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Effects of total saponins from Panacis majoris Rhizoma and its degradation products on myocardial ischemia-reperfusion injury in rats - 27/10/20

Doi : 10.1016/j.biopha.2020.110538 
Min Li a, Xuwen Li b, Limei Zhou c, Yongri Jin b,
a College of Food and Biological Engineering, Zhengzhou University of Light Industry, Zhengzhou, 450000, Henan, PR China 
b College of Chemistry, Jilin University, Changchun, 130012, Jilin, PR China 
c Jilin Modern Chinese Medicine Engineering and Research Center Co., Ltd, Changchun, 130012, Jilin, PR China 

Corresponding author at: College of Chemistry, Jilin University, No. 2699, Qianjin Road, Changchun, Jilin, 130012, PR China.College of ChemistryJilin UniversityNo. 2699Qianjin RoadChangchunJilin130012PR China

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Highlights

Both total saponins from Panacis majoris Rhizoma (TSPJ) and the degradation products of TSPJ (DTSPJ) were prepared.
The main constituents of TSPJ and DTSPJ were analyzed and the possible mechanisms were also investigated.
The protection of DTSPJ against myocardial ischemia-reperfusion injury was a little stronger than those of TSPJ.
DTSPJ represents a promising drug candidate for treating ischemic heart disease.

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Abstract

Ethnopharmacological relevance

Panacis majoris Rhizoma, which is a member of herbal medicine, is known for many years to remove blood stasis, promote blood circulation, and enrich the blood. The active ingredients of this plant are mainly attributed to saponins.

Aim of the study

The total saponins from Panacis majoris Rhizoma (TSPJ), and the degradation products of TSPJ (DTSPJ), were designed in this study to compare the protective effects on myocardial ischemia-reperfusion injury, and the aim of this approach is to discover more effective agents for the treatment of ischemic heart diseases. We analyzed the main constituents of TSPJ and DTSPJ, aiming to make clear which saponins played important roles in this protective effect, and also investigated the possible mechanisms.

Materials and methods

DTSPJ was prepared by the method of alkaline hydrolysis. High performance liquid chromatography (HPLC) were used to analyze the main chemical constituents of TSPJ and DTSPJ, which were isolated by chromatographic techniques and identified by comparison with the Nuclear Magnetic Resonance (NMR) data in reported literature. Male Wistar rats were randomized to sham-operated group, ischemia-reperfusion group, three TSPJ (50, 100 and 200 mg/kg) groups, three DTSPJ (50, 100 and 200 mg/kg) groups, and isosorbide dinitrate tablet (5.0 mg/kg) group. The rats in all groups were intragastrically administrated once per day for three successive days. The establishment of the model of myocardial ischemia-reperfusion injury was used the following method: firstly, the left coronary artery of experimental rat was ligated for 30 min and then reperfused for 120 min. Then the myocardial infarct size, hemorheological and biochemical parameters, whole blood viscosity, plasma viscosity, platelet adhesion rate, platelet aggregation and histopathology changes were assessed.

Results

Five C3,C28-bidesmosidic oleanane-type saponins and ginsenoside Rd were the main constituents of TSPJ, and their total content in TSPJ was 79.2 %. The main constituents of DTSPJ were five C3-monodesmosidic oleanane-type saponins and ginsenoside Rd, and their total content in DTSPJ was 72.6 %. The HPLC analysis revealed that the five C3,C28-bidesmosidic oleanane-type saponins in TSPJ were completely turned into five C3-monodesmosidic oleanane-type saponins in DTSPJ through the method of alkaline hydrolysis, but ginsenoside Rd remained unchanged. Both TSPJ and DTSPJ could significantly reduced myocardial infarct size, and improved heart function, and lowered the activities of aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatine kinase isoenzymes (CK-MB), and malonyldialdehyde (MDA) content, as well as the levels of whole blood viscosity, plasma viscosity, platelet adhesion rate, and platelet aggregation; on the contrary, both the level of glutathione peroxidase (GSH-Px) and the activity of superoxide dismutase (SOD) were notablely increased. The results of histopathological examination further supported the cardioprotective effects of TSPJ and DTSPJ.

Conclusion

Both TSPJ and DTSPJ can guard cardiomyocytes against myocardial ischemia-reperfusion injury. The underlying mechanisms may be closely related to its enhancing anti-oxidative properties, modifying blood viscosity, and inhibiting platelet aggregation and platelet adhesion. As a whole, the protection of DTSPJ against myocardial ischemia-reperfusion injury was a little stronger than those of TSPJ. The results display the prospect of DTSPJ as a drug candidate for treating ischemic heart disease.

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Abbreviations : TSPJ, DTSPJ, HPLC, LVSP, +dp/dt, LVEDP, −dp/dt, HR, DBP, SBP, MAP, MDA, LDH, AST, CK-MB, SOD, GSH-Px

Keywords : Panacis majoris Rhizoma, Myocardial ischemia-reperfusion, Total saponins, Degradation products


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Vol 130

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