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面包树叶片水提取物对异丙肾上腺素诱导的大鼠心肌损伤具有心脏保护作用:负性变时性和变力性作用。

Aqueous extract from leaf of Artocarpus altilis provides cardio-protection from isoproterenol induced myocardial damage in rats: Negative chronotropic and inotropic effects.

作者信息

Nwokocha Chukwuemeka, Palacios Javier, Simirgiotis Mario J, Thomas Jemesha, Nwokocha Magdalene, Young Lauriann, Thompson Rory, Cifuentes Fredi, Paredes Adrian, Delgoda Rupika

机构信息

Department of Basic Medical Sciences, Faculty of Medical Sciences, University of the West Indies, Mona Campus, Kingston, Jamaica.

Facultad de Ciencias de la Salud, Instituto de EtnoFarmacología (IDE), Universidad Arturo Prat, Chile.

出版信息

J Ethnopharmacol. 2017 May 5;203:163-170. doi: 10.1016/j.jep.2017.03.037. Epub 2017 Mar 22.

DOI:10.1016/j.jep.2017.03.037
PMID:28342858
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

The leaves of Artocarpus altilis (Parkinson ex F.A.Zorn, Fosberg) (Moraceae) are used in the management of hypertension; this study assessed the cardio-protective effects of the leaf extract on isoproterenol (ISO) induced myocardial damage in rats.

MATERIAL AND METHODS

Twenty (20) adult male Sprague-Dawley rats (175-230g) were divided into 5 groups. Group 1 (Control), 2 (AA) received 50mg/Kg Artocarpus altilis (AA) only; 3 (ISO) received 85mg/Kg ISO only; 4 (ISO+AA/50) and 5 (ISO+AA/100) received 50 and 100mg/Kg AA respectively for 6 days, after induced with ISO twice (85mg/Kg) at a 24-h period. Blood pressure readings were taken before and after the administering of ISO using the tail cuff method. ECG was performed on anaesthetized rats. Cardiac contractility was measured in isolated right atrial muscles. Assessment of myocardial infarct (MI) size, heart/body weight ratio, biochemical, hematological and histo-morphological parameters were conducted at the end of seven days. An aqueous extract from leaves of A. altilis was analyzed for organic compounds using UHPLC mass spectrometry.

RESULTS

ISO induced myocardial damage through an elevation of the heart rate (HR), infarct size and ECG distortions. Treatment with AA significantly (p˂0.05) reduced heart/body weight ratio (49%), MI (96%), HR (27%), sympathovagal imbalance (36%) and serum cardiac biomarkers (AST, LDH, HDL, triglycerides and CCK) caused by ISO. AA decreased the beat frequency of isolated right atrium (11%) cause by ISO, an action similar to propranolol (beta-adrenergic antagonist; 20%), but showed no significant changes in the QTc intervals of the ECG (suggesting no cardio-toxic drug-herb interactions), Thirty nine compounds were detected using high resolution LC-MS analysis (HPLC-Orbitrap-APCI-MS) in the extract. Pure compounds, as gallic acid and rutin, presented a higher negative chronotropic effect, similar to propranolol.

CONCLUSION

Oral administration of aqueous extract of Artocarpus artilis has cardio-protective functions in myocardial injury, in part, by decreasing the HR, reduced contractility and infarct size. These findings may explain the cardio-protective use of A. altilis in traditional medicine.

摘要

民族药理学相关性

面包树(Artocarpus altilis (Parkinson ex F.A.Zorn, Fosberg) (桑科))的叶子被用于治疗高血压;本研究评估了该叶提取物对异丙肾上腺素(ISO)诱导的大鼠心肌损伤的心脏保护作用。

材料与方法

20只成年雄性Sprague-Dawley大鼠(175 - 230克)被分为5组。第1组(对照组),第2组(AA组)仅接受50毫克/千克的面包树提取物(AA);第3组(ISO组)仅接受85毫克/千克的ISO;第4组(ISO + AA/50组)和第5组(ISO + AA/100组)在24小时内两次注射ISO(85毫克/千克)后,分别接受50和100毫克/千克的AA,持续6天。使用尾套法在注射ISO前后测量血压。对麻醉的大鼠进行心电图检查。在分离的右心房肌肉中测量心脏收缩力。在七天结束时评估心肌梗死(MI)面积、心脏/体重比、生化、血液学和组织形态学参数。使用超高效液相色谱-质谱联用技术分析面包树叶的水提取物中的有机化合物。

结果

ISO通过提高心率(HR)、梗死面积和心电图畸变诱导心肌损伤。用AA治疗显著(p˂0.05)降低了由ISO引起的心脏/体重比(49%)、MI(96%)、HR(27%)、交感神经-迷走神经失衡(36%)和血清心脏生物标志物(AST、LDH、HDL、甘油三酯和CCK)。AA降低了由ISO引起的分离右心房的搏动频率(11%),其作用类似于普萘洛尔(β-肾上腺素能拮抗剂;20%),但心电图的QTc间期无显著变化(表明无心脏毒性药物-草药相互作用),使用高分辨率液相色谱-质谱分析(HPLC-Orbitrap-APCI-MS)在提取物中检测到39种化合物。纯化合物,如没食子酸和芦丁,表现出更高的负性变时作用,类似于普萘洛尔。

结论

口服面包树水提取物对心肌损伤具有心脏保护作用,部分原因是降低了HR、降低了收缩力和梗死面积。这些发现可能解释了面包树在传统医学中的心脏保护用途。

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