Discovery of effective combination from Renshen-Fuzi herbal pair against heart failure by spectrum-effect relationship analysis and zebrafish models.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:

Traditional herbal pair Ginseng Radix et Rhizoma (roots and rhizomes of Panax ginseng C.A. Mey, Renshen in Chinese) and Aconiti Lateralis Radix Praeparata (lateral roots of Aconitum carmichaelii Debeaux, Fuzi in Chinese), composition of two traditional Chinese medicinal herbs, has been widely used in traditional Chinese medicine formula, in which Shenfu decoction has been used clinically in China for the treatment of heart failure at present.

AIM OF THE STUDY:

Although the ginsenosides and aconite alkaloids have been proven as the essential bioactive components in Renshen-Fuzi herbal pair, the exact composition of effective components to combat heart failure are still unclear. Therefore, spectrum-effect relationship analysis was performed to reveal its effective combination for anti-heart failure effect.

MATERIALS AND METHODS:

Firstly, the chemical constituents of Renshen-Fuzi herbal pair were identified using ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF MS). The 39 major compounds in Renshen-Fuzi with five different compatibility ratios were simultaneously quantified using ultra high-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UHPLC-QQQ MS/MS). Subsequently, zebrafish models induced by verapamil hydrochloride were constructed and four heart failure-related indexes were selected for pharmacodynamic evaluation of Renshen-Fuzi. To analyze the spectrum-effect relationships, partial least squares regression (PLSR) models were established among the contents of 39 compounds in Renshen-Fuzi with each pharmacodynamic index. According to the contribution of each compound to the whole efficacy, 12 compounds were finally screened out as the effective combination.

RESULTS:

A total of 157 chemical compounds of Renshen-Fuzi herbal pair were identified, in which 39 components were simultaneously determined. The pharmacological effects indicated that Renshen-Fuzi with 1:2 ratio exhibited the best effect based on zebrafish model, which could improve cardiac output and blood flow velocity and inhibit pericardial enlargement and venous blood stasis significantly. A combination of 9 ginsenosides and 3 aconite alkaloids based on a component-efficacy modeling by PLSR was screened, and exerted approximately equivalent pharmacological effects compared with Renshen-Fuzi herbal pair.

CONCLUSIONS:

Our findings elucidated the effective combination of Renshen-Fuzi herbal pair that has been used in clinic for the treatment of heart failure, which could also promote the pharmacological research and quality control of their formula such as Shenfu decoction.

• Authors: Chu-Jun Li, Rong-Rong Zhai, Xiao-Yu Zhu, Zi-Fan Guo, Hua Yang
• Journal: Journal of ethnopharmacology (J Ethnopharmacol) Vol. 317 Pg. 116832 (Dec 05 2023) ISSN: 1872-7573 [Electronic] Ireland
• PMID: 37352946 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 Elsevier B.V. All rights reserved.

Chemical References

• fuzi drug herbal
• Ginsenosides
• Drugs, Chinese Herbal
• Alkaloids

Topics

• Animals
• Zebrafish
• Tandem Mass Spectrometry (methods)
• Panax
• Ginsenosides
• Drugs, Chinese Herbal (pharmacology, therapeutic use, analysis)
• Alkaloids (pharmacology, therapeutic use, analysis)
• Heart Failure (drug therapy)
• Aconitum (chemistry)