Tarantula cubensis extract (Theranekron®) ınhibits ınflammation in carrageenan-ınduced acute paw edema in rats
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ABSTRACT The aim of this study was to investigate the anti-inflammatory effect of alcoholic extract of Tarantula cubensis alcoholic extract (TCAE) in experimentally induced inflammation in rats. Fifty-four adult Sprague-Dawley male rats were randomly divided into nine groups. Paw edema was induced by 0.2mL subplantar (s.p.) injection of 1% carrageenan (CAR) into the right hind paw. Rats were treated with the nonsteroidal anti-inflammatory drug (NSAID) indomethacin (INDO) (10mg/kg, p.o.) or TCAE at different doses (1, 10 or 100µg/kg) injected s.c. for systemic or s.p. for local anti-inflammatory effect. Saline was used as control. Changes in paw thickness, volume, and weight were calculated as percentages. Formalin-fixed paws were used for histopathological examination. We detected that TCAE applied s.c. at 10µg/kg and 100µg/kg doses resulted in thinner paw thickness, lower paw volume, and lower paw weights four hours after the induction of inflammation when compared with the INDO group (p<0.05). The paw edema inhibitory effect of TCAE applied at a dose of 10µg/kg, s.c. was 68% when compared with the INDO which had an inhibitory effect of 56%. These results were verified with similar histopathological findings. The anti-inflammatory feature of 10µg/kg of TCAE given systematically was similar to the effects of INDO. Our results suggest that TCAE has anti-inflammatory effects by reducing edema and decreasing inflammatory reaction. These results may be attributed to the inhibition of the production of proinflammatory mediators. Thus, TCAE may be considered as a potential anti-inflammatory agent for treating acute inflammatory conditions.Keywords:
Carrageenan
Anti-inflammatory
【Objectives : The present study was examined to evaluate the anti-inflammatory effects of the Humulus japonicus MeOH extracts (HJE) in the carrageenan-induced paw edema model in rats. Methods : The effects of HJE on anti-inflammation were measured in the carrageenan-induced paw edema model in rats and infiltrated Inflammatory Cells. Results : 1. HJE (1.0 g/kg) and dexamethasone effectively inhibited paw edema measured 1~4 h after carrageenan injection. HJE (0.3 g/kg) effectively inhibited paw edema measured 1, 3, 4 hr. 2. In histopathological study in rats, 1.0 g/kg HJE and dexamethasone effectively inhibited the increases of hind paw skin thicknesses and inflammatory cell infiltrations induced by carrageenan treatment. But quite similar histopathological changes were detected in 0.3 g/kg HJE treated group as compared with carrageenan control.】
Carrageenan
Anti-inflammatory
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Paw edema formation after the subplantar injection of carrageenan was enhanced in rats treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The enhanced carrageenan response could be detected as early as 4.5 hr after TCDD; however, the magnitude of enhancement was greatest when rats were challenged with carrageenan 5 days after TCDD. In the latter case, the ED50 of TCDD in enhancing the carrageenan response was 6 micrograms/kg. TCDD also enhanced dextran-induced paw edema, which follows a time course different from that of carrageenan-induced edema and is produced by a different mechanism. The enhancement of carrageenan and dextran paw edemas was due to an increase in the edema-producing potency of the irritants and not to a change in their maximum effect. The ability of other 3-methylcholanthene-type inducers to enhance carrageenan-induced paw edema and the inability of phenobarbital-type inducers to cause the response suggest that the TCDD binding protein might be involved in edema enhancement. TCDD also enhanced carrageenan-induced pleural edema; however, the number and type of leukocytes recovered in the pleural exudate was not affected. TCDD did not alter granuloma formation produced by the subcutaneous implantation of cotton pellets, indicating that enhancement by TCDD was peculiar to edema formation and not to inflammation in general. It is suggested that TCDD may enhance carrageenan and dextran edemas by increasing the availability of mediators involved in each type of edema formation and/or by increasing the responsiveness of the vasculature to mediators.
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NSAIDsの主たる副作用である消化管障害を抑制するために, 坐剤, 経皮吸収剤, プロドラッグなどのDDSが開発されてきたが, これらは完全に副作用を抑制しうるものではない. NSAIDsの標的であるCOXのうち, COX-2を選択的に阻害するように開発されたCOX-2選択的阻害薬は, 従来のNSAIDsと比較して消化管障害発生頻度は低いが, 一方で他の副作用は減らせない. NSAIDsはその剤形やCOX選択性に関わらず, 依然として副作用発現を無視できないため, 漫然と使用することは避けるべきである.
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Nonsteroidal anti-inflammatory drugs have the anti-inflammatory,antipyretic and analgesic effects,and are one of most prescribed drugs nowadays.Nonsteroidal anti-inflammatory drugs could be divided into two types:nonselective and selective.Recently,some retrospective study showed that selective nonsteroidal anti-inflammatory drugs might increase the risk of cardiovascular events.But the definite conclusion needs more studies.
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The anti-inflammatory effects of the aqueous extract of licorice (Glycyrrhizae Radix, GR), glycyrrhizin (GL). and 18β-glycyrrhetinic acid (GA) on carrageenan-induced edema of the rat hind-paw were compared. Tested drugs were administered orally 1 hr prior to the subplantar injection of 0.1 m1 mixture of 1 % lambda carrageenan into the right hind-paw of the rat. The edema formation during 1-6 hr was completely blocked by 5 mg/kg indomethacin (as a positive control) and was partially attenuated by 200 mg/kg GA. Both GL and GR, at the doses containing equivalent quantities of 100, 200, and 500 mg/kg of GL, had little effects on edema formation. In contrast to 200 mg/kg GA, 500 mg/kg GA facilitated and increased the carrageenan-induced edema formation. This result indicates that GA has very narrow margin of anti-inflammatory activity on carrageenan induced edema.
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Glycyrrhizin
Hindlimb
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1. Injection of carrageenan into the mouse paw produced a biphasic edema. During the first phase, which developed up to 24 h, edema was of low intensity and unrelated to the dose of carrageenan given. During the second phase, after 24 h, edema was more pronounced, presented a clear dose-response relationship and peaked at 72 h after injection. 2. Histological analysis of the subplantar area 4 h after carrageenan injection revealed a diffuse cellular infiltrate with predominance of polymorphonuclear neutrophils. Between 48 and 72 h, an intense accumulation of macrophages, eosinophils and lymphocytes was observed, together with a great increase in the number of circulating leukocytes and platelets. 3. Pretreatment with the anti-inflammatory drugs indomethacin and dexamethasone reduced both phases of edema in a dose-dependent fashion. 4. The present study shows that carrageenan-induced mouse paw edema constitutes a new and interesting model for the study of the mediators of inflammation and for the screening of new anti-inflammatory drugs.
Carrageenan
Infiltration (HVAC)
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Nonsteroidal anti-inflammatory drugs (NSAIDs) have analgesic, antipyretic, and anti-inflammatory effects.
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Carrageenan
Inflammatory response
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Dazzle Capsule, a Poly herbal formulation is marketed in management of Arthritis and joint-musculo skeletal pain.In this study, safety and efficacy of this polyherbal formulation was investigated in which it was being proved safe for use via acute toxicity study and efficacy was being evaluated by carrageenan-induced rat paw oedema test in rats in order to explore its anti-inflammatory activity at the dose level of 90 and 180 mg/kg, p.o, compared with Indomethacin (10 mg/kg, p.o.).It showed an highly significant reduction in oedema (p<0.001).Indomethacin inhibited oedema by 30.054% and 36.216% at 2 and 3 hr after carrageenan injection, respectively.The inhibitory effect of Dazzle Capsule began at 2 hr or later after carrageenan injection depending upon the administered dose.Low doses of Dazzle Capsule (90 mg/kg) gave highly significant inhibitory effects of 37.894-39.378%,and higher doses (180 mg/kg) caused highly significant inhibition of 19.125-30%.The reduction of oedema by Indomethacin and Dazzle Capsule at 2 hr or more after carrageenan injection suggested that both compounds produce anti-inflammatory effects in the second phase of oedema, indicating inhibition of prostaglandin synthesis.Hence, it was concluded that, Dazzle Capsule is having potent anti-inflammatory activity yet safe polyherbal formulation for use in arthritis management.
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Capsule
Anti-inflammatory
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