Reduction In Paw Volume Research Articles

Screening of Methanolic Extract of Pongamia Pinnata Leaves for its Antiarthritic and Analgesic Activity

The aim of present work was to screen traditional claim of methanolic extract of Pongamia pinnata (PP) leaves for its antiarthritic and analgesic activity. The antiarthritic activity of different doses of PP extract (100,200 and 400 mg/kg) in rats were evaluated on 7th and 14th day of treatment. The paw volume displacement, radiographic analysis, histopathological investigation and secondary changes were measured, as a mark of activity. The analgesic activity of the different doses of the extract in rats was evaluated using hot plate model. The PP extract at the dose of 200 and 400mg/kg showed significant reduction in paw volume on 7th and 14th day of treatment and also significant effect in radiographic and histopathological analysis but, none of the doses of PP extract showed any significant effect as analgesic. KEYWORDS: Pongamia pinnata, antiarthritic, analgesic

ANTIOXIDANT AND ANTI-INFLAMMATORY POTENTIAL OF MONOCHORIA VAGINALIS (BURM. F.) C. PRESL.: A WILD EDIBLE PLANT

In the present study, Monochoria vaginalis leaf and root extracts were evaluated for their antioxidant and anti-inflammatory property. Antioxidant property was estimated using 2,2′-azinobis(3-ethylbenzothiozoline-6-sulfonic acid) disodium salt +, metal ion chelating activity, ferric-reducing antioxidant power, superoxide anion radical scavenging, 2,2-diphenyl-1-picryl-hydrazyl, nitric oxide radical scavenging, phosphomolybdenum and hydrogen peroxide assays. Among these assays, leaf ethanolic extract showed maximum radical scavenging activity in ABTS•+, superoxide and hydrogen peroxide assays. Meanwhile, the leaf hot water extract showed highest inhibition of free radicals in metal ion chelating assay. Commendable antioxidant activity was also found in leaf and root while evaluating other antioxidant assays. In vivo anti-inflammatory study in M. vaginalis showed appreciable reduction in paw volume after oral administration of 250 and 500 mg/kg doses of methanolic leaf extract. Hence, the investigation in M. vaginalis clearly puts forward the immense potential of the plant as a competitive phytomedicine. PRACTICAL APPLICATIONS Only few studies have been reported on the health benefits of Monochoria vaginalis. The present study would be an addition to the medicinal value of this potent plant. Polyphenol present in this plant could significantly elevate healthy diet. The use of M. vaginalis against the burning sensation of body, vitiated condition of pitta, dipsia, gastropathy, hepatopathy, cough, asthma, scurvy, boils, hemorrhages, etc., and the current study of antioxidant and anti-inflammatory capacity could reveal their actual medicinal properties. As M. vaginalis is edible, these properties will increase its value as a food supplement and could help in producing health beneficial herbal products in the future.

Synergistic Effect of Nitric Oxide Synthase and Cyclooxygenase Inhibitors on Carrageenan-induced Paw Edema in Rats

The present study examined the effects of L-nitroarginine methylester (L-NAME, CAS 50903-99-6), a non-selective nitric oxide synthase (NOS) inhibitor, indometacin (IND, CAS 3305-29-1), a non-selective cyclooxygenase (COX) inhibitor, and a combination of these agents (L-NAME + IND) on carrageenan-induced paw edema for 4 h after the injection of carrageenan in rats. L-NAME at 10 and 30 mg/ kg but not 3 mg/kg (i.p.) decreased paw volume slightly but significantly only at 1 h after the carrageenan injection. IND reduced paw volume slightly at 1 and 3 mg/kg, and markedly at 10 mg/kg (p.o.). A combination of L-NAME and IND at a subthreshold dose (3 mg/kg, i.p. and 1 mg/kg, p.o., respectively) caused a marked reduction of paw edema, which was also confirmed by histopathological examinations. A combination of N-(3-(aminomethyl)benzyl)acetamidine (1400W, CAS 180001-34-7), a selective inhibitor of inducible NOS, and IND at 3 mg/kg, i.p., and 1 mg/kg, p.o., respectively, did not show synergistic anti-inflammatory effects. In conclusion, the combination of non-selective NOS and COX inhibitors had synergistic anti-inflammatory effects on carrageenan-induced paw edema at an early stage, suggesting negative crosstalk between the endogenous NOS-NO and COX-PG pathways in the early stages of acute inflammation.

ACUTE AND SUBACUTE MODELS OF INFLAMMATION OF NYCTANTHES ARBOR TRISTIS AND MAHARASNADI GHAN

Aqueous Methanolic extracts of Nyctanthes Arbor tristis and Maharasnadi ghan were studied for a inflammation parameter using carrageenin induced hind paw edema and cotton pellet granuloma . The natural plant was screened for acute toxicity and it did not show any toxic or deleterious effects indicating low toxicity of the extract even at high doses at two different dose levels. In carrageenin induced hind paw edema a significant reduction in paw volume was observed as compared to control group whereas in cotton pellet granuloma model marked inhibition in granuloma formation, reduction in the elevated levels of serum lysosomal enzymes (SGPT, SGOT, and ALP) and lipid peroxidation was noted as compared to control group. The extracts exhibited profound anti-inflammatory activity in both acute and subacute animal models warranting further investigations to establish its anti-inflammatory potential. The activity was thought due to flavonoids which might be present in the formulation which could play a significant role in preventing the release of histamine, leukotreins and prostaglandins. In future the extract needs to be studied for cellular line models of inflammation.

Anti-inflammatory and antihyperalgesic effects of the combination of ibuprofen and hemin in adjuvant-induced arthritis in the Wistar rat

Although, pharmacological activation of heme oxygenase (HO)-1 has shown to produce ameliorative effects in various experimental models of inflammation, but such beneficial effects have not been observed in adjuvant-induced arthritis. Further, the upregulated activity of HO-1 has been implicated in the pathogenesis of adjuvant arthritis. The present study was designed to investigate the anti-inflammatory and antihyperalgesic effects of the prophylactic use of hemin alone and/or in combination with ibuprofen using adjuvant-induced arthritis in Wistar rat. Arthritis was induced by an intradermal injection of complete Freund's adjuvant (CFA) into left hind paw. Paw volume, thermal hyperalgesia, mechanical allodynia, joint stiffness and mobility behaviors (score) were measured. Administration of ibuprofen (8.75, 17.5, 35mg/kg/day, p.o.) and hemin (1, 5, 10mg/kg/day, i.p.) were significantly effective in suppressing CFA-induced paw oedema, thermal and mechanical hyperalgesia, joint stiffness and mobility. The combination of low doses of ibuprofen (8.75mg/kg, p.o.) and hemin (1mg/kg, i.p.) significantly reduced paw volume, thermal and mechanical hyperalgesia, as compared to the individual dose of the ibuprofen and hemin alone. Hence, it may be concluded that the prophylactic administration of either hemin produced significantly enhanced anti-inflammatory and analgesic effects. Further, concurrent low dose administration of hemin and ibuprofen produced significantly enhanced anti-inflammatory and analgesic effects, as compared to the either treatment alone, in CFA-induced arthritis in Wistar rats.

Evaluation of antiarthritic activity of Strychnos potatorum Linn seeds in Freund's adjuvant induced arthritic rat model.

BackgroundStrychnos potatorum Linn (Loganiaceae) is a moderate sized tree found in southern and central parts of India, Sri Lanka and Burma. In traditional system of medicine, Strychnos potatorum Linn seeds were used for various ailments including inflammation, diabetes etc. To investigate the folkloric use of the seeds the present study was carried out on Freund's adjuvant induced arthritic rats.MethodsThe present study states the effect of the aqueous extract (SPE) and the whole seed powder (SPP) of Strychnos potatorum Linn seeds on the Freund's complete adjuvant (FCA) induced arthritic rat paw edema, body weight changes and alterations in haematological and biochemical parameters in both developing and developed phases of arthritis. Histopathology of proximal interphalangeal joints and radiology of hind legs were studied.ResultsIn FCA induced arthritic rats, there was significant increase in rat paw volume and decrease in body weight increment, whereas SPP and SPE treated groups, showed significant reduction in paw volume and normal gain in body weight. The altered haematological parameters (Hb, RBC, WBC and ESR) and biochemical parameters (blood urea, serum creatinine, total proteins and acute phase proteins) in the arthritic rats were significantly brought back to near normal by the SPP and SPE treatment at the dose of 200 mg/kg/p.o in both developing and developed phases of arthritis. Further the histopathological and radiological studies revealed the antiarthritic activity of SPP and SPE by indicating fewer abnormalities in these groups when compared to the arthritic control group.ConclusionIn conclusion, both SPP and SPE at the specified dose level of 200 mg/kg, p.o. showed reduction in rat paw edema volume and it could significantly normalize the haematological and biochemical abnormalities in adjuvant induced arthritic rats in both developing and developed phases of FCA induced arthritis. Further the histopathological and radiological studies confirmed the antiarthritic activity of SPP and SPE.

Antinociceptive and Anti-Inflammatory Effects of Solvent Extracts of Tagetes erectus Linn (Asteraceae

Purpose: Traditionally, the leaves of Tagetes erectus L. are used in India for the alleviation of pain and inflammation. The objective of this study was to investigate the antinociceptive and anti-inflammatory activities of this plant material in an animal model. Methods: The chloroform, methanol and ether extracts of the leaves of Tagetes erectus L. (family: Asteraceae) were tested against acetic acid-induced writhing in mice and carrageenan-induced paw oedema in rats in order to assess their antinoceciptive and anti-inflammatory activities, respectively. The doses administered intraperitoneally (I.P.) ranged from 100 to 400 mg/kg body weight, and acetylsalicylic acid (ASA) and phenylbutazone were the reference standards for the antinoceciptive and anti-inflammatory tests, respectively. Results: The extracts showed antinociceptive and anti-inflammatory properties at doses between 200400 mg/kg. They inhibited significantly (P < 0.005), in a dose-dependant manner, induced writhing reflexes in mice. The antinoceciptive effect was comparable to that of ASA which served as the reference standard. Similarly, the extracts significantly (P <0.05) reduced carragenan-induced paw oedema in rats and the reduction in paw volume was comparable to that of the reference standard (phenylbutazone). It also increased pain threshold in the oedematous right hind limb paw of the rats. Conclusion: The results obtained show that the extracts of Tagetes erectus L. (Asteraceae) has antinociceptive and anti-inflammatory properties. This finding provides a basis for the traditional use of the plant material.

Multivesicular Liposomes Bearing Celecoxib-β-Cyclodextrin Complex for Transdermal Delivery

In our work depot delivery systems of celecoxib were developed using multivesicular liposomes. Moreover, the solubility of celecoxib was enhanced by complexing drug with cyclodextrin to overcome the limitation of conventional therapy. The multivesicular liposomes (MVLs) bearing celecoxib-β -cyclodextrin inclusion complex were prepared by reverse phase evaporation method, and multilamellar vesicles (MLVs)-bearing drug complex was prepared by the cast film method. The formulations were characterized for vesicle size, encapsulation efficiency, and in vitro drug release. In vivo performance of multivesicular liposomes bearing celecoxib-β -cyclodextrin inclusion complex was evaluated by assessing anti-inflammatory activity using carrageenan-induced rat paw edema volume method. The results were compared with that of celecoxib-cyclodextrin complex and MLVs containing celecoxib-β -cyclodextrin inclusion complex in equal amounts. Phase solubility studies for the celecoxib-β -cyclodextrin inclusion complex clearly indicated an increase in aqueous solubility of celecoxib with an increase in β –CD concentration. The in vitro release studies reveal that MLVs release more than 80% drug within 48 hr whereas MVL formulations release nearly the same amount of drug in 120 hr. In vivo data reveal that reduction in paw volume with MVL formulation was not rapid and fast, but the effect was maintained for prolonged periods, and even after 24 hr there was 40.7 ± 3.40% reduction in paw volume. MVL formulation showed more sustained and prolonged anti-inflammatory effect compared with plain drug and MLVs. We concluded that multivesicular liposome can be successfully utilized for the sustained delivery of celecoxib.

IL-23 induces human osteoclastogenesis via IL-17 in vitro, and anti-IL-23 antibody attenuates collagen-induced arthritis in rats

This study demonstrates that IL-23 stimulates the differentiation of human osteoclasts from peripheral blood mononuclear cells (PBMC). Furthermore, in vivo blockade of endogenous IL-23 activity by treatment with anti-IL-23 antibody attenuates collagen-induced arthritis in rats by preventing both inflammation and bone destruction. IL-23 induced human osteoclastogenesis in cultures of PBMC in the absence of osteoblasts or exogenous soluble-receptor activator of NF-kappaB ligand (RANKL). This IL-23-induced osteoclastogenesis was inhibited by osteoprotegerin, anti-IL-17 antibody, and etanercept, suggesting that RANKL, IL-17, and TNF-alpha are involved. In addition, we found the ratio of production levels of IL-17 to those of IFN-gamma from activated human T cells was elevated at 1 to 10 ng/ml IL-23. The inductive effect of IL-17 and the inhibitory effect of IFN-gamma on osteoclastogenesis indicate that the balance of these two cytokines is particularly important. We also demonstrated that IL-23 administered at a later stage significantly reduced paw volume in rats with collagen-induced arthritis, in a dose-dependent manner. Furthermore, anti-IL-23 antibody reduced synovial tissue inflammation and bone destruction in these rats. These findings suggest that IL-23 is important in human osteoclastogenesis and that neutralizing IL-23 after onset of collagen-induced arthritis has therapeutic potential. Thus, controlling IL-23 production and function could be a strategy for preventing inflammation and bone destruction in patients with rheumatoid arthritis.

Anti-inflammatory activity of Justicia prostrata gamble in acute and sub-acute models of inflammation

In this study, the aqueous (AQJP) and alcoholic (ALJP) extracts of the whole plant of Justicia prostrata Gamble (Acanthaceae) were screened for their acute and subacute anti-inflammatory activities using carrageenan-induced acute inflammation and cotton-pellet-induced granuloma (subacute inflammation), respectively, in rats. In the carrageenan-induced rat paw oedema model, both extracts were found to exhibit maximum reduction in paw volume at the first hour in a dose-dependent manner. At the dose of 500 mg/kg p.o., both extracts AQJP and ALJP showed maximum inhibition (51.39% and 62.5%, respectively) in rat paw oedema volume at the first hour of carrageenan-induced acute inflammation. In the cotton pellet granuloma assay, AQJP and ALJP at the dose of 500 mg/kg p.o. suppressed the transudative, exudative and proliferative phases of chronic inflammation. These extracts were able to (i) reduce the lipid peroxide content of exudates and liver and (ii) normalize the increased activity of acid and alkaline phosphatases in serum and liver of cotton pellet granulomatous rats. Preliminary phytochemical screening revealed the presence of lignans, triterpenes and phenolic compounds in ALJP, whereas phenolic compounds and glycosides in AQJP. The anti-inflammatory properties of these extracts may possibly be due to the presence of phenolic compounds. The anti-inflammatory effects produced by the extracts at the dose of 500 mg/kg, p.o. was comparable with the reference drug diclofenac sodium (5 mg/kg p.o.).

Antinociception by tricyclic antidepressants in the rat formalin test: differential effects on different behaviours following systemic and spinal administration

The present study (1) examined analgesic effects of systemically and spinally administered antidepressants (ADs) on phase 2 flinching and biting/licking behaviours in the rat formalin test, a model considered to be of greater relevance to clinical pain than acute threshold tests, and (2) determined whether motor or anti-inflammatory effects contributed to such actions. Systemic administration of amitriptyline (3–20 mg/kg) produced a dose-related enhancement of flinching behaviours, while at the same time suppressing biting/licking behaviours. Imipramine (except for 20 mg/kg), nortriptyline, desipramine and fluoxetine had no significant effect on flinching behaviours, while producing a dose-related suppression of biting/licking behaviours. When administered spinally, either by acute lumbar puncture or via chronically implanted intrathecal cannulas, amitriptyline similarly augmented flinching behaviours. When given by lumbar puncture, amitriptyline suppressed biting/licking behaviours, but when intrathecal cannulas were used, this behaviour was not expressed in the formalin group. Other ADs also suppressed biting/licking behaviours without affecting flinching when given by lumbar puncture. Effects on paw volume were determined at the end of behavioural testing. Systemic administration of all ADs produced a dose-related reduction in paw volume. Spinal administration of nortriptyline by lumbar puncture also reduced paw volume, but for other agents, the reduction was not significant. Motor effects were noted qualitatively throughout these experiments, and considered in relation to nociceptive behaviours. These results indicate (a) a marked dissociation between the effects of systemic ADs on flinching and biting/licking behaviours in the formalin test, (b) spinal efficacy of ADs that essentially reproduces effects seen with systemic administration when given by lumbar puncture, (c) a lack of causality between anti-inflammatory effects of ADs and their analgesic properties in the formalin test, and (d) a contribution of motor effects to analgesic actions at higher doses affecting biting/licking but not flinching behaviours.

Analgesic and antiinflammatory effects of two novel kappa-opioid peptides.

This study investigates two new kappa-agonist tetrapeptides, FE 200665 and FE 200666, with high peripheral selectivity as a result of poor central nervous system penetration. Four days after administration of Freund adjuvant into the hind paw of male Wistar rats, antinociceptive effects of intraplantar and subcutaneous injection of FE 200665 and FE 200666 were measured by paw pressure algesiometry and compared with the kappa-agonist U-69,593. Peripheral and kappa-receptor selectivity was assessed by the antagonists naloxone methiodide (NLXM) and nor-binaltorphimine, respectively. Antiinflammatory effects were evaluated by paw volume plethysmometry and histologic score. Similar to intraplantar U-69,593, intraplantar FE 200665 (3-100 microg) and FE 200666 (1-30 microg) resulted in significant and dose-related increases of paw pressure thresholds. Higher doses of FE 200665 (0.2-20 mg) and FE 200666 (0.06-6 mg) were required by subcutaneous route to produce similar antinociceptive responses, supporting a peripheral site of action. nor-Binaltorphimine dose-dependently antagonized this effect, implying kappa-opioid selectivity. Analgesic effects of subcutaneous FE 200665 and FE 200666 were abolished by intraplantar nor-binaltorphimine, and both subcutaneous and intraplantar effects were dose-dependently antagonized by subcutaneous NLXM, further demonstrating a peripheral site of action. One to 6 days after Freund adjuvant inoculation, single and repeated intraplantar injections of FE 200665, FE 200666, and U-69,593 significantly reduced paw volume and histologic scores. Both changes were reversed by intraplantar nor-binaltorphimine and subcutaneous NLXM. FE 200665 is a peripherally selective kappa-agonist with potent analgesic and antiinflammatory properties that may lead to improved analgesic-antiinflammatory therapy compared with centrally acting opioids or standard nonsteroidal antiinflammatory drugs.