Preprocessing and Efficacy Analysis of Comprehensive Anti-Inflammatory Treatment for Lymphedema in Patients with Irritating Contact Dermatitis

Objective: To explore the pre-treatment and efficacy analysis of comprehensive anti-inflammatory treatment for lymphedema in patients with irritating contact dermatitis. Method: Convenience sampling method was used to observe the skin of 160 patients with upper limb lymphedema admitted to the lymphedema outpatient department of our hospital. They were divided into an observation group (80 cases) and a control group (80 cases), and both groups received a course of comprehensive anti-inflammatory treatment (20 treatments). The control group received routine skin care;On the basis of the control group, the observation group received pre-treatment of the affected limb skin: Laofuzi herbal ointment was applied externally to the prone areas of irritating contact dermatitis (such as the upper arm, inner forearm, and cubital fossa). Result: The incidence of irritating contact dermatitis in the observation group was significantly lower than that in the control group (P 0.05). Patients in the observation group felt significantly better in terms of comfort, skin moisture, and itching relief after being wrapped with low elasticity bandages than those in the control group (P Conclusion: Preventive treatment can effectively reduce the incidence of irritating contact dermatitis, prolong the time of stress treatment, thereby increasing efficacy and improving patient compliance.

Phytochemical constituents,analgesic and anti-inflammatory effects of methanol extract of Triumfetta rhomboidea leaves in animal models

Objective:To investigate the analgesic and anti-inflammatory effects of the methanolic extract of the leaves of Triumfetta rhomboidea on mice and rats respectively.And to screen the phytochemical constituent of the extract. Methods:The analgesic effect was determined by acetic acid-induced writhing test in mice.While the anti-inflammatory activity was determined by egg albumin-induced oedema of the rat paw.Phytochemical screening was done by standard procedures.Results:Triumfetta rhomboidea leaf extract(50 -400 mg/kg) caused a statistically significant inhibition on the egg albumin-induced eodema or inflammation in Wister albino rats with P【0.001(ANOVA).This effect was higher than the observed effect with Piroxicam(0.5 mg/kg) which was used as a standard.The effect was also dose-dependent.Furthermore,Triumfetta rhomboidea extract caused a statistically significant reduction in the number of acetic acid-induced writhing in mice,with P【0.001(ANOVA).These effects were also does-dependent and greater than the analgesic effects by paracetamol which was used as a reference drug.Phytochemical screening revealed the presence of flavonoids,steroids, triterpenoids alkaloids,tannins and saponins in Truimfetta rhomboidea leaf extract.Conclusion:Triumfetta rhomboidea can be recommended for acute inflammatory disorders and diseases associated with pains.This also supports its traditional use as an anti-snake bite and anti-cancer or anti-tumor agent.Further study is on the way to find out the mechanism of its action and also to isolate,identify and characterize the active principle responsible for these effects in this plant.

Anti-inflammatory and analgesic activities with gastroprotective effect of semi-purified fractions and isolation of pure compounds from Mediterranean gorgonian Eunicella singularis

Objective: To explore anti-inflammatory activities of organic extract and its semi-purified fractions(ethanol, acetone, methanol/dichloromethane) from the Mediterranean gorgonian Eunicella singularis. Methods: The anti-inflammatory and analgesic activities were evaluated, using the carrageenan-induced rat paw edema model and the acetic acid writhing test in mice. The gastroprotective activity was determined using HCl/Et OH induced gastric ulcers in rats. The purification and structure elucidation of compound(s) from the more effective fraction were determined by chromatographic and spectroscopic methods and in comparison with data reported in the literature. Results: The fraction F-Et OH showed an important antiinflammatory activity associated with significant analgesic and gastroprotective properties. The purification and structure elucidation of compound(s) from this fraction lead to the identification of one diterpenoid and four sterols. Conclusions: These results suggested that components from the active fraction can be used to treat various anti-inflammatory diseases.

A Preliminary Study on Anti-inflammatory and Analgesic Effects of Millettia speciosa and Tinpspora sinensis and Their Compatibility

[Objectives]To study the anti-inflammatory and analgesic effects of Millettia speciosa and Tinpspora sinensis and their compatibility.[Methods](i)In the glacial acetic acid writhing experiment,60 SPF-grade Kunming mice were adopted,and the mice were randomly divided into 6 groups at male-female ratio of 1∶1,namely,the blank control group,M.speciosa group,T.sinensis group,M.speciosa compatible with T.sinensis group at the ratio of 1∶2(expressed as 1∶2 compatibility group),M.speciosa compatible with T.sinensis group at the ratio of 1∶1(expressed as 1∶1 compatibility group),and M.speciosa compatible with T.sinensis group at the ratio of 2∶1(expressed as 2∶1 compatibility group),12 mice for each group.Mice of the experimental groups were administered at a dose of 20 mL/kg,and the corresponding concentration of the Chinese medicine extract was given at 1 g/mL.The control group was administered with an equal volume of 0.9%physiological saline,and was intragastrically administered once every 24 h for 14 d.After intragastric administration for one hour on day 14,intraperitoneal injection of 0.5%glacial acetic acid solution was performed to induce pain.(ii)In the hot plate experiment,60 Kunming female SPF mice were adopted,grouped,intragastrically administered with the same glacial acetic acid writhing experiment for 14 d.After intragastric administration for one hour on day 14,the mice were placed on a hot plate apparatus at(55±0.5)℃.to measure the time of licking their hind feet.(iii)In the anti-inflammatory experiment,60 Kunming SPF mice were adopted,grouped,intragastrically administered with the same glacial acetic acid writhing experiment for 14 d.After intragastric administration for one hour on day 14,xylylene was administered to the left ears of mice at a dose of 50μL/piece to induce inflammation.[Results](i)In the glacial acetic acid writhing experiment,compared with the blank control group,the experimental group showed analgesic effects.Specifically,M.speciosa group,T.sinensis group,1∶2 compatibility group,1∶1 compatibility group,2∶1 compatibility group showed significant effect(P<0.05),the writhing inhibition rate was 17.65%,20.59%,29.41%,26.47%,and 44.12%,respectively,and 2∶1 compatibility group showed the most significant analgesic effects.(ii)In the hot plate experiment,compared with the control group,all experimental groups showed analgesic effect.Specifically,M.speciosa group,T.sinensis group,1∶2 compatibility group,1∶1 compatibility group,2∶1 compatibility group showed significant effect(P<0.05),the pain threshold improvement rates were 16.13%,14.55%,14.96%,29.95%,and 58.68%,respectively,and 2∶1 compatibility group showed the most significant analgesic effect.(iii)In the anti-inflammatory experiment,the swelling degree of the 1∶2 compatibility group was significantly different from that of the blank control group,M.speciosa group,T.sinensis group(P<0.05).and 1∶2 compatibility group showed the most significant anti-inflammatory effect.[Conclusions]M.speciosa,T.sinensis,and their compatibility had anti-inflammatory and analgesic effects.The 2∶1 compatibility group had the best analgesic effects,and 1∶2 compatibility group had the best anti-inflammatory effects.

Anti-inflammatory effect of extracts of Dendropanax dentige and Lycopodiastrum casuarinoides on rheumatoid arthritis and their underlying mechanism in rats

OBJECTIVE To investigate the anit-inflammatory effect of extracts of Dendropanax dentiger(Harms)Merr and Lycopodiastrum casuarinoides(Spring)Holub on rheumatoid arthritis(RA)using adjuvant arthritis(AA)rat model and possible mechanisms.METHODS The AA rat model of RA was induced in adult SparagueDawley(SD)rats by injecting of the adjuvant at base oftail.One-week-old male SD rats were randomly divided into the following groups:normal saline group(blank control),D.dentiger decoction group(80g·kg-1·d-1),L.Casuarinoides decoction group(80 g·kg·d-1),the total of glucoside Tripterygium(GTT)group(positive control,2 mg·kg-1·d-1).They were administered orally for 6weeks.Histopathology of tissues arthritis rats was observed by H.E staining.The volume of paw swelling was measured and the arthritis inflammation index was calculated.The expressions of tumor necrosis factor-α(TNF-α)and interlukin-1β(IL-1β)were detected by the ELISA assay.In addition,previous study has reported that plant-derived mi RNAs play a role for cross kingdom regulatory potential.Thus,we also performed RNA-seq technique to identify bioactive mi RNAs via comparative transcriptome analysis between D.dentiger and L.Casuarinoides.RESULTS Comparing with AA model group,the volume of paw swelling and the arthritis index were increased significantly in the AA rat model group(P<0.01),suggesting that the AA model rats were prepared properly.Compared with the AA model group,the volume of paw swelling of D.dentiger decoction group,L.Casuarinoides decoction group was decreased by 25.2%and 10.3%,respectively,and the arthritis index was decreased by 27.2%and 18.3%,respectively.Compared with AA model group,TNF-αprotein expression of D.dentiger decoction group and L.Casuarinoides decoction groups were decreased by 16.3%and 14.7%,and IL-1βprotein expression was decreased by 23.6%,18.9%(P<0.05,P<0.01),respectively.Besides,we found that some plant-derived homologous mi RNAs(such as mi RNA192 and mi RNA30a)associated with cell apoptosis processing have been screened out via comparative transcriptome analysis.But the underlying mechanisms about two mi RNAs function needs much more investigate.CONCLUSION Results showed significant anti-inflammatory effect of aqueous extracts of D.dentiger and L.Cauarinoides and justifying their therapeutic role in inflammatory condition.Furthermore,anti-inflammatory effect of D.dentiger and L.Cauarinoides may be attribute to the herb-derived mi RNAs cross-kingdom regulation.

Anti-inflammatory Effect and Mechanism of Characteristic Medicine Baeckea frutescens L. in Guangxi

[Objectives] This study aimed to investigate the anti-inflammatory effects of Baeckea frutescence L.in vitro and in vivo.[Methods]The anti-inflammatory activity of B.frutescence was measured by mouse peritoneal capillary permeability test,mouse auricle swelling test and rat cotton granuloma test.The RAW264.7 macrophage model was stimulated by lipopolysaccharide(LPS),and the effects of B.frutescence on tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) were detected by enzyme-linked immunosorbent assay(ELISA),and the relative expression of inducible nitric oxide synthase(i NOS) and cyclooxygenase-2(COX-2) proteins was detected by Western blot.Thus,the in vitro anti-inflammatory activity of B.frutescence was studied.[Results] B.frutescence significantly inhibited mouse peritoneal capillary permeability,inhibited xylene-induced mouse auricle swelling and rat cotton granuloma,significantly inhibited TNF-α and IL-6 levels,and down-regulated the expression of i NOS and COX-2 proteins in cells.[Conclusions]B.frutescence showed good anti-inflammatory activity both in vitro and in vivo,and the mechanism may be related to the release inhibition of inflammatory factors TNF-α and the regulation of COX-2.

Anti-inflammatory Effects of Volatile Oil of Ocimum basilicum L. in Bozhou and Its Mechanisms

[Objectives] The research aimed to study the anti-inflammatory effects of volatile oil from Ocimum basilicum L. in Bozhou through the experimental animal model of inflammation.[Methods] Xylene-induced mouse ear swelling model and carrageenan-induced mouse paw swelling model were used to compare the anti-inflammatory effects of volatile oil from O. basilicum L.[Results] The extremely high, high, medium, and low doses of volatile oil from O. basilicum L. had a certain inhibitory effect on the ear swelling of mice induced by xylene ( P <0.05), and the inhibitory effect of high-dose group on the ear swelling of mice was better. The swollen degree of the mice s toes in the different dose groups of volatile oil from O. basilicum L. was significantly lower ( P <0.05), and the high-dose and middle-dose groups had better inhibition.[Conclusions] The volatile oil from O. basilicum L. in Bozhou had a significant inhibitory effect on xylene-induced mouse ear swelling and carrageenan-induced mouse paw swelling. It proved and clarified the anti-inflammatory effects of volatile oil from O. basilicum L. in Bozhou.

玉米黄素减轻脂多糖诱导的3T3-L1脂肪细胞慢性炎症

目的:探究一种天然类胡萝卜素——玉米黄素(ZEA),基于NF-κB信号通路减轻脂多糖(LPS)诱导的3T3-L1脂肪细胞慢性炎症并发挥抗炎的作用机制。方法:以LPS刺激成熟的3T3-L1脂肪细胞建立炎症模型,用不同浓度的ZEA(0,5,10,15μmol/L)进行干预,检测脂肪细胞炎症相关因子的含量,并通过实时荧光定量PCR(qPCR)检测其mRNA表达水平,用蛋白免疫印迹法检测信号通路因子的蛋白表达水平。结果:与LPS组相比,ZEA干预显著抑制炎症细胞模型中促炎因子IL-1β、IL-6、TNF-α和MCP-1分泌(P<0.001),同时促进抗炎因子IL-10和ADPN产生(P<0.001)。此外,qPCR结果显示ZEA能有效抑制促炎因子,同时恢复抗炎因子的mRNA表达水平(P<0.001)。蛋白免疫印迹结果表明,ZEA能明显降低IκB激酶催化亚基IKKα和IKKβ的蛋白和磷酸化表达(P<0.001),增强抑制蛋白IκBα与核转录因子NF-κB p65的结合,最终抑制NF-κB p65进行核内转录。结论:ZEA可通过抑制NF-κB信号通路激活及调控炎性因子的分泌,改善肥胖引起的慢性炎症。

炒白芍-炙甘草配伍前后化学成分与抗炎作用相关性研究

目的明确炒白芍-炙甘草配伍对化学成分的影响及其与抗炎作用的相关性。方法采用HPLCDAD建立同时测定炒白芍-炙甘草中芍药苷、芍药内酯苷、苯甲酰芍药苷、氧化芍药苷、甘草酸、甘草苷多成分含量的分析方法;建立佐剂性关节炎大鼠模型,给药组分别灌胃炒白芍、炙甘草、炒白芍-炙甘草药液2周,ELISA检测大鼠血清炎症因子白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、前列腺素E_(2)(PGE_(2))含量;采用析因设计、双变量相关分析、多元线性回归方法研究配伍对化学成分的影响及其与抗炎药效的相关性。结果建立HPLC-DAD分析方法,炒白芍-炙甘草配伍后氧化芍药苷、芍药内酯苷、苯甲酰芍药苷含量增加(P<0.05);与模型组比较,各给药组大鼠血清IL-1β、TNF-α、PGE_(2)含量降低(P<0.01),且配伍组血清IL-1β、TNF-α、PGE_(2)含量低于炒白芍组、炙甘草组(P<0.05,P<0.01);析因设计结果显示炒白芍-炙甘草配伍存在交互效应,双变量相关分析结果显示氧化芍药苷、芍药内酯苷、芍药苷、甘草苷、苯甲酰芍药苷、甘草酸含量分别与IL-1β、TNF-α、PGE_(2)含量呈负相关,多元线性回归结果显示甘草苷、甘草酸与IL-1β、TNF-α、PGE_(2)含量呈负相关。结论本研究建立的炒白芍-炙甘草多成分含量分析方法简便快捷、专属性强、准确可靠,可用于其质量评价与控制。炒白芍-炙甘草配伍可抑制炎症因子IL-1β、TNF-α、PGE_(2)表达,且化学成分含量与抗炎作用具有相关性。

Non-steroidal anti-inflammatory drugs:What is the actual risk of liver damage?

Non-steroidal anti-inflammatory drugs (NSAIDs) constitute a family of drugs, which taken as a group, represents one of the most frequently prescribed around the world. Thus, not surprisingly NSAIDs, along with antiinfectious agents, list on the top for causes of DrugInduced Liver Injury (DILI). The incidence of liver disease induced by NSAIDs reported in clinical studies is fairly uniform ranging from 0.29/100 000 [95% confidence interval (CI): 0.17-051] to 9/100 000 (95% CI: 6-15). However, compared with these results, a higher risk of liver-related hospitalizations was reported (3-23 per 100 000 patients). NSAIDs exhibit a broad spectrum of liver damage ranging from asymptomatic, transient, hyper-transaminasemia to fulminant hepatic failure. However, under-reporting of asymptomatic, mild cases, as well as of those with transient liver-tests alteration, in conjunction with reports non-compliant with pharmacovigilance criteria to ascertain DILI and flawed epidemiological studies, jeopardize the chance to ascertain the actual risk of NSAIDs hepatotoxicity. Several NSAIDs, namely bromfenac, ibufenac and benoxaprofen, have been withdrawn from the market due to hepatotoxicity; others like nimesulide were never marketed in some countries and withdrawn in others. Indeed, the contro-versy concerning the actual risk of severe liver disease persists within NSAIDs research. The present work intends (1) to provide a critical analysis of the dissimilar results currently available in the literature concerning the epidemiology of NSAIDS hepatotoxicity; and (2) to review the risk of hepatotoxicity for each one of the most commonly employed compounds of the NSAIDs family, based on past and recently published data.

Safety of anti-tumor necrosis factor therapy during pregnancy in patients with inflammatory bowel disease

Treatment of inflammatory bowel disease has significantly improved since the introduction of biological agents, such as infliximab, adalimumab, certolizumab pegol, and golimumab. The Food and Drug Administration has classified these factors in category B, which means that they do not demonstrate a fetal risk. However, during pregnancy fetuses are exposed to high anti-tumor necrosis factor(TNF) levels that are measurable in their plasma after birth. Since antibodies can transfer through the placenta at the end of the second and during the third trimesters, it is important to know the safety profile of these drugs, particularly for the fetus, and whether maintaining relapse of the disease compensates for the potential risks of fetal exposure. The limited data available for the anti-TNF drugs to date have not demonstrated any significant adverse outcomes in the pregnant women who continued their therapy from conception to the first trimester of gestation. However, data suggest that antiTNFs should be discontinued during the third trimester, as they may affect the immunological system of the newborn baby. Each decision should be individualized, based on the distinct characteristics of the patient and her disease. Considering all the above, there is a need for more clinical studies regarding the effect of antiTNF therapeutic agents on pregnancy outcomes.

艾纳香油通过NF-κB非经典信号影响花生四烯酸代谢缓解LPS所致巨噬细胞的炎症反应

【目的】本文旨在探讨艾纳香油(BBO)通过核转录因子κB(NF-κB)非经典通路影响花生四烯酸(AA)代谢通路发挥抗炎作用。【方法】采用豚鼠离体回肠法检测BBO对慢反应物质(SRS-A)生成的影响,ELISA法检测BBO对脂多糖(LPS)诱导巨噬细胞前列腺素E_(2)(PGE_(2))及白三烯B_(4)(LTB_(4))产生的影响,qRT-PCR检测BBO对LPS诱导巨噬细胞COX-2、5-LOX、FLAP和RelB表达的影响,Western blot检测BBO对NF-κB非经典通路蛋白肿瘤坏死因子受体作用因子3(TRAF3)、肿瘤坏死因子受体作用因子2(TRAF2)、NF-κB诱导激酶(NIK)、p100和RelB浓度的影响。【结果】在1mg·mL^(-1)的BBO药物浓度下减弱了豚鼠回肠的收缩张力(P<0.001),对SRS-A的生成抑制率达到65.34%;与LPS模型组相比,BBO在40-80μg·mL^(-1)浓度下降低AA代谢通路中PGE_(2)(P<0.05)和LTB_(4)(P<0.05)的浓度,降低COX-2(P<0.05)、5-LOX(P<0.05)和FLAP(P<0.05)的表达;此外,40-80μg·mL^(-1)浓度下BBO还降低LPS导致的NF-κB非经典通路中TRAF3(P<0.05)、TRAF2(P<0.05)和NIK(P<0.05)的浓度,进一步抑制p100蛋白的磷酸化(P<0.05),同时抑制转录因子RelB的表达(P<0.05)和RelB蛋白的水平(P<0.05),而BBO自身不引起这些基因与蛋白的变化。【结论】BBO可能通过抑制NF-κB非经典信号中调节蛋白TRAF3和TRAF2,转录因子RelB的浓度,造成NIK蛋白的诱导激酶作用受到抑制,进一步抑制了p100蛋白的磷酸化及其与转录因子RelB的结合,从而影响到下游AA通路中重要限速酶COX-2、5-LOX和FLAP的表达与炎症介质PGE_(2)和LTB_(4)的水平发挥抗炎作用。

鞣花酸通过TLR4-SRC/MAPK/NF-κB途径抑制脂多糖诱导RAW264.7巨噬细胞的炎症反应

目的基于Toll样受体4(TLR4)-酪氨酸激酶(SRC)/丝裂原活化蛋白激酶(MAPK)/核转录因子-κB(NF-κB)通路探讨鞣花酸的抗炎机制。方法采用不同浓度(0、0.5、5、25、50、75、100μmol·L^(-1))鞣花酸对RAW264.7巨噬细胞[或脂多糖(LPS)诱导的RAW264.7细胞]干预24 h,噻唑蓝(MTT)法检测RAW264.7巨噬细胞存活率,筛选最适给药浓度。实验分为空白对照组,模型组(0.5 mg·L^(-1)LPS),阳性对照地塞米松组(10μmol·L^(-1)),鞣花酸(5、25、50μmol·L^(-1))给药组。Griess法检测细胞上清液中一氧化氮(NO)的含量;采用ELISA法检测细胞上清液中前列腺素-2(PGE2)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)的表达水平;采用Western blot法检测诱导型一氧化氮合酶(iNOS)、环氧合酶-2(COX-2)蛋白以及TLR4-SRC/MAPK/NF-κB通路相关蛋白的表达水平。结果MTT结果筛选出鞣花酸的干预浓度为5~50μmol·L^(-1)。与空白对照组比较,模型组PGE_(2)、NO和炎症因子IL-6、IL-1β、TNF-α表达显著升高(P<0.01);炎症标志物iNOS、COX-2蛋白表达水平显著升高(P<0.01),说明炎症模型建立成功。与模型组比较,鞣花酸能显著抑制LPS诱导NO、PGE_(2)的产生和降低TNF-α、IL-1β、IL-6水平(P<0.05,P<0.01),降低i NOS、COX-2蛋白表达水平(P<0.05,P<0.01),且呈浓度依赖性;显著抑制TLR4蛋白的表达水平以及SRC、P38、JNK、p65、IκBα蛋白的磷酸化水平,并呈浓度依赖性。但对ERK1/2蛋白磷酸化没有显示出明显的抑制作用。结论鞣花酸可能通过TLR4-SRC/MAPK/NF-κB信号通路的调控抑制LPS诱导RAW264.7巨噬细胞的炎症反应,具体的调控机制有待进一步研究。

基于斑马鱼模型及网络药理学研究植物乳植杆菌HCS03-001抗细菌炎症的作用

过度炎症严重危害人体健康,为了验证植物乳植杆菌HCS03-001的抗炎功效并探讨其抗炎机理,以转基因中性粒细胞绿色荧光斑马鱼为模型,使用细菌脂多糖(lipopolysaccharide,LPS)诱导炎症发生,以吲哚美辛为阳性对照,探究10、20、40 mg·mL-1植物乳植杆菌HCS03-001的抗细菌性炎症功效。通过SwissTargetPrediction、GeneCards和DisGeNET数据库获取植物乳植杆菌代谢产物的主要成分和炎症靶点。靶点取交集后通过STRING数据库构建蛋白质-蛋白质相互作用(the protein-protein interaction,PPI)网络;使用Cytoscape 3.9.0构建菌株代谢产物“成分-靶点-炎症”网络;利用DAVID平台工具对共有靶点进行GO富集分析及KEGG通路富集分析。斑马鱼实验结果显示,不同剂量的HCS03-001均能降低斑马鱼卵黄囊中性粒细胞数量,其中高剂量(40 mg·mL-1)的效果与模型组相比达到显著水平(P<0.05)。网络药理学结果发现,植物乳植杆菌代谢产物缓解炎症的过程中,作用较强的活性成分主要是异吡啶硫胺素、吲哚乙醛和麦角硫因等,可能作用于甘油醛-3-磷酸脱氢酶(glyceraldehyde-3-phosphate dehydrogenase,GAPDH)、环氧合酶2(prostaglandin endoperoxide synthase 2,Ptgs2)、过氧化物酶体增生激活受体γ(peroxisome proliferator-activated receptor gamma,PPARγ)等核心靶点,富集结果显示影响最显著的生物学过程是对LPS的反应,涉及的细胞组分为细胞膜,影响最显著的通路为癌症通路。结果表明,植物乳植杆菌HCS03-001具有显著的抗细菌性炎症功效,其具体机制可能是代谢成分异吡啶硫胺素、吲哚乙醛和麦角硫因等通过抑制细菌LPS与机体细胞膜的结合,以及通过调控GAPDH、Ptgs2、PPARγ等关键靶点影响癌症相关通路实现的。

Design, Synthesis and Pharmacological Evaluation of New Nonsteroidal Anti-Inflammatory Derived from 3-Aminobenzothieno[2,3-<i>d</i>]pyrimidines

During the last few years, condensed thienopyrimidine derivatives have received considerable attention. The therapeutic importance of thienopyrimidines prompted us to synthesize some of spiro(benzothieno[2,3-d]pyrimidine-4-one) derivatives. Some of the novel benzothino-pyrimidine derivatives 3a, 9b, 10b, 11a, 11b, and 11c showed considerable potent anti-inflammatory and analgesic activity of superior G.I.T. safety profile in experimental rats in comparing to indomethacin and tramadol as reference drugs.

Anti-Inflammatory Efficacy of Product Containing “Skin Calm Complex” <i>in Vitro</i>Reconstructed Epidermis

Atopic dermatitis is classified as a chronic inflammatory skin disease, which is characterized by alterations in barrier function and immune system of the skin. In a previous study, the efficacy of REPAVAR ATOPIC SKIN BODY CREAM EXTREME (a product containing “SKIN CALM COMPLEX”) on the epidermal barrier structure was demonstrated. However, the product has also been formulated to improve inflammation and itching. The aim of this study is to analyze product effectiveness on skin inflammation and itching which is associated with atopic dermatitis, by quantification of IL-1α and IL-8 interleukins secreted by human keratinocytes from reconstructed epidermis by ELISA assay. Mature (aged 17 days) sample tissues were treated with pro-inflammatory agents (PBS 1X and LPS) and with the product containing synergistic mix from plants extracts and Dihydroavenanthramide D, among other ingredients (“SKIN CALM COMPLEX”) for 24 hours. Measuring the amounts of interleukins by ELISA assay showed 1) decreased levels of IL-1α and 2) no differences about IL-8 secretion. Product REPAVAR ATOPIC SKIN BODY CREAM EXTREME has an anti-inflammatory effect on the release of pro-inflammatory cytokines, becoming an effective preventive agent on inflammation and itching due to maintenance and improvement of the keratinocyte epidermal structure.

Anti-inflammatory Activity of Phenolic Acids on HAECs Induced by TNF-α

[Objectives] To study the anti-inflammatory activity and mechanism of salvianolic acid A(Sal A), salvianolic acid C(Sal C), and rosmarinic acid(RA) on HAECs induced by TNF-α. [Methods] VE was used as a positive control and TNF-α induced human aortic endothelial cells(HAECs) were selected as the inflammation model cells. The levels of IL-6, MCP-1 were determined using ELISA. The mRNA levels of IL-6, MCP-1, ICAM-1, P-selectin and NF-κB were analyzed by quantitative RT-PCR. The protein expression of NF-κB was determined by western blot. The adhesion of U937 to HAECs was assessed by BCECF/AM labeling assay. Immunohistochemistry detection was used for ICAM-1 and P-selectin expression levels in TNF-induced HAECs, and DHE detection for the ROS production in HAECs induced by TNF-α. [Results] TNF-α-induced over-expressions of IL-6, MCP-1, NF-κB, ICAM-1 and P-selectin in HAECs were down-regulated by Sal A, Sal C and RA both in mRNA or protein levels, respectively. Meanwhile Sal A, Sal C and RA could significantly inhibit the production of ROS and U937 cells adhesion to HAECs. [Conclusions] Phenolic acids could inhibit TNF-α-induced inflammatory responses on HAECs and the mechanism might be related to inhibition of the production of ROS and blocking NF-κB signaling pathway.

复方柏连制剂对小鼠抗炎镇痛作用及湿热型UC模型大鼠TNF-α、IL-6、IL-1β表达的影响

目的探讨复方柏连灌肠剂和凝胶剂的急性毒性、抗炎镇痛和药效学作用,为临床安全用药提供思考方案。方法给小鼠以最大浓度24 h内重复2次灌肠,给大鼠以折算浓度灌肠7 d,分别观察其毒性反应和死亡情况;建立小鼠二甲苯致耳肿胀模型、冰醋酸致扭体模型、环境因素加三硝基苯磺酸(TNBS)/乙醇法致大鼠溃疡性结肠炎(UC)模型,分别观察复方柏连灌肠剂和凝胶剂药效学作用。结果复方柏连制剂灌肠最大给药量生药为161.6 g·kg^(-1),相当于人每日用量的96倍;复方柏连灌肠剂和凝胶剂大、中、小剂量组均能显著降低小鼠耳肿胀率,减少扭体次数,改善湿热型UC模型大鼠结肠组织的病理损伤及降低TNF-α、IL-6、IL-1β含量(P<0.05)。结论复方柏连灌肠剂和凝胶剂临床拟用剂量安全且对直肠黏膜没有刺激性,具有一定的抗炎、镇痛、治疗UC的作用。

Efficacy of boswellic acid on lysosomal acid hydrolases,lipid peroxidation and anti-oxidant status in gouty arthritic mice

Objective:To evaluate the efficacy of boswellic acid against monosodium urate crystal-induced inflammation in mice.Methods:The mice were divided into four experimental groups.GroupⅠserved as control;mice in groupⅡwere injected with monosodium urate crystal;groupⅢconsisted of monosodium urate crystal-induced mice who were treated with boswellic acid(30mg/kg/b.w.);groupⅣcomprised monosodium urate crystal-induced mice who were treated with indomethacin(3mg/kg/b.w.).Paw volume and levels/activities of lysosomal enzymes,lipid peroxidation,anti-oxidant status and inflammatory mediator TNF-αwere determined in control and monosodium urate crystal-induced mice.In addition,the levels ofβ-glucuronidase and lactate dehydrogenase were also measured in monosodium urate crystal-incubated polymorphonuclear leucocytes(PMNL)in vitro.Results:The activities of lysosomal enzymes,lipid peroxidation,and tumour necrosis factor-αlevels and paw volume were increased significantly in monosodium urate crystal-induced mice,whereas the activities of antioxidant status were in turn decreased.However,these changes were modulated to near normal levels upon boswellic acid administration.In vitro,boswellic acid reduced the level ofβ-glucuronidase and lactate dehydrogenase in monosodium urate crystal-incubated PMNL in concentration dependent manner when compared with control cells.Conclusions:The results obtained in this study further strengthen the anti-inflammatory/antiarthritic effect of boswellic acid,which was already well established by several investigators.

Inhibitory Effect of Tanshinones on TNF-α-induced Inflammation in Human Aortic Endothelial Cells

[Objectives] To study the anti-inflammatory activity and mechanism of tanshinone I,cryptotanshinone and 15,16-dihydrotanshinone I on HAECs induced by TNF-α. [Methods]Vitamin E was used as a positive control and TNF-α-induced human aortic endothelial cells( HAECs) were selected as the inflammation model cells. The m RNA levels of IL-6,ICAM-1,VCAM-1,and NF-κB were analyzed by quantitative RT-PCR. The protein expression of NF-κB,ICAM-1,VCAM-1 and phosphorylation of ERK1/2 were determined by Western blot. The adhesion of U937 to HAECs was assessed by BCECF/AM labeling assay. [Results] TNF-α-induced over-expression of IL-6,NF-κB,ICAM-1,and VCAM-1 in HAECs were down-regulated by tanshinone I( TAN),cryptotanshinone( CPT) and 15,16-dihydrotanshinone I( DHT) both in m RNA and protein levels,respectively. Meanwhile 15,16-dihydrotanshinone I and cryptotanshinone could inhibit phosphorylation of ERK1/2 and tanshinone I inhibited U937 adhesion to HAECs significantly. [Conclusions] Tanshinones could inhibit TNF-α induced inflammatory responses on HAECs and the mechanism might be related to inhibition of phosphorylation of ERK1/2 and blocking NF-κB signaling pathway.