It has been documented that SPA0355 exerts anti-inflammatory effects via the inhibition of nuclear factor¬kappaB activation. In present study, we investigated the inhibitory effects of SPA0355 on periodontitis in an animal model. Periodontitis was induced by ligation of the cervix of the 1st molar in the left mandible in rats. After ligature, the rats were randomly divided into four groups and topically applied with SPA0355 (0.5, 1, and 2%) or the vehicle alone once daily for 10 days. Body weight and food intake were measured daily throughout the experimental period. At day 10 post-ligature, the infiltration of inflammatory cells and distance of the cementoenamel junction (CEJ) to the alveolar bone crest (ABC) in the distal area of ligatured tooth were estimated histopathologically. No changes in body weight or food intake were found between the control and SPA0355 groups. The degree of inflammation was decreased in all three SPA0355 application groups. A decrease CEJ-ABC distance was observed in the 0.5% and 1% SPA0355 groups. These results indicate that SPA0355 inhibits the infiltration of inflammatory cells and alveolar bone resorption and suggests its potential as a therapeutic agent for periodontitis.

Calcineurin-binding protein 1 (Cabin1) regulates calcineurin phosphatase activity as well as the activation, apoptosis, and inflammatory responses of fibroblast-like synoviocytes (FLSs), which actively participate in the chronic inflammatory responses in rheumatoid arthritis (RA). However, the mechanism of action of Cabin1 in FLS apoptosis is not clear. The aim of this study was to define the regulatory role of Cabin1 in FLSs of mice with collagen-induced arthritis (CIA). Transgenic mice overexpressing human Cabin1 in joint tissues, under the control of a type II collagen promoter, were generated. hCabin1 expression in joints and FLSs was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis. The expression of cytokines, matrix metalloproteinases (MMPs), and apoptosis-related genes in FLSs was determined by enzyme- linked immunosorbent assay, gelatin zymography, and RT-PCR, respectively. Joints were histologically examined after H&E and TRAP staining. hCabin1-transgenic CIA mice had less severe arthritis than wild-type CIA mice, based on hind paw thickness and histology. This was accompanied by significantly enhanced apoptosis in transgenic mice, evidenced by significantly more TUNEL-positive cells in synovial tissues. The expression of inflammatory cytokines and MMPs was reduced, and the transgenic CIA mice exhibited decreased Akt activation and increased expression of p53, caspase-3, caspase-9, and Bax. hCabin1 plays a critical role in promoting apoptosis of FLSs and in attenuating inflammation and the destruction of cartilage and bone in RA. These findings help elucidate the pathogenic mechanisms of RA and suggest that Cabin1 is a potential target for RA treatment.

The anti-inflammatory effect of PHBV/Collagen (PHCP) was examined in a mouse model of lipopolysaccharide (LPS)-induced skin inflammation. Vascular permeability on the back skin was measured by the local accumulation of Evan’s blue dye after subcutaneous injection of LPS (30 µg site^-1 ). Dye leakage in the skin showed a significant increase at 2 h after injection of LPS. This LPS-induced dye leakage was also completely inhibited by HO-1 inhibitor, ZnPP, and antioxidants, including methyl gallate, trolox, and mannitol. To study the possible mechanisms underlying the in vivo anti-inflammatory effect of PHCP against LPS-induced inflammation, we also examined the effects of PHCP on malondialdehyde (MDA) and glutathione levels in skin tissues and found that pretreatment with PHCP resulted in inhibited MDA elevation and a remarkable reduction of glutathione level. In addition, similar results were obtained after pretreatment with antioxidants, including trolox and mannitol, and HO-1 inhibitor, ZnPP. Histopathologically, an influx of neutrophils into the skin dermis was detected between 24 h and 72 h after LPS injection (30, 100 µg site^-1), compared to control animals after injection of saline. This increase was greater in mice treated with 100 µg of LPS than in those treated with 30 µg of LPS and was significantly suppressed by pretreatment with PHCP, antioxidants, and HO-1 inhibitor. These results collectively suggest that PHCP has an anti-inflammatory effect against LPS-induced inflammation model in vivo and may be a good candidate for the skin tissue engineering biomedical application primarily through manipulation of the redox state.

This study was conducted for evaluation of the alleviating effects of Phellodendrin cortex water extract (PCWE) on skin inflammation in hairless mice. Skin inflammation was induced by UVB irradiation and application of squalene monohydroperoxide (Sq-OOH) to the back skin of hairless mice for six weeks. At the same time, saline (C), jojoba oil (VC), PCWE (E), and 0.01% retinoic acid diluted with polyethylene glycol (PC) were applied topically twice per day, six days per week for a period of six weeks. The skin erythema index of the E group was lower than that of the C group. Epidermis and dermis of the C group were remarkably thickened, compared to the PC or E group. In the C group, infiltration of many inflammatory cells, including neutrophils and lymphocytes, was observed in dermis, and a large number of mast cells were observed in dermis and hypodermis; the degree of degranulation was remarkable. However, these phenomena were alleviated in the PC and E2 groups. The E group showed a lower activity in skin xanthine oxidase but a higher activity in skin superoxide dismutase, compared to the C group (P<0.05). The VC, PC, and E groups also showed a high activity of skin catalase by 25.3%, 58%, and 42%, respectively, compared to the C group. Taken together, these results indicate that PCWE could have an alleviating efficacy on skin inflammation induced by UVB irradiation and application of Sq-OOH in hairless mice.

Taraxaci Herba has long been used in herbal medicine for their choleretic, anti-heumatic and diuretic properties. In the present study, we investigated the effects of origin plants of Taraxaci Herba, Taraxacum coreanum Nakai, as an anti-inflammatory agent in lipopolysaccharide(LPS)-induced microglial activation in BV2 cells. NNMBS273, the EtOH extracts of roots T. coreanum was examined for anti-neuronal inflammatory activity as new drug development. The roots of T. coreanum, showed the potent anti-neuroinflammatory effects on LPS-induced inflammation in microglial BV2 cells. The anti-inflammatory effects of NNMBS273, the EtOH extracts of roots T. coreanum was demonstrated by the suppression of pro-inflammatory mediators, including pro-inflammatory enzymes (inducible nitric oxide synthase and cyclooxygenase-2) and cytokines (tumor necrosis factor-α and interleukin-1β). These results suggest that the roots T. coreanum may be a promising candidate for the treatment of neurodegenerative diseases related to neuroinflammation.

Coumarin derivatives were shown to possess valuable pharmacological properties such as anticancer/anti carcinogenic, anti-inflammatory, anti helicobacter, anti genotoxic, neuroprotective and dietary effect. In this study, novel coumarin derivatives structurally related to 7-geranyloxycoumarin were effectively synthesised in good yields by Cs2CO3/acetonitrile in mild condition. The synthesis of geranyloxycoumarin derivatives in weak base(Na2CO3, K2CO3, Cs2CO3 etc)/CH3CN at room temperature obtained in good yield. On the other hand, the reaction of geranyloxycoumarin formation in strong base(NaOH, KOH, CsOH etc)/CH3CN at reflux condition obtained in low yield.

The aim of this study was to evaluate the alleviative effects of a nude pack containing black tea water extract (NPBT) on inflammation and skin barrier damage in hairless mice. Skin inflammation and skin barrier damage were induced by UVB irradiation to the backs of hairless mice for five weeks. And, at the same time, saline (C), NPBT (1%: E1, 2%: E2), and 0.01% retinoic acid diluted with polyethylene glycol (PC) were applied topically twice per day, five days per week, for a period of five weeks. The skin erythema indices of the E1 and E2 groups were significantly lower (p<0.05) than those of the C group through one week after the beginning of the experiment. Meanwhile, water contents of the E1 and E2 groups were significantly higher (p<0.05) than those of the C group through two weeks after the beginning of the experiment. Remarkable thickening of epidermis and dermis was observed in the C group, compared with the PC, E1, or E2 groups. In the C group, infiltration of many inflammatory cells, including neutrophils and lymphocytes, was observed in dermis and a large number of mast cells were observed in dermis and hypodermis, and the degree of degranulation was remarkable. However, these phenomena were alleviated in the PC, E1, and E2 groups. Therefore, NPBT could have considerable inhibitory efficacy on inflammation and skin barrier damage induced by UVB irradiation.

We investigated the role of the central MAPK pathways in extra-territorial (referred) pain resulting from inflammation of the temporomandibular joint (TMJ). Experiments were carried out on male Sprague-Dawley rats weighing 220-280 g. Under anesthesia, these animals were injected with 50 μL of complete Freund's adjuvant (CFA) into the TMJ using a Hamilton syringe. In the control group, saline was injected into the TMJ. To identify the extent of inflammation of the TMJ, Evans blue dye (0.1%, 5 mg/kg) was injected intravenously at 1, 3, 6, 9, 12 and 15 days after CFA injection. The concentration of Evans blue dye in the extracted TMJ tissue was found to be significantly higher in the CFA-treated animals than in the saline-treated group. Air-puff thresholds in the vibrissa pad area were evaluated 3 days before and at 3, 6, 9, 12, 15 and 18 days after CFA injection into the TMJ. Referred mechanical allodynia was established at 3 days, remained until 12 days, and recovered to preoperative levels at 18 days after CFA injection. This referred mechanical allodynia was observed in contralateral side area. To investigate the role of central MAPK pathways, MAPK inhibitors (10 μg) were administrated intracisternally 9 days after CFA injection. SB203580, a p38 MAPK inhibitor, significantly attenuated referred mechanical allodynia, as compared with the vehicle group. PD98059, a MEK inhibitor, also reduced CFA-induced referred mechanical allodynia. These results suggest that TMJ inflammation produces extra-territorial mechanical allodynia, and that this is mediated by central MAPK pathways.

Periodontal disease is a major oral disorder and comprises a group of infections that lead to inflammation of the gingiva and the destruction of periodontal tissues. PPARy plays an important role in the regulation of several metabolic pathways and has recently been implicated in inflammatory response pathways. However, its effects on periodontal inflammation have yet to be clarified. In our current study, we evaluated the anti-inflammatory effects of PPARy on periodontal disease. Human gingival fibroblasts (HGFs) treated with lipopolysaccharide (LPS) showed high levels of intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), matrix metalloproteinase-2 (MMP-2), and -9 (MMP-9). Moreover, these cells also showed upregulated activities for extracellular signal regulated kinase (ERK1/2), inducible nitric oxide synthase (iNOS) and cyclooxygnase-2. However, cells treated with Ad/PPARy and rosiglitazone in same culture system showed reduced ICAM-1, VCAM-1, MMP-2, -9 and COX-2. Finally, the anti-inflammatory effects of PPARy appear to be mediated via the suppression of the ERK1/2 pathway and consequent inhibition of NF-kB translocation. Our present findings thus suggest that PPARy indeed has a pivotal role in gingival inflammation and may be a putative molecular target for future therapeutic strategies to control chronic periodontal disease.

Ischemia that causes stroke induces inflammation of brain cells and apoptosis and as a result, it influences much on the functional part of a man. The needle electrode electrical stimulation (NEES) that combines acupuncture of oriental medicine with electric therapy of western medicine relieves inflammation of cells and has effect on regrowth of nerve tissues. This study was conducted to verify the influence of NEES on the occurrence of c-Fos of cerebrum after applying NEES to the meridian point, Zusanli (ST 36) of a rats with induced ischemia. Global ischemia was induced by using ligation method on common carotid artery of male Sprague Dawley (SD) rats. The ligation was maintained for 5 minutes and then suture was removed for blood reperfusion. After inducing global ischemia, NEES was done to the left and right meridian points of Joksamri of a rat for 30 minutes after 12 hours, 24 hours, and 48 hours. The findings were as follows. 1. In the result of immunohistochemical method, the number of c-Fos immune response cells significantly decreased (P<.05) in NEES group than the control group (GI) that did not get NEES. 2. In the result of western blotting, the occurrence of c-Fos after 24 hours from the inducement of ischemia significantly decreased (P<.05) in NEES group than the control group (GI) that did not get NEES. Therefore, as the effect of NEES was shown highest after 24 hours from the ischemia, it is suspected that NEES would take important role in early treatment after cerebral stroke.

This study was carried out to investigate inflammation-related gene expression altered in ovary and endometrium of Korean cattle with reproductive disorders using microarray. In the present study, nine inflammation-related differential1y expressed genes (DEGs) were identified in the cystic ovary and endometrium with endometritis. In the follicular cyst, eotaxin and alpha-2-HS-glycoprotein (AHSG) were up-regulated, whereas complement component 3 (C3) and oxidised low density lipoprotein (lectin-like) receptor 1 (OLR1) were down-regulated. Complement component 4A (C4A) was up-regulated in luteal cyst. In the endometritis, chemokine 1igand l and 2 (CXCL1 and CXCL2), protein C (inactivator of coagulation factors Va and VIIIa), and complement component C5 were up-regulated, whereas kininogen was down-regulated. Of these genes, we focused on eotaxin and kininogen, which were highly regulated in the follicular cyst and endometritis, respectively and on C3 commonly regulated in both reproductive disorders. The microarray data of eotaxin, kininogen, and C3 were validated by semi-quantitative PCR. Consistent with microarray data, eotaxin was up-regulated by 4-fold in the follicular cyst, while kininogen was down-regulated by 5-fold in the endometritis. C3 was down-regulated in the both follicular cyst and endometritis. Our results suggest that these inflammation-related genes could be useful markers for diagnosis of cystic ovary and endometritis of Korean cattle.

까le orofacial pain is one of the most common types of acute or chronic pain, and many forms of orofacial pain have an inflammatory component. The aim of this study was to develop a behavioral model of orofacial pain associated with chronic int1ammation in rats. 까le int1ammatory agent, CFA suspended in an oil/saline (1 :1) emulsion (50 씨) was injected into the vibrissal pad of adult male rats. A s따피ar application of saline was served as control. Spontaneous and mechanically evoked behaviours were monitored daily in awake rats before and up to 6 weeks after injection. As for the spontaneous behaviour, total time rat spent in face gr∞ming was counted. For the measurement of mechanically evoked behaviour, the threshold and frequency of head withdrawal response (HWR) were determined at the vibrissal pad with the use of von Frey nylon monofilaments. CFA injection did not produce any significant changes in face gr∞ming， but produced a s핑nificant reduction in HWR threshold and a s핑nificant increase in HWR frequency to mechanical stimulation of the vibrissal pad on the ipsilateral side for approximately 4-6 weeks. Saline injection into the vibrissal pad did not produce any significant changes in spontaneous and mechanically evoked behaviours. These results indicate that the injection of CFA into orofacial cutaneous tissues can induce persistent behavioral allodynia and hyperalgesia, and easily quantified behavioral model will provide a better understanding of mechanisms and control of orofacial chronic pain conditions associated with int1ammation.

Adenophorae Radix (AR) has been used as a traditional medicine for various diseases. However, the regulatory mechanisms of AR in allergic inflammation are not yet understood. The present study was conducted to investigate the effect and mechanisms of AR on the mast cell-mediated allergic response. To determine the pharmacological mechanisms of AR in allergic inflammation, we evaluated the effects of AR on the production of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β and IL-8 as well as the activation of nuclear factor-κB (NF-κB) and caspase-1 in phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cells (HMC-1). Our results demonstrated that AR effectively attenuated the PMACI-induced production of TNF-α, IL-6, IL-1β and IL-8 in stimulated HMC-1. Additionally, we showed that the inhibitory effect of AR on inflammatory cytokines in PMACI-stimulated HMC-1 cells involved the suppression of the activation NF-kB/caspase-1 in PMACI-stimulated HMC-1. Collectively, these findings provide experimental evidence that AR may be a useful candidate for the treatment of allergic inflammation.

Lilium lancifolium (LL) is widely cultivated in East Asia and used to attenuate airway diseases. Our current study aimed to investigate the therapeutic effect of LL on pain level and inflammatory response in a rat model of monosodium iodoacetate (MIA)-induced osteoarthritis (OA). We first examined the effect of LL on inflammatory cytokines and inflammatory mediators in IL-1β-treated HTB-94 cells. The LL extract was found to significantly inhibit the levels of Interleukin-6 (IL-6), Interleukin-8 (IL-8), and prostaglandin-E2 (PGE-2) in Interleukin-1 β (IL-1β)-stimulated HTB-94 cells in a dose-dependent manner. Moreover, chronic oral administration of LL effectively restored the weight-bearing distribution in the rat model of MIA-induced OA. In addition, administration of LL inhibited inflammatory cytokines and inflammatory mediators, such as C-reactive protein (CRP), IL-6, leukotriene B4 (LTB-4), PGE-2, and matrix metalloproteinase-9 (MMP-9). Our findings collectively suggested LL as one of the potential therapeutic agents for OA, owing to its properties of reducing pain and inflammatory responses.

염증은 신체 특정 조직의 감염 및 손상에 관한 생체 반응이며, 매개하는 주요 대상은 면역세포이다. 염증은 급성과 만성 염증으로 나뉘며 신체 조직의 감염 및 손상부위의 규모에 따라 구분 할 수 있다. 염증의 범위가 크게 발현되거나 급성염증 형태로 진행되지 않을 때 만성 염증으로 진행되며 대표적인 만성 염증 질환인 장 질환(Inflammatory bowel disease)의 일종인 크론병 (Crohn’s disease)이나 관절질환인 류머티스성 관절염(Rheumatoid arthritis)으로 나타난다. 낮은 수준이기는 하나 비만 역시 염증성 질환으로 분류할 수 있다. 연리초속 식물이 고래에 신장염을 치료하는 민간처방으로 주로 사용됐기에 이에 착안하여 털연리초(Lathyrus palustris)를 이용하여 세포독성과 항염증 활성 효과를 평가하였다. 대식세포인 RAW 264.7 세포에서 염증 유발 인자인 lipopolysaccharide (LPS)로 자극 후 NO와 PGE2 같은 염증 매개 물질들의 억제 효과를 확인하였다. 털연리초 에탄올 추출물을 처리한 후 염증 매개 물질의 저해율(%)을 측정했을 때 NO 및 PGE2 생성을 농도 의존적으로 현저하게 억제하는 농도는 40 ㎍/mL이었으며 특이적으로 PGE2 발현을 74% 이상 강력히 억제함을 확인하였다. 따라서 본 연구결과는 털연리초의 에탄올 추출물이 유의성 있는 항염증 효과를 나타내었고 이러한 생리활성 효과는 예방의학적 소재로서의 가능성을 충분히 제시할 수 있기에 염증 질환의 예방 및 비만 억제를 위한 기능성 건강식품의 개발로 이어질 것으로 기대된다. 또한 염증 과 관련된 사이토카인 물질인 IL-4, IL-13 및 염증 지표 단백질 인 iNOS, COX-2의 억제 메커니즘과 항염증 활성을 나타내는 핵심 성분의 추가적인 연구가 차후 필요할 것으로 판단된다.

The root extracts of Paeonia lactiflora cv. ‘Red Charm’ has been studied by many groups, however, little attention has been paid to its flower petal. Paeonia is the genus in the Paeoniaceae family. ‘Red Charm’ Paeonia is a soft-stemmed herbaceous peony hybrid of P. officinalis and P. lactiflora. We previously showed the flower petal extract of Red Charm might have anti-oxidant and anti-inflammatory activities, however, it was not clear which components might be involved in this activity. Bioinformatics analysis previously indicated these extracts have potential anti-oxidant materials. One of them is identified as paeoniflorin, which is major component in root extract of Red Charm. In this study, we compared paeoniflorin and oxypaeoniflorin using DPPH assays to measure its anti-oxidant activities. Oxypaeoniflorin showed higher levels of radical scavenging activity, similar to ascorbic acid control, whereas paeoniflorin did not. Furthermore, nitric oxide assay showed they have similar anti-inflammatory effects. Taken together, these results suggest oxypaeoniflorin may play a more important role in the anti-oxidant activity of the flower petal and root extracts of Red Charm, compared to paeoniflorin. Further studies may be able to provide a platform to develop potential dual effects therapeutics for oxidant-mediated and inflammation-mediated disease in the near future.

Avocado, superfood, contains a variety of essential nutrients and phytochemicals. The purpose of this study was to explore whether avocado could modulate skin inflammation in vivo. We elucidated the pharmacological effects of avocado on compound 48/80- or histamine-induced scratching behaviors and 2, 4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD)-like skin lesions in mice. Additionally, we investigated the anti-inflammatory activity of avocado and its underlying mechanism including its effect on the expression levels of inflammatory-related genes and nuclear factor -κB (NF-κB) in DNCB-induced AD-like skin lesions. The findings of this study demonstrate that avocado attenuated AD clinical symptoms including itching, eczematous, erythema and dryness and histamine levels in mice. Moreover, avocado suppressed both inflammatory cytokines expression as well as NF-κB and caspase-1 activation in AD-like skin lesions in mice. Taken together, these results demonstrate that avocado may be a potential candidate for treating skin inflammatory diseases like AD.

Zanthoxylum piperitum D.C. (ZP) peels has been used as a natural spice and herb medicine for hypertension reduction, for strokes, and for its anti-bacterial and anti-oxidant activity. However, the anti-inflammatory mechanisms employed by ZP have yet to be completely understood. In this study, we elucidate the anti-inflammatory mechanism of ZP in lipopolysaccharide (LPS)-induced RAW264.7 cells. We evaluated the effects of ZP in LPS-induced levels of inflammatory cytokines, prostaglandin E2 (PGE2), and caspase-1 using ELISA. The expression levels of inflammatoryrelated genes, including cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS), were assayed by Western blot analysis. We elucidated the effect of ZP on nuclear factor (NF)-κB activation by means of a luciferase activity assay. The findings of this study demonstrated that ZP inhibited the production of inflammatory cytokine and PGE2 and inhibited the increased levels of COX-2 and iNOS caused by LPS. Additionally, we showed that the anti-inflammatory effect of ZP arises by suppressing the activation of NF-κB and caspase-1 in LPS- induced RAW264.7 cells. These results provide novel insights into the pharmacological actions of ZP as a potential candidate for development of new drugs to treat inflammatory diseases.