflammatory mediators, and leukocyte counts in the exudate fluid. Animals administered with AVSBE showed no stomach ulceration. The LD50 of AVSBE is over 5000 mg/kg, p.o. GC-MS analysis revealed 19 phytochemical compounds in AVSBE, including eicosanoic, octadecatrienoic, linoleic, palmitoleic, and 9,12-octadecanoic acids, phytol, among others. ConclusionThese findings suggest that AVSBE demonstrated activities that can reduce inflammation and alleviate pain by inhibiting oxido-nitrosative stress and inflammatory mediators, contributing validity to the ethnomedicinal benefit of AVSBE in managing inflammatory and pain-related crisis.

Phytochemistry, Analgesic and Anti-Inflammatory Activities and Acute Toxicity Studies of Phragmanthera Usuiensis (Oliv.) M.G. Gilbert

Plants have played a significant role in healthcare throughout history by providing medicinal substances. Phragmanthera usuiensis leaves have been used by traditional practitioners for the treatment of oxidative stress-related diseases in the study area, primarily for treating arthritis. The objective of the study was to investigate the phytochemical composition, analgesic effect, anti-inflammatory effect, and acute toxicity of the methanolic extract of P. usuiensis leaves. The phytochemical composition of the methanolic extract of P. usuiensis leaves was studied using qualitative and quantitative methods. The analgesic effect was investigated through the hotplate method, and the anti-inflammatory activity through the carrageenan-induced paw edema model. Investigation of acute toxicity was carried out as per the OECD guidelines on acute oral toxicity – Acute Toxic Classic (ATC) method, with the acute toxicity being administered orally by gavage. Treatment of the animals was initiated at the starting dose level of 300 mg/kg body weight and carried out with six animals (three animals per step). Treatment of animals at the next dose of 2000 mg/kg body weight was delayed until the survival of the previously dosed animals was ensured. The methanolic extracts of P. usuiensis possess several phytochemicals that exhibited promising free analgesic and anti-inflammatory effects. The phytochemicals found in the methanol extract include alkaloids, tannins, glycosides, saponins, steroids, flavonoids, terpenoids, phenols, coumarins, and free sugars. All groups of test animals did not exhibit any serious toxic or lethal effects even at the administration of the limit dose, 2000 mg/kg body weight. The study has successfully validated the use of Phragmanthera usuiensis leaf as having activity that potentially can be used to treat oxidative stress-related disorders like arthritis. Moreover, the study confirmed that these plants exhibit analgesic and anti-inflammatory actives. Additionally, it established the safety of the extracts for use as medicinal agents in the management of oxidative stress.

Polyphenolics of purple devil fruits potentiate anti-inflammatory action by regulating the expression of inflammatory cytokines and apoptotic signaling molecules evident in extensive and combined experimental models

This research investigated the anti-inflammatory effects of Purple Devil fruit’s chloroform extract (SAF-CFE) using LPS-stimulated RAW264.7 macrophage cells and in-vivo histamine- and carrageenan-induced paw edema models as well as membrane stabilization model. Writhing and licking tests for nociception and delayed-type hypersensitivity reaction (DTHR) for immunomodulation were accomplished. SwissADME, ProTox-II, and PASS tests assessed a ligand-receptor binding affinity, and network-pharmacological tests explored the modulatory linked-genes. The MCF-7 cells were strongly inhibited by SAF-CFE, which reduced LPS-induced PGE2, IL-6, TNF-α, and IL-1β expression. The upregulation of proapoptotic (p53 and Bax) and downregulation of antiapoptotic (Bcl-2) genes were observed by SAF-CFE. It significantly reduced inflammatory indexes in anti-inflammatory models. Tris (2,4-di-tert-butylphenyl) phosphate, a natural biometabolite from SAF-CFE, had the highest target receptor-binding and drug-likeness; while NOS2, PTGER1, TRPV1, HMGCR, and TBXAS1 hub genes were highly modulated by the SAF-CFE. The results demonstrate that SAF-CFE could be a functional food source for anti-inflammatory action.

Nitrogen-containing Heterocyclic Derivatives of 1,3-Thiazolidine-2,4- Diones as Dual Anti-inflammatory and Anti-oxidant Agents and their Docking Studies

Aim: The aim of this study was to carry out synthesis and characterization of nitrogencontaining heterocyclic derivatives of 1,3-thiazolidine-2,4-diones as dual anti-inflammatory and antioxidant agents and their docking studies. Background: Inflammation is a protective mechanism of our body to reduce injury and infection by microorganisms. The COX-2 enzyme is responsible for the production of prostaglandins (PG1), which are responsible for pain, fever, and a variety of other inflammatory symptoms. Reactive oxygen species (ROS) are important signalling molecules during inflammatory diseases. In an inflammatory state, polymorphonuclear neutrophils (PMNs) produce oxidative stress, which causes inter-endothelium junctions to open and the transfer of inflammatory cells over the endothelial barrier to increase. Tissue damage is caused by these inflammatory cells. Objective: The objective was to club thiazolidinediones with benzimidazole, triazole, and indole to achieve an enhanced anti-inflammatory effect. Method: In the current report, we have synthesized three new series of indole/ benzimidazole/benzotriazole clubbed with 5-arylidene-2,4-thiazolidinediones. The synthesized compounds were tested for in vivo anti-inflammatory activity using a carrageenan-induced rat paw edema model and in vitro antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing ability of plasma (FRAP) and hydrogen peroxide methods. Result: The results demonstrated that the compound PC-5 exhibited significant anti-inflammatory activity with 61.9% inhibition in comparison to the standard drug diclofenac sodium (71.4% inhibition) after 3h. The compound PC-5 exerted the highest antioxidant activity with an IC50 value of 24.68 μM amongst all synthesized compounds. Acute toxicity was also evaluated for all synthesized compounds, and the results indicated that all evaluated compounds were nontoxic in animals. The replacement of benzotriazole with benzimidazole and indole moieties diminished the anti-inflammatory activity. The hydroxysubstituted arylidene showed higher activity than methoxy, chloro substituted arylidene-2,4- thiazolididiones. Docking studies revealed that the compound PC-5 showed higher inhibition activity against the COX-2 receptor rather than COX-1. The ADME properties were also assessed that showed no violation of Lipinski’s rule and no toxicity. Conclusion: The substituents were found to exert varied activity. The docking studies revealed that the compounds showed lesser binding energy with COX-1 as compared to standard drug diclofenac. Moreover, the binding with COX-2 exhibited more binding energy, thereby proving to have specific COX2 inhibitory activity. All synthesised compounds have shown good antioxidant activity in addition to antiinflammatory activity. PC-5, PC-4, PB-5, PB-4, PA-5, and PA-4 were found to have increased antioxidant activity. Because of the presence of an electron-releasing hydroxyl group, PC-5 has proven to be a highly potent antioxidant agent.

Synthesis of some Curcumin derivatives of Non-Steroidal Anti-Inflammatory (NSAIDs) Prodrugs for Treatment of Inflammatory Bowel Diseases

Inflammatory Bowel Disease (IBD) is the most prevalent chronic gastrointestinal disorder in children and adolescents. IBD is a collection of recurrent and remitting inflammatory gastrointestinal illnesses that mostly includes ulcerative colitis (UC) and Crohn's disease (CD). Amino salicylates, corticosteroids, and biological agents are drugs that are now utilized to treat inflammatory bowel disorders. The research envisaged and plan of work to be carried out can be summarized as adetailed review of curcumin derivatives, synthesis of compound and their derivatives, physio-chemical properties, structure elucidation, and biological evaluation of synthesized compounds for anti-inflammatory potential. Prodrugs are synthesized by conjugation of NSAID derivatives with some curcumin derivatives by the reflux in different solvents in the presence of thionyl chloride as an acid catalyst.The synthetic compounds YK-01 and YK-02 were obtained in a series. The FTIR, NMRspectroscopy, and other physiochemical properties have characterized the structure of the synthesized prodrugs. The anti-inflammatory activity of the synthesized compounds was tested in a carrageenan-induced rat paw oedema model, and it was discovered that the prodrugs treated compound (YK-02) showed decreased inflammation and paw oedema volume, as well as a better activity than synthesized prodrugs (YK-01).

Caffeic Acid-Zinc Basic Salt/Chitosan Nanohybrid Possesses Controlled Release Properties and Exhibits In Vivo Anti-Inflammatory Activities.

Caffeic acid (CA) exhibits a myriad of biological activities including cardioprotective action, antioxidant, antitumor, anti-inflammatory, and antimicrobial properties. On the other hand, CA presents low water solubility and poor bioavailability, which have limited its use for therapeutic applications. The objective of this study was to develop a nanohybrid of zinc basic salts (ZBS) and chitosan (Ch) containing CA (ZBS-CA/Ch) and evaluate its anti-edematogenic and antioxidant activity in dextran and carrageenan-induced paw edema model. The samples were obtained by coprecipitation method and characterized by X-ray diffraction, Fourier transform infrared (FT-IR), scanning electron microscope (SEM) and UV-visible spectroscopy. The release of caffeate anions from ZBS-CA and ZBS-CA/Ch is pH-dependent and is explained by a pseudo-second order kinetics model, with a linear correlation coefficient of R2 ≥ 0.99 at pH 4.8 and 7.4. The in vivo pharmacological assays showed excellent anti-edematogenic and antioxidant action of the ZBS-CA/Ch nanoparticle with slowly releases of caffeate anions in the tissue, leading to a prolongation of CA-induced anti-edematogenic and anti-inflammatory activities, as well as improving its inhibition or sequestration antioxidant action toward reactive species. Overall, this study highlighted the importance of ZBS-CA/Ch as an optimal drug carrier.

Anti-inflammatory Activity of Azima tetracantha Root Bark Extract in Rats

Inflammation is associated with many pathological conditions such as arthritis, inflammatory bowel syndrome, cancer, etc. The side effects associated with the long term use of current anti-inflammatory drugs necessitates the need for the development of new drug with fewer side effects. The present study was aimed at evaluating anti-oxidant and anti-inflammatory activity of Azima tetracantha root bark, a plant widely used by tribal people and in Siddha medicine for the treatment of arthritis and rheumatism. Aqueous and methanolic extracts of Azima tetracantha root bark were prepared. Total phenol, flavoid, alkaloid, terpenoid and saponin content were analyzed. The anti-oxidant activity was determined by DPPH assay and total antioxidant capacity. The anti-inflammatory activity was evaluated by carrageenan induced paw edema model in rats. The total phenol and flavonoid contents were higher in methanolic extract compared to aqueous extract. The extracts were found to have anti-oxidant activity and dose-dependent anti-inflammatory activity in both male and female rats with highest average inhibition at 400 mg/kg. The results confirm the traditional use of this plant against inflammatory disorders and could be source for the development of novel drugs.

Analgesic and anti-inflammatory studies of the methanol extract of Globimetula braunii (Loranthaceae) growing on Terminalia catappa Linn (Combretaceae)

This study was carried out to investigate the phytochemical constituents, analgesic and anti-inflammatory activity of methanol stem extract of Globimetula braunii. Preliminary phytochemical screening was done using standard protocols, median lethal dose (LD50) was determined by Lorke’s method. Analgesic and anti-inflammatory activities of extract were determined using acetic acid induced writhing and hot-plate model and the carrageenan-induced rat's paw edema model respectively at graded doses of 1000 mg/kg, 500 mg/kg and 250mg/kg. The phytochemical screening revealed the presence of flavonoids, steroid, triterpenes and saponins. Intraperitoneal median lethal dose of the extract was estimated to be greater than 5000 mg/kg bodyweight in mice. The extract exhibited highest percentage inhibition of writhing (99.24%) at a dose of 1000 mg/kg. However, the extract showed no central analgesic activity. Furthermore, the extract at lowest and highest dose (250 mg/kg and 1000 mg/kg) significantly (p<0.05) reduced paw size when compared to control group. The findings of this study suggest that the methanol stem extract of Globimetula braunii contains bioactive compounds with peripherally mediated analgesic and anti-inflammatory activity.

Anti-inflammatory potential of 1-O-methyl chrysophanol from Amycolatopsis thermoflava ICTA 103: an exploratory study.

The present study was designed to investigate the anti-inflammatory potential of Amycolatopsis thermoflava producing 1-O-methyl chrysophanol (OMC), a member of the hydroxyanthraquinone family. The anti-inflammatory potential was evaluated initially through in silico analysis against tumor necrosis factor- α and cyclooxygenase-2. The same activity was further confirmed based on the in vitro protein denaturation method as well as in vivo by a carrageenan-induced paw edema model in rats. The OMC compound was isolated, purified, and characterized from the fermentation broth of Amycoloptosis thermoflava. In vitro data revealed that the OMC possesses significant protein denaturation properties with an IC50 of 63.50±2.19µg/ml higher than the standard drug, with an IC50 value of 71.42±0.715µg/ml. The percentage of inhibition in paw swelling was observed to be 40.03±5.5 in OMC-treated group, which is comparable to the standard group (52.8±4.7). The histopathological evaluation and immunohistochemistry revealed the anti-inflammatory potential of OMC.

Toxicological and pharmacological effects of Eugenia brasiliensis Lam. (Myrtaceae) leaves in mice.

Eugenia brasiliensis Lam., popularly known as "grumixama" or "Brazilian cherry", is widely used in folk medicine with astringent, diuretic, energizing, anti-rheumatic, and anti-inflammatory properties. Despite its traditional use, detailed toxicological studies of Eugenia brasiliensis are few. Thus, in the current study, we evaluate the toxicological effects of hydroalcoholic extract of Eugenia brasiliensis (HEEb) and its antinociceptive and anti-inflammatory activity. We used male, and female Swiss mice. Acute toxicity study was performed following the Organization for Economic Cooperation and Development (OECD) guideline 425, and subacute toxicity was assessed following OECD guideline 407. We observed behavioral responses, in addition to hematological, biochemical, and histological evaluations. The antinociceptive and anti-inflammatory activity of HEEb were assessed using the Carrageenan-induced mechanical allodynia and paw edema model. Mechanical allodynia, levels of inflammatory cytokines, and oxidative damage were evaluated. The treatment with HEEb was not able to generate important toxicological alterations. Moreover, doses of 100 and 300mg/kg of HEEb were able to reduce mechanical allodynia, paw edema, and inflammatory cytokines (TNF-α, IL-1β, and IL-6), decrease malondialdehyde and increase superoxide dismutase enzyme activity in the paw. This study demonstrated that HEEb does not present important toxic effects. Additionally, an important antinociceptive, anti-inflammatory, and antioxidant potential were observed.

Targeting Anti-Inflammatory Pathways to Treat Diabetes-Induced Neuropathy by 6-Hydroxyflavanone.

It is evident that inflammation and metabolic syndrome instigated by diabetes mellitus can precipitate diabetes-induced neuropathy (DIN) and pain. In order to find an effective therapeutic method for diabetes-related problems, a multi-target-directed ligand model was used. 6-Hydroxyflavanone (6-HF) carrying anti-inflammatory and anti-neuropathic pain potential due to its quadruplicate mechanisms, targeting cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), and opioid and GABA-A receptors was investigated. The anti-inflammatory potential of the test drug was confirmed utilizing in silico, in vitro, and in vivo tests. A molecular simulation approach was utilized to observe the interaction of 6-HF with the inflammatory enzyme COX-2 as well as opioid and GABA-A receptors. The same was confirmed via in vitro COX-2 and 5-LOX inhibitory assays. In vivo tests were performed to analyze the thermal anti-nociception in the hot-plate analgesiometer and anti-inflammatory action in the carrageenan-induced paw edema model in rodents. The potential anti-nociceptive effect of 6-HF was evaluated in the DIN model in rats. The Naloxone and Pentylenetetrazole (PTZ) antagonists were used to confirm the underlying mechanism of 6-HF. The molecular modeling studies revealed a favorable interaction of 6-HF with the identified protein molecules. In vitro inhibitory studies revealed that 6-HF inhibited the COX-2 and 5-LOX enzymes significantly. The 6-HF at dosages of 15, 30, and 60 mg/kg substantially reduced heat nociception in a hot plate analgesiometer as well as carrageenan-induced paw edema in rodent models. The authors discovered that 6-HF had anti-nociception properties in a streptozotocin-induced diabetic neuropathy model. According to the findings of this study, 6-HF was demonstrated to diminish inflammation caused by diabetes as well as its anti-nociception effect in DIN.

The inhibitory potential of chemical constituents of Ficus carica targeting interleukin-6 (IL-6) mediated inflammation.

Inflammation is an innate reaction of the body of an individual when subjected to the noxious factors repeatedly. Pharmacological approaches focused at disrupting cytokine signaling networks have become significant therapeutic alternatives for the treatment of inflammatory illnesses, cancer and autoimmune disorders. High levels of inflammatory mediators, particularly interleukin IL-1, IL-6, IL-18, IL-12, and tumor necrosis factor alpha leads to a cytokine storm in the body. Among all the released cytokines in a patient suffering from inflammatory disorder, IL-6 mediator has a pivotal role in this inflammatory cascade which progresses to a cytokine storm. Therefore, the blockage of the IL-6 inflammatory mediator could be a promising treatment option for the patients with hyper inflammatory conditions. The phytochemicals could provide the new lead compounds against the IL-6 mediator. Ficus carica has been the ideal plant of research and investigation due to its commercial, economic and medical importance. The anti-inflammatory properties of F. carica were further investigated by in silico and in vivo approaches. The docking scores of Cyanidin-3,5-diglucoside, Kaempferol-7-O-rutinoside, Cyanidin-3-rhamnoglucoside, and Rutin are -9.231, -8.921, -8.840, and -8.335 Kcal/mole respectively. The free energy of binding and stability of the docked complexes of these top four phytochemicals with the IL-6 were further analyzed by Molecular Mechanics-Generalized Born Surface Area and Molecular Dynamic simulations, respectively. The in vivo anti-inflammatory carrageenan-induced rat paw edema model was used for the validation of in silico results. The maximum percentage paw edema inhibition with petroleum ether and ethyl acetate was 70.32% and 45.05%, respectively. The in vivo anti-inflammatory activity confirms the anti-inflammatory potential of F. carica. Therefore, it is predicted that Cyanidin-3,5-diglucoside, Kaempferol-7-O-rutinoside, Cyanidin-3-rhamnoglucoside, and Rutin have the potential to inhibit the IL-6 mediator which will aid in mitigating the cytokine storm in patients with acute inflammations.

In vitro and in vivo anti-inflammatory, antibacterial and pharmacokinetic properties of baicalein

Baicalein is a bioactive flavone originally isolated from the roots of Scutellaria baicalensis, Scutellariala teriflora and Oroxylum indicum. The in vitro and in vivo anti-inflammatory and antibacterial properties of baicalein and pharmacokinetics after its single intramuscular administration were studied in Wistar rats. The in vitro anti-inflammatory activity of baicalein (10, 50 and 100 µM) was tested for its ability to inhibit the COX-2 enzyme by measuring PGE2 levels and determination of nitric oxide (NO) production in lipopolysaccharide (LPS) treated RAW 264.7 macrophage cells, in which baicalein was found to have significant inhibition of NO and PGE2 production in RAW 264.7 macrophage cells as compared with the LPS control group. The in vivo anti-inflammatory activity of baicalein (200 mg/kg) was assessed using the carrageenan-induced rat paw oedema model, following intramuscular injection. A significant percentage of inhibition of oedema volume was observed when compared with the carrageenan control group. In vitro and in vivo antibacterial activities of baicalein were determined by the micro broth dilution technique and neutropenic rat thigh infection model, wherein baicalein did not show any antibacterial property. Concentrations of baicalein were determined in rat plasma by high performance liquid chromatography (HPLC) after a single intramuscular administration at a dose of 200 mg/kg body weight, in which the mean peak plasma drug concentration (Cmax) of 0.77 ± 0.02 μg/mL was achieved at 0.08 h. The mean elimination half-life (t½β), the apparent volume of distribution (Vd(area)), total body clearance (Cl(B)) and mean residence time (MRT) were observed as 0.63 ± 0.06 h, 601.03 ± 28.18 L/kg, 677.39 ± 35.36 L/h/kg and 0.76 ± 0.06 h, respectively. Conclusively, in the present study, baicalein did not show in vitro or in vivo antibacterial property, but proved to have good anti-inflammatory activity. The available anti-inflammatory drugs have proved to have side effects in veterinary and human therapeutics. In this situation, baicalein may become an effective alternative to non-steroidal anti-inflammatory drugs and should also be studied in target animal species. Further research should be carried out to improve the solubility and bioavailability of baicalein through injectable routes.

In vitro and in vivo anti-inflammatory activity of Cupressus torulosa D.DON needles extract and its chemical characterization

Ethnopharmacological relevanceCupressus torulosa (family Cupressaceae), widely distributed in the north western Himalayan region of India, is a coniferous aromatic tree with various traditional uses of its aerial parts. Its needles have been used for anti-inflammatory, anticonvulsant, antimicrobial, and wound-healing properties. Aim of the studyThe study aimed at investigating the previously unknown anti-inflammatory activity of the hydromethanolic extract of the needles employing in vitro and in vivo assays and scientifically validate traditional claim of their use in treatment of inflammation. Chemical characterization of the extract with the aid of UPLCQTOFMS was also of interest. Materials and methodsC. torulosa needles were first defatted with hexane and sequentially extracted with chloroform and 25% aqueous methanol (AM). Since the presence of phenolics (TPCs, 208.21 ± 0.95 mg GAE/g needles) and flavonoids (TFCs, 84.61 ± 1.21 mg QE/g needles) was observed in the AM extract only, it was chosen for biological and chemical examinations. Acute toxicity of the AM extract on female mice was evaluated following the OECD guideline 423. In vitro anti-inflammatory activity of the AM extract was examined using egg albumin denaturation assay while carrageenan-induced paw edema and formalin-induced paw edema models at doses of 100, 200 and 400 mg/kg po were used to determine the in vivo activity of the AM extract on Wistar rats of either sex. The components of the AM extract were analyzed by UPLC-QTOF-MS method using non-targeted metabolomics approach. ResultsAM extract was found to be non-toxic at 2000 mg/kg b.w. with no signs of abnormal locomotion, seizures and writhing. The extract demonstrated promising in vitro anti-inflammatory activity (IC50 160.01 μg/mL) compared to standard diclofenac sodium (IC50 73.94 μg/mL) in egg albumin denaturation assay. In carrageenan-induced paw edema and formalin-induced paw edema tests the extract showed significant anti- inflammatory activity (57.28% and 51.04% inhibition of paw edema, respectively) at the dose of 400 mg/kg p.o. after 4 h in comparison to the standard diclofenac sodium which displayed 61.39% and 52.90% inhibition, respectively, at the dose of 10 mg/kg p.o. after 4 h in these models. A total of 63 chemical constituents, majority of them being phenolics, were found in the AM extract of the needles. Two compounds namely monotropein (iridoid glycoside), (±)12-HETE (eicosanoid) and fraxin (coumarin glycoside) were reported to have anti-inflammatory effect. ConclusionsFor the first time our study demonstrated that hydro-methanolic extract of C. torulosa needles exhibit anti-inflammatory activity thereby supporting their traditional use in the treatment of inflammatory disorders. UPLCQTOFMS assisted chemical profile of the extract was also unveiled.

Antinociceptive and anti-inflammatory activities of Ferula elaeochytris Korovin methanolic extract in rat model

Today, the current chemical agents for pain control have relatively many complications. They are associated with the occurrence of disorders in the digestive system, kidney damage, or addiction, which has caused people to find newer drugs that, in addition to removing side effects, are cheap and available. The present in vivo survey aimed to assess the antinociceptive and anti-inflammatory activity of Ferula elaeochytris Korovin methanolic extract (FEME) in male Swiss mice. After obtaining the methanolic extract through the maceration process, the antinociceptive efficacy of FEME at doses of 25 to 100 mg/kg was assessed by the tail-flick, hot-plate, and formalin tests. In addition, anti-inflammatory evaluation was performed by the Carrageenan-induced paw edema model. We found that in the tail-flick and hot plate test, FEME mainly at the dose of 100 mg/kg significantly reduced the latency time as well as better the time of the observance of licking or jumping in comparison with normal saline (P<0.001). We reported that FEME at 50, and 100 mg/kg considerably declined the pain behaviors in the acute and chronic phase in comparison with normal saline (p<0.001). FEME markedly (p < 0.05) declined paw edema in a dose- and time-dependent response, so a significant difference was observed in paw edema followed by treatment with FEME at 50 and 100 mg/kg (p<0.001). To conclude, this study reported the potent analgesic and inflammatory effects of F. elaeochytris methanolic extract to control peripheral and central pain. However, additional experiments are mandatory to clear the accurate mechanisms of action of this plant.