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Heme perbxidases are responsible for the dehydrogenation and oxidation metabolism of harmaline into harmine

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Chinese Journal of Natural Medicines 2022年第3期20卷 194-201页

作者： WANG You-Xu CAO Ning GUAN Hui-Da CHENG Xue-Mei WANG Chang-Hong Institute of Chinese Materia Medica Shanghai University of Traditional Chinese MedicineThe MOE Key Laboratory for Standardization of Chinese MedicinesShanghai Key Laboratory of Compound Chinese MedicinesShanghai 201203China

Harmaline and harmine areβ-carboline alkaloids with effective pharmacological effects.Harmaline can be transformed into harmine after oral administration.However,enzymes involved in the metabolic pathway remain unclear.In this study,harmaline was incubated with rat liver microsomes(RLM),rat brain microsomes(RBM),blood,plasma,broken blood cells,and heme peroxidases including horseradish peroxidase(HRP),lactoperoxidase(LPO),and myeloperoxidase(MPO).The production of harmine was determined by a validated UPLC-ESI-MS/MS method.Results showed that heme peroxidases catalyzed the oxidative dehydrogenation of harmaline.All the reactions were in accordance with the Hill equation.The reaction was inhibited by ascorbic acid and excess H_(2)0_(2).The transformation of harmaline to harmine was confirmed after incubation with blood,plasma,and broken blood cells,rather than RLM and RBM.Harmaline was incubated with blood,plasma,and broken cells liquid for 3 h,and the formation of harmine became stable.Results indicated an integrated metabolic pathway of harmaline,which will lay foundation for the oxidation reaction of dihydro-P-carboline.Moreover,the metabolic stability of harmaline in blood should not be ignored when the pharmacokinetics study of harmaline is carried out.

关键词： Harmaline Harmine Oxidative dehydrogenation Heme peroxidases myeloperoxidase Horseradish peroxidase Lactoperoxidase

Protective effects of L-arginine on pulmonary oxidative stress and antioxidant defenses during exhaustive exercise in rats

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Acta Pharmacologica Sinica 2005年第8期26卷 992-999页

作者： Wan-teng LIN~(2,5), Suh-ching YANG~3, Kung-tung CHEN~4, Chi-chang HUANG~3, Ning-yuean LEE~(2,6) ~2 Department of Nutrition and Food Sciences, Fu-Jen Catholic University, Taipei, China ~3 School of Nutrition and Health Sciences, Taipei Medical University, Taipei, China ~4 Department of General Education, Ming Hsin University of Science and Technology Hsinchu, China ~5 De Lin Institute of Technology, Taipei, China Department of Nutrition and Food Sciences Fu-Jen Catholic University Taipei China De Lin Institute of Technology Taipei China School of Nutrition and Health Sciences Taipei Medical University Taipei China Department of General Education Ming Hsin University of Science and Technology Hsinchu China

Aim: To assess the effects of L-arginine (L-Arg) supplementation on pulmonary oxidative stress and antioxidant defenses in rats after exhaustive exercise. Methods: Rats were randomly divided into four groups: sedentary control (SC), sedentary control with L-Arg treatment (SC+Arg), exhaustive exercise with control diet (E) and exhaustive exercise with L-Arg treatment (E+Arg). Rats in groups SC+Arg and E+Arg received a 2% L-Arg diet. Rats in groups E and E+Arg underwent an exhaustive running test on a motorized treadmill. Pulmonary oxidative stress indices [xanthine oxidase (XO), myeloperoxidase (MPO), and malondialdehyde (MDA)] and antioxidant defense systems [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR), and glutathione (GSH)] were investigated in this study. Results: L-Arg supplementation significantly reduced exercise-induced elevations of XO and MPO activities in lung. LArg reversed the exercise-induced increase in SOD and GR activities, but increased CAT and GPX activities. L-Arg administration also significantly increased the GSH levels in plasma. Conclusion: L-Arg supplementation can prevent elevations of XO and MPO activities in the lung and favorably influence pulmonary antioxidant defense systems after exhaustive exercise.

关键词： L-arginine oxidative stress xanthine oxidase myeloperoxidase exhaustive exercise lung

Topical application of glycyrrhizin preparation ameliorates experimentally induced colitis in rats

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World Journal of Gastroenterology 2011年第17期17卷 2223-2228页

作者： Tomohiro Kudo Shinichi Okamura Yajing Zhang Takashige Masuo Masatomo Mori Department of Medicine and Molecular Science Gunma University Graduate School of Medicine Gunma 371-8511 Japan Department of Medical Informatics and Decision Sciences Gunma University School of Medicine Gunma 371-8511 Japan

AIM:To examine the efficacy of glycyrrhizin preparation(GL-p) in the treatment of a rat model of ulcerative colitis(UC).METHODS:Experimental colitis was induced by oral administration of dextran sodium sulfate.Rats with colitis were intrarectally administered GL-p or saline.The extent of colitis was evaluated based on body weight gain,colon wet weight,and macroscopic damage score.The expression levels of pro-inflammatory cytokines and chemokines in the inflamed mucosa were measured by cytokine antibody array analysis.The effect of GL-p on myeloperoxidase(MPO) activity in the inflamed mucosa and purified enzyme was assayed.RESULTS:GL-p treatment significantly ameliorated the extent of colitis compared to sham treatment with saline.Cytokine antibody array analysis showed that GL-p treatment significantly decreased the expression levels of pro-inflammatory cytokines and chemokines,including interleukin(IL)-1β,IL-6,tumor necrosis factor-α,cytokine-induced neutrophil chemoattractant-2,and monocyte chemoattractant protein-1 in the inflamed mucosa.Furthermore,GL-p inhibited the oxidative activity of mucosal and purified MPO.CONCLUSION:GL-p enema has a therapeutic effect on experimental colitis in rats and may be useful in the treatment of UC.

关键词： Glycyrrhizin 大肠炎葡聚糖钠硫酸盐 Ulcerative 大肠炎 Cytokine Chemokine 蛋白质数组 myeloperoxidase 灌肠 Carboxymethylcellulose

myeloperoxidase Aggravates Myocardial Vulnerability to Ischemia/Reperfusion Injury via Disruption of the Nitric Oxide-cGMP Pathway in Rats with Hypercholesterolemia

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Myeloperoxidase Aggravates Myocardial Vulnerability to Ische...

Inflammatory reaction after focal cerebral ischemia in mouse

2019年中国生理学会心血管生理学术研讨会

作者： Ye Wu Huirong Liu Department of Physiology and Pathophysiology School of Basic Medical SciencesCapital Medical University Beijing Key Laboratory of Metabolic Disorders Related Cardiovascular Disease Capital Medical University

Aims:Hypercholesterolemia(HC) and inflammatory reaction are known to increase myocardial vulnerability to myocardial ischemia/reperfusion(MI/R) injury;however,the underlying mechanisms are not fully understood.The present study was designed to determine whether myeloperoxidase(MPO),an inflammatory cytokine expressed in cardiomyocytes following MI/R injury,exacerbated myocardial vulnerability to MI/R injury by interfering with the protective function of nitric oxide(NO) in HC rats.Methods:Male Wistar rats were fed either a normal or a high-cholesterol diet for 10 weeks,treated with vehicle or MPO inhibitor(ABAH,25.0 mg/kg/d for the last week),and subjected to MI/R(30 min/3 h or 24 h).MPO activity and distribution,cardiac function,serum LDH and CK level,myocardial infarct size,cardiomyocyte apoptosis,cardiac caspase-3 activity,NOx,nitrotyrosine(NT) level,iNOS expression,and cGMP content were assessed.Results:Compared with rats on a normal diet,MPO activity in MI/R hearts was significantly increased(1.33-fold;P <0.05).MPO immunostaining was not only observed in perivascular and extracellular spaces in MI/R hearts,but also in cardiomyocytes.This intra-cardiomyocyte MPO staining was further intensified by HC.We observed a strong positive correlation between cardiac MPO activity and LDH,CK,infarct size,apoptotic index,and caspase-3 activity,while there was a negative correlation between cardiac MPO activity and cardiac function.In HC rats MI/R tissue,the level of NOx and NT increased,the expression of iNOS increased,but the content of cGMP decreased.Treatment with ABAH significantly inhibited HC-induced MPO overexpression and activation,improved cardiac function,serum LDH and CK level,infarct size,myocardial cell apoptosis,MI/R injury,reduced NOx,NT,and iNOS,and increased cGMP.In addition,a scavenger of peroxynitrite(FeTMPyP) or iNOS inhibitor(1400 W) partially reversed MI/R injury in HC rats by lowering NT expression and MPO activity and raising the level of cGMP.Conclusion:Our results demonstrated that HC increased t

关键词： myeloperoxidase hypercholesterolemia myocardial ischemia/reperfusion injury myocardial vulnerability nitric oxide

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Chinese Medical Journal 2004年第4期117卷 586-591页

作者：王知秋陈衔城杨国源周良辅 Department of Neurosurgery Center for Cerebrovascular Research

Background In response to the inflammatory reaction, circulating leukocytes aggregate and adhere to the endothelial cells and eventually pervade into tissues, resulting in cell damage. This study was to detect the inflammatory reactions in mouse focal cerebral ischemia and their distinct characteristics in the ischemic basal ganglia and surrounding cortex.Methods Mice were subjected to permanent occlusion of the left middle cerebral artery (MCAO) by introducing a suture for 2 to 120 hours. The expression of intercellular adhesion molecule 1 (ICAM-1) and Mac-1 was determined immunohistochemically. The myeloperoxidase (MPO) activity of the ischemic regions was measured.Results Four hours after MCAO, the number of ICAM-1 positive vessels in the ischemic basal ganglia increased (9.2±2.8 per mm 2), peaked at 48 hours (29.6±4.8 per mm 2), and decreased after 72 hours. In the ischemic cortex, the number increased rapidly 4 hours after MCAO (19.4±6.1 per mm 2), peaked at 48 hours (44.4±16.8 per mm 2), and declined after 72 hours. Mac-1 positive cells were seen in the ischemic basal ganglia (3.4±1.2 per mm 2) 12 hours after MCAO, peaked after 48 hours (20.2±6.3 per mm 2), and decreased after 72 hours. In the ischemic cortex, however, the number increased 4 hours after MCAO (4.3±1.7 per mm 2), peaked after 48 hours (20.9±8.4 per mm 2), and remained high at 120 hours. The MPO activity increased in the ischemic basal ganglia 12 hours after MCAO (0.111±0.023 U/g), peaked after 24 hours (0.194±0.059 U/g), and decreased after 72 hours. In the ischemic cortex, the MPO activity increased 12 hours after MCAO (0.110±0.032 U/g), peaked after 24 hours (0.210±0.067 U/g), and remained elevated at 120 hours.Conclusions The increased expression of ICAM-1 in the ischemic brain of mouse in the early phase of MCAO followed by the over-expression of Mac-1 and the increased MPO activity suggests that focal ischemia leads to early onset of inflammation. The inflammatory response is more persistent and intensive in the

关键词： cerebral ischemia regional blood flow inflammation endothelium cell adhesion molecules leukocytes myeloperoxidase mice

Atorvastatin protects against cerebral ischemia/ reperfusion injury through anti-inflammatory and antioxidant effects

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Neural Regeneration Research 2014年第3期9卷 268-275页

作者： Qiuyun Tu Hui Cao Wei Zhong Binrong Ding Xiangqi Tang Department of Geriatrics Third Xiangya Hospital of Central South University Department of Neurology Second Xiangya Hospital of Central South University

In addition to its lipid-lowering effect, atorvastatin exerts anti-inflammatory and antioxidant effects as well. In this study, we hypothesized that atorvastatin could protect against cerebral isch-emia/reperfusion injury. The middle cerebral artery ischemia/reperfusion model was established, and atorvastatin, 6.5 mg/kg, was administered by gavage. We found that, after cerebral ischemia/ reperfusion injury, levels of the inflammation-related factors E-selectin and myeloperoxidase were upregulated, the oxidative stress-related marker malondialdehyde was increased, and super- oxide dismutase activity was decreased in the ischemic cerebral cortex. Atorvastatin pretreatment significantly inhibited these changes. Our findings indicate that atorvastatin protects against ce-rebral ischemia/reperfusion injury through anti-inflammatory and antioxidant effects.

关键词： nerve regeneration brain injury cerebral ischemia/reperfusion atorvastatin E-selectin myeloperoxidase superoxide dismutase malondialdehyde inflammation free radicals blood-brainbarrier stroke NSFC grant neural regeneration

Heat-sensitive moxibustion attenuates the inflammation after focal cerebral ischemia/ reperfusion injury

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Neural Regeneration Research 2012年第33期7卷 2600-2606页

作者： Aijiao Xiao Rixin Chen: Mingfei Kang Shenghai Tan Basal Medical College of Jiangxi University of Traditional Chinese Medicine Nanchang 330004 Jiangxi Province China Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine Nanchang 330006 Jiangxi Province China Jiangxi University of Traditional Chinese Medicine Nanchang 330004 Jiangxi Province China

Heat-sensitive moxibustion has neuroprotective effects against focal cerebral ischemia/reperfusion injury, however its mechanism of action remains unclear. In this study, rat models of focal cerebral ischemia/reperfusion injury were treated with suspended moxibustion at acupoint Dazhui （DU14） for 35 minutes. Results showed that suspended moxibustion decreased infarct volume, reduced cortical myeloperoxidase activity, and suppressed serum levels of proinflammatory cytokines in rats with focal cerebral ischemia/reperfusion injury. Our experimental findings indicated that heat-sensitive moxibustion can attenuate inflammation and promote repair after focal cerebral ischemia/reperfusion injury.

关键词： suspended moxibustion heat-sensitive moxibustion traditional suspended moxibustion middlecerebral artery occlusion cerebral ischemia/reperfusion injury infarct volume proinflammatorycytokines interleukin myeloperoxidase traditional Chinese medicine neural regeneration

Coronary leukocyte activation in relation to progression of coronary artery disease

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Frontiers of Medicine 2016年第1期10卷 85-90页

作者： Marijke A. de Vries Arash Alipour Erwin Bimie Andrew Westzaan Selvetta van Santen Ellen van der Zwan Anho H. Liem Noelle van der Meulen Manuel Castro Cabezas Department of Internal Medicine Centre for Diabetes and Vascular Medicine Rotterdam P.O. Box 10900 3004 BA The Netherlands Department of Statistics and Education Rotterdam P.O. Box 10900 3004 BA The Netherlands Department of Clinical Chemistry Rotterdam P.O. Box 10900 3004 BA The Netherlands Department of Cardiology Sint Franciscus Gasthuis Rotterdam P.O. Box 10900 3004 BA The Netherlands

Leukocyte activation has been linked to atherogenesis, but there is little in vivo evidence for its role in the progression of atherosclerosis. We evaluated the predictive value for progression of coronary artery disease （CAD） of leukocyte activation markers in the coronary circulation. Monocyte and neutrophil CDllb, neutrophil CD66b expression and intracellular neutrophil myeloperoxidase （MPO） in the coronary arteries were determined by flow cytometry in patients undergoing coronary angiography. The primary outcome included fatal and nonfatal myocardial infarction or arterial vascular intervention due to unstable angina pectoris. In total 99 subjects who were included, 70 had CAD at inclusion （26 patients had single-vessel disease, 18 patients had two- vessel disease and 26 patients had three-vessel disease）. The median follow-up duration was 2242 days （interquartile range： 2142-2358）. During follow-up, 13 patients （13%） developed progression of CAD. Monoeyte CDllb, neutrophil CDllb and CD66b expression and intraceilular MPO measured in blood obtained from the coronary arteries were not associated with the progression of CAD. These data indicate that coronary monocyte CDllb, neutrophil CDllb and CD66b expression and intracellular MPO do not predict the risk of progression of CAD.

关键词： coronary artery disease inflammation integrin myeloperoxidase leukocyte activation

Amaranthus roxburghianus root extract in combination with piperine as a potential treatment of ulcerative colitis in mice

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Journal of Integrative Medicine 2013年第3期11卷 206-212页

作者： Sunil A.Nirmal Jayashri M.Ingale Shashikant R.Pattan Sanjay B.Bhawar Department of Pharmacognosy Pravara Rural College of PharmacyLoni 413736MaharashtraIndia Department of Pharmaceutical Chemistry Pravara Rural College of PharmacyLoni 413736MaharashtraIndia Department of Pharmacology Pravara Rural College of PharmacyLoni 413736MaharashtraIndia

OBJECTIVE： The present work was undertaken to determine the effects of Amaranthus roxburghianus Nevski. （Amaranthaceae） root alone and in combination with piperine in treating ulcerative colitis （UC） in mice. METHODS： Swiss albino mice were divided into seven groups （n = 6）. Standard group received prednisolone （5 mg/kg, intraperitoneally）. Treatment groups received hydroalcoholic extract of roots of A. roxburghianus （50 and 100 mg/kg, per oral） and a combination of hydroalcoholic extract of roots of A. roxburghianus （50 and 100 mg/kg, per oral） and piperine （5 mg/kg, per oral）. Ulcer index, colitis severity, myeloperoxidase （MPO）, malondialdehyde and glutathione were estimated from blood and tissue. Column chromatography of the extract was done and purified fractions were analyzed by gas chromatography-mass spectroscopy （GC-MS）. RESULTS： Treatment with the combination of hydroalcoholic extract of A. roxburghianus and piperine showed minimal ulceration, hemorrhage, necrosis and leucocyte infiltration by histopathological observation. Acetic acid increased MPO levels in blood and colon tissue to 355 U/mL and 385 U/mg, respectively. The combination of hydroalcoholic extract of A. roxburghianus （100 mg/kg） and piperine （5 mg/kg） significantly decreased MPO in blood and tissue to 182 U/mL and 193 U/mg, respectively （P 〈 0.05）. Similarly, this combination significantly reduced malondialdehyde levels and increased glutathione levels in blood and tissue. Various phytoconstituents were detected by GC-MS. CONCLUSION： The combination of hydroalcoholic extract of A. roxburghianus and piperine is effective in the treatment of UC and the effects are comparable with the standard drug prednisolone. 4H-pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl, eugenol and benzene, and 1-（1,5-dimethyl-4-hexenyl）-4-methyl are reported having analgesic, anti-inflammatory, and antioxidant properties; they may play a role in the biological activity of A. roxburghianus root.

关键词： Amaranthus plant extracts ulcerative colitis myeloperoxidase malondialdehyde glutathione mice