Paw Edema Research Articles

Using Quality by Design Tools to Study Gel Formulation from Brassica juncea Leaves and Conducting its In vitro, In vivo, Molecular Docking, and ADMET Analyses.

This research aims to create a gel formulation of Brassica juncea leaf extract and assess its anti-inflammatory properties using an in silico study. The anti-inflamma-tory activity has been compared with Diclofenac molecules in PDB id: 4Z69. Further, the Ab-sorption, Distribution, Metabolism, Excretion, and Toxicity analysis has been performed to en-sure the therapeutic potential and safety of the drug development process. The Quality by De-sign tool has been applied to optimize formulation development. The extracted gel is characterized by performing Fourier transformer infrared, zeta potential, particle size, Scanning Electron Microscope, and entrapment efficiency. Further, the formulation is evaluated by examining its viscosity, spreadability, and pH measurement. An In-vitro study of all nine extract suspensions was conducted to determine the drug contents at 276 nm. The optimized suspension has shown the maximum percentage of drug release (82%) in 10 hours of study. Animal study for anti-inflammatory activity was performed, and results of all five groups of animals compared the % inhibition of paw edema at three hours; gel (56.70 %), standard (47.86 %), and (39.72 %) were found. The research could conclude that the anti-inflammatory activity of gel formulation is high compared to extract, and a molecular docking study validates the anti-inflammatory ther-apeutic effects. ADMET analysis ensures the therapeutic effects and their safety.

Evaluation of Anti-arthritic and in-vitro Anti-inflammatory activity of Vaisvanara Churna

Ethnopharmacological relevanceVaisvanara Churna used traditionally for the treatment of Amavata (Rheumatoid arthritis), Shotaprasamana (Anti-inflammatory) and as Saraka (Laxative). AimAim of the study is to evaluate anti arthritic activity and in vitro anti-inflammatory potential of Vaisvanara Churna in experimental animals. Materials and methodsIn-vitro anti-inflammatory activity of aqueous extract of Vaisvanara Churna (100–500 μg/ml) was evaluated by using membrane stabilization methods. Anti arthritic activity was evaluated by using 0.1 ml of Complete Freund's Adjuvant (CFA) injected into sub plantar surface of left hind paw of each wistar rat on day 1 followed by treatment with Vaisvanara Churna at various dose levels (450, 900, and 1800 mg/kg b.w) and standard drug Prednisolone (5 mg/kg) for 21 days. The following parameters namely change in the body weight of animals, paw volume, ankle joint thickness were measured at 0, 3, 8, 17 & 21 day intervals and radiographic changes were assessed. In addition to this, response to painful stimuli by application of forced pressure was measured by using Pressure Application Measurement (PAM) method. ResultsIn-vitro anti-inflammatory activity Vaisvanara Churna exhibited dose dependent membrane stabilizing activity. Treatment with Vaisvanara Churna showed significant (p < 0.05) inhibition of paw edema, reduction in ankle joint thickness and increase in the body weight of wistar albino rats was observed. There is a significant increase (p < 0.001) in the latency of limb withdrawal response, reduction in the organ indices (spleen and thymus) were noted. ConclusionThis study demonstrates that Vaisvanara Churna possesses in vitro anti inflammatory and anti-arthritic potential and supports its folklore use in the treatment of arthritis.

Phytochemical screening, antioxidant and anti-edematous activities of aqueous extract of Sarcocephalus latilolius (sm.) Bruce ripe fruits in rat

Background: The vegetative system of Sarcocephalus latifolius represents a natural source of active substances, as the species is used in traditional african medicine to treat several diseases involving inflammation and oxidation. Objective: The aim of the study is to determine the phytochemical composition and evaluate the antioxidant and anti-inflammatory properties of the aqueous extract of Sarcocephalus latifolius ripe fruits in rats. Material and method: DPPH radical scavenging and iron reduction were used to assess antioxidant activity in vitro. Rat paw edema induced by carrageenan, dextran and formalin was used to assess acute and subacute anti-inflammatory activity in vivo. Results: Extract at 10 mg/mL yielded 92.95±11.44 mg EAG/g total polyphenols, 0.082±0.005 mg ERu/g total flavonoids and 0.14 ± 0.003 mg EAT/g condensed tannins. Aqueous extract of Sarcocephalus latifolius ripe fruits showed DPPH radical inhibition with an IC50 greater than 25 μg/mL. DPPH inhibition by gallic acid was 92.91% at 25 μg/mL. IC50 of ascorbic acid and aqueous extract of Sarcocephalus latifolius on Fe3+reducing antioxidant power (FRAP) were 18.9 μg/mL and 111.6 μg/mL, respectively. For carrageenan, the aqueous extract of Sarcocephalus latifolius ripe fruits showed a maximal anti-inflammatory effect at five hours, with inhibitions (p&lt;0.05) of 48.49% at the dose of 200 mg/kg and 56.16% at 300 mg/kg. For dextran, the inhibitions (p&lt;0.01) observed at the thirtieth minute were 34.55% at the dose of 200 mg/kg and 44.44% at 300 mg/kg. For formalin, significant inhibitions (p&lt;0.05) on the first day were 29.19% at 200 mg/kg and 30.60% at 300 mg/kg.

Unlocking the in vitro and in vivo antioxidant and anti-inflammatory activities of polysaccharide fractions from Lepidium sativum seed-coat mucilage

Inflammation coupled with oxidative stress contribute to the pathogenicity of various clinical disorders. Oxidative stress arises from an imbalance between production of reactive oxygen species (ROS) and antioxidant defense system, leading to cellular damages. The study investigated the antioxidant and anti-inflammatory effects of polysaccharides isolated from Lepidium sativum seed-coat mucilage. The water-soluble polysaccharides were extracted from mucilage and fractionated using gel permeation chromatography. The radical scavenging potential of various fractions was determined using DPPH, H2O2, and lipid peroxidation assays. The most effective EC50 was recorded for F53 (57.41 ± 1.34 μg/mL), followed by F20 (69.19 ± 0.61 μg/mL) and F52 (75.06 ± 0.45 μg/mL). In vitro anti-inflammatory effect was determined through human membrane stabilization assay while the in vivo effect was evaluated using a carrageenan-induced paw edema in mouse model where F53 demonstrated significant (P = 0.05) anti-inflammatory potential (92.60 % compared to diclofenac sodium 91.46 %). GC-MS analysis revealed the presence of galacturonic acid and glucuronic acid as main acidic monosaccharides along with varying quantities of rhamnose, arabinose, and maltose as prominent neutral monosaccharides. The study concludes that cress seed mucilage contains potent antioxidant and anti-inflammatory polysaccharides. Further studies on the mode of action of these polysaccharides could provide deeper insights into their potential use as antioxidant and anti-inflammatory agents.

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.

Effects of resveratrol on rheumatic symptoms and hepatic metabolism of arthritic rats.

Resveratrol has been studied as a potential agent for treating rheumatic conditions; however, this compound suppresses glucose synthesis and glycogen catabolism when infused in perfused livers of both arthritic and healthy rats. This study investigated the effects of oral administration of resveratrol on inflammation and liver metabolism in rats with arthritis induced by Freund's adjuvant, which serves as rheumatoid arthritis model. Holtzman rats, both healthy and exhibiting arthritic symptoms, were orally treated with resveratrol atdoses varying from 25 to 500 mg/kg for a 5-day period preceding arthritis induction, followed by an additional 20-day period thereafter. Paw edema, arthritic score and hepatic myeloperoxidase activity were assessed to evaluate inflammation. Glycogen catabolism and gluconeogenesis from lactate were respectively evaluated in perfused livers from fed and fasted rats. Resveratrol decreased the liver myeloperoxidase activity at doses above 100 mg/kg, and decreased the paw edema and delayed the arthritic score at doses above 250 mg/kg. The hepatic gluconeogenesis was decreased in arthritic rats and resveratrol did not improve it. However, resveratrol did not negatively modify the gluconeogenesis inlivers of healthy and arthritic rats. Glycogen catabolism was in part and slightly modified by resveratrol in the liver of arthritic and healthy rats. It is improbable that resveratrol negatively affects the liver metabolism, especially considering that gluconeogenesis is highly fragile to changes in cellular architecture. The findings suggest that resveratrol could serve as alternative for treating rheumatoid arthritis. Nevertheless, prudence is advised regarding its transient effects on liver metabolism.

Bioactivity Profiling and Phytochemical Analysis of Carissa carandas Extracts: Antioxidant, Anti-Inflammatory, and Anti-Urinary Tract Infection Properties.

Carissa carandas L. (Apocynaceae) is widely distributed in tropical and subtropical regions of Asia including Pakistan, India, Afghanistan, and Sri Lanka. C. carandas is considered as an integral component of traditional medicinal systems to combat several health ailments. The present study aimed to assess this plant's phytochemical contents and biological potential by performing sequential extraction, adopting a bioassay-guided approach. C. carandas powder was extracted with n-hexane to remove fatty substances and then residues were sequentially extracted with dichloromethane, methanol, and 50% methanol. All the sequential crude extracts were evaluated for phytochemical contents (total phenolics, flavonoids, and anthocyanins), in vitro antioxidant activity (FRAP, DPPH), in vitro anti-inflammatory activity (serum and egg albumin denaturation), in vivo anti-inflammatory activity (carrageenan- and formaldehyde-induced paw edema), and in vitro antimicrobial activity. Active crude extract was then partitioned using the liquid-liquid separation method followed by further separation of the active fraction by RP-HPLC. The active fraction was then subjected to LC-ESI-MS/MS analysis for tentative identification of bioactive metabolites responsible for its bioactive properties, followed by HPLC quantification. The analysis revealed methanol extract to have more phytochemical contents, radical scavenging properties, reduced inflammation in both models (in vitro and in vivo), and antimicrobial properties against urinary tract infection-causing agents as compared to dichloromethane and 50% methanol extracts. The ethyl acetate fraction obtained after liquid-liquid partitioning (LLP) of the active methanol extract exhibited more activity as compared to C. carandas methanol extract. RP-HPLC sub-fractionation yielded seven sub-fractions, but a slight decrease in biological potential was recorded. Therefore, LLP fraction B was subjected to further analysis. LC-ESI-MS/MS analysis led to the tentative identification of phenolic acids (chlorogenic acid, quinic acid), flavonoids (quercetin), and anthocyanins (peonidin-3-arabinoside, delphinidin-3-galactoside, delphinidin-3-rutinoside) in the active LLP ethyl acetate fraction. Chlorogenic acid, ellagic acid, and quinic acid were quantified as 17.6 µg/mg, 5.90 µg/mg, and 3.30 µg/mg, respectively, on a dry weight basis by HPLC. C. carandas may be considered a promising therapeutic plant, and the results of the current study provide more evidence to support the assertions made in ancient medical traditions. These findings highlight its promising applications in health, medicine, cosmetics, preservatives, and as a natural coloring agent.

Uncovering the mechanisms of Zhubi decoction against rheumatoid arthritis through an integrated study of network pharmacology, metabolomics, and intestinal flora

Ethnopharmacological relevanceZhubi Decoction (ZBD) is a modified formulation derived from the classic traditional Chinese medicine prescription “Er-Xian Decoction” documented in the esteemed “Clinical Manual of Chinese Medical Prescription”. While the utilization of ZBD has exhibited promising clinical outcomes in treating rheumatoid arthritis (RA), the precise bioactive chemical constituents and the underlying mechanisms involved in its therapeutic efficacy remain to be comprehensively determined. Aim of the studyThis study aims to systematically examine ZBD's pharmacological effects and molecular mechanisms for RA alleviation. Materials and methodsUtilizing the collagen-induced arthritis (CIA) rat model, we comprehensively evaluated the anti-rheumatoid arthritis effects of ZBD in vivo through various indices, such as paw edema, arthritis index, ankle diameter, inflammatory cytokine levels, pathological conditions, and micro-CT analysis. The UPLC-MS/MS technique was utilized to analyze the compounds of ZBD. The potential therapeutic targets and signaling pathways of ZBD in the management of RA were predicted using network pharmacology. To analyze comprehensive metabolic profiles and identify underlying metabolic pathways, we conducted a serum-based widely targeted metabolomics analysis utilizing LC-MS technology. Key targets and predicted pathways were further validated using immunofluorescent staining, which integrated findings from serum metabolomics and network pharmacology analysis. Additionally, we analyzed the gut microbiota composition in rats employing 16 S rDNA sequencing and investigated the effects of ZBD on the microbiota of CIA rats through bioinformatics and statistical methods. ResultsZBD exhibited remarkable efficacy in alleviating RA symptoms in CIA rats without notable side effects. This included reduced paw redness and swelling, minimized joint damage, improved the histopathology of cartilage and synovium, mitigated the inflammatory state, and lowered serum concentrations of cytokines TNF-α, IL-1β and IL-6. Notably, the effectiveness of ZBD was comparable to MTX. Network pharmacology analysis revealed inflammation and immunity-related signaling pathways, such as PI3K/AKT, MAPK, IL-17, and TNF signaling pathways, as vital mediators in the effectual mechanisms of ZBD. Immunofluorescence analysis validated ZBD's ability to inhibit PI3K/AKT pathway proteins. Serum metabolomics studies revealed that ZBD modulates 170 differential metabolites, partially restored disrupted metabolic profiles in CIA rats. With a notable impact on amino acids and their metabolites, and lipids and lipid-like molecules. Integrated analysis of metabolomics and network pharmacology identified 6 pivotal metabolite pathways and 3 crucial targets: PTGS2, GSTP1, and ALDH2. Additionally, 16 S rDNA sequencing illuminated that ZBD mitigated gut microbiota dysbiosis in the CIA group, highlighting key genera such as Ligilactobacillus, Prevotella_9, unclassified_Bacilli, and unclassified_rumen_bacterium_JW32. Correlation analysis disclosed a significant link between 47 distinct metabolites and specific bacterial species. ConclusionZBD is a safe and efficacious TCM formulation, demonstrates efficacy in treating RA through its multi-component, multi-target, and multi-pathway mechanisms. The regulation of inflammation and immunity-related signaling pathways constitutes a crucial mechanism of ZBD's efficacy. Furthermore, ZBD modulates host metabolism and intestinal flora. The integrated analysis presents experimental evidence of ZBD for the management of RA.

Fabrication of lornoxicam loaded into curcumin reinforced nanoemulgel: In-vitro characterization and in-vivo anti-inflammatory potential

Current research aimed to fabricate and characterize lornoxicam-curcumin (LRX-CUR) co-loaded nanoemulgel (NEG) for transdermal delivery. Nanoemulgel was prepared by emulsification method using high sheared homogenization. The prepared NEG was subjected to physicochemical characterizations including thermodynamic analysis, FTIR, pH, drug content, zeta analysis (size distribution, PDI, zeta potential), rheological behavior, spreadability, in vitro drug release, and ex vivo permeation analysis. In vivo anti-inflammatory effects were assessed in experimental animals (in albino rats) using carrageenan for inducing paw edema. The NEG showed optimum and acceptable thermodynamic stability. No phase separation was observed. The pH was acceptable for use on human skin as its range was 5.5–6.5. In drug content analysis, 95.52 ± 5.63 % of LRX and 93.47 ± 8.53 % of CUR were obtained which were in official limit of USP i.e. 100 ± 10 %. No interactions and incompatibility were found between the drugs and NEG components after FTIR analysis. The viscosity and spreadability were optimum for topical application. The LRX-CUR nanoemulsion exhibited droplet size of 215.6 ± 7.89, PDI 0.219 ± 0.03 and zeta potential −12.0 ± 6.41. The LRX-CUR NEG released 85.69 ± 3.54 % of LRX and 86.89 ± 3.34 % of CUR. The permeation of LRX and CUR was 79.43 ± 5.54 % and 83.96 ± 6.21 respectively after 12 h. The optimized LRX-CUR NEG formulation significantly (p < 0.05; ANOVA) inhibited the paw edema in experimental animals as compared to the control and standard groups. Thus, LRX-CUR nanoemulgel formulation can serve as an effective substitute to the oral administration.

Synthesis, characterization, anti-inflammatory activity and molecular docking studies of aromatic aldehydes substituted oxazine derivatives derived from 3-methoxy chalcone

In this study, a novel synthesis series (R4, D1-D10) of 4-[2-Amino-4-(3‑methoxy-phenyl)-6H-[1,3]oxazin-6-yl]-phenol derivatives was synthesised by the condensation of substituted aromatic aldehydes. Structures of the synthesised compounds were characterised using 1H and 13C nuclear magnetic resonance (NMR), fourier transform infrared spectroscopy (FT-IR), and mass spectrometry (MS) spectroscopic data. Further, the compounds were screened for in vivo anti-inflammatory activity by the carrageenan-induced paw edema method. Tested compounds have shown mild-to-moderate anti-inflammatory activity. The COX-2 selective compounds anti-inflammatory of five-oxazine derivatives (D7, D9, D5, D10, and D2) was modest. In comparison to the reference drug parecoxib (% edema inhibition = 29.2, 1 h; 23.30, 3 h; 21, 6 h), the most active compounds demonstrated exceptional In vivo anti-inflammatory action (% edema inhibition = 40–52, 1 h; 40.70–60.40, 3 h; 30–47.80, 6 h). Also, compounds 4-{6-(3-Methoxy-phenyl)-2-[(4-nitro-benzylidene)-amino]-6H-[1,3]oxazin-4-yl}-phenol (D7) and 4-[2-[(3-Fluoro-benzylidene)-amino]-6-(3-methoxy-phenyl)-6H-[1,3]oxazin-4-yl]-phenol (D9) have shown excellent anti-inflammatory action (% edema inhibition = 52–59.3 & 46.7–60.40). The molecular docking studies were also carried out at the active sites of COX-1 and COX-2 enzymes (PDB ID: 4O1Z, 4M11) using the docking algorithm offered by AutoDock Vina. The compounds D7, D9, and D5 exhibited good docking scores of −10.30, −10.20, and −10.10 onto the active site of COX-2 and least dock scores of −10.10, −9.80, and −10.00 on COX-1 enzymes and were comparable with standard COX-2 inhibitor parecoxib. A significant correlation was observed between the in silico and the in vivo studies. The anti-inflammatory and docking results highlight the fact that the synthesised compounds D7, D9, and D5 could be considered as possible hits as therapeutic agents.

Molybdenum Disulfide Nanosheet-Based Nanocomposite for the Topical Delivery of Umbelliferone: Evaluation of Anti-inflammatory and Analgesic Potentials.

This study aimed to develop a nanocomposite formulation comprising umbelliferone (UMB) and molybdenum disulfide (MoS2) nanosheets as a carrier, termed as the UMB-MoS2 nanocomposite in gel for topical delivery. MoS2 nanosheets were successfully synthesized via a green-hydrothermal reaction of 10 mg of ammonium molybdate and 10 mg of thiourea in 80 mL of deionized water under predetermined conditions. The UMB-MoS2 nanocomposite was prepared by sonicating UMB and MoS2 nanosheets (each of 1 mg/mL) in dimethylformamide. Scanning electron microscopy revealed crumpled nanosheets with an open-ended structure and a nanocomposite as a layered structure. The X-ray diffraction pattern revealed the amorphous nature of UMB in the UMB-MoS2 nanocomposite. Fourier-transform infrared spectra of the UMB-MoS2 nanocomposite had modified bands of the functional group, which confirmed the formation of the nanocomposite. The size and polydispersity-index (435 nm and 0.415, respectively) of the nanocomposite were within the limit for an efficient topical application. Carbopol 934 (2%) was used to prepare the UMB-MoS2 nanocomposite gel (F1) and UMB-Carbopol gel (F2, for comparative evaluation). The pH, spreadability, and viscosity of F1 were found to be 5.56, 5.89 g·cm/s, and 32.5 Pa-sec, respectively, which were optimal for the topical application of gel-based formulations. In vitro release characteristics of both formulations were deemed to be suitable for topical application, where F1 exhibited a biphasic drug release profile and a superior release rate of 94.8% compared to 43.5% for F2 at 24 h. In the carrageenan-induced rat paw edema model, the animal group treated with F1 demonstrated the lowest increase in paw thickness of 26.6%, which was significantly lower as compared to the F2-treated group (52.9%) and the diclofenac sodium-treated group (32.2%). Similarly, in the tail immersion method, F1 exhibited the highest peak tail withdrawal latency of 10.9 s, significantly greater than F2 (8.9 s) and standard treatment (10 s), indicating the superior analgesic activity of F1. This pioneering work introduces a novel UMB-MoS2 nanocomposite with promising anti-inflammatory and analgesic potentials, paving the way for further research into the biomedical applications of MoS2-based nanocarriers.

In-silico based Designing of benzo[d]thiazol-2-amine Derivatives as Anal-gesic and Anti-inflammatory Agents.

Benzo[d]thiazoles represent a significant class of heterocyclic com-pounds renowned for their diverse pharmacological activities, including analgesic and anti-inflammatory properties. This molecular scaffold holds substantial interest among medicinal chemists owing to its structural versatility and therapeutic potential. Incorporating the benzo[d]thiazole moiety into drug molecules has been extensively investigated as a strategy to craft novel therapeutics with heightened efficacy and minimized adverse effects. The aim of the present research work was to design, synthesize and characterize the new benzo[d]thiazol-2-amine derivatives as potent analgesic and anti-inflammatory agents. The synthesis of the presented benzo[d]thiazol-2-amine derivatives was performed by condensing-(4-chlorobenzylidene) benzo[d]thiazol-2-amine with a number of substituted phenols in the presence of potassium iodide and anhydrous potassium carbonate in dry acetone. IR spectroscopy, 1HNMR spectroscopy, 13CNMR spectroscopy and Mass spectroscopy methods were used to characterize the structural properties of all 13 newly syn-thesized derivatives. The molecular properties of these newly synthesized derivatives were estimated to study the attributes of drug-like candidates. Benzo[d]thiazol-2-amine derivatives were molecularly docked with selective enzymes COX-1 and COX-2. Analgesic and anti-inflammatory activities of synthesized compounds were evaluated by us-ing albino rats. Findings of the research suggested that compounds G3, G4, G6, G8 and G11 possess higher binding affinity than diclofenac sodium, when docking was performed with enzyme COX-1. Compounds G1, G3, G6, G8andG10 showed lower binding affinity than Indometha-cin when docking was performed with enzyme COX-2.In vitro evaluation of the COX-1 and COX-2 enzyme inhibitory activities was performed for synthesized compounds. Compounds G10 and G11 exhibited significant COX-1 and COX-2 enzyme in-hibitory action with an IC50 value of 5.0 and 10 μM, respectively. Using the hot plate method and the carrageenan-induced rat paw edema model, the synthesized compounds were screened for their biological activities, including analgesic and anti-inflammatory activities. Highest analgesic action was exhibited by derivative G11 and the compound G10 showed the highest anti-inflammatory response. Inhibition of COX may be considered as a mechanism of action of these compounds. It was concluded that synthesized derivatives G10 and G11 exhibited significant analgesic and anti-inflammatory effect; therefore, the said compounds may be subjected to further clinical investigation for establishing these as future compounds for the treatment of pain and inflammation.

Novel analgesic peptide derived from Cinobufacini injection suppressing inflammation and pain via ERK1/2/COX-2 pathway

Inflammatory pain is a chronic pain caused by peripheral tissue inflammation, seriously impacting the patient’s life quality. Cinobufacini injection, as a traditional Chinese medicine injection preparation, shows excellent efficacy in anti-inflammatory and analgesic treatment in patients with advanced tumors. In this study, a novel analgesic peptide CI5 with anti-inflammatory and analgesic bio-functions that naturally presents in Cinobufacini injection and its regulatory mechanism are reported. Our results showed that the administration of CI5 significantly relieved the pain of mice in the acetic acid twisting analgesic model and formalin inflammatory pain model. Furthermore, CI5 effectively reduced the inflammatory cytokines (IL-6, TNF-α and IL-1β) and inflammatory mediator (PGE2) expressions, and prevented the carrageenan-induced paw edema in mice. Further LC-MS/MS results showed the anti-inflammatory and analgesic bio-functions of CI5 depended on its interaction with the Rac-2 protein upstream of ERK1/2 and the inflammatory signaling pathway (ERK1/2/COX-2 axis). In summary, CI5, as a novel natural candidate identified from Cinobufacini injection, showed substantial clinical promise for inflammatory pain treatments.

Chemical characterization of the essential oil from the leaves of Eugenia flavescens DC. (Myrtaceae) and its potential in the treatment of pain, inflammation, and ethanol- and ethanol/HCL-induced gastric ulcers in mice.

Eugenia flavescens is a species cultivated in Brazil for food purposes. Given the potential application of essential oils from plants of the genus Eugenia, this study was carried out to investigate the chemical composition, acute toxicity, antioxidant, antinociceptive, gastroprotective activities, and possible mechanisms of action of the essential oil from the leaves of E. flavescens (EOEf). The EOEf was extracted by hydrodistillation, and the chemical composition was obtained using gas chromatography-mass spectrometry. The antioxidant activity was evaluated, as well as the acute toxicity and the antinociceptive and anti-inflammatory effects in mice. In addition, the gastroprotective effect was investigated using an acute gastric lesion model, considering possible mechanisms of action. The major components found in the EOEf were guaiol (19.97%), germacrene B (12.53%), bicyclogermacrene (11.11%), and E-caryophyllene (7.53%). The EOEf did not cause signs of toxicity in the acute oral toxicity test and showed in vitro antioxidant activity with IC50 ranging from 247.29 to 472.39µg/mL in the tests ABTS and DPPH. In the nociceptive test, EOEf showed a 72.05% reduction in nociception at a dose of 100mg/kg. In evaluating the anti-inflammatory effect, the essential oil inhibited paw edema by 95.50% and 97.69% at doses of 50 and 100mg/kg. The results showed that EOEf has a gastroprotective effect, acting through the sulfhydryl compounds (-SH), nitric oxide (NO), and synthesis PGE2 pathways. The results suggested that EOEf is a promising source of constituents with antioxidant, antinociceptive, anti-inflammatory, and gastroprotective properties with application in the food and pharmaceutical industries.

Preclinical Evaluation of Soluble Epoxide Hydrolase Inhibitor AMHDU against Neuropathic Pain.

Inhibition of soluble epoxide hydrolase (sEH) is a promising therapeutic strategy for treating neuropathic pain. These inhibitors effectively reduce diabetic neuropathic pain and inflammation induced by Freund's adjuvant which makes them a suitable alternative to traditional opioids. This study showcased the notable analgesic effects of compound AMHDU (1,1'-(hexane-1,6-diyl)bis(3-((adamantan-1-yl)methyl)urea)) in both inflammatory and diabetic neuropathy models. While lacking anti-inflammatory properties in a paw edema model, AMHDU is comparable to celecoxib as an analgesic in 30 mg/kg dose administrated by intraperitoneal injection. In a diabetic tactile allodynia model, AMHDU showed a prominent analgesic activity in 10 mg/kg intraperitoneal dose (p < 0.05). The effect is comparable to that of gabapentin, but without the risk of dependence due to a different mechanism of action. Low acute oral toxicity (>2000 mg/kg) and a high therapeutic index makes AMHDU a promising candidate for further structure optimization and preclinical evaluation.

Chemical Composition Analysis and Assessment of Antioxidant and Anti-Inflammatory Activities of Crude Extract of Flueggea leucopyrus on Carrageenan-Induced Paw Edema in Wistar Albino Rats.

A member of the Phyllanthaceae family, Flueggea leucopyrus is a well-known plant in the tribal areas of Sri Lanka, India's Shaurastra region, Australia, and Malaysia. This study provides information about Flueggea leucopyrus, a plant with a wide range of therapeutic uses in India. Different extracts from the leaves and roots of Flueggea leucopyrus were evaluated for their physical and chemical properties, preliminary phytochemical parameters, and pharmacological activities in the current study, followed by their fourier transform infrared spectroscopy (FTIR), gas chromatography-mass spectrometry (GC-MS), antioxidant, and anti-inflammatory properties. The aqueous extract of Flueggea leucopyrus leaves and roots have more different phytochemical elements than other solvent extracts, according to physico-chemical tests and phytochemical screening. As a result, the FT-IR, GC-MS, antioxidant, and anti-inflammatory activities of an aqueous extract were tested. Studies on hind paw edemas caused by carrageenan in albino rats examined the mean increase in paw volume and the percentage inhibition in paw volume at various time points following the injection of carrageenan (1% w/v). In comparison to the norm, these inhibitions were statistically significant (p < 0.001). The aqueous extract of Flueggea leucopyrus leaves and roots have both antioxidative and anti-inflammatory activities, indicating that it has the potential to be used in the formulation of antioxidant and anti-inflammatory medications in the future.

Therapeutic potential of sulfated glycosaminoglycan from seafood Asian green mussel (Perna viridis): Insights from an in vivo study

The Asian green mussel, Perna viridis, is widely consumed as seafood throughout the coastal regions of the Indo-Pacific area owing to its significant pharmaceutical and biomedical benefits. A pharmacologically active (1 → 3)/(1 → 4) linked sulfated glycosaminoglycan (PVP-2) with β-(1 → 3)-GlcNSp, and α-(1 → 4)-GlcAp units was isolated from P. viridis. PVP-2 (at 1–10 μg/mL) demonstrated a suppression of nitric oxide (NO) secretion in lipopolysaccharide-induced RAW 264.7 cells. Notably, PVP-2 at 5 μg/mL effectively restored NO levels (0.32 μg/mL) to homeostasis by downregulating excessive production (1.22 μg/mL). Furthermore, PVP-2 (at 22 mg/kg body weight) showed effective reduction of carrageenan-induced paw edema (82% inhibition at 5 h) in time dependent manner. This reduction was found to be comparable with standard treatment (87% inhibition of paw edema at 5 h). Treatment with PVP-2 (at 110 mg/kg body weight) resulted substantial inhibition of formalin-induced paw edema up to 10 days. At the end of the 10th day, the reduction in paw thickness was significantly greater (a four-fold increase) in the PVP-2 treated group compared to the formalin-induced group. Furthermore, PVP-2 displayed potent anti-inflammatory effect by attenuating cyclooxygenases (COX-1, 2) and 5-lipoxygenase (5-LOX) (IC50 < 2 mg/mL) enzymes with a higher selectivity index (IC50 COX-1/IC50 COX-2 ∼ 1.7) towards inducible pro-inflammatory COX-2. Therefore, inhibition of the NO production along with the reduction of paw edema, highlights the therapeutic potential of sulfated glycosaminoglycan from seafood Asian green mussel, as a naturally derived functional food to mitigate inflammation related disorders.

Trolox, Ferulic, Sinapic, and Cinnamic Acid Derivatives of Proline and GABA with Antioxidant and/or Anti-Inflammatory Properties.

Degenerative conditions, such as neurodegenerative disorders (Alzheimer's disease (AD), Parkinson's disease (PD)) and cardiovascular diseases, are complex, multifactorial disorders whose pathophysiology has not been fully elucidated yet. As a result, the available treatment options cannot eliminate these diseases radically, but only alleviate the symptoms. Both inflammatory processes and oxidation are key factors in the development and evolution of neurodegeneration, while acetylcholinesterase inhibitors are the most used therapeutic options against AD. In this work, following the multi-targeting compound approach, we designed and synthesized a series of proline and gamma-aminobutyric acid (GABA) amides with various acidic moieties that possess an antioxidant and/or anti-inflammatory potency. Proline is the pharmacophore of nootropic drugs (e.g., piracetam) used for memory improvement, while GABA is the main inhibitory neurotransmitter in the central nervous system. The designed molecules were subjected to a preliminary screening of their bioactivity in antioxidant and anti-inflammatory assays, as well as against acetylcholinesterase. Most of the synthesized compounds could inhibit lipid peroxidation (IC50 as low as 8 μΜ) and oxidative protein glycation (inhibition of up to 48%) and reduce the 2,2-diphenyl-1-picrylhydrazyl free radical (DPPH). In addition, all of the compounds were moderate inhibitors of lipoxygenase (LOX) (up to 46% at 100 μΜ) and could decrease carrageenan-induced paw edema in rats by up to 55%. Finally, some of the compounds were moderate acetylcholinesterase inhibitors (IC50 as low as 219 μΜ). The results confirmed the design rationale, indicating that the compounds could be further optimized as multi-targeting molecules directed against degenerative conditions.

Thermoresponsive lipids engineered magnetic nanoparticles for spatiotemporal delivery of hesperidin to inflammatory sites in animal model

Thermoresponsive nanoparticles are exploited as drug-delivery vehicles that release their payload upon increment in temperature. We prepared and characterized thermoresponsive lipid-anchored folic acid engineered magnetic nanoparticles (LP-HP-FANPs) that combine receptor-based targeting and thermoresponsive sustained release of hesperidin (HP) in response to endogenous inflammation site temperature. The progressive surface engineering of NPs was validated by FTIR analysis. Our LP-HP-FANPs had a particle size of 100.5 ± 1.76 nm and a zeta potential of 14.6 ± 2.65 mV. The HP encapsulation effectiveness of LP-HP-FANPs is around 91 ± 0.78%. AFM scans indicated that our modified nanoparticles were spherical. LP-HP-FANPs exhibit increased drug release (85.8% at pH 4.0, 50.9% at pH 7.0) at 40 °C. Animal studies showed no toxicity from nanoparticles. Compared to conventional drugs and HP, LP-HP-FANPs effectively decreased paw edema, cytokine levels, and total cell recruitment in thioglycollate-induced peritonitis (p < 0.05). LP-HP-FANPs substantially decreased cytokines compared to HP, HP-FA-NPs, and the standard medication (p < 0.05, p < 0.01, and p < 0.001). These findings imply that the synthesized HP-loaded formulation (LP-HP-FANPs) may be a potential anti-inflammatory formulation for clinical development.

Antinociceptive and Anti-Inflammatory Activities of Acetonic Extract from Bougainvillea x buttiana (var. Rose).

Background:Bougainvillea x buttiana is an ornamental plant with antioxidant, anti-inflammatory, and cytotoxic activities, which has been traditionally used to treat respiratory diseases. This study aimed to investigate whether the acetonic extract of Bougainvillea x buttiana var. Rose (BxbRAE-100%) has analgesic and anti-inflammatory properties and its potential action mechanisms. Methods: Analgesic and anti-inflammatory activities were evaluated using three murine pain models and two acute inflammation models. In vitro, the ability of the extract to inhibit proteolytic activity and the activities of the enzymes phospholipase A2 (PLA2) and cyclooxygenase (COX) were evaluated. In silico analysis was performed to predict the physicochemical and Absorption, distribution, metabolism, and excretion (ADME) profiles of the compounds previously identified in BxbRAE-100%. Results: In vivo BxbRAE-100% decreased the nociceptive behaviors in the writhing model, the tail immersion, and the formalin test, suggesting that the extract has the potential to relieve pain at peripheral and central levels. Additionally, topical or oral BxbRAE-100% treatment reduced dose-dependent 12-O-Tetradecanoylphorbol-13-acetate (TPA)-induced ear inflammation and carrageenan-induced paw edema, respectively. In vitro, BxbRAE-100% significantly inhibited proteolytic activity and PLA2, COX-1 and COX-2 activities. In silico, the compounds previously identified in BxbRAE-100% met Lipinski's rule of five and showed adequate ADME properties. Conclusions: These results support the use of B. x buttiana in Traditional Mexican Medicine and highlight its potential for the development of new treatments for pain and inflammation.