• Biomolecules & Therapeutics
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• v.2 no.1
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• pp.71-76
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• 1994

Anti-inflammatory and analgesic activities and skin irritation of piroxicam patch were investigated. Piroxicam patch increased the pain threshold in rat hind paw inflamed by carrageenan and inhibited writhing induced by acetic acid in mice. Piroxicam patch also inhibited the carrageenan-induced edema in rat hind paw as well as the increased vascular permeability induced by histamine in rats. In adjuvant arthritis of rats, piroxicam patch showed anti-inflammatory effects. Skin irritation of piroxicam patch was tested in Newzealand White rabbits and evaluated by Primary Irritation Index of Draize. The results from skin irritation test showed that piroxicam patch seemed practically non-irritating. The result from the present study indicates that piroxicam may be useful without serious side effects as anti-inflammatory analgesics in this patch form.

• Journal of Pharmaceutical Investigation
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• v.29 no.2
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• pp.137-143
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• 1999

Ketoprofen together with various permeation enhancers was incorporated into a novel soft hydrogel which is semi-solid in a container and to form a thin film within a few minutes after applying on the skin. The effect of various enhancers on the skin permeation of ketoprofen from a soft hydrogel was investigated using in vitro and in vivo method. In vitro rat skin permeation of ketoprofen from soft hydrogel was conducted using modified Keshary-Chien diffusion cells. In vivo ketoprofen absorption was also investigated in rats, and the results were compared with that of commercial products. Anti-inflammatory activities were determined using carrageenan-induced paw edema method and adjuvant-induced arthritis method in rats. The anti-inflammatory activity of ketoprofen soft hydrogel formulation with that of commercial products were compared. In vitro as well as in vivo studies showed that $HPE-101^{\circledR}$ was the most effective skin permeation enhancer among those used in this study. Addition of an adhesive (polyisobutylene) in the soft hydrogel decreased skin permeation of ketoprofen. Paw edema and anti-arthritis tests showed that soft hydrogel containing $HPE-101^{\circledR}$ was more effective than the commercial products, which was consistent with the in vivo absorption experiment results.

• Archives of Pharmacal Research
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• v.27 no.2
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• pp.189-193
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• 2004

Clerodendron trichotomum Thunberg Leaves (CTL) have been used for centuries in Chinese folk medicine for their anti-inflammatory properties. We have studied the anti-inflammatory effects of CTL extracts in rats, mice and in Raw 264.7 cells. 1 mg/kg solutions of the 30％ and 60％ methanol extracts of CTL were used and a 1 mg/kg of indomethacin was used as a positive anti-inflammatory standard; these were then administrated to rats. Carrageenan was injected subcutaneously to induce hind paw edema in rats. The result of carrageenan-induced rat paw oedema showed that a 1 mg/kg of the 30％, and 60％ methanol fraction of CTL and 1 mg/kg of indomethacin inhibited the hind paw edema by 19.5％, 23.0％, and 20.5％ respectively. The effect of CTL on inflammation in mice by a capillary permeability assay was examined by detecting Evans blue leakage from capillaries after the intraperitoneal injection of acetic acid, a potent inflammatory stimulus. The 60％ methanol fraction of CTL inhibited Evans blue dye leakage by 47.0％, which was 10％ higher than that of the inhibition of 1 mg/kg of indomethacin. Also, the 60％ methanol fraction of CTL suppressed the prostaglandin $E_2$ ($PGE_2$) generation in RAW 264.7 macrophage cells after treatment with lipopolysaccharide (LPS) by as much as the inhibition of 1 mg/kg of indomethacin and this led to the synthesis of $PGE_2$ by COX-2 induction. The inhibition of the carrageenan-induced rat paw oedema, vascular permeability and the $PGE_2$ generation demonstrates that the 60％ methanol fraction of CTL contains a potent anti-inflammatory activity.

• Herbal Formula Science
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• v.29 no.4
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• pp.205-227
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• 2021

Objectives : Jigal-san (JGS, 止渴散) has been used in East Asia including Korea, Japan and China for the treatment of breast inflammatory disorders and severe thirst. JGS originated from Euimunpalbeob (醫門八法; Yimenbafa) composed of Lonicerae Flos and Taraxaci Herba. According to previous studies Lonicerae Flos and Taraxaci Herba have an anti-inflammatory effect, respectively. But, there is no studies regarding on the effects of JGS in the immunological activities. The present study evaluated the anti-inflammatory effects of JGS in vitro and in vivo. Methods : Cell viability was evaluated by MTT assay, and NO was evaluated by content of the nitrite content in culture medium. TNF-α, IL-1β and IL-6 were quantified by ELISA. The protein expression of NF-κB, MAPKs, and iNOS were assessed by western blot analysis. Furthermore, the effects of JGS on acute inflammation were observed in rat paw edema model. Results : The JGS ameliorates the LPS-activated changes in the protein expression of NF-κB, p-JNK, and iNOS, as well as the production of NO and pro-inflammatory cytokines. In rat paw edema study, administration of 0.3 and 1.0 g/kg of JGS for 4 consecutive days inhibited the carrageenan (CA)-induced increases of edema and iNOS expression. Conclusions : These results demonstrate that JGS has anti-inflammatory effect in LPS-stimulated RAW 264.7 cells through decreasing the production of inflammatory mediators, via suppression of the NF-κB and MAPK pathways (JNK, not p-38 and ERK). In addition, the results of the CA-induced paw edema indicate that JGS ameliorates an inflammatory edema. Therefore, the present study could provide scientific evidence for the anti-inflammatory effect of JGS as well as the underlying mechanisms.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.261.1-261.1
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• 2002

The leaves of Clerodendron trichotomum Thunberg(CTL) is used in Chinese folk medicine for anti-inflammatory properties. We studied on the anti-inflammatory effects of CTL extracts in rat. mouse and Raw 264.7cell. 1 mg/kg of 30%. 60% methanol fraction of CTL and 1 mg/kg of indomethacin as the standard anti-inflammatory drug were administrated into rats, respectively. Carrageenan was injected subcutaneously to induce hind paw edema in rats. (omitted)

• Archives of Pharmacal Research
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• v.25 no.3
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• pp.336-342
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• 2002

MeOH extract of Kochia scoparia was fractionated into $CHCl_3-$, EtOAc- and BuOH extracts and the last fraction were hydrolyzed by 3%-NaOH ($MeOH-H_2O$) to compare the bioactivities on antinociceptive and anti-inflammatory effects. Silica gel column chromatography of BuOH fraction afforded a large amount of $3-Ο-{\beta}-D-xylopyranosyl {\;}(1{\rightarrow}3)-{\beta}-D-glucuronopyranosyl$ oleanolic acid (momordin Ic, 4) and that of acid hydrolysate of BuOH fraction gave $3-Ο-{\beta}-D-glucuronopyranosyl oleanolic$ acid (momordin Ib, 3), its 6'-Ο-methyl ester (2) and oleanolic acid (1). Silica gel column chromatography of alkaline hydrolysate afforded a large amount of 4. MeOH extract and both EtOAc- and BuOH fractions were active in the rheumatoidal rat induced Freund's complete adjuvant reagent (FCA) whereas $CHCl_3$ fraction was inactive. Compound 1 and 4 showed significant activities in the same assay but oleanolic acid 3-Ο-glucuronopyranoside (3) showed no activity. These fashions were also observed in carrageenan-induced edema of the rat and in the antinociceptive activity tests undertaken in hot plate- and writhing methods. These results suggest that momordin Ic and its aglycone, oleanolic acid, could be active principles for rheumatoid arthritis.

• Archives of Pharmacal Research
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• v.21 no.4
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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.

• Biomolecules & Therapeutics
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• v.7 no.2
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• pp.198-203
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• 1999

Loxoprofen-Na (sodium 2-〔4-(2-oxocyclopentylmethyl)pheny)propionate dihydrate) is a potent analgesic drug. We developed loxoprofen-Na plasters to extend duration time of analgesic activity and to reduce side effect on gastrointestinal tract. Analgesic effect of Loxoprofen-Na plasters was investigated. Loxoprofen-Na plaster had good analgesic effect in rat paw pressure test, Tail-flick latency test and acetic acid-induced writhing test. Also, it had anti-inflammatory effect on carrageenan-induced rat hind paw edema. In pharmacokinetic study of Loxoprofen-Na, plasters dosage form showed that plasma drug concentration was prolonged up to 14 hours. So, we can conclude that loxoprofen-Na plasters, when applied on skin, will be a new type of drug for controlling the various local pain or inflammation.

• Archives of Pharmacal Research
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• v.16 no.1
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• pp.18-24
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• 1993

In this inverstigation, the various flavonoid aglycones were evaluated for their inhibitory activities against croton-oil or arachidonic acid induced mouse ear edema by oral or topical administration. The compounds tested were thirteen derivatives of flavan-3-ol(catechin and epicatechin), flavanone (flavanone and naringenin), flavone (flavone, chrysin and apigenin), flavonol(favonol, galangin, quercetin and morin) and isoflavone (biochanin A and 2-carbethoxy-5,7-dihydroxy-4'-methoxyisoflavone), along with hydrocortisone, indomethacin, 4-bormophenacyl bromide, nordihydroguaiaretic acid and phenidone as positive controls. A(isoflavone) were found to show broad inhibitoty activities (14-52%) against croton-oil or arachidonic acid induced ear edema by oral or topical application at the dose of 2 mg/mouse, although they showed less activity than hydrocortisone (26-88%) or indomethacin (36-80%). Flavonoid agtlycones tested showed higher activity when aplied topically than by the oral administration. It was also found that they inhibited arachidonic acid induced edema more profoundly than croton-oil induced edema by topical application. In arachidonic acid induced edema when applied topically, flavone derivatives such as flavone, chrysin and apigenin were revealed to be the good inhibitory agents in addition to flavonols and isoflavones. When quercetin and biochanin. A were selected for evaluating in carrageenan induced rat pleurisy and biochanin both flavonoids showed antiinflammatory activity at the dose of 70 mg/kg by the oral adminis-tration. All of these results revealed that flavonoid aglycones, especially 5,7-dihydroxy-flavonols having hydroxyl group(s) in B-ring and biochanin A (isoflavone) possessed in vivo antiinflammatory activity.

• Herbal Formula Science
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• v.27 no.2
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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.