Reduced Paw Edema Research Articles

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.

Evaluating the Efficacy of a Polyherbal Formulation in Ameliorating Arthritis Induced by Complete Freund’s Adjuvant

Background: This study investigates the antiarthritic potential of a polyherbal formulation (PHF) comprising extracts from Tinospora cordifolia, Rosa damescena, and Acacia leucoploea in a rat model of rheumatoid arthritis (RA). RA is a chronic autoimmune disorder with debilitating consequences. PHF's impact on joint inflammation, bone degradation, and cartilage preservation were evaluated. Methods: Arthritis was induced using complete Freund’s adjuvant (CFA), and animals were treated with PHF (200 and 400 mg/kg), prednisolone, or control treatments for 28 days. Parameters including body weight, paw volume, arthritis severity score, hematological parameters, serum markers (creatinine, ALP, total proteins), cytokine levels (IL-1β, IL-6, TNF-α, IL-10), and radiographic changes were assessed. Results: CFA-treated rats exhibited significant body weight loss, paw edema, increased arthritis severity scores, altered hematological parameters, and elevated serum markers compared to normal controls. PHF treatment at both doses mitigated body weight loss, reduced paw edema, and improved arthritis severity scores. Hematological changes induced by CFA were also attenuated by PHF treatment. Serum creatinine, ALP, and total protein levels, elevated in CFA-treated rats, were significantly improved by PHF. Furthermore, PHF modulated cytokine levels, decreasing IL-6, IL-1β, and TNF-α while increasing IL-10. Radiographic analysis displayed reduced joint damage in PHF-treated rats compared to CFA controls. Conclusion: This comprehensive investigation highlights PHF's potential to mitigate the inflammatory processes associated with RA, as evidenced by improved clinical, hematological, and biochemical parameters. The study underscores the promise of traditional botanical compounds in managing RA and suggests PHFs as novel therapeutic options. Further mechanistic studies are warranted to elucidate the exact pathways involved.

Molecular insights of Eucalyptol (1,8-Cineole) as an anti-arthritic agent: in vivo and in silico analysis of IL-17, IL-10, NF-κB, 5-LOX and COX-2.

The monoterpene oxide, Eucalyptol (1,8-Cineole), a primary component of eucalyptus oil, has been evaluated pharmacologically for anti-inflammatory and analgesic activity. Current research aimed to evaluate Eucalyptol's anti-arthritic potential in a Complete Freund's adjuvant induced arthritis that resembles human rheumatoid arthritis. Polyarthritis developed after 0.1mL CFA injection into the left hind footpad in rats. Oral administration of Eucalyptol at various doses (100, 200 and 400mg/kg) significantly reduced paw edema, body weight loss, 5-LOX, PGE2 and Anti-CCP levels. Real-time PCR investigation showed significant downregulation of COX-2, TNF-α, NF-κB, IL-17, IL-6, IL-1β and upregulation of IL-4 and IL-10 in Eucalyptol treated groups. Hemoglobin and RBCs counts significantly increased post-treatment with Eucalyptol while ESR, CRP, WBCs and platelets count significantly decreased. Eucalyptol significantly increased Superoxide Dismutase, Catalase and Glutathione levels compared to CFA-induced arthritic control however, MDA significantly decreased post-treatment. Further, radiographic and histopathological examination of the ankle joints of rodents administered Eucalyptol revealed an improvement in the structure of the joints. Piroxicam was taken as standard. Furthermore, molecular docking findings supported the anti-arthritic efficacy of Eucalyptol exhibited high binding interaction against IL-17, TNF-α, IL-4, IL-10, iNOS NF-κB, 5-LOX, and COX-2. Eucalyptol has reduced the severity of CFA induced arthritis by promoting anti-inflammatory cytokines for example IL-4, IL-10 and by inhibiting pro-inflammatory cytokines such as 5-LOX, COX-2, IL-17, NF-κB, TNF-α, IL-6 and IL-1β. Therefore, Eucalyptol might be as a potential therapeutic agent because of its pronounced anti-oxidant and anti-arthritic activity.

Sodium Cromolyn Modulates Carrageenan-Induced Acute Inflammation Through the Interleukin-6 Levels

Background: Previous studies have indicated that sodium cromolyn does not negatively affect steroidal and nonsteroidal anti-inflammatory drugs (NSAIDs). Objective: This study aimed to investigate the anti-inflammatory effects of sodium cromolyn on carrageenan-induced paw edema in rats and assess its impact on IL-6, an anti-inflammatory cytokine. Methods: The carrageenan-induced paw edema model is widely used for studying inflammatory mechanisms and evaluating anti-inflammatory drugs. The test groups received intraperitoneal injections of sodium cromolyn at doses of 25, 50, and 100 mg/kg alongside a positive control group (indomethacin at 5 mg/kg) and a negative control group (which received the solvent, saline). Thirty minutes after drug administration, carrageenan (1% w/v) was injected into the right hind paws of the rats. Changes in paw volume were measured using a plethysmometer at 0.5, 1, 2, and 3 hours post-carrageenan injection. Blood and paw tissue samples were collected three hours after carrageenan administration, and IL-6 levels were determined using the standard rat Interleukin-6 ELISA kit. Results: The plasma and tissue IL-6 levels in the group treated with cromolyn (25 mg/kg) were significantly higher than those in the positive control group (indomethacin 5 mg/kg). Sodium cromolyn at a dose of 25 mg/kg had a negligible effect on reducing paw edema and IL-6 levels in serum and paw tissues compared to indomethacin (5 mg/kg). The IL-6 levels in plasma and tissues for the group receiving 50 mg/kg of cromolyn were not significantly different from those in the indomethacin group (5 mg/kg). However, IL-6 levels in the group treated with 100 mg/kg of cromolyn were significantly lower than those in the indomethacin group. Among the groups treated with sodium cromolyn, the highest and lowest IL-6 levels were observed in the groups receiving 25 mg/kg and 100 mg/kg of sodium cromolyn, respectively. The anti-inflammatory effects of sodium cromolyn at doses of 25 mg/kg, 50 mg/kg, and 100 mg/kg were analyzed, revealing that 25 mg/kg of cromolyn sodium was not significantly effective at any time point (P < 0.05). Additionally, no significant differences (P < 0.05) were observed between the 50 mg/kg and 100 mg/kg doses at any study hour. Sodium cromolyn at a 50 mg/kg dose was as effective as indomethacin (5 mg/kg) in significantly reducing paw edema. Conclusions: Sodium cromolyn, at doses of 50 and 100 mg/kg, effectively reduced paw edema and the concentration of serum and paw tissue IL-6 (P < 0.05), demonstrating significant anti-inflammatory activity. Sodium cromolyn at a 50 mg/kg dose is recommended as the anti-inflammatory dose of this drug.

Insight into antioxidant and anti-inflammatory effects of marine bacterial natural exopolysaccharide (EPSSM) using carrageenan-induced paw edema in rats

Inflammation is a part of the body’s intricate biological reaction to noxious stimuli and defensive reactions. So, the aim of this investigation was to study the anti-inflammatory activity of exopolysaccharide (EPSSM) using carrageenan-induced paw edema in rats. A halophilic bacterial strain was isolated from marine sediments in the Red Sea in Egypt. The isolate has been visually and physiologically recognized, as well as by analyzing its 16S rRNA gene, which confirms Kocuria sp. clone Asker4. This particular isolate can be referenced using the accession number OL798051.1. EPSSM was subjected to purification and fractionation by a DEAE-cellulose column. Preliminary chemical analysis of EPSSM indicated that the monosaccharides were fructose, glucuronic acid, and xylose, with 2.0, 0.5, and 1.0, respectively. The antioxidant potential of EPSSM was investigated, and it was discovered that the level of activity increased independently of the concentrations, reaching a maximum threshold of 94.13% at 100 µg/mL of EPSSM for 120 min. Also, EPSSM at 50 mg/kg orally produced a significant anti-inflammatory effect on the carrageenan model at 2, 3, and 4 intervals. The EPSSM intervention resulted in reductions in the levels of catalase and superoxide dismutase enzymes, as well as a decrease in glutathione. Furthermore, the levels of nitric oxide, lipid peroxidation, and reactive oxygen species resulting from carrageenan-induced edema showed a significant reduction subsequent to the administration of EPSSM. Moreover, the findings indicated that the protein expression levels of cyclooxygenase-2 and interleukin-6 were reduced following treatment with EPSSM, resulting in a reduction of paw edema.

Phytochemical analysis and immunomodulatory activities in vitro and in vivo of Aframomum melegueta K Schum seed extracts.

Aframomum melegueta K Schum (A. melegueta), an herbaceous plant renowned for its medicinal seeds, was investigated for its potential immunomodulatory effects in vitro and in vivo using ethanolic and methanolic extracts. The immunomodulatory effect was evaluated by measuring antibody titers using the agglutination technique, while anti-inflammatory activity was assessed in a carrageenan-induced mouse paw edema model. In vitro immunomodulatory activity was measured by lysozyme release from neutrophils. Additionally, white blood cell counts were analyzed post-extracts treatment. The MTT assay was employed to determine cytotoxicity, and the biochemical parameters of liver toxicity were evaluated. Remarkably, both extracts exhibited a dose-dependent reduction in paw edema (p < 0.001), with the most significant reduction observed at 1g/kg (78.13 and 74.27% for ethanolic and methanolic extracts, respectively). Neutrophil degranulation was significantly inhibited in a dose-dependent manner (p < 0.003), reaching maximal inhibition at 100μg/mg (60.78 and 39.7% for ethanolic and methanolic extracts, respectively). In comparison to the control group, both antibody production and white blood cell counts were reduced. Neither of the extracts showcased any cytotoxicity or toxicity. These findings suggest that A. melegueta extracts exhibit immunosuppressive and anti-inflammatory activities due to the presence of various biomolecules.

Design and development of high-dose bioactive oil-loaded transdermal patch with the aid of natural waste as an adsorbent- optimization with SeDeM-SLA tool

PurposeRheumatoid arthritis (RA) is an autoimmune disease that affects joints significantly. Its prevalence varies globally, with more impact on females than males. Presently it is treated using NSAIDs which unfortunately show significant adverse effects on the liver and renal system after long-term use. Conventional topical use of bioactive oils like ginseng oil is one of the best natural options to treat RA, but poor retention time has limited its usefulness. By considering the involvement of ginseng oil in managing RA and the associated limitations, the proposed study investigated the impact of the transdermal patch prepared by ginseng oil loaded-natural biocompatible adsorbent in treating RA. MethodAt early stage of research, the flow property of ginseng oil-loaded adsorbent was optimized by using advanced technology, viz. Brookfield powder flow tester and SeDeM model. In the lateral stage, the transdermal patches of oil-loaded adsorbent were prepared by variable concentrations of HPMC and PEG using the solvent casting method. Prepared patches were evaluated for various parameters. ResultOptimized patch showed average thickness, average weight, folding endurance, tensile strength, and moisture content as 0.38 ± 0.10 mm, 0.215 ± 0.41 gm/ 2 sq. inch, 145 ± 0.20, 3.370 ± 0.16 MPA/mm and 3.770 ± 0.81 %, respectively, along with satisfactory skin adherence property. In vitro diffusion study showed increased ginseng oil release from the prepared patch at a specific interval of up to 10 h, and then release diminished. ConclusionAnti-inflammatory test and measurement of cytokines levels (IL-6 and TNF-α) on male Wistar rats showed a significant reduction in paw edema and notable control on the cytokines level compared to a conventional approach.

Potential Effects of Essential Oil from Plinia cauliflora (Mart.) Kausel on Leishmania: In Vivo, In Vitro, and In Silico Approaches.

In the search for new chemotherapeutic alternatives for cutaneous leishmaniasis (CL), essential oils are promising due to their diverse biological potential. In this study, we aimed to investigate the chemical composition and leishmanicidal and anti-inflammatory potential of the essential oil isolated from the leaves of Plinia cauliflora (PCEO). The chemical composition of PCEO showed β-cis-Caryophyllene (24.4%), epi-γ-Eudesmol (8%), 2-Naphthalenemethanol[decahydro-alpha] (8%), and trans-Calamenene (6.6%) as its major constituents. Our results showed that the PCEO has moderate cytotoxicity (CC50) of 137.4 and 143.7 μg/mL on mice peritoneal exudate cells (mPEC) and Vero cells, respectively. The PCEO was able to significantly decrease mPEC infection by Leishmania amazonensis and Leishmania braziliensis. The value of the inhibitory concentration (IC50) on amastigote forms was about 7.3 µg/mL (L. amazonensis) and 7.2 µg/mL (L. braziliensis). We showed that PCEO induced drastic ultrastructural changes in both species of Leishmania and had a high selectivity index (SI) > 18. The in silico ADMET analysis pointed out that PCEO can be used for the development of oral and/or topical formulation in the treatment of CL. In addition, we also demonstrated the in vivo anti-inflammatory effect, with a 95% reduction in paw edema and a decrease by at least 21.4% in migration immune cells in animals treated with 50 mg/kg of PCEO. Taken together, our results demonstrate that PCEO is a promising topical therapeutic agent against CL.

The annonalide diterpene extracted from Casimirella ampla (Miers) reduces inflammatory and antinociceptive events in general models of inflammation

Ethnopharmacological relevanceThe plants of the genus Casimirella ampla (Miers) (C. ampla) are extensively used in folk medicine. For a long time, rural communities have been using extracts from its roots for food and therapeutic purposes. The extract is rich in diterpenoid annonalide (Annona), which has antiophidic, anti-inflammatory and antinociceptive properties. Inflammation is the body's primary defense mechanism against cell damage and invasion by pathogens, which can trigger acute and chronic inflammatory processes. The first line of treatment for this condition consists of the use of non-steroidal anti-inflammatory drugs, but these have numerous associated collateral damages, based on scientific knowledge about diterpenoids from C. ampla, as well as their already reported antinociceptive and anti-inflammatory properties. Aims of the studyEvaluate the effect of Annona in classic models of inflammation and pain. Materials and methodsAnimals were pretreated with Annona (0.1, 1.0 and 10 mg/kg), or Tween 80 (2%), or indomethacin (Indo) (10 mg/kg) orally in the paw edema tests induced by carrageenan (Cg), serotonin (5-HT), histamine, bradykinin, 48/80 and, prostaglandin E2 (PGE2), evaluating microscopic lesion scores, migration of leukocytes to the peritoneal cavity, concentration of myeloperoxide (MPO), malonyldialdehyde (MDA) and glutathione (GSH), abdominal contortion test by acetic acid and formalin test. ResultsTreatment with Annona compound at a dose of 0.1 mg/kg was more effective in reducing inflammatory, oxidant and nociceptive parameters, as it reduced paw edema induced by carrageenan, through different mediators and migration of inflammatory cells. Furthermore, it worked by reducing the concentration of MPO, MDA, preserving GSH levels and reducing nociception caused by formalin and acetic acid.

Design and synthesis of novel dithiazole carboxylic acid Derivatives: In vivo and in silico investigation of their Anti-Inflammatory and analgesic effects

Inflammation is a complex set of interactions that can occur in tissues as the body's defensive response to infections, trauma, allergens, or toxic compounds. Therefore, in almost all diseases, it can be observed because of primary or secondary reasons.Since it is important to control and even eliminate the symptoms of inflammation in the treatment of many diseases, anti-inflammatory and analgesic drugs are always needed in the clinic. Therefore, the discovery of new anti-inflammatory/analgesic drugs with increased effectiveness and safer side effect profiles is among the popular topics of medicinal chemistry. Therefore, in this study, in order to synthesize and diversify new molecules, we focused on the N,N-dithiazole carboxylic acid core and linked it with the chalcone functional group.The final eleven molecules were analyzed via HRMS, 1H NMR, and 13C NMR. The antinociceptive effects of the test compounds were examined by tail-clip, hot-plate, and formalin methods in mice, while their anti-inflammatory activities were investigated by carrageenan-induced inflammation tests in rats. The motor activities of the experimental animals were evaluated using an activity-meter device. Obtained findings revealed that none of the test compounds (10 mg/kg) were effective in the tail-clip and hot-plate tests. However, compounds 4b, 4c, 4f, 4 h, and 4 k in the serial shortened the paw-licking times of mice in the late phase of the formalin test indicating that these compounds had peripherally-mediated antinociceptive effects. The same compounds, moreover, showed potent anti-inflammatory effects by significantly reducing paw edema of rats in the inflammation tests. To provide an approach to pharmacological findings regarding possible mechanisms of action, the binding modes of the most active compounds were investigated by in silico approaches. The results of molecular docking studies indicated that the anti-inflammatory and analgesic activities of the compounds might be related to the inhibition of both COX-1 and COX-2 isoenzymes. Findings obtained from in silico studies showed that 4 k, which was chosen as a model for its analogs in the series, forms strong bindings to the basic residues (Arg120, Tyr355), side pocket loop area and deep hydrophobic regions of the enzyme. Moreover, results of the molecular dynamics simulation studies revealed that ligand-COX enzyme complexes are quite stable. Obtained results of in vivo and in silico studies are in harmony, and all together point out that compounds 4b, 4c, 4f, 4 h, and 4 k have significant anti-inflammatory and analgesic activities with good ADME profiles.The potential of the derivatives, whose pharmacological activities were revealed for the first time in this study, as anti-inflammatory and analgesic drug candidates, needs to be evaluated through comprehensive clinical studies.

Noni (Morinda citrifolia L.) fruit juice reduces paw edema and protects gastric mucosal injury in rats

Edema is a reliable parameter to evaluate the anti-inflammatory process. Noni (Morinda citrifolia L.) fruit has been shown to decrease inflammation. However, studies on the impact of noni juice on gastric mucosal injury are still limited. Thus, the current study aimed to assess the effect of noni fruit juice as an anti-inflammatory agent in rat paw edema and gastric mucosal injury. The rats were divided into five groups such as control, carrageenan only, carrageenan and diclofenac sodium, carrageenan and 90% noni, and carrageenan + 100% noni. Paw edema was measured, and histopathological examination of the gastric tissues was performed. The administration of noni juice significantly reduced paw edema in the carrageenan + 90% noni and carrageenan + 100% noni groups of rats. Compared to the carrageenan + diclofenac sodium group, the carrageenan + 90% noni and carrageenan + 100% noni groups were not significantly different in reducing paw edema. It suggests that the administration of noni juice can reduce paw edema with the same potential as diclofenac sodium. Gastric mucosal injury in the carrageenan + diclofenac sodium group (scores 2 to 3) was higher than in the carrageenan + 90% noni and carrageenan + 100% noni groups (scores 1 to 2), both of them had significant differences (p&lt;0.05). In conclusion, noni juice can reduce paw edema and protect against gastric mucosal injury.

Development and Evaluation of Nano-Vesicular Emulsion-Based Gel as a Promising Approach for Dermal Atorvastatin Delivery Against Inflammation.

Atorvastatin (ATV), a medication used to reduce cholesterol levels, possesses properties that can counteract the damaging effects of free radicals and reduce inflammation. However, the administration of ATV orally is associated with low systemic bioavailability due to its limited capacity to dissolve in water and significant first-pass effect. This study aimed to assess the appropriateness of employing nano-vesicles for transdermal administration of ATV in order to enhance its anti-inflammatory effects. ATV-loaded transethosomes (ATV-TEs) were optimized using the 33 Box-Behnken design. The ATV-TEs that were created were evaluated for their vesicle size, encapsulation efficiency (% EE), and percent release of drug. The optimum formulation was integrated into a hydroxypropyl methylcellulose (HPMC) emulsion-based gel (ATV-TEs emulgel) using jojoba oil. ATV-TEs emulgel was examined for its physical characteristics, ex vivo permeability, histological, and anti-inflammatory effect in a rat model of inflamed paw edema. The optimized transethosomes exhibited a vesicle size of 158.00 nm and an encapsulation efficiency of 80.14 ± 1.42%. Furthermore, the use of transethosomal vesicles effectively prolonged the release of ATV for a duration of 24hours, in contrast to the pure drug suspension. In addition, the transethosomal emulgel loaded with ATV exhibited a 3.8-fold increase in the transdermal flow of ATV, in comparison to the pure drug suspension. ATV-TEs emulgel demonstrated a strong anti-inflammatory impact in the carrageenan-induced paw edema model. This was evident from the significant reduction in paw edema, which was equivalent to the effect of the standard anti-inflammatory medicine, Diclofenac sodium. In summary, transethosomes, as a whole, might potentially serve as an effective method for delivering drugs via the skin. This could improve the ability of ATV to reduce inflammation by increasing its absorption through the skin.

In vivo analgesic, anti-inflammatory and molecular docking studies of S-naproxen derivatives

In the current studies two naproxen derivatives (NPD) were evaluated for analgesic and anti-inflammatory properties. The acetic acid and hot plate animal models were used to screen the compounds for analgesic potential. While the anti-inflammatory potential was evaluated through animal paw edema, induced by several inflammatory mediators (carrageenan, bradykinin, and prostaglandin E2), the xylene-induced ear edema was also used as an inflammatory model. Both NPDs showed significant (p < 0.001) antinociceptive effects in the acetic acid-induced writhing paradigm. In the case of the hot plate, the NPD 1 at the tested dose of 5 mg/kg enhanced the latency time after 60 min of injection, which remained significant (p < 0.001) up to the end of the experiment duration. The maximum percent inhibition of NPD 1 was 87.53. The naloxone injection significantly lowered the latency time of NPD 1 as compared to NPD 2. Regarding the anti-inflammatory effect, both of the tested NPDs demonstrated a significant reduction in paw edema against various inflammatory mediators, as mentioned above; however, the anti-inflammatory effect of NPD 1 was better. The maximal percent inhibition by NPD 1 and 2 was 43.24 (after 60 min) and 45.93 (after 90 min). A considerable effect also resulted from xylene-induced ere edema. Further, a molecular docking study was carried out to investigate the binding modes of the NPD. The docking analysis revealed that the NPD significantly interacted with the COX2 enzyme. Furthermore, molecular dynamics simulation was carried out for the docked complexes. The MD simulation analysis revealed the high stability of the two naproxen derivatives.

Quercetin and ibuprofen combination displayed anti-inflammatory effects and also extenuates the enteric neurons damage of arthritic rats.

This study aimed to investigate the antioxidant and anti-inflammatory properties of quercetin on the cellular components of the Enteric Nervous System in the ileum of rats with arthritis. Rats were distributed into five groups: control (C), arthritic (AIA), arthritic treated with ibuprofen (AI), arthritic treated with quercetin (AQ) and arthritic treated with both ibuprofen and quercetin (AIQ). The ileum was processed for immunohistochemical techniques for HuC/D, calcitonin gene-related peptide, and vasoactive intestinal polypeptide. Measurements in histological sections, chemiluminescence assays, and total antioxidant capacity were also performed. Rheumatoid arthritis resulted in a decrease in neuronal density, yet neuroplasticity mechanisms were evident through observed changes in varicosities size and neuronal area compared to the control group. Reduced paw edema and neuroprotective effects were predominantly noted in both plexuses, as evidenced by the increased density preservation of HuC/D-IR neurons in the AIQ group. The increase of lipoperoxidation levels and paw edema volume in the AQ group was observed compared to the arthritic, whereas the AIQ group mainly showed similar results to those observed in the control. The enteropathy associated with arthritis proved to be significant in the field of gastroenterology, and the combination of quercetin and ibuprofen demonstrated promising anti-inflammatory and neuroprotective effects.

Inter-Varietal Variation in Phenolic Profile, Antioxidant, Anti-Inflammatory and Analgesic Activities of Two Brassica rapa Varieties: Influence on Pro-Inflammatory Mediators.

The present research study aims to appraise the potential of polyphenol-rich extracts from two Brassica rapa varieties on antioxidant, anti-inflammatory and analgesic activities using carrageenan-induced paw edema model in rats. Methanol extracts of peels and pulps of Brassica rapa yellow root (BRYR) and Brassica rapa white root (BRWR) were prepared using the soxhlet extraction technique. All four extracts were analyzed by reversed-phase high-pressure liquid chromatography (RP-HPLC) for the polyphenols, and results showed that 10 phenolic acids and 4 flavonoids were detected. Gallic acid was the major phenolic acid (174.6-642.3 mg/100 g of dry plant material) while catechin was the major (34.45-358.5 mg/100 g of dry plant material) flavonoid detected in the extracts. The total phenolic contents (TPC) of BRYR peel, BRWR peel, BRYR pulp and BRWR pulp extracts were in the range of 1.21-5.01 mg/g of dry plant material, measured as GAE, whereas the total flavonoid contents (TFC) were found in the range of 0.90-3.95 mg/g of dry plant material, measured as QE. BRYR peel extract exhibited the best DPPH radical scavenging activity (IC50, 3.85 µg/mL) and reducing potential as compared with other extracts. The in vivo anti-inflammatory potential was assessed by carrageenan-induced rat paw edema, and the analgesic potential was investigated by a hot plate test. Suppression of biochemical inflammatory biomarkers including C-reactive protein (CRP), rheumatoid factor (RF) and tumor necrosis factor (TNF-α), and interleukin-6 (IL-6) concentration were also determined. Results showed that BRYR peel extracts reduced paw edema and suppressed the production of TNF-α, IL-6, CRP and RF most significantly, followed by BRWR peel, BRYR pulp and BRWR pulp extracts. In addition, histopathology observation also supports the anti-inflammatory effect of peel extracts as being greater than that of root pulp extracts. Moreover, it was observed that the analgesic effect of the root-peel extracts was also more pronounced as compared with root-pulp extracts. It can be concluded that BRYR peel extract has higher phenolic contents and showed higher suppression of TNF-α, IL-6, CRP and RF, with strong antioxidant, anti-inflammatory and analgesic effects.

Spirulina as a promising agent in rheumatoid arthritis with no observed hepatic injury

Aim of the workTo examine early mitigation and conservative effects of low-dose gamma radiation (LDR) or spirulina (SPR) algae on inflammation, oxidative stress and liver function in experimentally-induced arthritis in rats, and comparing such effects to conventionally used rheumatoid arthritis (RA) drugs; methotrexate (MTX) and hydroxychloroquine (HCQ) in an attempt to unleash a safer remedy/therapeutic modality for RA management. Materials and methodsMale Wister albino rats were rendered arthritic by sub-plantar injection of 0.1 ml Freund's complete adjuvant (FCA). Adjuvant-induced arthritis (AIA) rats were treated with each of LDR (0.5 Gy at day 0 of arthritis induction), MTX (1 mg/kg/week, intra-peritoneal), HCQ sulphate (15 mg/kg/day, orally), MTX + HCQ, and SPR (1 g/kg/day, orally) for 28 days. ResultsSub-plantar injection of FCA led to marked increase in paw volume accompanied with increased serum level of C-reactive protein (CRP) and oxidative stress markers including malondialdehyde (MDA) and nitric oxide (NO) levels. Exposure to LDR did not induce any significant alteration in the estimated parameters. Treatment with MTX and HCQ alone or combined induced deterioration in liver function (transaminases), insignificantly reduced paw edema, yet failed to attenuate CRP, MDA and NO levels. Instead, treatment with SPR significantly guarded against changes in nearly all measured parameters and kept liver function at normal level. ConclusionThis is a leading work showing the hepato-preservative impact of spirulina as a promising alternative therapy during the course management of RA. It could thus be considered as a potential option in the management armamentarium of RA.

Drug Polymeric Carrier of Aceclofenac Based on Amphiphilic Chitosan Micelles.

Amphiphilic micelles based on chitosan (CS) were applied as drug carriers of aceclofenac (ACF) as a potential method to induce its bioavailability and therapeutic efficiency. N-octyl-N,O-succinyl CS (OSCS), an amphiphilic CS derivative, was successfully synthesized and loaded physically by ACF at different pH values and using different dosages of ACF, forming ACF-loaded polymeric micelles (PMs). The obtained PMs and ACF-loaded PMs were characterized by different analytical techniques, including AFM, TEM, DLS, UV-vis spectrophotometry, 1H NMR spectroscopy, and FT-IR spectroscopy. The pH 5 sample with a 30% ACF/polymer ratio showed the highest ACF loading capacity (LC) and entrapment efficiency (EE). In vitro release behaviors of pure ACF and ACF-loaded PMs at each release point indicated that the release profile of pH-responsive PMs loaded with ACF demonstrated quicker release rates (94% after 480 min) compared to the release behavior noticed for free ACF (59.56% after 480 min). Furthermore, the release rates exhibit a notable rise when the pH is increased from 1.2 to 4.7. In the carrageenan-induced inflammation model of paw edema in rats, it has been demonstrated that the injection of ACF-loaded PMs (at a dose of 10 mg/kg) resulted in a strengthened inflammatory activity compared to the injection of free ACF at equivalent dosages as well as at time intervals. However, the use of ACF-loaded PMs for a duration of 6 h displayed a notable reduction of paw edema, with an inhibition percentage of 85.09%, in contrast to the 74.9% inhibition percentage observed for the free ACF medication.

EVALUATION OF ANTI-INFLAMMATORY ACTIVITY OF SIDDHA HERBOMINERAL FORMULATION RATHINAGARA RASA MEZHUGU IN ANIMAL MODEL

The usage of Nonsteroidal and steroidal drugs in the treatment of Musculoskeletal disorders often results in adverse effects such as renal damage, gastric irritation, etc. Alternative therapies with less or no side effects are the need of the hour. Siddha system offers a lot of Anti-inammatory drugs that are polyherbal or Herbo-mineral in nature and devoid of the above-mentioned adverse effects. This research work deals with the Anti-inammatory screening of a Siddha Herbo-mineral Formulation Rathinagara rasa mezhugu (RNM) documented in classic Siddha literature Anuboga vaidhaya naveneetham Part 5 indicated for inammatory disease conditions. Anti-inammatory activity was evaluated by Carrageenan-induced paw edema in Wistar rats. Indomethacin (10 mg/kg, orally) was used as standard. The formulation in doses of 20mg/kg, 45mg/kg, and 90 mg/kg showed 56%, 61.53%, and 90.47% inhibition of paw edema, respectively at the end of 5 h. The result of the study showed that RNM at all dose levels signicantly(p&lt;0.5) reduced the inammation in a dose-dependent manner when compared to the control. RNM at 90mg/kg was found to be signicant (**p&lt;0.01) and effective in the reduction of paw edema after 5hrs.From the results, it can be concluded that Rathinagara rasa mezhugu (RNM) was found to exhibit high anti-inammatory potential which conrmed the traditional use of the drug.

Antinociceptive and anti-inflammatory properties of α-D-mannan from the yeast Kluyveromyces marxianus: evidence for a role in interleukin-6 inhibition.

The management of inflammatory states typically involves non-steroidal anti-inflammatory drugs (NSAIDs) and opiates. Understanding the mechanisms underlying the processing of nociceptive information from potential alternatives such as some polysaccharides may enable new and meaningful therapeutic approaches. In this study, α-D-mannan isolated from the Kluyveromyces marxianus cell wall produced antinociceptive effects in models of inflammatory pain (formalin and complete Freund's adjuvant tests). Furthermore, α-D-mannan reduced paw edema and interleukin-6 (IL-6) production after carrageenan-induced inflammation. The polysaccharide α-D-mannan was characterized by gas chromatography-mass spectrometry, methylation analysis, and spectroscopic techniques. Moreover, the Doehlert experimental design was applied to find the optimal conditions for biomass production, with the best conditions being 10.8g/L and 117h for the glucose concentration and the fermentation time, respectively. These results indicate that α-D-mannan from K. marxianus exerts anti-inflammatory and antinociceptive effects in mice, possibly via a mechanism dependent on the inhibition of IL-6 production.

Evaluation of Anti-Inflammatory Activity of the Methanol Extracts of Premna schimperi Engl (Lamiaceae) Leaves in Rats.

Even though it is a protective reaction, inflammation continues to be one of the most challenging medical disorders. The current conventional anti-inflammatory drugs have many undesirable health effects and are in need of newer drugs. The purpose of this study was to evaluate the anti-inflammatory effects of an aqueous methanol crude extract of Premna schimperi leaves. Premna schimperi leaf was extracted with 80% methanol and concentrated; the concentrated extract was used to evaluate the acute toxicity and anti-inflammatory effects. For the acute toxicity study, a single dose of Premna schimperi extract at a dose of 2000 mg/kg was administered and observed for 14 days. Acute, sub-acute, and chronic anti-inflammatory models were employed to evaluate the anti-inflammatory effect of the extract compared to the standard drug. Data were analyzed with SPSS V. 27, and the significance was established with a one-way ANOVA followed by a post hoc Tukey's test. Acute oral toxicity testing at a dose of 2000 mg/kg did not show any sign of toxicity. According to the phytochemical study, the plants contained flavonoids, terpenoids, tannins, cardiac glycosides, steroids, phenolics, and anthraquinones. The extract doses of 200 mg/kg, 400 mg/kg, and 800 mg/kg of extracts effectively (p<0.001) reduced paw edema in the acute and sub-acute models of inflammation. When compared to the negative control group, all tested doses in the chronic model significantly (p<0.05) decreased the production of exudates and the amount of granuloma tissue. Premna schimperi displayed significant anti-inflammatory activity. The tested doses inhibit the formation of edema, granulomas, and exudates.