色满酮类化合物的合成及其抗炎活性研究

设计合成了4种色满酮类化合物,并利用熔点、红外光谱、核磁共振氢谱等手段确定了其结构。采用二甲苯致小鼠耳肿胀法,测定了该化合物的抗炎活性,实验结果表明在200mg／kg剂量下所合成的3个目标化合物6-[2-（4-吗啉基）乙氧基]色满酮、6-[（喹啉-2-基）甲氧基]色满酮、7-[2-（4-吗啉基）乙氧基]色满酮对二甲苯所致小鼠耳肿胀具有显著的抑制作用。     

杜鹃花活性提取物镇痛抗炎作用的初步研究

目的:研究中药杜鹃花活性提取物总黄酮的抗炎镇痛作用,为进一步临床应用开发提供依据。方法:采用热板法致小鼠疼痛观察杜鹃花的镇痛作用,通过大鼠足注射弗氏完全佐剂诱导大鼠足肿胀,通过测定不同时间点的足趾容积评价抗炎作用。结果:杜鹃花中、高剂量可明显延长小鼠热板舔足反应潜伏期,与空白对照组比较有显著性差异(p0.01),且有一定的量效关系。杜鹃花低、中、高剂量组对大鼠足肿胀具有明显的抑制作用,与模型组比较有显著性差异(p0.01)。结论:杜鹃花活性提取物总黄酮具有显著的镇痛抗炎作用,且抗炎效果较好,为该药物临床上用于关节炎的治疗提供了依据。     

虎床方提取物的抗过敏及抗炎作用研究

目的:选用虎杖、蛇床子、苦参、川芎等四味中药按中医配伍理论组成虎床方,并探讨组方提取物的抗过敏及抗炎作用。方法:采用煎煮法提取其有效组分,分为低中高三个剂量组,分别为1,2,3 g/m L;通过高浓度的DNCB致敏和低浓度的DNCB多次激发,构建湿疹小鼠模型,给药后测定小鼠耳肿胀厚度、脾指数和胸腺指数、耳组织中TNF-α的水平;通过对二甲苯致小鼠耳部急性炎症的抗炎模型,测定小鼠的耳廓肿胀度。结果:虎床方低、中、高剂量均能显著抑制湿疹小鼠的耳肿胀度,并且中剂量时可显著抑制湿疹小鼠的耳肿胀度,同时中剂量时显著降低耳组织表皮厚度和肥大细胞数,亦可降低湿疹小鼠的脾指数,并抑制胸腺指数;虎床方中剂量能显著减少湿疹小鼠耳组织TNF-α及血清Ig E和TNF-α含量,减轻炎性皮损;虎床方中、高剂量组显著降低二甲苯致小鼠耳廓肿胀度。结论:虎床方具有一定的抗过敏及抗炎作用。     

3,4-二氢-4-(1-哌啶甲基)-5H-1-苯并氧杂-5-酮盐酸盐的合成及其生物活性研究

α,β-不饱和环戊酮的Mannich碱和α,β-不饱和环己酮的Mannich碱具有显著的抗炎活性,为了寻求新的具有抗炎活性的环酮类化合物,设计了3,4-二氢-4-(1-哌啶甲基)-5H-1-苯并氧杂-5-酮盐酸盐作为目标化合物。以苯酚、γ-丁内酯、甲醛和哌啶等原料合成了目标化合物,并利用熔点、红外光谱、核磁共振氢谱等手段确定了其结构。采用二甲苯致小鼠耳肿胀法,测定了该化合物的抗炎活性,实验结果表明在200mg/kg剂量下该化合物对二甲苯所致小鼠耳肿胀的抑制率为54.5%。采用Born's比浊法测定了该化合物的抗血小板聚集活性,实验结果表明该化合物的抗血小板聚集活性比噻氯匹啶强约23倍。     

黄河三角洲产地管花肉苁蓉不同极性提取物抗炎镇痛活性的研究

目的:研究比较黄河三角洲产地管花肉苁蓉不同极性提取物抗炎镇痛的活性,为其临床试验和进一步应用提供参考依据。方法:采用耳肿胀法和棉球肉芽组织增生法致炎,研究管花肉苁蓉不同极性提取物灌胃给药对急性炎症的作用。采用热板法和醋酸扭体法致痛,研究管花肉苁蓉不同极性提取物灌胃给药的镇痛作用。结果:管花肉苁蓉不同极性提取物对小鼠的耳肿胀、棉球肉芽肿、热板痛阈值时间以及扭体次数有抑制作用,但同模型对照组比较差异不显著。结论:管花肉苁蓉有一定的抗炎镇痛作用。     

含与不含朱砂的七厘散抗炎作用的实验研究

目的 :比较七厘散和去朱砂七厘散的抗炎作用。方法:分别给各组小鼠、大鼠连续灌胃相应受试药物3 d,通过小鼠耳肿胀模型、大鼠足趾肿胀模型观察抗炎作用。结果:与模型对照组比较,各药物组均能不同程度的降低小鼠耳肿胀率与大鼠足趾肿胀率,其中七厘散高剂量组、去朱砂七厘散高剂量组能显著降低小鼠耳肿胀率;七厘散和去朱砂七厘散低、高剂量组(除七厘散低剂量组在第3 h外)在致炎3 h内均能显著降低大鼠足趾肿胀率。与七厘散低、高剂量组比较,去朱砂七厘散低、高剂量组对小鼠耳肿胀率和大鼠足趾肿胀率均无明显差异。结论:去朱砂七厘散的抗炎作用随着剂量的增加而增加,且与七厘散的抗炎作用无明显差异,就抗炎作用而论,可以去掉七厘散中的朱砂。     

藿香蓟抗炎活性部位筛选

目的:用藿香蓟不同极性的提取物,筛选藿香蓟抗炎的活性部位。方法:依次用石油醚、乙酸乙酯、正丁醇和水提取藿香蓟,得到不同极性部位提取物,分别进行二甲苯诱导小鼠耳肿胀实验和醋酸致小鼠腹腔毛血细管通透性增加实验。结果:正丁醇、乙酸乙酯和石油醚部位对小鼠的耳肿胀有明显的抑制作用(P0.01或P0.05);水部位能显著降低醋酸致小鼠腹腔毛细血管通透性(P0.05)。结论:藿香蓟各个极性部位提取物均有明显的抗炎作用,都可作为藿香蓟抗炎活性部位。     

清炎颗粒清咽、抗炎作用研究

[目的]研究清炎颗粒清咽、抗炎作用研究。[方法]采用2,4-二硝基苯酚溶液致热作用,采用二甲苯致小鼠耳肿胀法复制小鼠炎症模型观察清炎颗粒抗炎作用。[结果]清咽抗炎颗粒剂量组对2,4-二硝基苯酚致大鼠体温升高均有明显的抑制作用,对二甲苯致大鼠耳片急性炎症反应均有明显的抑制作用,清咽抗炎颗粒组对1%角叉菜胶引起的大鼠足跖肿胀性炎症反应均有明显的抑制作用。与空白对照组比较,差异均具有统计学意义(均P0.05)。[结论]清炎颗粒具有清咽、抗炎作用。     

王不留行提取物的急性毒理学研究

探究了王不留行提取物对小鼠的毒性剂量并对其毒性表现进行观察。采用常规急性毒理学研究的方法,选用ICR小鼠探究最小致毒量和最小致死量,HE染色观察其主要器官形态学变化,玻璃毛细管法测定血液凝固时间,生化法测定组织SOD活力、MDA含量及血清BUN、AST、ALT含量。结果显示:(1)致毒剂量:王不留行提取物对小鼠的最小致毒量为100 mg/kg,最小致死量为1500 mg/kg;(2)毒性表现:低剂量组(200 mg/kg)给药后1 d凝血时间缩短,其余指标与对照组相比无显著差异,高剂量组(1000 mg/kg)小鼠自主活动减少,体重增长率明显下降,给药后1 d血液凝固时间缩短,主要器官形态学明显改变,心脏SOD活性降低,MDA含量升高,血清BUN含量升高,其余指标未见明显改变。王不留行提取物高剂量(1000 mg/kg)对小鼠的血液凝固、心和肾脏有一定的毒性作用。     

鼠妇提取物对炎性渗出的抑制作用研究

本研究主要采用小鼠足肿胀模型,选用角叉菜胶、硫酸葡聚糖和化合物48/80等三种致炎剂开展抗炎实验,考察药材鼠妇对炎性渗出的抑制作用,并采用液质联用技术探索其活性成分。实验结果发现鼠妇提取物能够显著缓解不同炎症模型的炎性水肿程度,表明其具有抑制急性炎性渗出的作用。液相分析表明鼠妇中含有抗炎成分牛磺酸。     

Anti-Inflammatory Effects of 4-Methylcyclopentadecanone on Edema Models in Mice

The present study evaluated the anti-inflammatory effects of 4-methylcyclopentadecanone (4-MCPC) on edema models in mice and aimed to determine the safety of 4-MCPC after acute exposure. The acute toxicity of 4-MCPC was evaluated by oral administration to rats of single doses of 0, 5, 50, 500 and 5000 mg/kg. Toxic symptoms were observed for 14 days. The anti-inflammatory activity was evaluated in xylene-induced mouse ear edema and carrageenan-induced mouse paw edema. The animals were treated with 4-MCPC once every day for seven consecutive days. Edema index, % inhibition, IL-1β, TNF-α, PGE₂ and MPO levels in paws were detected after the treatment with xylene or carrageenan. Our results indicated that the LD₅₀ value of 4-MCPC in rats is greater than 5000 mg/kg. The ED₅₀ of 4-MCPC in xylene-induced mouse ear edema model was 7.5 mg/kg. 4-MCPC (8 or 16 mg/kg) remarkably inhibited carrageenan-induced mouse paw edema. Further study revealed that 4-MCPC treatment also decreased IL-1β, TNF-α, PGE₂ and MPO levels in mice paws. Intragastric administration of 4-MCPC exhibited more significant anti-inflammatory activity than muscone at a dose of 16 mg/kg. Taken together, our results suggest that 4-MCPC has potent anti-inflammatory activity and the mechanisms might be related to the decreases of the levels of IL-1β, TNF-α, PGE₂ and MPO in inflamed paws.     

The Extraction Solvent Influences the Anti-Inflammatory Effects of Jakyakgamcho-Tang in Lipopolysaccharide-Stimulated Macrophages and Mice with Gouty Arthritis

Jakyakgamcho-Tang (JGT) is a traditional medicine used to treat muscular tension, spasm, and pain. Several studies have reported its clinical use as an anti-inflammatory and in gynaecological treatment. This study aimed to compare the anti-inflammatory effects of JGT according to extraction solvent, water (JGTW) and 30% EtOH (JGTE) on lipopolysaccharide (LPS)—stimulated macrophages and in mice with monosodium urate (MSU)—induced gouty arthritis. We evaluated the production of inflammatory mediators and cytokines and the expression of inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX-2) in RAW 264.7 cells. We also examined oedema, pain, and inflammation in MSU-induced mice by measuring affected hind paw swelling, weight-bearing, pro-inflammatory cytokines levels, and myeloperoxidase (MPO) activity. In LPS-stimulated RAW264.7 cells, JGTW and JGTE significantly decreased prostaglandin (PG) E2(PGE2) production via suppressing COX-2 expression and cytokines interleukin-1β and interleukin-6. Only JGTE reduced the production of NO and cytokines and the mRNA levels of iNOS and cytokines. In MSU-induced mice, JGTE and JGTW efficiently decreased paw swelling and attenuated joint pain. JGTE (200 and 300 mg/kg) effectively suppressed inflammation by downregulating pro-inflammatory cytokines (tumour necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6) and MPO activity, which were only slightly reduced by JGTW. Our data demonstrate the anti-inflammatory activity of JGT in macrophage and gouty arthritis animal models and show that JGTE is more effective than JGTW at lower concentrations.     

New approaches to clarify antinociceptive and anti-inflammatory effects of the ethanol extract from Vernonia condensata leaves

The present study was aimed at evaluating the antinociceptive and anti-inflammatory effects of the ethanol extract from Vernonia condensata leaves in animal models, in order to afford a better understanding of these properties. The extract reduced the number of abdominal contortions at doses of 100 (51.00 ± 3.00), 200 (42.00 ± 2.98) and 400 mg/kg (39.00 ± 4.00). In formalin tests, a significant reduction in the licking time (p < 0.01) was observed in the first phase by 25.14 (200 mg/kg = 51.50 ± 4.44) and 31.15% (400 mg/kg = 48.00 ± 4.37). The doses of 100 (43.37 ± 5.15), 200 (34.62 ± 4.16) and 400 mg/kg (28.37 ± 3.98) inhibited (p < 0.001) the second phase. After 60 and 90 min of treatment, a dose of 400 mg/kg (10.13 ± 0.39 and 11.14 ± 1.33, respectively) increased the latency time. Doses of 200 and 400 mg/kg potentiated the sleeping time induced by diazepam, pentobarbital and meprobamate. The extracts (100, 200 and 400 mg/kg) showed anti-inflammatory effects by a decrease in paw edema. The extracts also reduced the exudate volume at the doses of 200 and 400 mg/kg. The leukocyte migration had significant effect (p < 0.001) at doses of 100, 200 and 400 mg/kg. The completion of additional experiments in the investigation of the antinociceptive and anti-inflammatory activities of V. condensata allowed a better understanding of the central and peripheral mechanisms involved.     

忍冬水提物对卵清蛋白致敏小鼠的疗效

目的研究忍冬水提物对卵清蛋白(Ovalbumin,OVA)致敏小鼠的疗效。方法建立OVA致敏小鼠模型,将OVA致敏BALB/c小鼠随机分为5组,即忍冬水提物高浓度组(H组)、中浓度组(M组)、低浓度组(L组)、模型对照组(CH组)及阴性对照组(NS组);采用小鼠足垫肿胀试验检测迟发型超敏反应;甲苯胺蓝及HE染色观察小鼠肠系膜、空肠肥大细胞及空肠绒毛上皮细胞形态;ELISA法检测小鼠血清OVA特异性IgE及IgG1、小肠黏液总IgA及OVA特异性IgA水平。结果 OVA致敏小鼠出现急性腹泻;致敏小鼠经足垫皮内激发,出现迟发型超敏反应;致敏小鼠肠系膜及空肠肥大细胞聚集、胞质颗粒外泄及空肠绒毛炎症细胞浸润;小鼠血清OVA特异性IgE及小肠黏液OVA特异性IgA水平明显升高(P均<0.01)。经H、M组忍冬水提物灌胃后致敏小鼠的一般状态、腹泻情况及空肠炎症明显缓解;OVA介导的足垫肿胀反应明显减弱;小鼠血清OVA特异性IgE及小肠黏液OVA特异性IgA水平明显降低(P均<0.01)。结论一定浓度忍冬水提物可有效缓解OVA致敏小鼠的速发型与迟发型超敏反应,其中高浓度金银花忍冬水提物效果较好。提示忍冬科植物中某些成分具有抗过敏作用。     

气相色谱-质谱联用分析化妆品中的四种氯代烃

建立了GC-MS联用分析化妆品中四种氯代烃的方法。样品中的四氯化碳、三氯乙烯、1,1,2-三氯乙烷和四氯乙烯经顶空加热提取后,用中等极性毛细管柱（HP-VOC）分离并采用质谱检测器（MS）测定。结果表明四氯化碳的标准曲线为Y＝18221500X-733803,相关系数0．9994,试样3个添加水平下的回收率为71．5％～112．3％,方法检出限为0．31 mg/kg;三氯乙烯的标准曲线为Y＝9633820X-338659,相关系数0．9989,试样3个添加水平下的回收率为73．8％～118．6％,方法检出限为0．83 mg/kg;1,1,2-三氯乙烷的标准曲线为Y＝189350X＋953532,相关系数0．9985,试样3个添加水平下的回收率为81．2％～109．6％,方法检出限为2．5 mg/kg;四氯乙烯的标准曲线为Y＝5738810X-3956440,相关系数0．9979,试样3个添加水平下的回收率为75．5％～111．1％,方法检出限为0．75 mg/kg。     

IL-37 Targets TSLP-Primed Basophils to Alleviate Atopic Dermatitis

Atopic dermatitis (AD) represents a severe global burden on physical, physiological and mental health. Innate immune cell basophils are essential for provoking allergic inflammation in AD. However, the roles of novel immunoregulatory cytokine IL-37 in basophils remain elusive. We employed in vitro co-culture of human basophils and human keratinocyte HaCaT cells and an in vivo MC903-induced AD murine model to investigate the anti-inflammatory mechanism of IL-37. In the in vitro model, IL-37b significantly decreased Der p1-induced thymic stromal lymphopoietin (TSLP) overexpression in HaCaT cells and decreased the expression of TSLP receptor as well as basophil activation marker CD203c on basophils. IL-37 could also reduce Th2 cytokine IL-4 release from TSLP-primed basophils ex vivo. In the in vivo model, alternative depletion of basophils ameliorated AD symptoms and significantly lowered the Th2 cell and eosinophil populations in the ear and spleen of the mice. Blocking TSLP alleviated the AD-like symptoms and reduced the infiltration of basophils in the spleen. In CRISPR/Cas9 human IL-37b knock-in mice or mice with direct treatment by human IL-37b antibody, AD symptoms including ear swelling and itching were significantly alleviated upon MC903 challenge. Notably, IL-37b presence significantly reduced the basophil infiltration in ear lesions. In summary, IL-37b could regulate the TSLP-mediated activation of basophils and reduce the release of IL-4. The results, therefore, suggest that IL-37 may target TSLP-primed basophils to alleviate AD.     

山奈酚对小鼠迟发型超敏反应的免疫抑制作用

目的探讨山奈酚(kaempferol,KA)对二硝基氟苯(dinitrofluorobenzene,DNFB)诱导的小鼠迟发型超敏反应(delayed type hypersensitivity,DTH)的免疫抑制作用。方法将BALB/c小鼠按体重随机分为6组:生理盐水对照组、DTH模型组、环磷酰胺(cytoxan,CTX)组(20 mg/kg)、KA低剂量(2 mg/kg)、中剂量(4 mg/kg)、高剂量(8 mg/kg)组,每组10只,用DNFB致敏,同时给药,连续给药7 d。致敏后第5天于小鼠右耳背涂1%DNFB 5μl诱发DTH,左耳涂等量的丙酮/橄榄油溶剂作为对照。连续给药7 d后,称量小鼠体重及脾脏和胸腺湿重,计算脾脏指数和胸腺指数;DNFB激发后48 h,剪下小鼠左右耳廓,称重,计算小鼠耳廓肿胀度,并将剪取的右耳耳廓制成冰冻切片,光学显微镜下观察小鼠耳廓局部组织的病理变化;无菌取脾,制备脾细胞,MTT法检测经ConA刺激的脾淋巴细胞的增殖活力。结果 KA高剂量组能显著降低DTH小鼠的脾脏指数和胸腺指数(P<0.01或P<0.05);KA中、高剂量组能明显抑制DNFB所诱发的小鼠耳廓肿胀度(P<0.05或P<0.01);KA能明显减少DTH小鼠耳廓局部组织淋巴细胞的浸润,并抑制脾脏淋巴细胞的增殖(P<0.05或P<0.01)。结论 KA对DTH小鼠具有明显的免疫抑制作用,抑制淋巴细胞的增殖可能是其作用机制之一。     

Pharmacological Proprieties of the Ethanol Extract of Muehlenbeckia platyclada (F. Muell.) Meisn. Leaves

Antinociceptive and anti-inflammatory activities of the Muehlenbeckia platyclada leaves' ethanol extract were investigated in animal models. The extract (p.o.) reduced the number of abdominal contortions induced by acetic acid by 21.57% (400 mg/kg). After intraplantar injection of formalin, a dose of 400 mg/kg (p.o.) inhibited the time spent paw licking in the first phase (26.43%), while the second phase was inhibited by 10.90 and 36.65% at the doses of 200 and 400 mg/kg, respectively. The extract (p.o.) increased the reaction time on a hot plate at a dose of 400 mg/kg (32.68 and 40.30%) after 60 and 90 minutes of treatment, respectively. The paw edema was reduced by extract (p.o.) at doses of 100 (15.46 and 16.67%), 200 (22.68 and 25.64%) and 400 mg/kg (29.50 and 37.33%) after 3 to 4 h of carrageenan application, respectively. Doses of 100, 200 and 400 mg/kg (p.o.), administered 4 h after the carrageenan injection, reduced the exudate volume (11.28, 21.54 and 45.13%), while leukocyte migration was reduced by 21.21 and 29.70% at the doses of 200 and 400 mg/kg, respectively. These results indicate that the ethanol extract from M. platyclada may constitute a potential target for the discovery of new molecules with antinociceptive and anti-inflammatory activities that can be explored for their therapeutic use.     

Effect of radiotherapy and chemotherapy on composition of tumor membrane phospholipids

Phospholipid extracts were made of a murine mammary adenocarcinoma implanted in the dorsum of the foot of C3H/He mice before and 96 h after 17 Gy irradiation or 150 mg/kg cyclophosphamide. Extracts of untreated tumors, which had grown for a further 96 h, were also studied. Although previous studies have shown significant changes in the precursors and catabolites of phosphatidylcholine and phosphatidylethanolamine following therapy, ³¹P nuclear magnetic resonance analysis of extracts showed no changes in these membrane constituents and other observed phospholipid species. A significant decrease in 1-alkyl-2-acyl-sn-glycero-3-phosphocholine, however, was observed 96 h following cyclophosphamide treatment.