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Asian Pacific Journal of Tropical Biomedicine 2024年第6期14卷 236-244页

作者： Hital Shah Tejal Gandhi Gujarat Technological University AhmedabadGujarat 382424India Department of Pharmacology Anand Pharmacy CollegeAnandGujarat 388001India

Objective:To investigate the cardioprotective potential of betulin in isoproterenol(ISO)-induced myocardial injury in rats.Methods:Wistar rats were divided into five groups(n=10):normal,ISO,nebivolol 5 mg/kg,and betulin(20&40 mg/kg).Nebivolol and betulin were administered orally for 29 days.ISO(85 mg/kg)was administered subcutaneously on day 27 and day 28 to induce myocardial injury.On day 29,blood was collected for determination of cardiac markers,and hemodynamic parameters were investigated.The levels of oxidative stress markers and the gene expressions of apoptotic markers and inflammatory mediators were evaluated.Moreover,2,3,5-triphenyltetrazolium chloride staining and histopathological analysis were also performed.Results:Betulin reduced the size of myocardial infarction,decreased elevated levels of cardiac enzymes,and maintained hemodynamic functions.It also inhibited ISO-induced upregulation of Bax,caspase-3,NF-κB,and IL-6,enhanced endogenous antioxidant enzymes,and reduced lipid peroxidation.Additionally,pretreatment with betulin alleviated myocardial ischemic damage,as reflected by reduced myonecrosis,edema,and inflammatory changes.Conclusions:Betulin exhibits strong cardioprotective activity against ISO-induced myocardial injury by anti-inflammatory,anti-apoptotic,and antioxidant activities.

关键词： NF-κB isoproterenol Betulin Myocardial injury Oxidative stress Inflammation Apoptosis

L-carvone attenuates myocardial injury and dyslipidemia in rats with isoproterenol-induced cardiac hypertrophy

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Asian Pacific Journal of Tropical Biomedicine 2023年第1期13卷 17-25页

作者： Anitha Nagarajan Victor Arokia Doss Department of Biochemistry PSG College of Arts and ScienceCoimbatore-641014Tamil NaduIndia

Objective:To explore the therapeutic efficacy of L-carvone from Mentha spicata L.leaf extracts against isoproterenol-induced cardiac hypertrophy in rats.Methods:isoproterenol(5 mg/kg)was injected intraperitoneally into rats for one month to induce cardiac hypertrophy.L-carvone(25 and 100 mg/kg)was administered orally to treat cardiac hypertrophy.The cardioprotective activity of L-carvone was evaluated by electrocardiogram,histopathological analysis as well as determination of biochemical parameters and enzymatic markers.Results:L-carvone from Mentha spicata L.at 25 and 100 mg/kg ameliorated isoproterenol-induced cardiac hypertrophy,as evidenced by reduced QRS interval on electrocardiogram,and decreased heart weight and heart index.In addition,both doses of L-carvone markedly lowered the levels of glucose,total protein,low-density lipoprotein cholesterol,aspartate transaminase,alanine transaminase,lactate dehydrogenase,creatine kinase MB,troponin-Ⅰ,N-terminal pro-B type natriuretic peptide and triglycerides while increasing high-density lipoprotein cholesterol and lipase level(Pisoproterenol-induced cardiac hypertrophy.Conclusions:L-carvone from Mentha spicata L.leaf extract can restore abnormal cardiac function and may be further explored as a therapeutic agent against the deleterious effects of cardiac hypertrophy after further evaluation.

关键词： Cardiac hypertrophy L-carvone Dyslipidemia Myocardial injury isoproterenol Mentha spicata

Beta-glucan protects against isoproterenol-induced cardiac remodeling by regulating the ACE-AT1R axis and attenuates cardiac inflammation and apoptosis

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亚太热带生物医学杂志:英文版 2023年第9期13卷 384-392页

作者： Anitha Roy Vasantha Mallenahalli Neelakantappa Jayashree Ganesan Balakrishnan Ramajayam Asokan Srinivasan Kulandaivel V.V.Sathibabu Uddandrao Sengottuvelu Singaravel Center for Transdisciplinary Research Department of PharmacologySaveetha Dental College and HospitalsSaveetha Institute of Medical and Technical SciencesChennaiTamil NaduIndia-600077 Department of Pharmacology Kasturba Medical CollegeMangoloreManipal Academy of Higher EducationManipalIndia-5750013 Department of Pharmacology Aarupadai Veedu Medical College&HospitalVinayaka Mission Research FoundationPuducherryIndia-607403 Department of Pharmaceutical Chemistry Nandha College of PharmacyErodeTamilnaduIndia-638052 Department of Biochemistry K.S.Rangasamy College of Arts and Science(Autonomous)TiruchengodeNamakkal DistrictTamilnaduIndia-637215 Department of Pharmacology Nandha College of PharmacyErodeTamil NaduIndia-638052

Objective:To investigate the cardioprotective effect of beta-glucan against isoproterenol-induced cardiotoxicity in rats,and elucidate the underlying mechanism.Methods:Rats were orally pretreated with beta-glucan(40 mg/kg body weight)for 30 d,and isoproterenol(20 mg/100 g body weight)was administered on days 31 and 32.The effects of beta-glucan on markers of cardiac injury,hemodynamic changes,production of proinflammatory cytokines,and the corresponding mRNA expressions were evaluated.In addition,histological analysis was performed.Results:Pretreatment with beta-glucan prevented isoproterenol-induced cardiac injury by preserving the structural and functional integrity of the plasma membrane and attenuating the production of proinflammatory cytokines(NF-κB,TNF-α,IL-6,IL-1β,and IFN-γ)in the heart.Moreover,beta-glucan significantly downregulated the mRNA expression of ACE,AT1R,TNF-α,IL-6,NF-κB,caspase-3,TLR-4,and Bax,and upregulated Bcl-2 in the heart.At the same time,pretreatment with beta-glucan alleviated myocardial damage as reflected in a reduction in myonecrosis,edema,and erythrocyte extravasation with almost imperceptible inflammation.Conclusions:Beta-glucan can protect against isoproterenol-induced cardiotoxicity by attenuating cardiac inflammation and apoptosis and regulating the ACE-AT1R axis,thereby preventing cardiac remodeling.

关键词： Βeta-glucan isoproterenol Cardiac inflammation Cardiac apoptosis Cardiovascular diseases Heart failure Myocardial infarction

Naringenin suppresses NLRP3 inflammasome activation via the mRNA-208a signaling pathway in isoproterenol-induced myocardial infarction

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Asian Pacific Journal of Tropical Biomedicine 2023年第10期13卷 443-450页

作者： Ayman Eldourghamy Toka Hossam Mohammed Abdalla Hussein Amal Abdel-Aziz Samir A.El-masry Environmental Biotechnology Department Genetic Engineering and Biotechnology Research InstituteSadat UniversityEgypt Department of Medical Labs Faculty of Applied Medical Sciences TechnologyOctober 6 UniversityEgypt Department of Biotechnology Faculty of Applied Health Sciences TechnologyOctober 6 UniversityEgypt Molecular Biology Department Genetic Engineering and Biotechnology Research InstituteSadat UniversityEgypt

Objective:To investigate the cardioprotective effect of naringenin against isoproterenol(ISO)-induced cardiotoxicity in rats.Methods:Rats were divided into five groups:the normal group,the ISO group(85 mg/kg b.w.);the ISO+naringenin(50 mg/kg b.w.)group,the ISO+naringenin(100 mg/kg b.w.)group and the ISO+propranolol(10 mg/kg b.w.)group.Plasma creatine kinase-MB(CK-MB),cardiac troponin T,lactate dehydrogenase,brain natriuretic peptide(BNP),and IL-10,as well as cardiac transforming growth factor-β1(TGF-β1),vascular endothelial growth factor(VEGF)and malondialdehyde(MDA)were examined.In addition,NLRP3 and mRNA-208a expressions were evaluated by RT-PCR analysis.Histopathological examination was also performed to assess cardiac damages.Results:Naringenin treatment significantly decreased plasma lactate dehydrogenase,CK-MB,cardiac troponin T,BNP,and IL-10,as well as cardiac TGF-β1,VEGF,and MDA while increasing p-Akt and superoxide dismutase in ISO-administered rats.It also reduced NLRP3 and mRNA-208a gene expression levels.Furthermore,naringenin improved ISO-induced cardiac damage.Conclusions:Naringenin attenuates myocardial dysfunction in ISO-treated rats by decreasing oxidative stress and increasing cardiac endogenous antioxidant system,which may be modulated partly by improvement of NLRP3 and mRNA-208a gene expression.

关键词： Naringenin isoproterenol Myocardial infarction Antioxidants NLRP3 mRNA-208a

Dalbergia odorifera Essential Oil Protects against Myocardial Ischemia through Upregulating Nrf2 and Inhibiting Caspase Signaling Pathways in isoproterenol-Induced Rats

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World Journal of Traditional Chinese Medicine 2023年第3期9卷 338-347页

作者： Can-Hong Wang Bao Gong Hui Meng Yu-Lan Wu Xiang-Sheng Zhao Jian-He Wei Hainan Provincial Key Laboratory of Resources Conservation and Development of Southern Medicine Hainan Branch of the Institute of Medicinal Plant DevelopmentChinese Academy of Medical Sciences and Peking Union Medical CollegeHaikouChina Key Laboratory of State Administration of Traditional Chinese Medicine for Agarwood Sustainable Utilization Hainan Branch of the Institute of Medicinal Plant DevelopmentChinese Academy of Medical Sciences and Peking Union Medical CollegeHaikouChina Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine Institute of Medicinal Plant DevelopmentChinese Academy of Medical Sciences and Peking Union Medical College Ministry of Education and National Engineering Laboratory for Breeding of Endangered Medicinal Materials Institute of Medicinal Plant DevelopmentChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Objective:Dalbergia odorifera has long been used as a Chinese herbal medicine for the treatment of cardiovascular and cerebrovascular diseases.This study aimed to determine the potential myocardial protective effect and possible mechanism of action of D.odor ife ra essential oil(DOEO).Materials and Methods:The essential oil of D.odorifera was extracted by hydrodistillation.The cardioprotective effects of DOEO were examined by histopathological observation,myocardial enzyme detection,peroxidation,anti-oxidant level detection,and related protein expression.The compounds in the blood were identified by gas chromatography-mass spectrometry.Results:These results showed that DOEO had significant myocardial cell protection,with IC50 values ranging from 17.64 to 24.78μg/mL in vitro.Compared to the myocardial ischemia group,the DOEO pretreatment groups had lower levels of myocardial injury,creatinine kinase,lactate dehydrogenase,alanine transaminase,aspartate transaminase,hydrogen peroxide,and nitric oxide,and higher levels of glutathione and superoxide dismutase.In addition,DOEO pretreatment significantly increased Na+-K+-ATPase and Ca2+-ATPase levels.Moreove r,immunohistochemical e xperiments showed that DOEO remarkably increased the protein levels of NF-E2-related nuclear factor 2(Nrf2)and heme oxygenase-1(HO-1)and reduced the expression of apoptotic caspases,including caspase 3 and caspase 9.The main components of the blood were transnerolidol and nerolidol oxide.Overall,the study showed that DOEO displayed myocardial protection by upregulating the NF-E2-related nuclear factor-antioxidant response element(Nrf2-ARE)and caspase pathways.DOEO has a therapeutic effect on MI by inhibiting the oxidant and apoptotic effects.Conclusions:D.odorifera may be a potential candidate drug for treating myocardial ischemic injury.

关键词： Anti-apoptosis Anti-oxidation Dalbergia odorifera essential oil isoproterenol Myocardial ischemia

Effect of acupuncture at Neiguan (PC 6) on cardiac function using echocardiography in myocardial ischemia rats induced by isoproterenol

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Journal of Traditional Chinese Medicine 2015年第6期35卷 653-658页

作者： Wang Songzi Ren Lu Jia Lianqun Gu Zhongyue Fan Xu Chen Wenna Hou Ping Liang Fanrong Rong Peijing Ma Tieming Liu Xulai Chen Yiguo Department of Acupuncture and Moxibustion Liaoning University of Traditional Chinese Medicine Experimental Center Liaoning University of Traditional Chinese Medicine Vasculocardiology Department Liaoning Hospital of Traditional Chinese Medicine Affiliated to Liaoning University of Traditional Chinese Medicine Department of Acupuncture and Moxibustion Chengdu University of Traditional Chinese Medicine Department of Acupuncture and Moxibustion China Academy of Chinese Medical Sciences

OBJECTIVE: To investigate the effect of acupuncture at Neiguan(PC 6) on cardiac function using echocardiography in rat models of myocardial ischemia(MI) induced by isoproterenol(ISO).METHODS: Twenty-seven Sprague-Dawley rats were randomly assigned to normal, model, and acupuncture groups. The model and acupuncture groups were given injections of ISO(85 mg/kg) to establish the MI model. After model establishment,the acupuncture group was treated with acupuncture at Neiguan(PC 6) for 30 min. Echocardiography was used to monitor diastolic and systolic function for 30 min starting from the time after the acupuncture needles were removed. Changes in the length of left ventricular internal diameter at end-diastole(LVIDd), length of left ventricular internal diameter at end-systole(LVIDs), the ratio of mitral peak velocity at early diastole and atrial contraction(E/A), ejection fraction(EF), fractional shortening(FS), and stroke volume(SV) were measured.RESULTS: Compared with the model group at 0and 15 min after needles were removed, the means of LVIDd and LVIDs were significantly lower(P <0.01) and E/A, EF, FS, and SV significantly higher(P < 0.01) in the acupuncture group. In the acupuncture group, the means of LVIDd and LVIDs15 min after the needles were removed were significantly higher(P < 0.01) than those at 0 min. The means of E/A, EF, FS, and SV significantly decreased(P < 0.01) from 0 to 15 min in the acupuncture group.CONCLUSION: These findings indicate that acupuncture at Neiguan(PC 6) can affect cardiac function by increasing left ventricular diastolic and systolic function in MI rat models, but the effect only lasts for 15 min.

关键词： Acupuncture Point PC 6 (Neiguan) Myocardial ischemia Heart function tests Echocar-diography isoproterenol

Cardioprotective effects of ghrelin and des-octanoyl ghrelin on myocardial injury induced by isoproterenol in rats

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Acta Pharmacologica Sinica 2006年第5期27卷 527-535页

作者： LLian LI~2 Li-ke ZHANG~5 Yong-zheng PANG~(2.4) Chun-shui PAN~(3.4) Yong-fen QI~(3.4) Li CHEN~4 Xian WANG~(3,4) Chao-shu TANG~(3,4) Jing ZHANG~(2,4,6) ~2Institute of Cardiovascular Research,Peking University First Hospital,Beijing 100034,China:~3Department of Physiology and Pathophysiology,Peking University Health Science Center,Beijing 100083,China ~4Key Laboratory of the Ministry of Education on Molecular Cardiology,Beijing 100083,China:~5Department of Pathophysiology,Capital University of Medicine,Beijing 100054,China Institute of Cardiovascular Research Peking University First Hospital Beijing China Department of Pathophysiology Capital University of Medicine Beijing China Key Laboratory of the Ministry of Education on Molecular Cardiology Beijing China Department of Physiology and Pathophysiology Peking University Health Science Center Beijing China

Aim:To determine the cardioprotective action of ghrelin and des-octanoyl ghrelinin rats with isoproterenol-induced myocardial injury.Methods:Rats were subcu-taneously injected with isoproterenol （ISO;20,10,and 5 mg/kg） on d 1,2 and 3,respectively,and then 3 mg/kg for the next 7d with or without ghrelin or des-octanoyl-ghrelin （100μg/kg,twice daily）.Plasma ghrelin and growth hormonelevels were assayed using radioimmunoassay methods.Growth hormone secreta-gogue receptor （GHSR） and ghrelin mRNA were determined using RT-PCR.Themaximal binding capacity and the affinity for [3H]ghrelin were determined by re-ceptor binding assays.Results:Compared with controls,ISO-treated rats showedsevere myocardial injury,cardiomegaly,infarction-like necrosis and massive fi-brosis with increases in irradiated-ghrelin （ir-ghrelin） content in plasma by 67%and myocardia by 66% and in the mRNA level in the myocardia by 93% （P<0.01）.ISO-treated rats had 95% （P<0.01） higher GHSR mRNA levels in the myocardia.The maximal binding capacity of [3H]ghrelin for myocardial sarcolemma was higherin ISO-treated rats than in controls.Ghrelin administration improved cardiac func-tion and ameliorated cardiomegaly and attenuated myocardial lipid peroxidationinjury and relieved cardiac fibrosis as compared with ISO treatment alone.Admin-istration of des-octanoyl ghrelin effectively antagonized ISO-induced myocardialinjury and improved all parameters measured.However,the therapeutic effect ofdes-octanoyl ghrelin was significantly weaker than that of ghrelin.The plasmagrowth hormone level increased markedly,by 1.5-fold （P<0.01）,with ghrelinadministration as compared with that in controls,but was unaltered in the des-octanoyl ghrelin group.Conclusion:Myocardial ghrelin and GHSR were up-regulated during ISO-induced myocardial injury.The protective effect of ghrelinagainst ISO-induced cardiac function injury and fibrosis was more potent thanthat of des-octanoyl ghrelin,which suggests that ghrelin could be an endog-enous cardioprotective factor in ischemic heart

关键词： ghrelin des-octanoyl ghrelin myocardium fibrosis isoproterenol

Role of peroxisome proliferator-activated receptor a activation in acute myocardial damage induced by isoproterenol in rats

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Chinese Medical Journal 2008年第16期121卷 1569-1573页

作者： YUAN Jie WU Jian HANG Zhi-gang ZHONG Xue-kuan ZHOU Ling-wang YU Bo Cardiovascular Center Second Affiliated Hospital of Harbin Medical University Harbin Heilongjiang 150086 China Institute of Keshan Disease Harbin Medical University Harbin Heilongjiang 150086 China

Background Peroxisome proliferator-activated receptor （PPAR） a is one of the subtypes of PPARs. It regulates metabolism of lipid and lipoprotein, as well as glucose homeostasis. In addition, PPARa influences cellular proliferation, inflammation, differentiation and apoptosis, which plays a vital role in cardiovascular diseases. The purpose of this study was to investigate the role and mechanisms of PPARa activation in relation to acute myocardial damage induced by isoproterenol in rats. Methods Thirty male Wister rats were randomly divided into control group, isoproterenol （Iso） injured group and fenofibrate （FF） treatment group. Acute myocardial damage caused by isoproterenol intraperitoneal injection induced ischemia was established. We determined the levels of creatine kinase （CK） and lactic dehydrogenase （LDH） in serum as well as the concentrations of free fatty acids （FFA） in serum and myocardium. The mRNA expressions of PPARa, muscular type carnitine palmitransferase （M-CPT-I） and medium chain lipid acetyl coenzyme A dehydrogenase （MCAD） were analyzed by reverse transcription-polymerase chain reaction （RT-PCR）. Results Compared with the control group, the levels of serum CK and LDH were significantly increased after FF and Iso treatments. Moreover, the concentrations of FFA in both serum and myocardium were obviously increased in the Iso group and FF group, while the mRNAexpressions of PPARa, M-CPT-I and MCAD declined, respectively （P〈0.01）. When compared with the Iso group, significant decreases in serum CK and LDH were observed in the FF group. The concentrations of FFA both in serum and myocardial tissue were markedly decreased in the FF group, while the expressions of PPARa, M-CPT-I and MCAD mRNA were increased （vs Iso, P〈0.01）. Conclusions The utilization of FFA was reduced in isoproterenol induced acute myocardial damage. PPARa activation by its activator fenofibrate may play a key role in energy metabolism in acute myocardial damage induced by isoproterenol in rats.

关键词： peroxisome proliferator-activated receptor isoproterenol fenofibrate myocardial damage free fatty acids

A Cardiomyopeptin Preparation Protects against isoproterenol-Induced Chronic Heart Failure in Rats

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Chinese Medicine 2023年第4期14卷 242-254页

作者： Zumeng Xia Hoi Yan Leung Hoi Ling Siu Chung Wai Chan Kam Ming Ko R&D Center Infinitus China Limited Guangzhou China Division of Life Science Hong Kong University of Science & Technology Hong Kong China

The present study investigated the effect of an herbal extract-supplemented cardiomyopeptin preparation (HECP), in the rat model of chronic heart failure. HECP pre-/co-treatment at a daily dose of 0.072 to 0.124 g/kg for 30 days protected against isoproterenol (ISO)-induced chronic myocardial damage in rats in a dose-dependent manner, with the extent of protection, as assessed by plasma cardiac troponin I level, being up to 76%. The cardioprotection afforded by HECP was associated with the enhancement of myocardial mitochondrial antioxidant status, amelioration of plasma parameters on cardiac dysfunction and hypertrophy, as well as an increase in myocardial endothelial nitric oxide synthase activity. Myocardial apoptotic and anti-apoptotic parameters were suppressed and stimulated, respectively. The cardioprotection afforded by HECP was accompanied by an increase in exercise capacity, an indirect functional index of the myocardium, in ISO-challenged rats. In conclusion, HECP may offer a promising prospect in preventing chronic heart failure in human subjects.

关键词： Cardiomyopeptin Herbal Extract Chronic Heart Failure isoproterenol

Metabonomics and Molecular Biology-based Effects of Sugemule-3 in an isoproterenol-induced Cardiovascular Disease Rat Model

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Chemical Research in Chinese Universities 2018年第4期34卷 590-597页

作者： WANG Xiye WANG Yu WEI Chengxi YU Lijun Inner Mongolia Key Laboratory for the Natural Products Chemistry and Functional Molecular Synthesis College of Chemistry and Chemical Engineering Inner Mongolia University for the Nationalities Tongliao 028005 P. R. China Inner Mongolia Autonomous Region Key Laboratory of Mongolian Medicine Pharmacology for Cardio-cerebral Vascular System Medicinal Chemistry and Pharmacology Institute Inner Mongolia University for the Nationalities Tongliao 028005 R R. China

Cardiovascular disease（CVD） is a common and serious disease in the elderly, which has characteristically high prevalence, disability, and mortality rates. However, the etiology of CVD is still not very clear. The traditional Mongolian medicine Sugemule-3（SM） is usually used for the treatment of CVD and exhibits a good curative effect. In this study, a sentm metabolite profile analysis was used to identify potential biomarkers associated with isoprote- renol（ISO）-induced CVD and investigate the mechanism of the action of SM. Ultra-perfornlance liquid chromato- graphy coupled with quadrupole time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was used for the metabono- mics analysis. Principal component analysis（PCA） was used to process the acquired data to differentiate the results of the control, CVD, and SM treatment groups. Orthogonal partial least squares discriminant analysis（OPLS-DA） enabled the identification of 21 metabolites as potential biomarkers that were relevant to phospholipid and energy metabolism. The results indicate that SM played a protective role against ISO-induced CVD in rats by regulating phospholipid and energy metabolic pathways. Fttrther, we verified the apoptotic metabolic pathway using molecular biology methods, such as terminal deoxynucleotidyl transferase（TdT） deoxyuridine 5＇-triphosphate（dUTP） nick-end labeling（TUNEL） assay and Western blot analysis. Furthermore, this study identified early biomarkers of CVD and elucidated the underlying mechanism of the therapeutic actions of SM, which is worth further to be investigated for development as a clinical therapy.

关键词： Sugemule-3 Metabonomics Molecular biology Ultra-perfbrmance liquid chromatography coupled withmass spectrometry（UPLC-MS） Cardiovascular disease isoproterenol