Inhibition Of Edema Research Articles

Exploring the therapeutic potential of ethanol extract of Erythrina fusca Lour. roots as an analgesic, antipyretic, and anti-inflammatory agent in experimental animals

Erythrina fusca Lour., renowned in traditional medicine for its soothing, analgesic, anti-inflammatory, and neuroinhibitory properties, is the focus of our investigation. Expanding on its traditional applications, we assessed the analgesic, anti-inflammatory, and antipyretic characteristics of the ethanol extract from E. fusca root (REEF). Administered orally to mice at varying doses (50, 100, and 150 mg/kg for pain and fever reduction; 100, 150, and 200 mg/kg for anti-inflammatory experiments), REEF's effects were systematically evaluated through parameters such as reaction time, pain inhibition ratio, COX2 and PGE2 levels, rectal temperature, fever inhibition ratio, paw diameter, paw edema inhibition ratio, and inflammatory cytokines. Results reveal that REEF consistently reduced licking and biting time (p < 0.05) in response to formalin-induced pain in mice. Particularly noteworthy was the more pronounced reduction in COX2 and PGE2 during the late phase, with the most significant decrease observed at the 150 mg/kg REEF treatment (p < 0.05). The licking time graph substantiated the analgesic efficacy of REEF, illustrating simultaneous and sustained pain reduction over time. Moreover, REEF significantly alleviated fever (p < 0.05) in mice, with the most substantial effect observed three hours post-yeast injection. REEF not only efficiently reduced body temperature but also countered the fever-inducing effects of yeast at evaluated time points (p < 0.05). In the context of carrageenan-induced inflammation, paw swelling markedly diminished after 4 and 5 hours (p < 0.05). Notably, at the 5-hour mark, REEF treatment at 150 mg/kg dose exhibited significantly superior anti-inflammatory effects (p < 0.05). Additionally, mice treated with REEF (100, 150, and 200 mg/kg) exhibited a considerable decrease (p < 0.05) in serum concentrations of TNF-?, IL-1?, and IL-6 compared to the control treatment. The ethanol extract from Erythrina fusca roots demonstrates substantial potential for pain relief, fever reduction, and anti-inflammatory effects, positioning it as a promising herbal resource for the research and development of natural medicinal products with these therapeutic properties.

Anti-Inflammatory and Antitussive Activity of Asthpadose, a Phytomedicine used in the Treatment of Asthma in Côte d'Ivoire

Introduction: The aim of this study is to contribute to the valorisation of an anti- asthmatic phytomedicine (Asthpadose) traditionally used in Côte d'Ivoire. Aims: Evalute antiasthma’s activity of the aqueous extract of Asthpadose (EAA) was. Methodology: The antiasthma’s activity of the aqueous extract of Asthpadose (EAA) was evaluated by the determining of its anti-inflammatory activity using the carrageenan oedema induction method. This anti-asthmatic activity was also evaluated by its antitussive action on the frequency of cough induced in rats exposed to liquid ammonia. Results: The results revealed that EAA showed a very significant strong anti- inflammatory activity with an oedema inhibition rate ranging from 34.29% to 70.9 5%. This activity was much better than that of diclofenac sodium (a reference molecule against inflammation) with an oedema inhibition rate ranging from 12.24% to 58.39%. As for its antitussive activity, the results also showed good antitussive activity of the extract. EAA presented a cough inhibition rate of 74.22% compared to 58.76% for dextrometaphan which is also a reference molecule against cough. Conclusion: This observed activity could therefore justify the use of Asthpadose in the treatment of asthma which is a disease manifested by inflammation and cough. In view of the very promising results of this study, it would therefore be necessary to continue studies on this phytomedicine to understand its mechanism of action on asthma.

New Perspectives on the Therapeutic Potentials of Bioactive Compounds from Curcuma longa: Targeting COX-1 & 2, PDE-4B, and Antioxidant Enzymes to Counteract Oxidative Stress and Inflammation

Background Inflammations, oxidative stress, and pains underlie the pathogenesis of non-communicable diseases (NCDs) like respiratory disorders and cancer; however, they are scientifically treated with Curcuma longa. Therefore, the pharmacological screening (antioxidant, anti-inflammatory, and analgesic) of the plant's rhizome, isolation and characterization of its compounds, as well as their in silico profiling with cyclooxygenases, phosphodiesterase, superoxide dismutase, glutathione peroxidase, and catalase could yield lead compounds with better benefit-to-risk ratio against oxidative stress and inflammation. Methods The collection of the plant's rhizomes , extract preparation, anti-inflammatory, analgesic, and antioxidant studies, retrieval of target proteins, GC-MS, ADME, and docking analyses were done using standard protocols. Results Curcuma longa's percentage edema inhibition and analgesic potentials were better than aspirin in both acute and sub-acute inflammations as well as chemical and thermal-induced pains; moreover, its antioxidant activities were better than vitamin C. Moreover, twenty compounds with anti-inflammatory, analgesic, and antioxidant activities were unraveled from the GC-MS analysis. Ar-tumerone, curcumin, γ-sitosterol, α-tocopherol, isocurcumenol, adamantane, and curdione were the lead compounds based on their binding affinities (for PDE-4B, COX-1, COX-2, SOD, CAT, GPx), lower molecular weights, non-permeation of blood brain barrier, bioavailability profiles, non-inhibition of metabolizing enzymes, faster renal clearance, and non-violation of Lipinski's rules. Conclusion Adamantane, α-tocopherol, and γ-sitosterol reported for the first time in the plant's rhizome could mitigate oxidative stress and inflammation as mediators of apoptosis, cytotoxic impaired autophagy, DNA damages, and mitochondrial dysfunction that contributes to the progression of non-communicable diseases (NCDs).

Thermoresponsive gel containing bilirubin nanoparticles exerts anti-inflammatory effects by inhibiting neutrophil infiltration and augmenting interleukin-10 levels in carrageenan-induced rat paw edema.

Topical corticosteroids treat cutaneous inflammation but have side effects. In earlier studies, bilirubin exhibited anti-inflammatory effect, but its hydrophobicity and poor absorption limit its potential. Synthesis of bilirubin nanoparticles (BNP) and bilirubin nanoparticles gels (BNP gel) to study the anti-inflammatory effect of topical BNP gel against carrageenan-induced rat paw edema in Wistar rats. BNP were synthesized, and BNP gels were prepared by mixing BNP of different concentrations with pluronic F-127 (PF-127). A different group for each formulation was assigned with five rats in each group. After 1 h of carrageenan (1% [w/v]) injection in each group, different gels were applied topically to their respective groups. Paw edema size, percent inflammation, percent edema inhibition, and inhibition time50 were evaluated. Interleukin-10 (IL-10) levels and neutrophil infiltration in rat paw tissue were evaluated by enzyme-linked immunosorbent assay and hematoxylin and eosin, respectively. Synthesized spherical-shaped BNP had negative zeta potential. BNP gels markedly reduced paw edema size and % inflammation as compared to carrageenan and bulk bilirubin gel (Bulk B gel) treated group and significantly increased IL-10 levels and inhibited neutrophil infiltration. BNP gels exhibited a better anti-inflammatory effect than bulk B gel and comparable anti-inflammatory potential with clobetasol.

Exploring the anti-inflammatory, sedative, antidiabetic, and antioxidant potential in in-vitro and in-vivo models and phenolic profiling of Atractylis aristata Batt.

Ethnopharmacological relevanceAtractylis aristata batt., as an endemic plant from the Asteraceae family, holds a significant position in the Ahaggar region of southern Algeria's traditional medicine. The aerial parts of Atractylis aristata was used to cure inflammation, fever, and stomach disorders. Aim of the studyThe objective of the present investigation was to ascertain the overall bioactive components and phytochemical components and examine the antioxidant, antidiabetic, anti-inflammatory, acute toxicity, and sedative properties of the crude extract obtained from the aerial portions of Atractylis aristata (AaME). Materials and methodsThe AaME's antioxidant activity was assessed by the use of pyrogallol autoxidation, (1,1 diphenyl-2-picrylhydrazyl) (DPPH), 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), and reducing power (RP) techniques. 1 mg/mL of AaME was used to evaluate the antidiabetic activity by applying the enzyme α-amylase inhibitory power test. At the same time, the bovine serum albumin (BSA) denaturation method was employed to quantify the in vitro anti-inflammatory activity at different concentrations (1.5625, 0.78125, 0.390625, 0.1953125 and 0.09765625 mg/mL). In contrast, following the Organization for Economic Co-operation and Development (OECD) guideline No. 423, which covers acute oral toxicity testing protocols, the limit dosage test was employed to assess in vivo acute toxicity. At the dose of 0.08 mg/mL, the carrageenan-induced paw edema approach was used to assess the anti-inflammatory efficacy in vivo, and the sedative activity was carried out at the dose of 0.08 mg/mL using the measurement of the locomotor method. Different bioactive compounds were identified within AaME using LC-MS/MS and HPLC-UV analysis. ResultsThe acute toxicity study showed no fatalities or noticeable neurobehavioral consequences at the limit test; this led to their classification in Globally Harmonized System (GHS) category Five, as the OECD guideline No 423 recommended. At a concentration of 0.08 mg/mL (2000 mg/kg), AaME showed apparent inhibition of paw edema and a significant (p = 0.01227) reduction in locomotor activity compared to the control animals. Our findings showed that AaME exhibited considerable antioxidant (IC50 = 0.040 ± 0.003 mg/mL (DPPH), IC50 = 0.005 ± 5.77 × 10-5 mg/mL (ABTS), AEAC = 91.15 ± 3.921 mg (RP) and IR% = 23.81 ± 4.276 (Inhibition rate of pyrogallol) and rebuts antidiabetic activities (I% = 57.6241% ± 2.81772). Our findings revealed that the maximum percentage of BSA inhibition (70.84 ± 0.10%) was obtained at 1.562.5 mg/mL. Thus, the AaME phytochemical profile performed using phytochemical screening, HPLC-UV, and LC-MS/MS analysis demonstrated that A. aristata can be a valuable source of chemicals with biological activity for pharmaceutical manufacturers. ConclusionThe phytochemical profiling, determined through HPLC-UV and LC-MS/MS applications, reveals this plant's therapeutic value. The aerial parts of Atractylis aristata contain bioactive molecules such as gallic acid, ascorbic acid, and quercetin, contributing to its significant antioxidant capabilities. Furthermore, identifying alizarin, the active compound responsible for its anti-inflammatory properties, could provide evidence supporting the anti-inflammatory capabilities of this subspecies.

Synthesis and biological evaluation of some novel benzoxazin-4-one and quinazolin-4-one derivatives based on anti-inflammatory commercial drugs

Benzoxazine and quinazoline are nitrogen-containing heterocyclic scaffolds found in various biologically active compounds. Due to their diverse biological actions, these heterocyclic rings serve as crucial frameworks for designing medicinal compounds. This study aimed to synthesize and assess in vivo anti-inflammatory, analgesic, and low ulcerogenic potential of a few novel benz[d][1,3]-oxazin-4-one and quinazolinone derivatives. Benzoxazinones (3a-e) were synthesized by cyclizing the carboxylic group (-COOH) of five nonsteroidal anti-inflammatory drugs viz., aceclofenac, ibuprofen, diclofenac, mefenamic acid and ketoprofen (2a-e) with anthranilic acid (1) using dry phosphorus oxychloride (POCl3) in pyridine. The corresponding quinazolinone derivatives (5a-e) were obtained by reacting 3a-e with isonicotinic acid hydrazide (4). Both sets of compounds were evaluated for their anti-inflammatory, analgesic effects, and ulcerogenicity in animal models. Structural characterization was performed using spectral analysis. Among the benzoxazinone derivatives, compound 2-(2-((2,6-dichlorophenyl) amino) benzyl)-4H-benzo[d][1,3]oxazin-4-one (3d) exhibited significant anti-inflammatory activity (62.61% inhibition of rat paw edema) and analgesic activity (62.36% protection in acetic acid-induced writhings) with tolerable gastrointestinal toxicity (2.67 ulcerogenicity index) compared to quinazolinone derivatives. The results of anti-inflammatory and analgesic activities of both the series are comparable with the respective, positive control. Compound 3d, a benzoxazinone-diclofenac hybrid, emerged as a lead molecule with potent anti-inflammatory, analgesic activities and moderate gastric toxicity showcasing the promising potential for further development.

Insight on novel oxindole conjugates adopting different anti-inflammatory investigations and quantitative evaluation.

Background: A dual COX/5-LOX strategy was adopted to develop new oxindole derivatives with superior anti-inflammatory activity. Methods: Three series of oxindoles - esters 4a-p, 6a-l and imines 7a-o - were synthesized and evaluated for their anti-inflammatory and analgesic activities. Molecular docking and predicted pharmacokinetic parameters were done for the most active compounds. A new LC-MS/MS method was developed and validated for the quantification of 4h in rat plasma. Results: Compounds 4h, 6d, 6f, 6j and 7m revealed % edema inhibition up to 100.00%; also, 4l and 7j showed 100.00% writhing protection. Compound 4h showed dual inhibitory activity with IC50=0.0533 and 0.4195μM for COX-2 and 5-LOX, respectively. Molecular docking rationalized the obtained biological activity. The pharmacokinetic parameters of 4h from rat plasma were obtained.

Discovery of new 2-(3-(naphthalen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl)thiazole derivatives with potential analgesic and anti-inflammatory activities: In vitro, in vivo and in silico investigations

Joining the global demand for the discovery of potent NSAIDs with minimized ulcerogenic effect, new pyrazole clubbed thiazole derivatives 5a-o were designed and synthesized. The new derivatives were initially evaluated for their analgesic activity. Eight compounds 5a, 5c, 5d, 5e, 5f, 5h, 5m, and 5o showed higher activity than Indomethacin (potency = 105–130 % vs. 100 %). Subsequently, they were picked for further evaluation of their anti-inflammatory activity, ulcerogenic liability as well as toxicological studies. Derivatives 5h and 5m showed a potential % edema inhibition after 3 h (79.39 % and 72.12 %, respectively), with a promising safety profile and low ulcer indices (3.80 and 3.20, respectively). The two compounds 5h and 5m were subjected to in vitro COX-1 and COX-2 inhibition assay. The candidate 5h showed nearly equipotent COX-1 inhibition (IC50 = 38.76 nM) compared to the non-selective reference drug Indomethacin (IC50 = 35.72 nM). Compound 5m expressed significant inhibitory activities and a higher COX-2 selectivity index (IC50 = 87.74 nM, SI = 2.05) in comparison with Indomethacin (SI = 0.52), with less selectivity than Celecoxib (SI = 8.31). Simulation docking studies were carried out to gain insights into the binding interaction of compounds 5h and 5m in the vicinity of COX-1 and COX-2 enzymes that illustrated the importance of pyrazole clubbed thiazole core in hydrogen bonding interactions. The thiazole motif of compounds 5h and 5m exhibited a well orientation toward COX-1 Arg120 key residue by hydrogen bonding interactions. Compound 5h revealed an additional arene-cation interaction with Arg120 that could rationalize its superior COX-1 inhibitory activity. Compounds 5h and 5m overlaid the co-crystallized ligand Celecoxib I differently in the active site of COX-2. Compound 5m showed an enhanced accommodation with binding energy of − 6.13 vs. − 1.70 kcal/mol of compounds 5h. The naphthalene ring of compound 5m adopted the Celecoxib I benzene sulfonamide region that is stabilized by hydrogen-arene interactions with the hydrophobic sidechains of the key residues Ser339 and Phe504. Further, the core structure of compound 5m, pyrazole clubbed thiazole, revealed deeper hydrophobic interactions with Ala513, Leu517 and Val509 residues. Finally, a sensitive and accurate UPLC-MS/MS method was developed for the simultaneous estimation of some selected promising pyrazole derivatives in rat plasma. Accordingly, compounds 5h and 5m were suggested to be promising potent analgesic and anti-inflammatory agents with improved safety profiles and a novel COX isozyme modulation activity.

Exploring the Anti-Inflammatory Potential of Cyperus pangorei Rhizome Extracts An In Vitro and In Vivo Study

Background and aim: Inflammation is a pivotal process implicated in various physiological and pathological conditions, necessitating the exploration of alternative anti-inflammatory agents with minimal side effects. This study aimed to investigate the anti-inflammatory potential of the standardized ethyl acetate (EtAc) fraction derived from Cyperus pangorei rhizomes. Methods: The rhizomes of C. pangorei were collected, processed, and subjected to extraction and fractionation to obtain the EtAc fraction. RP-HPLC analysis was employed to standardized the EtAc fraction against standard quercetin, luteolin, and apigenin. In vitro studies utilized peritoneal macrophages isolated from male Swiss albino rats to assess NO production and cytokine levels (IL-1β, IL-6, TNF-α) upon treatment with the EtAc fraction. In vivo evaluation was conducted using a carrageenan-induced rat paw edema model. Results: RP-HPLC analysis revealed the presence of quercetin, luteolin, and apigenin in the EtAc fraction. In vitro studies demonstrated dose-dependent inhibition of LPS-induced NO production and suppression of inflammatory cytokines (IL-1β, IL-6, TNF-α) by the EtAc fraction. Furthermore, in the carrageenan-induced rat paw edema model, the EtAc fraction exhibited dose-dependent inhibition of paw edema. Conclusion: The findings of this study highlight the significant anti-inflammatory potential of C. pangorei rhizome extracts, particularly the EtAc fraction. The identified compounds, quercetin, luteolin, and apigenin, contribute to its anti-inflammatory activity by modulating key inflammatory mediators. These results support the potential therapeutic use of C. pangorei in managing inflammation-related disorders. Further research is warranted to elucidate the underlying mechanisms and evaluate the long-term efficacy and safety of C. pangorei extracts as anti-inflammatory agents.

Chemical Constituents from Agave applanata and Its Antihyperglycemic, Anti-inflammatory, and Antimicrobial Activities Associated with Its Tissue Repair Capability.

Agave applanata is a Mexican agave whose fresh leaves are employed to prepare an ethanol tonic used to relieve diabetes. It is also applied to skin to relieve varicose and diabetic foot ulcers, including wounds, inflammation, and infections. In this study, the chemical composition of this ethanol tonic is established and its association with antihyperglycemic, anti-inflammatory, antimicrobial, and wound healing activities is discussed. The fresh leaves of A.applanata were extracted with ethanol : H2O (85 : 15). A fraction of this extract was lyophilized, and the remainder was partitioned into CH2Cl2, n-BuOH, and water. CH2Cl2 and n-BuOH fractions were subjected to a successive open column chromatography process. The structure of the isolated compounds was established using nuclear magnetic resonance and mass spectrometry spectra. The antihyperglycemic activity was evaluated through in vivo sucrose and glucose tolerance experiments, as well as ex vivo intestinal absorption and hepatic production of glucose. Wound healing and edema inhibition were assayed in mice. The minimum inhibitory concentrations (MICs) of the hydroalcoholic extract, its fractions, and pure compounds were determined through agar microdilution against the most isolated pathogens from diabetic foot ulcers. Fatty acids, β-sitosterol, stigmasterol, hecogenin (1: ), N-oleyl-D-glucosamine, β-daucosterol, sucrose, myo-inositol, and hecogenin-3-O-α-L-rhamnopyranosyl-(1 → 3)-β-D-xylopyranosyl-(1 → 2)-[β-D-xylopyranosyl-(1 → 3)-β-D-glucopyranosyl-(1 → 3)]-β-D-glucopyranosyl-(1 → 4)-β-D-galactopyranoside (2: ) were characterized. This research provides evidence for the pharmacological importance of A.applanata in maintaining normoglycemia, showing anti-inflammatory activity and antimicrobial effects against the microorganisms frequently found in diabetic foot ulcers. This plant plays an important role in wound healing and accelerated tissue reparation.

Evaluation of Anti-inflammatory activity of Jacquemontia caerulea Leaf Methanolic Extract in Wistar rats

Objective: To evaluate anti-inflammatory activity of methanolic extract of obtained from the leaves of plant, Jacquemontia caerulea in Wistar rats. Methods: Fresh leaves of Jacquemontia caerulea (Family: Convolvulaceae) were extracted using methanol and subjected to phytochemical analysis using standard procedures. The anti-inflammatory nature of the methanolic leaf extract (JCLME) was assessed on Wistar rats, with Indomethacin serving as the standard reference drug. Two established methods were employed: Paw edema method by using Carrageenan and Cotton pellet granuloma method. Results: Phytochemical analysis of methanolic extract was found to have phytoconstituents such as saponins, flavonoids, glycosides, steroids, proteins, amino acids, phenols, and tannins. The anti-inflammatory evaluation showed that JCLME produced anti-inflammatory effect. In the paw edema model by Carrageenan, JCLME demonstrated remarkable (p<0.05) inhibition of paw edema with reduction of 23% and 30% at dose of 250 mg/kg and 500 mg/kg, respectively. Similar result was observed in the Cotton pellet granuloma method. Conclusion: The leaf methanolic extract of Jacquemontia caerulea contains a high concentration of various phytochemicals and exhibits significant (p<0.05) anti-inflammatory effect in both Carrageenan-induced paw edema and Cotton pellet granuloma model in Wistar rats.

Evaluation of the Anti-Inflammatory and Antioxidant, Activities of Parinari Curatellifolia Planch. Ex Benth (Chrysobalanaceae) Methanol Stem Bark Extract

It is used as human food and beverage, and in traditional medicine it is used to treat pneumonia and fever. The aim of this was to investigate its anti-inflammatory and antioxidant activities of Parinari curatellifolia methanol stem bark extract. A 2kg of the dried and powdered plant material was extracted with 80% methanol through cold maceration to obtain the crude methanol extract. The crude methanol extract was sequentially fractionated using n-hexane, ethyl acetate and methanol to yield n-hexane, ethyl acetate and methanol fractions respectively. Acute toxicity study was conducted following the OECD guidelines. The anti-inflammatory activity of the fractions was evaluated was evaluated using inhibition of albumin denaturation, inhibition of egg albumin-induced paw edema in rats and phospholipase A2 (PLA2) inhibition assay models. In vitro antioxidant activity was evaluated using DPPH de-colourizing, Nitric oxide scavenging activity and Ferric Reducing Antioxidant Power (FRAP) assays. Oral acute administration of the extract revealed an LD50 dose > 5000 mg/kg in rats. The extract caused a dose- and time-dependent inhibition of rat paw edema, and a concentration-dependent inhibition of Phospholipase A2 activity. IC50 of the extract for Albumin Denaturation inhibition was 37.22 ug/ml. In the antioxidant assays the IC50 of the extract against DPPH was 25.91 ug/ml, while the Nitric oxide Equivalence (mM)/mg was 42.38.

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.

Investigation of anti-nociceptive, anti-inflammatory potential and ADMET studies of pure compounds isolated from Isodon rugosus Wall. ex Benth.

The strong ethnopharmacological utilization of Isodon rugosus Wall. Ex. Benth is evident in the treatment of several types of pain and inflammation, including toothache, earache, abdominal pain, gastric pain, and generalized body pain and inflammation. Based on this background, the antinociceptive effects of the crude extract, various fractions, and essential oil have been reported previously. In this research work, we isolate and characterize pure bioactive compounds from I. rugosus and evaluate possible mechanisms using various in vivo and in vitro models. The pure compounds were analyzed for analgesic and anti-inflammatory activities through various assays. The column chromatography of the chloroform fraction of I. rugosus led to the identification of two pure compounds, i.e., 1 and 2. Compound 1 demonstrated notable inhibition (62% writhing inhibition, 72.77% COX-2 inhibition, and 76.97% 5-LOX inhibition) and anti-inflammatory potential (>50% paw edema inhibition at various intervals). The possible mechanism involved in antinociception was considered primarily, a concept that has already been elucidated through the application of naloxone (an antagonist of opioid receptors). The involvement of adrenergic receptors was investigated using a hot plate model (an adrenergic receptor antagonist). The strong ethnomedicinal analgesic background of I. rugosus, supported by previous reports and current observations, leads to the conclusion that I. rugosus is a potential source of antinociceptive and anti-inflammatory bioactive compounds. It may be concluded from the results that the isolated analgesic compounds of I. rugosus may be a possible alternative remedy for pain and inflammation management with admirable efficacy and safety profiles.

Exploring new imines as anti-inflammatory COX and 5-LOX inhibitors with an improved pharmacokinetic profile.

Background: Dual COX/5-LOX inhibition is a bright strategy for developing new potent and safe anti-inflammatory agents. Methods: New imines were synthesized and evaluated for their anti-inflammatory activity. The most active compounds were further investigated for their safety profile. Their molecular docking and physicochemical parameters were assessed. A new LC-MS/MS method was developed for the quantification of compound 4d in rat plasma. Results: Synthesized compounds were found to have anti-inflammatory activity (77-88% edema inhibition). In addition, 4d, 5m and 7d showed analgesic activity (92.50, 95.71and 96.28% protection, respectively). 4d showed dual COX-2/5-LOX activity. Molecular docking expected the binding pattern of compounds in COX-1, COX-2and 5-LOX active sites. The in vivo pharmacokinetic parameters of compound 4d were also obtained.

QbD-assisted optimisation of liposomes in chitosan gel for dermal delivery of aceclofenac as synergistic approach to combat pain and inflammation.

Aceclofenac (ACE) is a drug that was precisely devised to circumvent the shortcomings associated with diclofenac. However, ACE too corresponds to nonsteroidal anti-inflammatory drug (NSAID)-related adverse effects, but with a lower amplitude. The present investigation seeks to develop liposomes loaded with ACE adopting a central composite design (CCD) and formulate a chitosan-based hydrogel for synergistic anti-inflammatory efficacy and improved ACE dermal administration. On the basis of preliminary vesicle size, Poly Dispersity Index (PDI), and drug entrapment, the composition of lipid, cholesterol, and vitamin E TPGS were chosen as independent variables. The formulation composition met the specifications for an optimum liposomal formulation, with total lipid concentration (13.5% w/w), cholesterol concentration (10% w/w), and surfactant concentration (2% w/w). With particle size and PDI of 174.22 ± 5.46nm and 0.285 ± 0.01 respectively, the optimised formulation achieved an entrapment effectiveness of 92.08 ± 3.56%. Based on the CCD design, the optimised formulation Acec-Lipo opt was chosen and was subsequently transformed to a chitosan-based gel formulation for in vitro drug release, penetration through the skin, in vivo analgesic therapeutic activity, and skin irritation testing. % age oedema inhibition was found to be greatest with the Acec-Lipo opt gel formulation, followed by Acec gel. These results reinforce the notion that the inclusion of chitosan resulted in a synergistic effect despite the same strength of the drug. The findings suggested that Acec-Lipo incorporated in chitosan gel for skin targeting might be an effective formulation for topical ACE administration in clinical subjects.

Phytochemical Analysis, Antioxidant, Analgesic, Anti-Inflammatory, Hemagglutinin and Hemolytic Activities of Chemically Characterized Extracts from Origanum grosii (L.) and Thymus pallidus (L.)

Origanum grosii (L.) and Thymus pallidus (L.) are medicinal plants recognized for their uses in traditional medicine. In this context, the aim of this article is to highlight the results of a phytochemical analysis (HPLC), with particular emphasis on the antioxidant (DPPH, TAC, and FRAP), analgesic, anti-inflammatory, haemagglutinin-test-related, and hemolytic activities of the total extracts of these plants. Phytochemical analysis via HPLC revealed that licoflavone C (30%) is the main compound in Origanum grosii, while hesperidin (43%) is found in T. pallidus. Evaluation of the antioxidant capacity of Origanum grosii and Thymus pallidus using the DPPH, TAC, and FRAP methods revealed an IC50 of the order of 0.085 mg/mL and 0.146 mg/mL, an EC50 of the order of 0.167 mg/mL and 0.185 mg/mL, and a total antioxidant capacity of between 750 mg EQ/g and 900 mg EQ/g, respectively. Analgesic evaluations revealed writhes inhibition of the order of 97.83% for O. grosii and 90% for T. pallidus. In addition, both plant extracts showed limited hemolytic activity, not exceeding 30% at a concentration of 100 mg/mL. Evaluation of the anti-inflammatory potential showed edema inhibition of the order of 94% (800 mg/kg) for O. grosii and 86% (800 mg/kg) for T. pallidus. These results highlight the potential applications of these extracts in pharmacological research.

Self-assembling Organogels Loaded with Tenoxicam for Local Intensive Pain and Inflammation Cure: In Vitro and In Vivo Correlation.

Due to tenoxicam (TX)'s poor aqueous solubility (0.072 mg/ml), it is poorly absorbable in the GIT, and the long-term oral administration of TX may cause severe GIT disturbances. Topical administration of TX can help in bypassing the GIT adverse effects. Therefore, in the present work, we constructed different pluronic/lecithin organogels (PLOs) for topical delivery of TX. PLO was constructed simply via direct mixing of an aqueous pluronic solution with lecithin solution. The prepared PLO formulations were characterized for their physicochemical properties including pH, drug content, visual inspection, viscosity, and spreadability. Also, the in vitro release and kinetic studies were carried out to investigate the mechanism of drug release. Moreover, the in vivo studies were carried out by investigating the anti-inflammatory and analgesic activities using albino male rats. The results showed that the modified PLOs have good physicochemical properties. The viscosity of the modified gels is a direct proportionality with both lecithin and pluronic concentrations. Also, subsequently, the drug release rate is directly proportional to gel viscosity. Moreover, the in vivo studies showed that the modified PLOs (F19) showed a significant ( < 0.05%) paw edema inhibition and pain analgesia compared with other investigated groups. Also, the results indicated that the increase in dose is accompanied by higher activity and a longer duration of action which extended to 12 h. Hence, the modified PLOs are promising safe candidates or vehicles for effective TX loading with sustained delivery behavior.

In-Vitro and in-Vivo Evaluation of the Developed Curcumin-Cyclosporine-Loaded Nanoemulgel for the Management of Rheumatoid Arthritis

ABSTRACT Background Topical nanogel-based formulations have shown potential in the management of rheumatoid arthritis (RA). The aim of this research work was to explore the synergistic effect of Curcumin (CUR) and Cyclosporine (CYC) in combination via a topical route for the management of RA. Methods The CUR+CYC loaded nanoemulsion was developed using the spontaneous emulsification technique and was subsequently incorporated into Carbopol® Ultrez 30-NF gel. The effect of the developed formulation on levels of proinflammatory cytokines (IL-6, TNF-α) and anti-inflammatory cytokine (IL-10) was evaluated using lipopolysaccharide (LPS) induced RAW 264.7 cell culture model. The anti-arthritic activity was evaluated in a Complete Freund’s Adjuvant (CFA) induced arthritic rat model. Results The optimized nanoemulgel (CUR + CYC NE gel) exhibited average globule size of 15.32 nm ±2.7 nm, poly-dispersity index of 0.181 ± 0.034 and zeta potential of −16.3 mV ± 0.9 mV. The cumulative drug release from ex-vivo diffusion studies on porcine ear skin was 99.189% ± 1.419% at the of 24 h and 99.177% ± 1.234% at the end of 18 h for CUR and CYC, respectively. The cell culture studies revealed that the formulation was able to significantly lower (p < .001) the levels of IL-6 and TNF-α, inhibited prostaglandin E2 (PGE2) while significantly elevating (p < .001) the levels of anti-inflammatory cytokine (IL-10). The gel was found to be non-irritating and showed the inhibition of paw edema and substantial reduction of arthritic symptoms in an arthritic rat model as compared to commercial and other conventional alternatives. Conclusion This study highlights the potential of the developed nanoemulgel for the management of RA by enhancing the topical permeation of CUR and CYC.

Sustained release polymer and surfactant based solid dispersion of andrographolide exhibited improved solubility, dissolution, pharmacokinetics, and pharmacological activity

Andrographolide (AD) is a potent natural product with a wide range of pharmacological activities. However, it has low oral bioavailability due to poor solubility and dissolution rate. Solid dispersion (SD) is a promising technique to improve the solubility and dissolution rate of such molecules. In this study, SD formulation of AD was prepared using Kollidon-SR (KSR) and Poloxamer-407 (P-407) as carriers. SD was prepared using the solvent evaporation method and evaluated for the modulation of solubility of AD. The developed SD formulation was characterized using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR). Further, dissolution rate, yield, drug content, stability, flowability, and pharmacokinetic profile of SD were evaluated. The compatibility of SD with the Caco-2 cells and its impact on the P-glycoprotein (P-gp) mediated efflux was also investigated. Furthermore, carrageenan-induced paw edema, and adjuvant-induced arthritic model were used to evaluate the efficacy of SD. The results showed that SD3 (AD + KSR + P-407, 1:6:8) exhibited the highest solubility and dissolution rate, and significantly improved pharmacokinetic profile compared to native AD. SD3 was found to be stable during storage and displayed excellent yield, drug content, and flowability. This formulation was found to be compatible with the Caco-2 cells and retarded the efflux of P-gp substrate. SD3 also demonstrated substantially better efficacy than native AD in terms of paw edema inhibition (carrageenan-induced paw edema, Wistar rats), and overall improvement of disease condition (in terms of paw edema, arthritic score, AST, ALT, cytokines, radiological changes, and histopathology) in arthritic Wistar rats. In conclusion, SD3 exhibited improved solubility, dissolution rate, pharmacokinetic profile, and pharmacological activity than native AD.