Pellet-induced Granuloma In Rats Research Articles

Pharmacognostical Standardization, Isolation of Phytoconstituents (β-sitosterol), HPTLC Analysis of Extracts of Operculina turpethum (Linn.) Roots and Evaluation of Cytotoxic, In vitro, and In vivo Anti-inflammatory Activities

Abstract: Operculina turpethum (Linn.) Silva Manso belongs to the family convolvulaceae. It is an important plant in the Indian conventional system of medicine, which is extensively employed by different tribes in many countries to cure edema and painful conditions like arthritis, back pain, hyperlipidemia, diabetes mellitus, liver disorders, skin disorders, and regulation of bowel functions. The roots of O. turpethum (Linn.) were subjected to physicochemical and phytochemical standardization and chromatographic separation, which was accomplished by column chromatography, TLC, and HPTLC. Further, the acute toxicity, cytotoxic and anti-inflammatory activities of Operculina turpethum roots were estimated by in vivo and in vitro models. This study includes percentage yield of extraction and organoleptic evaluation, along with the analysis of its physicochemical investigations and preliminary phytochemical estimation. The isolation of active phytoconstituents was done by column chromatography, and the isolated compound was then exposed to TLC and HPTLC analysis. Cytotoxic activity was tested by WST-1 based cell viability assay on HepG2 cells. The anti-inflammatory activity of methanol extract (ME) was evaluated against inflammation occur by both in vitro and in vivo methods. The methanolic extract exhibited the presence of most of the phytoconstituents out of all the extracts. The phytoconstituent phytosterol, i.e., β-sitosterol, was isolated by column chromatography, identified, and quantified by TLC and HPTLC, which was liable for anti-inflammatory activity. The amount of β- sitosterol was estimated to be 14.09 μg in a 10.00 mg fraction of MEOT. MEOT was devoid of toxicity up to 2000 mg/kg in Wistar albino rats. It was analysed that in vitro anti-inflammatory activity of MEOT by egg albumin denaturation method exhibited an incredible decrement in turbidity and increased the percentage inhibition of albumin denaturation (60.52%) in MEOT treated group as compared with the control group. In egg albumin-induced edema in rats, MEOT at the dose of 400 mg/kg reduced the edema formation (3.03 ± 0.02) induced by egg albumin at 4th h. In cotton pellet-induced granuloma in rats, MEOT at the dose of 400 mg/kg displayed maximum granuloma inhibition (51.06%), which was similar to that of indomethacin. From the obtained findings, it is confirmed that O. turpethum contains β-sitosterol, which is responsible for potent anti-inflammatory activity without causing cytotoxicity to the plant. The results suggested that ME of O. turpethum roots had a high potential for application as an anti-inflammatory agent. The recognization and confirmation of the plant can be obtained from the study and will present data that is aidful in determining the quality and purity of a crude drug which further helps in preventing its adulteration.

Anti-Inflammatory Activity of Gingko Biloba Extract in Cotton Pellet-Induced Granuloma in Rats: A comparative Study with Prednisolone and Dexamethasone

The current study was designed to evaluate the anti-inflammatory effect of GKB in the rat model of granulomatous inflammation. Thirty rats were distributed into five groups: The first group served as negative control group that received distilled water (DW) only without inducting inflammation, positive control group; treated with DW with the induction of inflammation and they were assigned to cotton pellet-induced granuloma, ginkgo biloba (GKB) treated group (200mg/kg/day), dexamethasone-treated group (1mg/kg), and Prednisolone treated group (5mg/kg). All the treatments were given orally for seven consecutive days. On day eight, the rats were anesthetized and the pellets together with granulation tissue were carefully removed and made free from extraneous tissue. The weight and the percent of the exudate and granuloma were determined and samples of the tissues were sent for histopathological examination. Blood samples were collected by cardiac puncture and used for the analysis of the inflammatory markers: TNF-alfa, IL10, VCAM-1, and hs-CRP. The study revealed a significant reduction in the weight and the percent of exudate (p-value = 0.019), (17%) and granuloma (p-value = 0.013), (20%) by GKB which was comparable to that produced by prednisolone. All the treatment groups showed a significant reduction in serum TNF-?, VCAM-1, and hs-CRP concentration compared with the positive control. The histopathological finding revealed pronounced improvement. In the current study, GKB was effective in attenuating the level of inflammation by decreasing the exudate, granuloma, and inflammatory markers. The underlying mechanisms could be the inhibitory effect on the expression of the inflammatory cytokines and endothelial adhesion molecule. These findings suggest GKB as a good contender to be tested in the treatment of inflammatory diseases.

Computational and Biological Comparisons of Plant Steroids as Modulators of Inflammation through Interacting with Glucocorticoid Receptor

Despite the usefulness of glucocorticoids, they may cause hazardous side effects that limit their use. Searching for compounds that are as equally efficient as glucocorticoids, but with less side effects, the current study compared plant steroids, namely, glycyrrhetinic acid, guggulsterone, boswellic acid, withaferin A, and diosgenin with the classical glucocorticoid, fluticasone. This was approached both in silico using molecular docking against glucocorticoid receptor (GR) and in vivo in two different animal models. All tested compounds interacted with GR, but only boswellic acid and withaferin A showed docking results comparable to fluticasone, as well as similar in vivo anti-inflammatory effects, by significantly decreasing serum levels of interleukin-6 and tumor necrosis factor-α in cotton pellet-induced granuloma in rats. In addition, both compounds significantly decreased the percent of change in ear weight in croton oil-induced ear edema in mice and the granuloma weight in cotton pellet-induced granuloma in rats, to levels comparable to that of fluticasone. Both boswellic acid and withaferin A had no effect on adrenal index, but only withaferin A significantly increased the thymus index. In conclusion, boswellic acid may have comparable anti-inflammatory effects to fluticasone with fewer side effects.

Analgesic and Anti-Inflammatory Activities of Quercetin-3-methoxy-4'-glucosyl-7-glucoside Isolated from Indian Medicinal Plant Melothria heterophylla.

Background:Melothria heterophylla (family: Cucurbitaceae), commonly known as kudari, is used in the Indian traditional medicine to treat various inflammation-associated diseases, such as asthma, arthritis and pain. However, the anti-inflammatory active components of this plant have not been identified yet. The aim of this study was to investigate the potential analgesic and anti-inflammatory activities of a compound, quercetin-3-methoxy-4′-glucosyl-7-glucoside, isolated from M. heterophylla. Methods: The anti-inflammatory activity was determined using carrageenan- and dextran-induced rat paw edema as well as cotton pellet-induced granuloma in rats, whereas the analgesic activity was analyzed using acetic acid-induced writhing, hot plate and tail flick response in mice. The test compound was orally administered at a dose of 5, 10 or 15 mg/kg. The cyclooxygenase-1 (COX-1)- and COX-2-inhibitory capacity of the test compound was studied by enzyme immunosorbent assay. Results: Quercetin-3-methoxy-4′-glucosyl-7-glucoglucoside at 15 mg/kg exhibited a maximum inhibition of carrageenan-induced inflammation (50.3%, p < 0.05), dextran (52.8%, p < 0.05), and cotton pellets (41.4%, p < 0.05) compared to control animals. At the same dose, it showed a 73.1% inhibition (p < 0.05) of the pain threshold in acetic acid-induced writhing model. It also exhibited a considerable analgesic activity by prolonging the reaction time of the animals based on hot plate as well as tail flick response. The test compound was found to inhibit COX-1 (IC50 2.76 µg/mL) and more efficiently, COX-2 (IC50 1.99 µg/mL). Conclusions: Quercetin-3-methoxy-4′-glucosyl-7-glucoside possessed substantial analgesic and anti-inflammatory activities possibly due to inhibition of prostaglandin production, supporting the ethnomedicinal application of M. heterophylla to treat various inflammatory disorders.

Anti-inflammatory effect of external use of escin on cutaneous inflammation: possible involvement of glucocorticoids receptor

Escin, as an internally applied anti-inflammatory agent, has been widely used in the treatment of inflammation and edema resulting from trauma or operation in the clinic. However, the effect of its external use on cutaneous inflammation and edema remains unexplored. In the present study, the anti-inflammatory and anti-edematous effects of external use of escin were studied in carrageenan-induced paw edema and histamine-induced capillary permeability in rats, paraxylene-induced ear swelling in mice, and cotton pellet-induced granuloma in rats. Effects of external use of escin gel on prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were determined by ELISA. The anti-inflammatory mechanism was explored by detecting the expression of glucocorticoid receptor (GR) with Western blotting and Real-time PCR analyses, with further exploration of nuclear factor-κB (NF-κB), p38 mitogen-activated protein kinase (P38MAPK) and activator protein-1 (AP-1) expressions. We demonstrated that external use of escin showed significant anti-inflammatory effects on acute and chronic inflammation in different animal models and its anti-inflammatory effects might be related to down-regulation of PGE2, TNF-α, and IL-1β. The results also showed that escin exerted its anti-inflammatory effects by promoting the expression of GR, with the possible mechanism being inhibition of the expressions of GR-related signaling molecules such as NF-κB and AP-1.

Antioxidant and anti-inflammatory activities of ethyl acetate extract of Gynura formosana (Kitam) leaves.

Gynura formosana Kitam (family Compositae) has traditionally been used for the prevention of diabetes, cancer and inflammation in China. However, there are few reports of its anti-inflammatory effects. In the present study, after assessing the in vitro antioxidant activities of extracts from Gynura formosana Kitam leaves, the anti-inflammatory and antioxidant activities of ethyl acetate extract of Gynura formosana Kitam leaves (EAEG) were further investigated in rats using a cotton pellet-induced model of granuloma. EAEG significantly inhibited the formation of cotton pellet-induced granuloma in rats in a dose-dependent manner. Moreover, EAEG treatment significantly decreased the level of plasma C-reactive protein and suppressed the activities of plasma glutamate pyruvate transaminase and lactate dehydrogenase in model groups. Furthermore, EAEG increased the hepatic levels of anti-oxidative enzymes or antioxidants, including catalase, superoxide dismutase and reduced glutathione, and reduced the level of lipid peroxidation in the rat model of inflammation. In addition, EAEG decreased plasma levels of tumor necrosis factor-α and interleukin-1β in the rat model of inflammation. Therefore, our results indicated that EAEG had potent anti-inflammatory effects, which was achieved at least in part through activating antioxidant enzyme activities and suppressing the production of proinflammatory mediators by macrophages.

Anti-inflammatory and analgesic effects of Bi-yuan-ling granules.

Bi-yuan-ling granule (BLG) is a traditional Chinese medicine compound composed mainly of baicalin and chlorogenic acid. It has been demonstrated to be clinically effective for various inflammatory diseases such as acute rhinitis, chronic rhinitis, atrophic rhinitis and allergic rhinitis. However, the underlying mechanisms of BLG against these diseases are not fully understood. This study aimed to explore the anti-inflammatory and analgesic activities of BLG, and examine its protective effects on mouse acute lung injury (ALI). The hot plate test and acetic acid-induced writhing assay in Kunming mice were adopted to evaluate the pain-relieving effects of BLG. The anti-inflammatory activities of BLG were determined by examining the effects of BLG on xylene-caused ear swelling in Kunming mice, the cotton pellet-induced granuloma in rats, carrageenan-induced hind paw edema and lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. The results showed that BLG at 15.5 mg/g could significantly relieve the pain by 82.5% (P<0.01) at 1 h after thermal stimulation and 91.2% (P<0.01) at 2 h after thermal stimulation. BLG at doses of 7.75 and 15.5 mg/g reduced the writhing count up to 33.3% (P<0.05) and 53.4% (P<0.01), respectively. Additionally, the xylene-induced edema in mice was markedly restrained by BLG at 7.75 mg/g (P<0.05) and 15.5 mg/g (P<0.01). BLG at 5.35 and 10.7 mg/g significantly reduced paw edema by 34.8% (P<0.05) and 37.9% (P<0.05) at 5 h after carrageenan injection. The granulomatous formation of the cotton pellet was profoundly suppressed by BLG at 2.68, 5.35 and 10.7 mg/g by 15.4%, 38.2% (P<0.01) and 58.9% (P<0.001), respectively. BLG also inhibited lung W/D ratio and the release of prostaglandin E2 (PGE2) in ALI mice. In addition, the median lethal dose (LD50), median effective dose (ED50) and half maximal inhibitory concentration (IC50) of BLG were found to be 42.7, 3.2 and 12.33 mg/g, respectively. All the findings suggest that BLG has significantly anti-inflammatory and analgesic effects and it may help reduce the damage of ALI.

Phytochemical screening and anti-inflammatory properties of Algerian Hertia cheirifolia methanol extract

Context: Hertia cheirifolia L. (Asteraceae) is traditionally used in Northern Africa to treat various inflammatory infections. However, few studies on this plant have been reported.Objective: The anti-inflammatory activity of methanol extract of H. cheirifolia leaves was investigated using different experimental models.Materials and methods: Phytochemical analysis was performed to determine phenolic compounds. Acute toxicity of the extract (2000 mg/kg) was examined in Swiss albino mice for 14 days, before croton oil-induced ear oedema in mice, carrageenan-induced paw oedema in Swiss albino rats, cotton pellet-induced granuloma in rats and carrageenan-induced air pouch in mice were conducted. The IL-1β and TNF-α release from concanavalin A-stimulated monocytes was measured by ELISA.Results: Methanol extract of H. cheirifolia is rich in polyphenols and flavonoids. Cinnamic acid and rutin represent the major constituents. Methanol extract up to 2000 mg/kg did not produce any toxic effects. Topical application of 2 mg/ear of the extract produced 78.7% of inhibition on ear swilling. Oral pre-treatment of rats with 200 and 400 mg/kg of the extract inhibited paw oedema by 70% and 89%, respectively. At 200 mg/kg, granuloma dry and wet weights were reduced by 41.85% and 61.72%, respectively. Moreover, the treatment with methanol extract at 1 mg/kg exerted 62.7% of inhibition on leucocytes migrated into the ear pouch. TNF-α and IL-1β release was reduced by 69% and 78%, respectively, with 1 μg/mL of the extract.Conclusion: Methanol extract of H. cheirifolia possesses a strong anti-inflammatory activity and may be considered an interesting source of effective anti-inflammatory compounds.

Anti-inflammatory effects of boron alone or as adjuvant with dexamethasone in animal models of chronic and granulomatous inflammation

Background: Side effects of anti-inflammatory agents are a major problem during clinical use. The development of a newer, effective, and safe anti-inflammatory agent should be considered. Boron-containing compounds are found effective as anti-inflammatory agents with relatively low side effects. We aimed to evaluate the anti-inflammatory activity of boron in animal models of chronic and granulomatous inflammation. Methods: Sixty-six Wistar rats were allocated into five groups; 1st (6 rats) treated with vehicle only without induction as a negative control; 2nd (12 rats) allocated into two subgroups, treated with vehicle only, with induction of chronic and granulomatous inflammation, as appositive control. 3rd group (24 rats) allocated into four subgroups, treated with different doses of boron (3 and 6 mg/kg) in both models. Fourth group (12 rats) treated with dexamethasone (1 mg/kg) in the same models. 5th group (12 rats used) treated with boron (3 mg/kg) with dexamethasone (1 mg/kg) in the same models. Results: Boron, in a dose-dependent pattern significantly decreases inflammation in rat models of chronic and granulomatous inflammation. Combination of boron with dexamethasone significantly suppresses inflammation in both models, which is significantly higher than all of the effects produced by other approaches of treatment. Conclusion: Boron, in a dose-dependent pattern, effectively suppresses formaldehyde-induced chronic inflammation and cotton pellet-induced granuloma in rats when used alone or as an adjuvant with dexamethasone. It may be considered as a potential treatment for chronic inflammatory conditions.

Phytochemical analysis, antioxidant and anti-inflammatory activities of Phyllanthus simplex

Ethnopharmacological relevancePhyllanthus simplex (Family: Euphorbiacae) is widely used in traditional medicines for treatment of various diseases including inflammation. Materials and methodsPetroleum ether extract (PSPE) and ethanol extract (PSEE) of the whole plant of Phyllanthus simplex were characterized for their total phenolics, tannins and flavonoids content. These extracts were standardized by HPTLC using phyllanthin and gallic acid respectively as markers. Antioxidant activity of extracts was evaluated by the DPPH, hydroxyl and superoxide radicals scavenging assay. The total antioxidant capacity of extracts was determined. Anti-inflammatory activity was evaluated by their effect on nitric oxide (NO) production in isolated rat peritoneal macrophages; carragennan-induced paw edema and formation of cotton pellet-induced granuloma in rats. ResultsAbundance of phenolics was found in PSEE. Phyllanthin and gallic acid content in PSPE and PSEE were found to be 14.5 and 0.65% (w/w) respectively. PSEE showed concentration dependent significant scavenging of DPPH, hydroxyl and superoxide radicals with IC50 values 102.219, 171.485 and 24.73μg/ml respectively. PSEE significantly inhibited NO production in isolated rat peritoneum macrophages. Moreover, it also exhibited significant inhibition of carragennan-induced paw edema (58.48±0.028%, p<0.001, at 6h, 200mg/kg oral dose) and cotton pellet-induced granuloma formation (45.671±0.712%, p<0.001, at 200mg/kg oral dose). Anti-inflammatory activity of PSEE was found to be comparable to diclofenac sodium. ConclusionsSignificant antioxidant and anti-inflammatory activities were found in PSEE which may be attributed to its high phenolic content.

Topical and Systemic Anti-Inflammatory Effects of Echinodorus macrophyllus (Kunth) Micheli (Alismataceae)

Echinodorus macrophyllus leaf has been used in Brazilian folk medicine to treat inflammatory conditions and kidney dysfunctions. The present study evaluated the effects of leaf ethanolic extract from E. macrophyllus (EEEm) in acute and subchronic models of inflammation. The EEEm was found to cause significant and potent inhibition of carrageenan- and dextran-induced paw edema in rats and marked decreases in the exudate volume and leukocyte migration in rats with carrageenan-induced pleurisy, the vascular permeability increase induced by intraperitoneal acetic acid, and the croton oil-induced topical ear edema in mice. On the other hand, the EEEm was not active in the test model of cotton pellet-induced granuloma in rats. Phytochemical analysis with E. macrophyllus leaves revealed the presence of triterpenoids, steroids, flavones, flavonols, and xanthones. Two flavonoids were isolated from the ethyl acetate fraction and identified as isovitexin and vitexin. Our results support the traditional use of E. macrophyllus leaves in the treatment of acute inflammatory conditions.

Anti-inflammatory activity of Aconitum heterophyllum on cotton pellet-induced granuloma in rats

The anti-inflammatory activity of ethanolic root extract of Aconitum heterophyllum(225, 450 and 900 mg/kg p.o) has been evaluated in cotton pellet-induced granuloma in rats. The extract has reduced inflammation as evidenced by decreased weight of cotton pellet in cotton pellet-induced granuloma in rats. The results demonstrate the anti-inflammatory properties of extract and the effects were comparable to diclofenac sodium, a standard non-steroidal anti-inflammatory drug. Key words: Aconitum heterophyllum, cotton-pellet, inflammation.

Antiinflammatory activity of an herbal preparation (HemoHIM) in rats

This study evaluated a new herbal preparation, HemoHIM, for its antiinflammatory activity against carrageenan-induced edema, the formation of granulation tissues by cotton pellet and experimental colitis by 2,4,6-trinitrobenzene sulfonic acid (TNBS). The HemoHIM was prepared by adding its ethanol-insoluble polysaccharide fraction to the total water extract of Angelica Radix, Cnidii Rhizoma and Paeonia Radix. The preparation (4 mg of solids/mL of drinking water, p.o., 50-100 mg/kg of body weight, i.p.) produced a dose-related inhibition of carrageenan-induced paw edema and cotton pellet-induced granuloma in rats. In addition, HemoHIM also reduced the degree of TNBS-induced colitis and improved the gross and histological changes such as thickening, dilatation, ulceration, and infiltration by polymorphonuclear leukocytes and multiple erosive lesions. These results demonstrate that the HemoHIM has a potent antiinflammatory effect.

Preparation of low-molecular-weight polyguluronate sulfate and its anticoagulant and anti-inflammatory activities

Low-molecular-weight polyguluronate sulfate (LPGS) was prepared as a heparinoid by chemical sulfation of polyguluronic acid (PG), which was isolated from the hydrolysate of alginate by pH-fractionated precipitation. The structure of LPGS was elucidated based on FT-IR and 2D NMR spectroscopy. Sulfation was demonstrated to occur at the C-2 and C-3 positions of the guluronic acid residues and the degree of substitution (DS) was 1.53 per monosaccharide residue. The weight-averaged molecular weight of LPGS was 11.4 kDa determined by high performance gel permeation chromatography (HPGPC). The in vitro anticoagulant activity and in vivo anti-inflammatory activity of LPGS were evaluated. Results showed that LPGS significantly prolonged the whole blood clotting time and activated partial thrombinplastin time (APTT), and exhibited considerable anti-inflammatory activity in cotton pellet-induced granuloma in rats.

Studies on the anti-inflammatory and analgesic properties of Tithonia diversifolia leaf extract

A methanol extract of the dried leaves of Tithonia diversifolia was investigated for anti-inflammatory and analgesic activities. The extract (50–200 mg/kg, p.o.) produced dose-related inhibition of carrageenan-induced paw oedema and cotton pellet-induced granuloma in rats. At the same doses, analgesic effect was also observed with hot plate latency assays maintained at (55 °C) as well as on the early and late phases of formalin-induced paw licking in rats. The results of the present study further confirm the use of Tithonia diversifolia traditionally for the treatment of painful inflammatory conditions.

Anti-inflammatory and analgesic activities of Mallotus spodocarpus Airy Shaw

The chloroform extract from the roots of Mallotus spodocarpus was investigated for anti-inflammatory and analgesic activities in animal models. In acute inflammatory models, the extract significantly inhibited ethyl phenylpropiolate-induced ear edema and carrageenin- and arachidonic acid-induced hind paw edema in rats. In the chronic inflammatory model using the cotton pellet-induced granuloma in rats, the extract exhibited inhibitory activity on the formation of granuloma. The extract also elicited pronounced inhibitory effect on acetic acid-induced writhing response in mice in the analgesic test. The results obtained suggest marked anti-inflammatory and analgesic activity of the extract.

Evaluation of the anti-inflammatory and analgesic properties of Chasmanthera dependens leaf methanol extract

A methanol extract of the dried leaves of Chasmanthera dependens was investigated for anti-inflammatory and analgesic activities. The extract (100–400 mg/kg, p.o.) produced dose-related inhibition of carrageenan-induced paw oedema and cotton pellet-induced granuloma in rats. Furthermore, an inhibition in the leakage of Evan's blue induced by acetic acid was observed in mice. At same doses, analgesic effect was also observed on writhing response induced by acetic acid as well as on the early and late phase of formalin-induced paw licking in mice.

Viper venom-induced inflammation and inhibition of free radical formation by pure compound (2-hydroxy-4-methoxy benzoic acid) isolated and purified from anantamul ( Hemidesmus indicus R.Br) root extract

The present investigation explored the possible venom neutralizing effect of a pure compound (2-hydroxy-4-methoxy benzoic acid) isolated and purified from the methanolic root extract of Hemidesmus indicus R.Rr. 2-OH-4-MeO benzoic acid possessed potent anti-inflammatory, antipyretic and antioxidant properties. The compound effectively neutralized inflammation induced by Vipera russelli venom in male albino mice and reduced cotton pellet-induced granuloma in rats. The compound produced a significant fall in body temperature in yeast-induced pyrexia in rats but did not change the normothermic body temperature. The compound effectively neutralized viper venom-induced changes in serum phosphatase and transaminase activity in male albino rats. It also neutralized free radical formation as estimated by TBAPS and superoxide dismutase activities. The antisnake venom activity of the pure compound is partly mediated through the above physiological process.

漢薬・炮附子の薬理活性研究(第1報)アジュバント関節炎に及ぼす炮附子水抽出エキスの影響

Anti-inflammatory activity of a hot water extract (A-ext) of Aconiti Tuber (Aconitum calmicaeli DEBX.) has been studied by using various experimental models. The successive administration of A-ext from the day of injection of adjuvant agent or 5 d after the injection it significantly inhibited the adjuvant-induced arthritis developed in the primary and secondary lesions in rats. However, when A-ext was administered from 11 d after the injection of adjuvant, the arthritic paw edema was not reduced. A-ext did not inhibit an acetic acid-induced increase in vascular permeability in mice and carrageenin-induced paw edema in rats. A-ext inhibited cotton pellet-induced granuloma in rats, but did not suppress the weight of thymus and adrenal gland. In vitro experiment, A-ext contracted the isolated ileum of guinea pig, but the contractive activity was reduced by pretreatment of anti-histamine agent, diphenhydramine, but not by pretreatment of papaverine or atropine. A-ext did not release histamine from peritoneal mast cell. These results suggest that A-ext prevents the adjuvant-induced arthritis and has a histamine-like effect.