Reduced Paw Edema Research Articles

In vitro Antioxidant Activity and In vivo Anti-inflammatory Effect of Ricinus communis (L.) and Withania somnifera (L.) Hydroalcoholic Extracts in Rats

HIGHLIGHTS Ricinus communis and Withania somnifera extracts contain considerable polyphenol compounds. R. communis and W. somnifera extracts showed significant in vitro antioxidant activities. R. communis and W. somnifera extracts markedly inhibited xylene-induced ear edema in rats. Both herbal extracts significantly reduced paw edema induced by egg albumin and carrageenan.

Synthesis, Characterization and Preliminary Anti-inflammatory Evaluation of New Fenoprofen Hydrazone Derivatives

New hydrazone derivatives of Fenoprofen were synthesized and evaluated for their anti-inflammatory activity by means of egg white induced paw edema method. All the synthesized target compounds were characterized by FT-IR spectroscopy, 1HNMR analysis and by measure of their physical properties. The synthesis of the target compounds(H1-H4) was accomplished by multistep reaction procedures. The synthesized target compounds were show activity in reducing paw edema thickness and their anti-inflammatory effect was comparable to that of the standard (Fenoprofen) except for compound H3 which show anti-inflammatory activity higher than Fenoprofen.

Costus spiralis (Jacq.) Roscoe leaves fractions have potential to reduce effects of inflammatory diseases

Ethnopharmacological relevanceSince drugs currently used to manage pain and inflammatory conditions present several side effects, the investigation of new anti-inflammatory and antinociceptive agents from folk-medicine plants is an important approach. Costus spiralis (Costaceae) has been used in Brazilian medicinal teas to treat urinary infection, cough, inflammation, arthritis, among others. Aim of the studyThe current study focused on investigating anti-inflammatory and antinociceptive effects of fractions from C. spiralis leaves using animal models. Materials and methodsAdults Swiss mice were used in the following experimental models: acetic acid-induced abdominal writhing, formalin-induced nociception, hot plate, zymosan-induced peritonitis, and arthritis induced by complete Freund's adjuvant. ResultsThe presence of steroids was confirmed in all fractions. Flavonoids, condensed tannins and saponins were observed in EFL. In methanolic fraction leaves (MFL), the presence of flavonoids and pentacyclic triterpenoids was confirmed. Orally administered leaf fractions significantly reduced abdominal writhing. Fractions were ineffective in the neurogenic stage of the formalin test, but in the inflammatory stage, ethyl acetate fraction levaes (AcFL), ethanolic fraction leaves (EFL), and MFL significantly reduced paw licking time by 69.6 ± 11.9%, 58.2 ± 9.4%, and 79.6 ± 8.3%, respectively. In the hot plate test, the reaction latency was similar for treated animals and controls. However, in the peritonitis test, cell migration was significantly reduced in animals treated with chloroform fractions leaves ClFL (61.8 ± 11.4%), AcFL (58.7 ± 8.3%), EFL (39.2 ± 5.0%), and MFL (64.8 ± 4.4%). This was similar to the result observed in the chronic inflammation model, this time only the chloroform fraction was able to reduce paw edema. ConclusionOur results show that leaf fractions of Costus spiralis are capable of modulating peripheral nociceptive and inflammatory responses without effects on central nervous system being potential substrates for phytochemical purification, structural and mechanistic studies.

Effects of photobiomodulation therapy on the local experimental envenoming by Bothrops leucurus snake

Bothrops leucurus is the major causative agent of snakebites in Brazil's Northeast. The systemic effects of its venom are effectively neutralized by antivenom therapy, preventing bitten patients' death. However, antivenom fails in neutralizing local effects that include intense pain, edema, bleeding, and myonecrosis. Such effects can lead to irreversible sequels, representing a clinically relevant issue for which there is no current effective treatment. Herein, the effects of photobiomodulation therapy (PBMT) were tested in the local actions induced by B. leucurus venom (BLV) in mice (n = 123 animals in 20 experimental groups). A continuous emission AlGaAs semiconductor diode laser was used in two wavelengths (660 or 780 nm). Mechanical nociceptive thresholds were assessed with the electronic von Frey apparatus. Local edema was determined by measuring the increase in paw thickness. Hemorrhage was quantified by digital measurement of the bleeding area. Myotoxicity was evaluated by serum creatine kinase (CK) activity and histopathological analysis. PBMT promoted anti-hypernociception in BLV-injected mice; irradiation with the 660 nm laser resulted in faster effect onset than the 780 nm laser. Both laser protocols reduced paw edema formation, whether irradiation was performed immediately or half an hour after venom injection. BLV-induced hemorrhage was not altered by PBMT. Laser irradiation delayed, but did not prevent myotoxicity caused by BLV, as shown by a late increase in CK activity and histopathological alterations. PBMT was effective in the control of some of the major local effects of BLV refractory to antivenom. It is a potential complementary therapy that could be used in bothropic envenoming, minimizing the morbidity of these snakebite accidents.

Targeted drug delivery of Methotrexate in situ gels for the treatment of Rheumatoid Arthritis

Rheumatoid arthritis (RA) is considered a debilitating disease that increases the risk of significant morbidity and premature mortality. To circumvent drug-related toxicity and ineffectiveness of anti-inflammatory drugs, there is a significant need for an advanced delivery system that increases bioavailability. The feasibility of in situ gel of methotrexate sodium (MTS) as an effective management for Rheumatoid arthritis was investigated. It was formulated with pluronic F-127 (PLF-127) as primary polymer, hydroxypropyl methylcellulose K4M (HK4M), and polycarbophil (PCL) as a copolymer and characterized by various parameters. The efficacy evaluation by Freund's complete adjuvant (FCA) model, biocompatibility assessment by histopathological studies conducted. The optimized in situ gel (M4) was thermoresponsive, released 93.26 ± 2.39% MTS at 96 hours. In addition, distribution of MTS was even in the optimized sterile and syringeable in situ gel. In vivo studies on wistar rats demonstrated a substantial reduction in paw oedema during the 28-day study period and were biocompatible with the tissues at the injection site. The study was successful in formulating, optimizing MTS in situ gel for effective management of RA.

Evaluation of the curative role, Anti-inflammatory and anti-oxidative activity of some dietary spices on carrageenan induced paw edema in albino Wistar rats

Background: Inflammation is a major burning problem worldwide and billions of individuals are affected. Some of the spices used daily in Algerian cuisine have been known to possess major anti-inflammatory effects. Turmeric, red pepper, ginger, cinnamon and cumin etc. are a few of the wide spectrum of spices used in Algeria.
 The aim of the study was to investigate the antiinflammatory effect and anti actvity of some dietary spices in carrageenan induced models of inflammation on Wistar rats.
 Methods: Albino wistar rats were divided into four groups. Inflammation was induced on the animal by injecting the right hand paw with carrageenan (0.1 ml of 1%). Group 1 was fed with food and water and treated with carrageenan (control) whereas group 2 and 3 treated with different doses (100 and 200 mg/kg/bw) of aqueous extract of some dietary spices with carrageenan, respectively. Group 4 treated with standard drug diclofenac sodium (10 mg/kg b.w., reference drug for inflammation), once for 24 hrs.
 Results: The content of total phenolic was 137.2±21.6 mg/g and flavonoids 122.3±5.8 mg/g. After 60, 120, 180, 240 and 300 min, the data indicate that some dietary spices 100 and 200 mg/kg was significantly effective reducing paw edema volumes induced by carrageenan compared to control (p <0.01). The levels of serum pro-inflammatory white blood cells, neutrophile, lymphocyte, monocyte, eosinophile, total protein and protein c reactive and total cephalin KADIN and platelts in the control group were significantly increased by carrageenan injection compared with the normal group. The rats pretreated with some spices 100 and 200 mg/kg had significantly lower levels of pro-inflammatory to compare control group. The paw edema in carrageenan-induced rats was considerably reduced by treating with 100 and 200 mg/kg aqueous extract of some dietary spices when compared to the untreated rats (p<0.001).
 Conclusion : The present results clearly demonstarted that carrageenan significantly increased paw edema whereas some dietary treated rats significantly decreased the paw edema. The study underlines the importance of some of the frequently used spices (Turmeric, red pepper, ginger, cinnamon and cumin) in the treatment of inflammation.

Dietary Supplementation with Palmitoyl-Glucosamine Co-Micronized with Curcumin Relieves Osteoarthritis Pain and Benefits Joint Mobility.

Simple SummaryCanine osteoarthritis is a chronic degenerative joint disease and a major cause of elective euthanasia. The disorder increasingly limits joint motion, might cause lameness as well as pain, and impacts quality of life. An unmet need remains for safe and effective therapies for osteoarthritis. Palmitoyl-glucosamine and curcumin are used in animal nutrition. A co-micronized formulation, with the two substances being jointly processed to reduce their particle size and increase the extent to which they can be absorbed, is currently available on the European market. The present study investigated if this formulation could relieve joint pain and benefit mobility. Two well-established rat models of inflammation and osteoarthritis pain were used. Results from the first set of experiments showed that the dietary supplement relieved experimentally induced paw edema, infiltration of inflammatory cells, and decreased sensitivity to painful stimuli (thermal hyperalgesia). In the osteoarthritis model, the supplement proved to protect joint cartilage against degradation and successfully address neuropathic pain (i.e., pain from normally non-painful stimuli). Locomotor function recovered by 45% under supplement administration. The present findings suggest that the dietary supplement with palmitoyl-glucosamine co-micronized with curcumin might help manage osteoarthritis.Chronic mixed pain and orthopedic dysfunction are the most frequently associated consequences of canine osteoarthritis (OA). An unmet need remains for safe and effective therapies for OA. Palmitoyl-glucosamine (PGA) and curcumin are safe and naturally occurring compounds whose use is limited by poor bioavailability. Micronization is an established technique to increase bioavailability. The aim of this study was to investigate if the dietary supplementation with PGA co-micronized with curcumin (PGA-Cur, 2:1 ratio by mass) could limit pathologic process in two well-established rat models of inflammation and OA pain, i.e., subplantar carrageenan (CAR) and knee injection of sodium monoiodoacetate (MIA), respectively. In CAR-injected animals, a single dose of PGA-cur significantly reduced paw edema and hyperalgesia, as well as tissue damage and neutrophil infiltration. The repeated administration of PGA-Cur three times per week for 21 days, starting the third day after MIA injection resulted in a significant anti-allodynic effect. Protection against cartilage damage and recovery of locomotor function by 45% were also recorded. Finally, PGA-cur significantly counteracted MIA-induced increase in serum levels of TNF-α, IL-1β, NGF, as well as metalloproteases 1, 3, and 9. All the effects of PGA-Cur were superior compared to the compounds used singly. PGA-Cur emerged as a useful dietary intervention for OA.

In vitro and In Vivo Immunomodulatory Activity of Physalis angulata Concentrated Ethanolic Extract.

The need for new immunomodulatory drugs is due to the side effects associated with the prolonged use of the currently used immunomodulatory drugs. In this context, the present work aimed to investigate the immunomodulatory effect of an ethanolic concentrated extract from Physalis angulata. The cytotoxicity of samples was determined using peritoneal macrophages though the Alamar Blue assay. The immunomodulatory activity of the ethanolic extract from P. angulata on activated macrophages was determined by measurement of nitrite and cytokine production. The immunosuppressive effects of the ethanolic extract from P. angulata was evaluated on lymphocyte proliferation and cytokine production. The effects of the extract on cell cycle progression and cell death on lymphocytes were evaluated by flow cytometry. Lastly, the ethanolic extract from P. angulata was tested in vivo in toxicological tests and in models of peritonitis and delayed-type hypersensitivity response. The ethanolic extract from P. angulata decreased nitrite, interleukin-6, interleukin-12, and TNF-α production by activated macrophages without affecting the cell viability. In addition, the ethanolic extract from P. angulata inhibited lymphoproliferation and the secretion of interleukin-2, interleukin-6, and IFN-γ, and increased interleukin-4 secretion by activated splenocytes. Flow cytometry analysis in lymphocyte cultures showed that treatment with the ethanolic extract from P. angulata induces cell cycle arrest in the G1 phase followed by cell death by apoptosis. Moreover, mice treated with the extract from P. angulata at 100 or 200 mg/kg did not show signs of toxicity or alterations in serum components. Finally, the ethanolic extract from P. angulata significantly reduced neutrophil migration and reduced paw edema in bovine serum albumin-induced the delayed-type hypersensitivity response model. Our results demonstrate the potential of the ethanolic extract of P. angulata as an alternative for the treatment of immune-inflammatory diseases.

A mechanistic study of Solenostemma argel as anti-rheumatic agent in relation to its metabolite profile using UPLC/HRMS

Ethnopharmacological relevanceSolenostemma argel (Argel) is a traditional perennial edible herb that is commonly used in folkloric medicine for the treatment of rheumatic pain, inflammation, bronchitis, cold, diabetes, gastrointestinal cramps, and urinary tract infections. No previous reports traced the mechanistic activity of this plant for treatment of rheumatoid arthritis in relation to its chemical constituents. Aim of the studyThe present study was designed to substantiate the anti-arthritic potential of S. argel and identification of its secondary metabolites responsible for the action using ultra-performance liquid chromatography coupled to high resolution mass spectrometry (UPLC/HRMS). Materials and methodsThe air-dried powder of S. argel was subjected to liquid-liquid fractionation method to yield polar metabolites fraction (PMF) and nonpolar metabolites fraction (NPMF) where the metabolites that represent each fraction were identified using UPLC/HRMS. The in-vitro anti-arthritic effects of both fractions were tested using protein denaturation, membrane stabilization and proteinase inhibition assays, in addition to in-vitro enzyme inhibition assays of COXs, LOX and collagenases. Adjuvant-induced arthritis (AIA) model was also established to evaluate their anti-arthritic effects in-vivo at two doses (200 and 400 mg/kg) in compared to the standard ibuprofen (5 mg/kg). Physical changes with hind paw edema and body weight gain as well as the assessment of serum rheumatoid biomarkers, inflammatory cytokines, oxidative stress markers, and the activity of hyaluronidase and β-glucouronidase enzymes were studied. The histopathological study of ankle and knee joints and immunohistochemistry of caspase-3 and TNF-α in joint synovium were also examined. ResultsThe PMF significantly (P < 0.05) reduced paw edema, serum rheumatoid markers, pro-inflammatory mediators, degeneration enzymes of cartilage and bone, and oxidative stress biomarkers. Interestingly, flavonoid glycosides and phenolic acids dominated the polar fraction, which showed the promising anti-arthritic activity of Argel compared to the NPMF which was dominated by pregnane glycosides. ConclusionsSince arthritis is a chronic disease and there are imperative needs for a lifelong treatment with desirable pharmacological action and lower cost than the currently approved synthetic drugs having severe side effects, the PMF of Argel could be used as a potent anti-rheumatic agent.

Antioedematogenic and anti-inflammatory actions of Phragmanthera incana (Schum) Balle leaf in carrageenan-induced inflammation models in rats

Phragmanthera incana (Schum) is a specie of mistletoe that has been mentioned in Nigeria ethnomedicine to be used in the treatment of inflammatory disorders. The aim of this study was to investigate the anti-inflammatory effect of Phragmanthera incana leaf ethanol extract (PIEE) in carrageenan-induced inflammation models in rats. In the carrageenan-induced rat paw oedema experiment, 0.1 mL of carrageenan (1%) was injected into the paw one hour after treatment with PIEE (125, 250 and 500 mg/kg). Paw volume was measured hourly for 4 h using the plethysmometer. The anti-inflammatory activity was investigated using the carrageenan-induced air pouch inflammation model. Leucocytes migration and pro-inflammatory mediators (TNF-α and IL-6) were evaluated in the air pouch exudate. Oxidative stress biomarkers (MDA, Nitrite, GSH and Catalase) were estimated in both the carrageenan-induced paw tissue homogenates and air pouch exudate. PIEE (125, 250 and 500 mg/kg) administration significantly (p < 0.05) reduced paw oedema hourly post-carrageenan injection. PIEE administration displayed dose-dependent significant (p < 0.05) reduction in fluid exudates and total leucocytes counts respectively. The extract administration also decreased elevated pro-inflammatory cytokines (TNF-α and IL-6) levels respectively. PIEE administration demonstrated antioxidant activity by attenuating carrageenan-induced increase in malondialdehyde and nitrite as well as decrease in reduced glutathione and catalase levels in rats. Phragmanthera incana leaf ethanol extract possess anti-inflammatory properties, suggesting protective function in inflammatory diseases.

Beyond inflammation: Centrally mediated antinociceptive properties of Spirulina platensis LEB-18 biomass via the opioid system

• Spirulina platensis biomass exhibits antinociceptive properties in animal models. • Anti-inflammatory properties of Spirulina platensis are mediated by IL-10. • Spirulina platensis biomass promotes centrally mediated antinociception. • Spirulina platensis has intrinsic analgesic properties mediated by opioid system. The management of pain is a world health issue. Available painkillers induce undesired side effects and are sometimes inefficient. Spirulina biomass has promoted anti-inflammatory activity in preclinical and clinical trials. This work characterizes the antinociceptive properties of Spirulina platensis LEB-18 biomass (SP-LEB18) and their mechanisms of action. In the CFA model in mice, SP-LEB18 reduced paw edema and mechanical allodynia, confirming its anti-inflammatory action and showing its antinociceptive activity. Cytokines levels were evaluated by ELISA; SP-LEB18 promoted an increase of IL-10 levels and a reduction of TNF-α and IL-1β levels. SP-LEB18 promoted centrally mediated antinociception, as indicated by the tail flick test. When the same set of experiments was conducted with IL-10 knockout mice, the antinociception was still detected in the tail flick test, but not in the CFA model. Pretreatment with naloxone abolished the effect of SP-LEB18, demonstrating a pure antinociceptive action of Spirulina biomass via the opioid system.

Antinociceptive and Anti-inflammatory Effects of Methanolic Extract of Laurencia caspica

Introduction: Seaweeds are valuable resources for the discovery of efficient and safe drugs for pain treatment. In the present investigation, we evaluated the antinociceptive and anti-inflammatory properties of, methanolic extract of Laurencia caspica, a red algae, in mice models. Methods: The analgesic effect of methanolic extract of L. caspica was assessed by hot-plate and acetic acid-induced writhing tests in male Swiss albino mice (weight = 20-25 g). The anti-inflammatory activity of methanolic extract of L. caspica was also evaluated by formalin-induced ear edema and xylene-induced paw edema tests. Results: The total flavonoid content of the extract was estimated as 0.0537 mg quercetin/g extract. Both first and second phases of the nociception were significantly inhibited at a dose of 120 mg/kg of methanolic extract of L. caspica. The observed anti-inflammatory effect was dose-dependent. Acetic acid-induced writhing test and hot plate test showed that the extract significantly reduced pain in all evaluated doses (15, 30, 60, and 120 mg/kg). The antinociceptive activity of the methanolic extract was significantly reduced by naloxone (4 mg/kg). Moreover, the extract significantly reduced paw edema at the dose of 120 mg/kg in all the animals. Conclusion: Methanolic extract of L. caspica exhibited central analgesic effect, as well as anti-inflammatory activity probably due to the presence of constituents like flavonoids and triterpenoids.

Phytol anti-inflammatory activity: Pre-clinical assessment and possible mechanism of action elucidation

Phytol (PHY) is an acyclic natural diterpene alcohol and a chlorophyll constituent that exhibits several pharmacological effects, such as anticancer, antioxidant, and antimicrobial. Here, we aimed to assess the PHY anti-inflammatory effect in vitro and in vivo, and to deepen knowledge on the possible mechanism of action. For this purpose, egg albumin (in vitro) test was performed by using acetyl salicylic acid (ASA) as a standard nonsteroidal anti-inflammatory drugs (NSAID). For in vivo test, male Wistar albino rats were treated (intraperitoneally) with 100 mg/kg of PHY and/or standard NSAIDs ASA (100 mg/kg) and diclofenac sodium (Diclo-Na, 10 mg/kg) to evaluate the combined effect of PHY in formalin-induced paw edema model. Furthermore, an in silico (CADD) study was accomplished to assess the effect of PHY against cyclooxygenase (COX)-1 and 2 enzymes, nuclear factor kappa B (NF-κB), and interleukin-1β (IL-1β). Results revealed that PHY exhibits dose-dependent anti-inflammatory effect using the egg albumin method. PHY (100 mg/kg) co-treated with ASA and/or Diclo-Na reduced paw edema better than PHY alone or NSAIDs individual groups. Computational study showed that PHY efficiently interacts with COX-1 and 2, NF-κB, and IL-1β. In conclusion, PHY exhibits anti-inflammatory activity, possibly via COX-1 and 2, NF-κB, and IL-1β dependent pathways.

Andrographolide attenuates complete freund's adjuvant induced arthritis via suppression of inflammatory mediators and pro-inflammatory cytokines

Ethnopharmacological relevanceTraditional plant-derived medicines have enabled the mankind in curing the wide spectrum of diseases throughout the ages. Andrographis paniculata (Burm.f.) Nees, is one of the traditional plant used as a folk medicine for the management of inflammation, arthritis, viral-bacterial infections and other ailments in India, China, Malaysia and other South-East Asian countries. Its major bioactive compound; andrographolide, a diterpenoid, also exerts cytoprotective properties and is reported to be effective in neuroprotection, hepatoprotection, etc. AimThe study is aimed to explore the role of andrographolide in treatment of complete freund's adjuvant (CFA) induced arthritis. Materials and methodsThe influx of immune cells, release of pro-inflammatory cytokines and subsequent accumulation of synovial fluid (swelling) and pain manifest into the disease. The present study used CFA induced Balb/c mice model and treated them intraperitoneally with andrographolide and dexamethasone (used as a positive control) on alternate days for six days. After 6 days, blood and peritoneal macrophages were collected to evaluate the expression of various arthritic markers and paw edema was measured on all days. ResultsThe in vitro and ex vivo experiments showed that andrographolide treated animal group had reduced paw edema, cell cytotoxicity and nitric oxide production than dexamethasone treated animal group. Further, the study revealed the mechanistic role of andrographolide in treatment of arthritis by suppressing battery of molecules like COX-2, NF-κB, p-p38, CD40, TNF-α, IL-1β and IL-6 involved in arthritis. ConclusionThe study showed the potent anti-arthritic effects of andrographolide and warrants further investigations on andrographolide for the development of safe and effective anti-arthritic drug.

Analgesic, anti-inflammatory and hypouricemic effects of GT1 film-coated tablets on experimental animals

Aim: To evaluate pain relief, anti-inflammatory and hypouricemic effects of GT1 tablets on experimental animals.&#x0D; Method: GT1 at the doses of 22.32 g/kg/day and 66.96 g/kg/day were evaluated for its analgesic effect in three models (hot plate, pain threshold, and acetic acid-induced writhing), its chronic anti-inflammatory effect in the granulomatous reaction model, and its hypouricemic effect in potassium oxonate-induced hyperuricemic mice. Acute anti-inflammatory effects of GT1 at the doses of 11.16 g/kg/day and 33.48 g/kg/day were evaluated in rats with two models: carrageenin-induced paw edema and peritonitis.&#x0D; Results: GT1 prolonged the temperature reaction time on the hot plate (22.73 s and 20.37 s at both doses of 22.32 g/kg and 66.96 g/kg, respectively, compared to 16.96 s in control group), reduced the number of acid acetic-induced writhing effects, decreased the weight of granulomas, and decreased the level of acid uric in blood and urine (p &lt; 0.05). GT1 caused a significant reduction in paw edema after subplantar injection of carrageenan in rats (p &lt; 0.05). Moreover, there was a substantial decline of GT1 at the dose of 11.16 g/kg/day in terms of the volume and the quantity of protein in the inflammation fluid of the peritonitis model (p &lt; 0.05).&#x0D; Conclusion: GT1 at both doses of 11.16 g/kg/day and 33.48 g/kg/day posed acute anti-inflammatory effects on rats. GT1 at both doses of 22.32 g/kg/day and 66.96 g/kg/day exerted analgesic, chronic anti-inflammatory and hypouricemic effects on mice.

Investigation of antihyperalgesic and antiedematous activities of three Hieracium species

Present study investigated triterpene profile, antihyperalgesic and antiedematous activities of Hieracium scheppigianum flowering aerial parts dichloromethane extract (SCH), and antihyperalgesic and antiedematous activities of previously chemically characterised polyphenol-rich H. glabratum and H. calophyllum flowering aerial parts methanol extracts (GLA and CAL, respectively). α- and β-Amyrin and their acetates, and lupeol acetate were identified and quantified in SCH by GC-FID and GC-MS. In carrageenan-induced localised inflammation model in rats, SCH and GLA (50–200 mg/kg, p.o.) produced significant and dose-dependent antihyperalgesic effect of 26.9%–56.2% (ED50=163.0 ± 26.5 mg/kg) and 25.3%–51.6% (ED50=211.6 ± 70.6 mg/kg), respectively, and CAL (200 mg/kg, p.o.) exhibited effect of 38.1%. Extracts did not significantly reduce paw edema. SCH and GLA, which demonstrated higher (over 50%) antihyperalgesic efficacy, were tested in a rotarod test (200 mg/kg, p.o.) and no alteration of motor coordination was observed. Also, acute administration of SCH and GLA in mice (2000 mg/kg, p.o.) caused neither mortality nor toxicity.

Neuroprotective and anti-inflammatory activity of DAT inhibitor R-phenylpiracetam in experimental models of inflammation in male mice.

R-phenylpiracetam (R-PhP, (4R)-2-(4-phenyl-2-oxopyrrolidin-1-yl)acetamide) is an optical isomer of phenotropil, a clinically-used nootropic drug that improves physical condition and cognition. Recently, R-PhP was shown to bind to the dopamine transporter (DAT). Since growing evidence suggests that dysfunction of the dopaminergic system is associated with persistent neuroinflammation, the aim of this study was to determine whether R-PhP, an inhibitor of DAT, has neuroprotective and anti-inflammatory effects in male mice. The pharmacokinetic profiles ofR-PhPin mouse plasma and its bioavailability in brain tissue were assessed. To study possible molecular mechanisms involved in the anti-inflammatory activity of R-PhP, target profiling was performed using radioligand binding and enzymatic activity assays. To clarify the neuroprotective and anti-inflammatory effects of R-PhP, we used a lipopolysaccharide (LPS)-induced endotoxaemia model characterized by reduced body temperature and overexpression of inflammatory genes in the brain. In addition, the antinociceptive and anti-inflammatory effects of R-PhP were tested using carrageenan-induced paw oedema and formalin-induced paw-licking tests. R-PhP (50mg/kg) reached the brain tissue 15min after intraperitoneal (ip) and peroral (po) injections. The maximal concentration of R-PhP in the brain tissues was 28µg/g and 18µg/g tissue after ip and po administration, respectively. In radioligand binding assays, DAT was the only significant molecular target found for R-PhP. A single ip injection of R-PhP significantly attenuated the LPS-induced body temperature reduction and the overexpression of inflammatory genes, such as tumour necrosis factor-α (TNF-α), interleukin 1 beta (IL-1β) and inducible nitric oxide synthase (iNOS). Seven-day po pretreatment with R-PhP dose-dependently reduced paw oedema and the antinociceptive response, as shown by the carrageenan-induced paw oedema test. In addition, R-PhP decreased the nociceptive response during the inflammatory phase in the formalin-induced paw-licking test. Our study showed that R-PhP possesses neuroprotective and anti-inflammatory effects, demonstrating the potential of DAT inhibitors as effective therapeutics.

Anti-inflammatory activity of the dietary supplement Houttuynia cordata fermentation product in RAW264.7 cells and Wistar rats.

Houttuynia cordata Thunb. has been used as a traditional medicine to treat a variety of ailments in Asian countries such as China, Japan, South Korea, and Thailand. In Thailand, H. cordata fermentation products (HCFPs) are commercially produced and popularly consumed throughout the country without experimental validation. Anti-inflammatory activity of H. cordata fresh leaves or aerial parts has previously been reported, however, the anti-inflammatory activity of the commercially available HCFPs produced by the industrialized process has not yet been investigated. The aim of this study was to evaluate in vitro and in vivo anti-inflammatory potential of the selected industrialized HCFP. LPS-induced RAW264.7 and carrageenan-induced paw edema models were used to evaluate the anti-inflammatory activity of HCFP. The phenolic acid components of HCFP aqueous and methanolic extracts were investigated using HPLC analysis. In RAW264.7 cells, the HCFP aqueous and methanolic extracts reduced NO production and suppressed LPS-stimulated expression of PGE2, iNOS, IL-1β, TNF-α and IL-6 levels in a concentration-dependent manner, however, less effect on COX-2 level was observed. In Wistar rats, 3.08 and 6.16 mL/kg HCFP reduced paw edema after 2 h carrageenan stimulation, suggesting the second phase anti-edematous effect similar to diclofenac (150 mg/kg). Whereas, 6.16 mL/kg HCFP also reduced paw edema after 1 h carrageenan stimulation, suggesting the first phase anti-edematous effect. Quantitative HPLC revealed the active phenolic compounds including syringic, vanillic, p-hydroxybenzoic and ferulic acids, which possess anti-inflammatory activity. Our results demonstrated for the first time the anti-inflammatory activity of the industrialized HCFP both in vitro and in vivo, thus validating its promising anti-inflammation potential.

Evaluation of rohitukine-enriched fraction of Dysoxylum binectariferum Hook.f. (leaves) as anti-arthritic phytopharmaceutical candidate: Chemical standardization, in-vivo validation, formulation development and oral pharmacokinetics

Ethnopharmacological relevanceRheumatoid arthritis is a chronic inflammatory disease of joints. Dysoxylum binectariferum Hook.f (Family: Meliaceae) is a Indian medicinal plant which is traditionally being used to heal inflammation of joints. Aim of the studyThis work was aimed to carry out chemical standardization, in-vitro/in-vivo validation, oral pharmacokinetics and formulation development of anti-arthritic botanical lead, the rohitukine-enriched fraction of D. binectariferum. Materials and methodsThe rohitukine-enriched fraction of D. binectariferum was standardized using four chemical markers and was checked for microbial load, heavy metal content, aflatoxins and pesticides. Its in-vitro inhibitory effect on the lipopolysaccharide (LPS) induced production of pro-inflammatory cytokines TNF-α and IL-6 was studied in THP-1 cells. The in-vivo anti-arthritic activity was investigated in collagen-induced arthritis model in DBA/1J mice. The sustained release capsule formulation was developed and characterized for physicochemical and pharmacokinetic properties. ResultsRohitukine and schumaniofioside A were found to be major chemical constituents of the botanical lead. The rohitukine-enriched fraction of D. binectariferum significantly reduced the production of both pro-inflammatory cytokines TNF-α and IL-6 (>50% inhibition at 3.12 μg/mL) in THP-1 cells. In LPS-treated wild-type mice model, the rohitukine-enriched fraction at 200 mg/kg (PO, QD) completely reduced serum TNF-α levels. In transgenic mice model (collagen-induced arthritis in DBA/1J mice), rohitukine-enriched fraction at 100 mg/kg (PO, QD) dose has resulted in >75% reduction of TNF-α/IL-6 serum levels, 68% reduction in anti-mouse type II collagen IgG1 antibody levels, decreased joint proteoglycan loss and reduced paw edema in DBA/1J mice. The sustained release capsule formulation of rohitukine-enriched fraction showed sustained-release of rohitukine over the period of 24 h, and resulted in an improved plasma-exposure of rohitukine in SD rats. ConclusionsThe data presented herein demonstrated anti-arthritic potential of rohitukine-enriched fraction of D. binectariferum and this study will serve as the benchmark for further research on this botanical lead and developed sustained release capsule formulation.

Synthesis, Characterization and Bioactivity Study of Bidentate NS Schiff Base of S-Benzyl Dithiocarbazate and its Zn(II) and Pd(II) Complexes

The bis-chelated four coordinate complexes (ML2, L = deprotonated ligand) of Zn(II) and Pd(II) ions were synthesized, derived from a new bidentate NS Schiff base called S-benzyl-β-N-(4-hydroxy-3- nitrophenyl)methylene dithiocarbazate (HL) which is the condensation product of S-benzyl dithiocarbazate (SBDTC) with 4-hydroxy-3-nitrobenzaldehyde. The synthesized ligand and complexes were characterized using conventional techniques like NMR, UV-visible, IR, mass spectroscopic techniques, magnetic susceptibility measurement and molar conductance. A single crystal X-ray crystallography data approved the proposed crystal structure of the ligand. Both in solid and solution phase, the ligand continues to exist in its thione tautomeric form. The chelates were formed by the reaction of ligand with the metal ions through the ligand azomethine nitrogen atom and the deprotonated thiolate sulfur anion. Magnetic susceptibility and electronic spectroscopic data suggested to have a tetrahedral geometry for ZnL2 complex whereas a square planar structure for PdL2 complex. The analgesic and anti-inflammatory bioactivity were assayed on both the ligand and its complexes by tail flick and carrageenan induced paw edema test. The ligand at the dose of 10 mg/kg, produced a significant (***p &lt; 0.001) increase in pain threshold in tail flick methods when compared to control but in case of complexes, it showed moderate activity. At the same dose, the ligand and complexes significantly (***p &lt; 0.001) reduced paw edema when compared to the control. Altogether, these results suggest that ligand and its complexes could be used as a potent anti-inflammatory agent.