白头翁总皂苷固体草药提取物的组成及其对实验性慢性心力衰竭的心脏保护作用。

Composition and cardioprotective effects of Primula veris L. solid herbal extract in experimental chronic heart failure.

机构信息

FSBEE HE Bashkirsky State Medical University, Lenina st., 8, Ufa 540008, Russia.

FSBEE HE Volgograd State Medical University, Pavshikh Bortsov sq., 1, Volgograd 400131, Russia.

出版信息

Phytomedicine. 2019 Feb 15;54:17-26. doi: 10.1016/j.phymed.2018.09.015. Epub 2018 Sep 5.

DOI:10.1016/j.phymed.2018.09.015

PMID:30668367

Abstract

BACKGROUND

High interest in chronic heart failure (CHF) is accounted for by its high incidence, poor prognosis, growing number of hospital admissions due to the heart failure relapse, and inadequate treatment. These facts necessitate a search for new pharmacological agents for the CHF correction. Herbal medicinal products appear to be very promising as they have a noticeable therapeutic effect and tend to be more harmless in comparison to the most of synthesized medications.

PURPOSE

Our aim was to study the composition of the Primula veris L. solid herbal extract (PVSHE) and its effects on the myocardial contractile function in animals with experimental CHF.

STUDY DESIGN

The study design involved the identification of the raw material composition of the P. veris L. extract. For the experimental part of our research, we used the model of CHF to elucidate the cardioprotective properties of PVSHE.

METHODS

The active extract constituents were isolated by thin-layer chromatography and column chromatography; the extract components were identified by high-performance liquid chromatography, ultraviolet spectroscopy (UVS), and nuclear magnetic resonance spectroscopy (NMRS). To model CHF, L-isoproterenol at a dose of 2.5 mg/kg was intraperitoneally injected to the experimental rats twice a day for 21 days. Cardiac output was assessed with the loading test, adrenoreactivity test, and maximum isometric loading test; CHF markers adrenomedullin and copeptin were detected in blood plasma with ELISA kit for adrenomedullin and copeptin (Coud-Clone Corp., USA).

RESULTS

P. veris L. solid herbal extract contains flavonoid aglycons (apigenin, quercetine, kaemferol), flavonoid glycosides (cinarozid, rutin, hyperozid), as well as polymethoxylated flavonoids acting as chemotaxonomic markers for the genus Primula (8-methoxy-flavone; 3',4'methylenedioxy-5'-methoxyflavone). The substance 3',4'methylenedioxy-5'-methoxyflavone has been isolated from the primrose herb for the first time. We showed that the PVSHE has a cardioprotective effect when it was administered at a dose of 30 mg/kg in the experimental CHF, as evidenced by a lower number of animal death, lower level of CHF markers in the blood plasma of the experimental animals, the higher increase in rate of myocardial contraction and relaxation, the higher level of left ventricular pressure (LVP) and of maximum intensity of structural performance (MISP), as compared to the control group.

CONCLUSION

P. veris L. solid herbal extract contains flavonoid aglycons, flavonoid glycosides, and polymethoxylated flavonoids. The herbal agent increases the myocardial contractility in experimental CHF.

摘要

背景

慢性心力衰竭（CHF）发病率高、预后差、因心力衰竭复发导致住院人数不断增加、治疗不充分，这些事实都说明人们对 CHF 有着浓厚的兴趣。因此，需要寻找新的药物来纠正 CHF。草药似乎很有前途，因为它们具有显著的治疗效果，而且与大多数合成药物相比，它们往往更安全。

目的

我们的目的是研究报春花属报春花固体草药提取物（PVSHE）的组成及其对实验性 CHF 动物心肌收缩功能的影响。

研究设计

本研究的设计包括鉴定报春花提取物的原料组成。在我们的研究的实验部分，我们使用 CHF 模型来阐明 PVSHE 的心脏保护特性。

方法

采用薄层色谱法和柱色谱法分离活性提取物成分；采用高效液相色谱法、紫外光谱法（UVS）和核磁共振光谱法（NMRS）鉴定提取物成分。为了建立 CHF 模型，将 L-异丙肾上腺素以 2.5mg/kg 的剂量每天两次腹腔注射给实验大鼠，共 21 天。通过负荷试验、肾上腺素反应试验和最大等长负荷试验评估心输出量；用 ELISA 试剂盒（Coud-Clone Corp.，美国）检测血浆中的 CHF 标志物肾上腺髓质素和 copeptin。

结果

报春花属报春花固体草药提取物含有黄酮苷元（芹菜素、槲皮素、山奈酚）、黄酮糖苷（芹菜素、芦丁、异槲皮苷）以及作为报春花属化学分类标志物的多甲氧基黄酮（8-甲氧基-黄酮；3'，4'-亚甲二氧基-5'-甲氧基黄酮）。首次从报春花属植物中分离出 3'，4'-亚甲二氧基-5'-甲氧基黄酮。我们表明，当 PVSHE 以 30mg/kg 的剂量在实验性 CHF 中给药时，具有心脏保护作用，表现为动物死亡率降低，实验动物血浆中 CHF 标志物水平降低，心肌收缩和舒张率增加，左心室压（LVP）和最大结构性能强度（MISP）水平升高，与对照组相比。