State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
J Ethnopharmacol. 2023 Dec 5;317:116832. doi: 10.1016/j.jep.2023.116832. Epub 2023 Jun 21.
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.
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.
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.
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.
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.
人参（Panax ginseng C.A. Mey，中国人参）和制乌头（Aconitum carmichaelii Debeaux，中国人制川乌）的草药组合，是两种中药的组成部分，已广泛用于中药方剂中，目前在中国临床上用于心力衰竭的治疗。
虽然已证明人参皂苷和乌头生物碱是人参附子药对的基本生物活性成分，但对抗心力衰竭的确切有效成分组合仍不清楚。因此，进行了谱效关系分析，以揭示其抗心力衰竭的有效组合。
首先，使用超高效液相色谱-四极杆飞行时间质谱联用技术（UHPLC-QTOF MS）鉴定人参附子药对的化学成分。使用超高效液相色谱-三重四极杆串联质谱联用技术（UHPLC-QQQ MS/MS）同时定量五种不同配伍比例的人参附子中的 39 种主要化合物。随后，构建了盐酸维拉帕米诱导的斑马鱼模型，并选择了四个心力衰竭相关指标进行人参附子的药效评价。为了分析谱效关系，建立了 39 种化合物的含量与每种药效指标之间的偏最小二乘回归（PLSR）模型。根据每个化合物对整体疗效的贡献，最终筛选出 12 种化合物作为有效组合。
鉴定了人参附子药对的 157 种化学化合物，其中同时测定了 39 种成分。药效学研究表明，基于斑马鱼模型，1:2 比例的人参附子组效果最佳，可显著改善心输出量和血流速度，抑制心包扩张和静脉淤血。通过 PLSR 进行的成分-功效建模筛选出了基于 9 种人参皂苷和 3 种乌头生物碱的组合，其药理作用与人参附子药对相当。
本研究阐明了用于治疗心力衰竭的人参附子药对的有效组合，也可促进其方剂如参附汤的药理研究和质量控制。
