天麻素对脊髓缺血再灌注损伤中脊髓微循环血流量的影响

目的:观察腹主动脉内灌注天麻素对兔脊髓缺血再灌注损伤(SCIRI)中脊髓微循环血流量(SCMBF)的影响。方法:60只健康新西兰大白兔随机分为正常组、模型组和天麻素低、中、高剂量组(25,50,100 mg·kg-1),除正常组外,采用肾下腹主动脉阻断法,建立SCIRI模型,分别于缺血前,再灌注15,30,60,120 min监测SCMBF变化。分别于缺血前、再灌注6,12,24 h神经功能评分(NFS)。分别于缺血前、缺血45 min,再灌注60,120 min监测血清神经特异性烯醇化酶浓度(NSE),脊髓组织丙二醛(MDA),活性氧(ROS),谷胱甘肽过氧化物酶(GSH-Px),超氧化物歧化酶(SOD),总抗氧化能力(T-AOC)及脊髓病理学变化。结果:与正常组比较,模型组缺血后NSE浓度,MDA和ROS明显增加(P0.01),GSH-Px,SOD及T-AOC明显降低(P0.01)。与模型组比较,缺血后天麻素组NSE,MDA和ROS明显降低(P0.01),GSH-Px,SOD及T-AOC明显升高(P0.01)。天麻素组SCMBF和脊髓灰质的病理损害程度明显轻于模型组(P0.01),NFS较模型组恢复迅速(P0.01)。结论:SCIRI中腹主动脉内灌注天麻素可通过提高脊髓抗氧化能力来减轻脊髓微循环障碍。     

丹参水提物对心肌缺血/再灌注损伤大鼠心率及心肌酶谱的影响

目的:观察丹参水提物对心肌缺血/再灌注(MI/R)损伤大鼠心率及心肌酶谱的影响.方法:SD大鼠随机分为6组:假手术组、模型组、丹参注射液(含生药4 g·kg-1)组、丹参水提物高、中、低剂量(12.8,6.4,3.2 mg·kg-1)组,每组8只.采用在体大鼠结扎冠状动脉前降支缺血30 min后,松扎再灌注30 min,造成MI/R损伤模型,于缺血最后5 min持续到再灌注前5 min通过股静脉推注给予,假手术组模型组予生理盐水.观察丹参水提物对MI/R损伤大鼠模型心率及心肌酶谱的影响.结果:丹参水提物可显著抑制MI/R引起的大鼠心率减慢,显著减少MI/R损伤大鼠血清中天门冬氨酸氨基转移酶(AST)、乳酸脱氢酶( LDH)、肌酸激酶(CK)的溢出.结论:丹参水提物对缺血/再灌注损伤心脏具有一定保护作用.     

Neuroprotective activity of Matricaria recutita Linn against global model of ischemia in rats

Ethnopharmacological relevance

Traditionally, the whole plant is used for various diseases, including neuronal disorders.

Aim of the study

To evaluate the neuroprotective effect of Matricaria recutita L. against global cerebral ischemia/reperfusion (I/R) injury-induced oxidative stress in rats.

Materials and methods

Neuroprotective activity was carried out by global cerebral ischemia on Sprague–Dawley rats by bilateral carotid artery (BCA) occlusion for 30 min followed by 60 min reperfusion. The antioxidant enzymatic and non-enzymatic levels were estimated along with cerebral infarction area and histopathological studies.

Results

The Matricaria recutita L. methanolic extract showed dose-dependent neuroprotective activity by significant decrease in lipid peroxidation (LPO) and increase in the superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and total thiol levels in extract treated groups as compared to ischemia/reperfusion group. Cerebral infarction area was significantly reduced in extract treated groups as compared to ischemia/reperfusion group.

Conclusion

The methanolic extract of Matricaria recutita L. showed potent neuroprotective activity against global cerebral ischemia/reperfusion injury-induced oxidative stress in rats.     

Study on antifibrotic effects of curcumin in rat hepatic stellate cells

Suppression of activation or fibrogenesis and induction of apoptosis, in hepatic stellate cells (HSCs) have been proposed as therapeutic strategies against liver fibrosis. Curcumin, an active compound isolated from yellow curry pigment of turmeric (Curcuma longa Linn), has been demonstrated to be an effective anti‐inflammatory and antioxidant compound. In this study, we investigated the in vitro antifibrogenic effects of curcumin on HSCs at the concentration range of (1–40 µM). A cell line of rat HSCs (HSC‐T6) was stimulated with transforming growth factor‐β1 (TGF‐β1). The inhibitory effects of curcumin (1.25～10 µM) on fibrosis‐related markers including α‐smooth muscle actin (α‐SMA) and collagen were assessed. In addition, the induction effects of curcumin (20～40 µM) on apoptosis in HSC‐T6 cells were also assessed by Hoechst and propidium iodide stains. Curcumin (1.25～10 µM) concentration‐dependently suppressed TGF‐β1‐induced α‐SMA expression and collagen deposition in HSC‐T6 cells, without cytotoxicity. Whereas, higher concentrations of curcumin (20～40 µM) induced cell apoptosis and cytochrome c release in HSC‐T6 cells. Our results suggest that curcumin exerted antifibrotic effects, possibly through two different mechanisms depending on its concentrations. At lower concentrations (1.25～10 µM), curcumin exerted antifibrogenic effects, whereas at higher concentrations (20～40 µM), curcumin exerted induction of apoptosis in HSCs. Copyright © 2009 John Wiley & Sons, Ltd.     

Lipid‐Lowering Effects of Curcumin in Patients with Metabolic Syndrome: A Randomized,Double‐Blind,Placebo‐Controlled Trial

Human studies of curcumin extract on lipid‐lowering effect have not been completely investigated and have had controversy results. This study tested the effect of daily curcumin extract for 12 weeks on weight, glucose, and lipid profiles in patients with metabolic syndrome. Sixty‐five patients were randomized into two groups; 33 patients taking curcumin extract capsule (630 mg thrice daily) and 32 patients taking a placebo capsule thrice daily for 12 weeks. At 12 weeks after the curcumin extract consumption, the level of high‐density lipoprotein cholesterol (HDL‐C) significantly increased from 40.96 ± 8.59 to 43.76 ± 2.79 mg/dL (p < 0.05), and the level of low‐density lipoprotein cholesterol (LDL) was significantly reduced (120.55 ± 36.81 to 106.51 ± 25.02 mg/dL, p < 0.05). The triglyceride‐lowering effect, a reduction of 65 mg/dL, was also found in this study. In subgroups analysis, the consumption of curcumin may have a lowering cholesterol effect in male patients and an increasing HDL‐C effect in female patients, both of which result in a decrease of T‐Chol/HDL‐C ratio. The intake of the curcumin extract of 1890 mg/day for 12 weeks was associated with lipid‐lowering effect but did not improve weight and glucose homeostasis in the patients with metabolic syndrome. Daily curcumin consumption may be an alternative choice to modify cholesterol‐related parameters, especially in metabolic syndrome patients. Copyright © 2014 John Wiley & Sons, Ltd.     

氧化苦参碱对实验性心肌缺血再灌注损伤的保护作用

 目的观察氧化苦参碱(OMT)对心肌缺血再灌注损伤中肿瘤坏死因子(TNF)、丙二醛(MDA)的含量及心肌超微结构的影响,并探讨其对心肌缺血再灌注损伤的保护作用及机制。方法结扎大鼠左冠状动脉前降支制备心肌缺血再灌注模型。雄性Wistar大鼠64只,随机分成假手术组,心肌缺血再灌注组(MIR),60和120 mg·kg^-1OMT处理组,OMT在缺血前5 min经腹腔缓慢注射。各组于缺血前,缺血30 min,再灌90,180 min检测TNF,MDA。TNF用免疫组化检测,MDA采用硫代巴比妥酸(TBA)法测定,并做电镜标本。结果①再灌注后TNF表达开始增加。再灌180 min后OMT组与同时相的MIR组比较TNF表达明显减少,而OMT 60 mg·kg^-1处理组与OMT 120 mg·kg^-1处理组相比无明显变化。②再灌注后MDA合成持续上升。OMT组再灌180 min与同时相MIR组比MDA明显减少(P<0.05),而不同剂量的OMT组之间MDA变化不显著。③电镜显示OMT能减少心肌超微结构的损伤。结论氧化苦参碱对心肌缺血再灌注损伤具有保护作用,且这种保护作用不具有剂量依赖性。     

Ex vivo Effects of an Oenothera paradoxa Extract on the Reactive Oxygen Species Generation and Neutral Endopeptidase Activity in Neutrophils from Patients after Acute Myocardial Infarction

Oxidative stress induced by reactive oxygen species (ROS) is considered to play an important part in the aetiology of coronary heart disease. Apart from ROS, neutrophils are a source of neutral endopeptidase (NEP) that inactivates protective natriuretic peptides. The aim of the present study was to evaluate the in vitro ROS generation and inhibition of NEP activity in neutrophils obtained from healthy volunteers and from patients after acute myocardial infarction (AMI) by an aqueous extract of Oenothera paradoxa. Neutrophils isolated from AMI patients showed two‐fold higher ROS generation compared with cells from healthy donors, especially in the lucigenin‐enhanced luminescence model, which suggests intensive O^‐₂ generation. The addition of O. paradoxa extract at concentrations of 0.2, 2 and 20 µg/mL resulted in a significant reduction in ROS generation. The extracellular NEP activity was higher in patients after AMI compared with healthy individuals (15.0 ± 0.9 versus 10.3 ± 0.5 nmol AMC/10⁶ cells/60 min; p = 0.001). The addition of O. paradoxa extract at concentrations of 20, 50 and 100 µg/mL resulted in a significant reduction in NEP activity in both groups. O. paradoxa extract appears to be an interesting candidate for supplementation in the prevention of cardiovascular diseases. Copyright © 2011 John Wiley & Sons, Ltd.     

姜黄素对大鼠心肌缺血再灌注损伤的保护作用

目的:观察姜黄素对大鼠心肌缺血再灌注损伤的保护作用.方法:结扎大鼠冠状动脉左前降支,使心肌缺血60 min,再灌注60 min,制成急性心肌缺血再灌注损伤模型,缺血前5 min,舌下静脉推注姜黄素.再灌结束时测量心肌梗死面积,测定血清肌酸磷酸激酶(CK),乳酸脱氢酶(LDH),心肌超氧化物歧化酶(SOD),谷胱甘肽过氧化物酶活性(GSH-Px)及心肌丙二醛(MDA)、游离脂肪酸(FFA)含量.结果:姜黄素(20,40 mg/kg)能减少心肌梗死面积,降低血清CK、LDH活性,提高心肌SOD、GSH-Px活性,减少心肌MDA、FFA含量.结论:姜黄素对心肌缺血再灌注损伤的保护作用,与减少脂质过氧化物和增加内源性抗自由基物质的产生,纠正心肌脂肪酸代谢紊乱有关.     

Calcium channel blocking activity of Mentha longifolia L. explains its medicinal use in diarrhoea and gut spasm

Mentha longifolia has a reputation in traditional medicine in the indications of diarrhoea and gut spasm. This study was carried out to provide a possible pharmacological basis for its medicinal use in hyperactive gut disorders. In a castor oil induced diarrhoeal model, the crude extract of Mentha longifolia (Ml.Cr), at doses of 100–1000 mg/kg, provided 31–80% protection, similar to loperamide. In isolated rabbit jejunum preparations, Ml.Cr caused inhibition of spontaneous and high K⁺‐induced contractions, with respective EC₅₀ values of 1.80 (1.34–2.24; n = 6–8) and 0.60 mg/mL (0.37–0.85; n = 6–8), which suggests spasmolytic activity, mediated possibly through calcium channel blockade (CCB). The CCB activity was further confirmed when pretreatment of the tissue with Ml.Cr (0.3–1 mg/mL) caused a rightward shift in the Ca⁺⁺ concentration–response curves (CRCs), similar to verapamil. Loperamide also inhibited spontaneous and high K⁺‐induced contractions and shifted the Ca⁺⁺ CRCs to the right. Activity‐directed fractionation revealed that the petroleum spirit fraction was more potent than the parent crude extract and aqueous fraction. These data indicate that the antidiarrhoeal and spasmolytic effects of the crude extract of Mentha longifolia are mediated through the presence of CCB‐like constituent(s), concentrated in the petroleum spirit fraction and this study provides indirect evidence for its medicinal use in diarrhoea and spasm. Copyright © 2010 John Wiley & Sons, Ltd.     

木豆叶提取物对心肌缺血再灌注损伤大鼠的保护作用

目的研究木豆叶提取物对大鼠心肌缺血再灌注损伤的保护作用。方法采用结扎冠状动脉前降支方法制备大鼠心肌缺血再灌注损伤模型,缺血前10 min大鼠ig给予不同剂量木豆叶提取物(125、200、500 mg/kg),复方丹参滴丸为阳性对照,再灌注30 min后以II导联心电图监测各组大鼠心律失常出现和持续时间,进行心律失常评分;再灌注90 min后测定心肌梗死范围,HE染色观察心肌形态学变化。结果模型组大鼠心律失常出现较早,持续时间较长,室性早搏、室速、室颤等发生率较高,且心律失常在缺血再灌注损伤末期仍非常明显。与模型组相比,木豆叶提取物能够降低大鼠缺血性心律失常的严重程度和发生率,明显缩小心肌梗死范围,减轻心肌细胞肿胀和炎性细胞浸润。结论木豆叶提取物对心肌缺血再灌注损伤大鼠有一定的保护作用。     

姜黄素预处理对体外循环大鼠心肌缺血再灌注损伤的保护与抗氧化作用

目的:探讨姜黄素预处理对体外循环期间大鼠心肌缺血再灌注引起的氧化应激损伤的保护作用.方法:将90只SD大鼠随机分为6组,每组15只,分别为假手术组,缺血再灌注损伤(MIR)组,溶剂组,姜黄素低、中、高(10,20,40 mg·kg-1)剂量组.建立心肌缺血再灌注模型.用不同剂量姜黄素在人为制造大鼠心肌缺血模型前30 min分别做预处理.再灌注结束后采血,测定丙二醛(MDA)、超氧化物歧化酶(SOD)、天门冬氨酸氨基转移酶(AST)、乳酸脱氢酶(LDH)、乳酸脱氢酶同工酶( LDH1),并测量心肌梗死面积.结果:姜黄素预处理能明显降低血浆中AST,LDH,LDH1,MDA的含量,MIR组血浆中各种心肌酶均明显高于假手术组,差异有统计学意义(P＜0.05),MIR组与溶剂组比较差异无统计学意义,姜黄素组血浆各心肌酶均明显低于MIR组,差异有统计学意义(P＜0.05),提高SOD活性,减少心肌梗死面积.结论:姜黄素对体外循环期大鼠心肌缺血再灌注引起的氧化应激损伤有保护作用.     

Dynamic Study of the Effect of Electroacupuncture on Dopamine in the Striatum for Rats with Cerebral Ischemia and Reperfusion

目的:观察脑缺血再灌注模型大鼠纹状体内多巴胺的动态变化,以及电针对该变化的影响.方法:运用微透析采样技术、高效液相检测技术,在多个时段对实验动物进行动态采样,观察缺血所致纹状体内多巴胺的变化,及电针风池穴对该变化的影响.结果:正常组、假手术组、假手术 电针组在观测时段内,细胞外多巴胺的变化没有显著差异,胞外多巴胺的含量在脑缺血后15_45 min及再灌注后0-30 min出现两个峰值(P<0.05).再灌注后120 min也观测到一次上升的趋势.经电针治疗后,胞外多巴胺的含量于再灌注后90min明显低于缺血组(P<0.05),再灌注后也未出现峰值.结论:电针风池穴能够调节多巴胺含量的紊乱,能够改善整体的神经功能.这可能是针灸治疗脑缺血再灌注损伤的机制之一.     

杭白菊总黄酮对大鼠缺血/再灌损伤大脑的保护作用

 目的观察杭白菊总黄酮(total flavones extracted from chrysanthemum morifolium,TFCM)对大鼠缺血/再灌损伤大脑的影响,并初步探讨其机制。方法采用大脑中动脉内栓线梗塞法造成大鼠局灶性脑缺血/再灌损伤模型,缺血90min,再灌注22h后,以盐酸2,3,5-三苯基四氮唑染色法测定脑梗死面积,比色法测定脑组织匀浆中超氧化物歧化酶(superoxide dismutase,SOD)活性及丙二醛(malondialdehycle,MDA)含量,采用“10分法”进行神经症状评分。用荧光分光光度计检测氧自由基(reactive oxygen species,ROS)的生成;测定分离脑线粒体540nm处吸光度。结果TFCM(50,100,200mg·kg^-1,ip)能明显改善脑缺血/再灌后大鼠神经症状,明显减小梗死面积与全脑面积之比,提高缺血脑组织SOD活性,降低MDA含量,并减少脑组织ROS的生成。TFCM减轻Ca²⁺诱导的脑线粒体肿胀,此作用可被苍术苷所拮抗。结论TFCM对大鼠缺血/再灌损伤大脑具有显著的保护作用,其作用机制可能与TFCM抗氧化作用进而抑制线粒体肿胀有关。     

小鼠血浆中姜黄素的含量测定及药动学研究

 目的建立血浆中姜黄素含量测定的HPLC,并研究姜黄素静注后在小鼠体内的药动学行为。方法血浆样品用乙腈沉淀蛋白后,采用Lichrospher-C₁₈分析柱(4.6 mm×250 mm,5μm),柱温:30℃;流动相:甲醇-5%醋酸溶液(85∶15);流速:0.5 mL·min^-1;检测波长:420 nm。结果本法可将姜黄素与其他内源性干扰成分成功分离。在0.25～10.0 mg·L^-1内,测定方法具有良好的线性关系;萃取回收率为64.91%,加样回收率为93.10%;日内、日间精密度RSD均小于10%。小鼠静注姜黄素后药动学行为符合三室模型,主要药动学参数为:t_1/2pi 0.42 min,t_1/2α 16.2 min,t_1/2β 73.82 h,CL1.22 L·h^-1。结论所建立的姜黄素体内血药浓度测定方法可行,姜黄素静注后在小鼠体内分布消除迅速。     

Influence of quercetin-rich onion peel extracts on adipokine expression in the visceral adipose tissue of rats

We examined the effects of quercetin‐rich onion peel extract supplementation on adipokine expressions from adipose tissues in a diet‐induced obese animal model. Male Sprague‐Dawley rats (n = 24) were randomly assigned into control (n = 8), high fat diet (HF, n = 8) and high fat diet with onion peel extract (HFOE, n = 8). After 8 weeks, serum biochemical parameters, weights of adipose tissues (epididymal, perirenal and mesenteric fats) and adipokine mRNA levels (adiponectin, IL (interleukin)‐6 and visfatin) along with PPAR (peroxisome proliferator‐activated receptor) γ2 from adipose tissues were measured. After the 8 week supplementation, mesenteric fat weights were lower in the HFOE group than the HF group (p < 0.05). Adiponectin mRNA levels (mesenteric fats) were remarkably higher in the HFOE group than the other groups (p < 0.05 for both). Levels of PPARγ2 mRNA (mesenteric fats) were significantly higher in the HF group (p < 0.05) than those in the control group, but those in the HFOE group were not different from those in the control group. The IL‐6 mRNA levels (perirenal and mesenteric fats) were higher in the HF and HFOE groups, but those in the HFOE group were slightly lower than those in the HF group. In conclusion, quercetin‐rich onion peel extract supplementation influenced adipokine expressions, particularly from mesenteric fat, addressing the modulatory effect of this substance on obesity‐induced inflammation. Copyright © 2011 John Wiley & Sons, Ltd.     

Protective effect of pinocembrin from Penthorum chinense Pursh on hepatic ischemia reperfusion injury via regulating HMGB1/TLR4 signal pathway

Hepatic ischemia–reperfusion injury (HIRI) is of common occurrence during liver surgery and transplantation. Pinocembrin (PIN) is a kind of flavonoid monomer extracted from the local traditional Chinese medicine Penthorum chinense Pursh (P. chinense). However, the effect of PIN on HIRI has not determined. We investigated the protective effect and potential mechanism of PIN against HIRI. Model mice were subjected to partial liver ischemia for 60 min, experimental mice were pretreated with PIN orally for 7 days, and H₂O₂-induced oxidative damage model in AML12 hepatic cells was established in vitro. Histopathologic analysis and serum biochemical levels revealed that PIN had hepatoprotective activities against HIRI. The variation of GSH, SOD, MDA, and ROS levels indicated that PIN treatments attenuated oxidative stress in tissue. PIN pretreatment obviously ameliorated apoptosis, and restrained the expression of HMGB1 and TLR4 in vivo. In vitro, compared with H₂O₂ group, the contents of ROS, mitochondrial membrane potential, apoptotic cells, and Bcl-2 protein were decreased, while the Bax protein expression was increased. Moreover, HMGB-1 small interfering RNA test and western blotting showed that PIN pretreatment reduced HMGB1 and TLR4 protein levels. In conclusion, PIN pretreatment effectively protected hepatocytes from HIRI and inhibited the HMGB1/TLR4 signaling pathway.     

Curcuminoids: Implication for inflammation and oxidative stress in cardiovascular diseases

It has been extensively verified that inflammation and oxidative stress play important roles in the pathogenesis of cardiovascular diseases (CVDs). Curcuminoids, from the plant Curcuma longa, have three major active ingredients, which include curcumin (curcumin I), demethoxycurcumin, and bisdemethoxycurcumin. Curcuminoids have been used in traditional medicine for CVDs' management and other comorbidities for centuries. Numerous studies had delineated their anti‐inflammatory, antioxidative, and other medicinally relevant properties. Animal experiments and clinical trials have also demonstrated that turmeric and curcuminoids can effectively reduce atherosclerosis, cardiac hypertrophy, hypertension, ischemia/reperfusion injury, and diabetic cardiovascular complications. In this review, we introduce and summarize curcuminoids' molecular and biological significance, while focusing on their mechanistic anti‐inflammatory/antioxidative involvements in CVDs and preventive effects against CVDs, and, finally, discuss relevant clinical applications.     

Curcumin and a Morus alba extract reduce pro-inflammatory effects of resistin in human endothelial cells

Resistin is a cytokine which plays an important role in cardiovascular disease by influencing systemic inflammation and endothelial activation. In human endothelial cells (HEC) it increases the expression of P‐selectin and fractalkine, and enhances monocyte adhesion by antioxidant mechanisms. This study investigated whether the natural antioxidants curcumin (CC) and an extract of Morus alba leaves (MA) have protective effects in resistin‐activated HEC. HEC were exposed to 100 ng/mL resistin for 6 and 18 h in the absence or presence of MA or CC and the expression of fractalkine and P‐selectin was determined by RT‐PCR and western blot. Intracellular accumulation of reactive oxygen species (ROS) was monitored by fluorimetry and NADPH oxidase activity by a lucigenin‐enhanced chemiluminescence assay. In addition, adhesion assays using the monocytic U937 cells were performed. The results showed that treatment of HEC exposed to resistin with MA and CC: (1) inhibited significantly P‐selectin and fractalkine expression, (2) inhibited the increase in the intracellular ROS level, (3) reduced NADPH activation and (4) reduced monocytes adhesion to HEC. The results indicate that MA and curcumin target resistin‐induced human endothelial activation partly via antioxidant mechanisms and suggest that they may represent therapeutic agents in vascular disease mediated by resistin. Copyright © 2011 John Wiley & Sons, Ltd.