• 대한한의학방제학회지
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• 제27권2호
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• pp.101-120
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• 2019

PURPOSE : Euonymi Lignum Suberalatum (EL) is the stem fin of Euonymi alatus. In traditional Korean medicine, EL is used for treatment of uterine bleeding, metritis and static blood. Recently, many studies have reported several pharmacological effects of EL including anticancer, antimicrobial, antidiabetic activity, and anti-oxidative stress. However, the mechanisms underlying anti-inflammatory effects by the EL is not established. METHODS : To investigate anti-inflammatory effects of Euonymi Lignum Suberalatum Water (ELWE), Raw 264.7 cells were pre-treated with $10-300{\mu}g/mL$ of ELWE, and then exposed to $1{\mu}g/mL$ of LPS. Levels of NO, IL-6, $IL-1{\beta}$ and $TNF-{\alpha}$ were detected by ELISA kit. Expression of pro-inflammatory proteins were determined by immunoblot analysis. To evaluate the anti-inflammatory effect in vivo, rat paw edema volume, and expressions of COX-2 and iNOS proteins in carrageenan (CA)-induced rat paw edema model. RESULTS : NO production activated by LPS, was decreased by $30-300{\mu}g/mL$ of ELWE. Production of inflammatory mediators such as $TNF-{\alpha}$, ILs, $PGE_2$ were decreased by ELWE 100 and $300{\mu}g/mL$. In addition, ELWE reduced LPS-mediated iNOS and COX-2 expression. Moreover, ELWE increased $I-{\kappa}B{\alpha}$ expression in cytoplasm and decreased $NF-{\kappa}B$ expression in nucleus. In vivo study, ELWE reduced the increases of paw swelling, and expression of iNOS and COX-2 proteins in paw edema induced by CA injection. CONCLUSION : The results indicate that ELWE could inhibit the acute inflammatory response, via modulation of $NF-{\kappa}B$ activation. Furthermore, inhibition of rat paw edema induced by CA is considered as clear evidence that ELWE may be a useful source to treat acute inflammation.

• Advances in Traditional Medicine
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• 제8권3호
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• pp.252-259
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• 2008

The chloroform extract of Croton roxburghii (Family: Euphorbiaceae) was evaluated for its antipyretic effects in Brewer's yeast induced hyperthermia in rats. The anti-inflammatory effect of the Croton roxburghii was also evaluated by using carrageenan, dextran, histamine, serotonin induced rat paw oedema and cotton pellet induced granuloma (chronic) models in rats. The chloroform extract of Croton roxburghii (CECR) exhibited significant anti-pyretic and anti-inflammatory effect at the dose 50, 100 and 200 mg/kg. Maximum inhibition (55.32%) was notedat the dose of 200 mg/kg after 3 h of drug treatment in carrageenan induced paw oedema, whereas the Indomethacin (standard drug) produced 61.33% of inhibition. The extract exhibited significant anti-inflammatory activity in dextran induced paw edema in a dose dependent manner. In the chronic model (cotton pellet induced granuloma) the CECR (200 mg/kg) and Indomethacin (10 mg/kg) showed decreased formation of granuloma tissue by 52.32% and 56.32% respectively. The extract also exhibited a significant antipyretic response in Brewer's yeast induced pyrexia in rats. Thus, the present study revealed that the CECR exhibited significant antipyretic and anti-inflammatory activity in the tested animal models.

• Toxicological Research
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• 제29권3호
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• pp.195-201
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• 2013

The anti-inflammatory effects of glycosaminoglycan (GAG) derived from Isaria sinclairii (IS) and of IS extracts were investigated in a complete Freund's adjuvant (CFA)-treated chronic arthritis rat model. Groups of rats were treated orally with 30 mg/kg one of the following: [1] saline control, extracts of [2] water-IS, [3] methanol-IS, [4] butanol-IS, [5] ethyl acetate-IS, or [6] Indomethacin(R) as the positive control for a period of two weeks. The anti-paw edema effects of the individual extracts were in the following order: water-IS ex. > methanol ex. > butanol ex. > ethyl acetate ex. The water/methanol extract from I. sinclairii remarkably inhibited UV-mediated upregulation of NF-${\kappa}B$ activity in transfected HaCaT cells. GAG as a water-soluble alcohol precipitated fraction also produced a noticeable anti-edema effect. This GAG also inhibited the pro-inflammatory cytokine levels of prostaglandin $E_2$-stimulated lipopolysaccharide in LAW 264.7 cells, cytokine TNF-${\alpha}$ production in splenocytes, and atherogenesis cytokine levels of vascular endothelial growth factor (VEGF) production in HUVEC cells in a dose-dependent manner. In the histological analysis, the LV dorsal root ganglion, including the articular cartilage, and linked to the paw-treated IS GAG, was repaired against CFA-induced cartilage destruction. Combined treatment with Indomethacin(R) (5 mg/kg) and IS GAG (10 mg/kg) also more effectively inhibited CFA-induced paw edema at 3 hr, 24 hr, and 48 hr to levels comparable to the anti-inflammatory drug, indomethacin. Thus, the IS GAG described here holds great promise as an anti-inflammatory drug in the future.

• 대한한의학회지
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• 제26권3호
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• pp.176-187
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• 2005

Objectives : This study was carried out to investigate the anti-inflammation, anti-development and curative effects of Oyaksunki-sangamibang (OSKM) on collagen-induced arthritis in Wistar rats and ICR mice. Materials & Methods : D experiment part II, the inhibitory effects of nitric oxide synthesis, pro-inflammatory cytokines, and cyclooxygenase were studied. In experiment part II, paw eduma volume and thickness of ankle joint were measured at 0, 10, 15, and 20 days after immunization. The incidence and arthritis score were evaluated 14 days after immunization, At 15 days after immunization, serum $TNF-\alpha$ was analyzed. In experiment part III paw edema volume and thickness of ankle joint were measured at 0, 10, and 15days after treatment. At 15 days after treatment, serum $TNF-\alpha$ was analyzed. Results : In experiment part I: 1. Nitric oxide synthesis ·md pro-inflammatory cytokines were inhibited significantly by OSKM extract. 2. Cyclooxygenase 2 (COX-2) was inhibited by OSKM extract. In experiment part II: Paw edema volume, thickness of ankle joint and serum $TNF-\alpha$ level of the teated group were significantly decreased compared with the control group at 20 days after immunization. In experiment part III: Incidence of arthritis was $70\%$. OSKM-treated group had no significant change on paw edema volume, thickness of ankle joint and serum $TNF-\alpha$ level. Conclusions : These results indicated that OSKM has anti-inflammation effects on the ICR mouse, and higher inhibitory effects on the onset but lower inhibitory effects on the progression of collagen-induced arthritis in rats.

• Journal of Acupuncture Research
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• 제15권2호
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• pp.97-103
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• 1998

Purpose: In order to study the anti-inflammatory and analgesic effects of Bee Venom Therapy, writhing syndrome, carrageenin induced edema, and complete adjuvant induced arthritis were experimented. Methods: 1. We used rats of writhing syndrom induced by acetic acid injection. Group I was treated with Acupuncture therapy. Group II was treated with Bee Venom thearpy. we compared with Group I, II and the control group. 2. We used rats of paw edema induced by carrageenin injection. Group I Was treated with Acupuncture therapy, Group II was treated with Bee Venom thearpy we compared with Group I, II and the control group. 3. We used rats of arthritis induced by Freud's complete adjuvant injection. Group I was treated with Acupuncture therapy, Group II was treated with Bee Venom thearpy we compared with GroupI,II and the control group. Results: 1. Analgesic effects on writhing syndrome induced by acetic acid injection showed statistical significance in Bee Venom treated group as compared with the control group. 2. The paw edema induced by carrageenin injection was decreased with statistical significance in Bee Venom treated group as compared with the control group. 3. The arthritis induced by Freud's complete adjuvant injection wasn't significant. Conclusion: Bee Venom Therapy was effective on inflammatory disease.

• 한국약용작물학회지
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• 제13권6호
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• pp.245-249
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• 2005

신이는 전통적으로 비염 등의 치료에 사용되어 왔는데, 신이 에탄올 추출물은 그람 양성균인 Staphylococcus aureus 그람 음성균인 Pseudomonas fluorescens균 및 곰팡이균인 Aspergillus niger에 대하여 모두 항균활성을 보였으며, proteinase로 활성화된 receptor-2에 의한 흰쥐 뒷발바닥 부종모델에서 신이 에탄올 추출물을 경구투여한 경우 typsin이나 $tc-NH_2$로 유발된 발바닥 부종, 혈관투과성, myoloperoxidase 활성도에서 유의성 있는 억제율을 보여 항염증 활성이 뚜렷함을 나타냈다.

• 생약학회지
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• 제16권1호
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• pp.18-25
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• 1985

Experimental studies were conducted to investigate for the effect of Tongkyu-tang on analgesic, antipyretic, sedative, anti-inflammatory, isolated ileum and anti-histamine actions. Tongkyu-Tang was composed of sixteen crude drugs including Astragali Radix, which has been used for the treatment of common cold, headache, rhinitis, nasal obstruction, rhincospasm, etc. The following results have been obtained; analgesic and antipyretic actions were obtained. Prolonged action against the hypnotic duration of pentobarbital were significantly noted in mice. Anti-inflammatory effects in the paw edema induced by 1% carrageenin and 1% dextran were significantly shown in rats. Spontaneous motilities of isolated ileum of mice were strongly suppressed, and contractions of isolated ileum of mice and guinea-pigs induced by acetylcholine chloride, barium chloride and histamine were remarkably inhibited. Antihistamine actions were noted. Considering the above experimental results, it is suggested that effects of Tongkyu-tang based on the Oriental Medical References were similarly consistent with the actual experimental results.

• Archives of Pharmacal Research
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• 제21권4호
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• pp.406-410
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• 1998

Biflavonoid is one of unique classes of naturally-occurring bioflavonoids. Certain biflavonoids including amentoflavone were previously reported to have inhibitory effect on the group 11 phospholipase $A_2$ activity. Amentoflavone was also found to inhibit cyclooxygenase from guinea-pig epidermis without affecting lipoxygenase. In this study, anti-inflammatory and analgesic activities of amentoflavone were evaluated. When amentoflavone was administered intraperitoneally, it showed a potent anti-inflammatory activity as determined by amelioration of croton-oil induced mouse ear edema. It also showed a potent anti-inflammatory activity in the rat carrageenan paw edema model ($ED_{50}$=42 mg/kg) compared to the activity of prednisolone (35 mg/kg) and indomethacin (10 mg/kg). However, amentoflavone did not show a significant inhibitory activity against rat adjuvant-induced arthritis, a chronic inflammatory model. In addition, amentoflavone was found to possess a potent analgesic activity in the acetic acid writhing test ($ED_{50}$=9.6 mg/kg) compared to the activity of indomethacin (3.8 mg/kg). These results suggest that amentoflavone may be a potential lead for a new type of anti-inflammatory agents having dual inhibitory activity of group 11 phospholipase $A_2$ and cyclooxygenase.

• Archives of Pharmacal Research
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• 제22권3호
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• pp.279-287
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• 1999

Therapeutic use of anti-inflammatory steroids is limited due primarily to their systemic suppressive effects on pituitary function and the immune system.. To overcome the clinical limitation, a new approach toward the discovery of non-systemic anti-inflammatory steroids is based upon the antedrug concept introduced by this laboratory. The new concept describes locally active agents which are designed to undergo a predictable biotransformation to inactive metabolites upon entry into systemic circulation from the applied site. Thus, true antedrugs are devoid of systemic adverse effects. In a continuing effort, 16$\alpha$-carboxylate and isoxazoline derivatives of prednisolone have been synthesized and screened. In the croton oil-induced ear edema bioassay, the following relative potencies were obtained setting hydrocortisone=1.0; 3a, 1.5; 3b, 3.1; 4a, 4.0; 4b, 12.2; 5b, 8.2; 6b, 11.2; 7a, 1.9; 7b, 4.1; 8a, 3.3; 8b 6.8; 9a, 0.7; 9b 8.6; 10a 2.6; 10b, 7.4. Results of the five-day bioassay indicated that, in contrast to the parent compound, the novel steroidal antedrugs did not significantly alter body weight gain, thymus weights, adrenal weights or plasma corticosterone levels. Taken together, the antedrug concept appears to be a fundamentally sound strategy for the separation of local anti-inflammatory activity form systemic adverse effects.

• 약학회지
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• 제34권6호
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• pp.407-414
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• 1990

The relationships of inhibitory activities of inflammation and wound healing of flavonoids were studied in vitro and in vivo. Generally flavonoids have not only significantly anti-inflammatory activity in carrageenin-induced paw edema and Freund's complete adjuvant-induced arthritis, but also inhibitory activity of wound healing. The more inhibitory activities of wound healing flavonoids have, the more they have the anti-inflammatory activities; apigenin > guercetin > flovone > rutin > hesperidin > naringin. Their inhibitory mechanism seems to be inhibition of the inflammatory cell infiltration and fibroblast proliferation, and so they decreased the granulomatous activity and tensile strength.