Quality evaluation of different processed products of Aconiti Lateralis Radix Praeparata combining bioassay and toxicity detection
10.16438/j.0513-4870.2019-0658
- VernacularTitle:基于生物毒效检测的附子不同炮制品质量评价研究
- Author:
Ding-kun ZHANG
1
,
2
;
Zhi-hao ZHAO
3
;
Chun-yu LI
4
;
Ming NIU
3
;
Peng TAN
5
;
Jin PEI
1
,
2
;
Ming YANG
6
;
Cheng PENG
1
;
Ping ZHANG
3
;
Xiao-he XIAO
3
;
Jia-bo WANG
3
Author Information
1. State Key Laboratory of Characteristic Chinese Medicine Resources in Southwest China, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
2. Sichuan Good Doctor Panxi Pharmaceutical Co., Ltd., Xichang 615000, China
3. China Military Institute of Chinese Medicine, the Fifth Medical Centre of Chinese People's Liberation Army General Hospital, Beijing 100039, China
4. Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021
5. State Key Laboratory of Quality Evaluation of Traditional Chinese Medicine, Sichuan Academy of Traditional Chinese Medicine, Chengdu 610041, China
6. Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China
- Publication Type:Research Article
- Keywords:
Aconiti Lateralis Radix Praeparata;
cardiotoxicity;
cardiac activity;
quality marker;
biological evaluation
- From:
Acta Pharmaceutica Sinica
2019;54(12):2169-2177
- CountryChina
- Language:Chinese
-
Abstract:
There are many kinds of processed products of Aconiti Lateralis Radix Praeparata (ALRP), but their differences in toxicity and efficacy have not been identified. The minimum premature ventricular contraction (PVC) method was used to evaluate the biological toxicity of eight processed products. The results showed that the minimal toxic dose (MTD) of an ethanol extract of Shengfupian (SFP) was 0.16 g·kg-1, which was much lower than that of Heishunpian (HSP), Baifupian (BFP), Baofupian (BAP), Paofuzi (PFZ) or Zhengfupian (ZFP), with MTDs ranging from 2.64 to 5.75 g·kg-1. No cardiotoxicity was detected with Chaofupian (CFP) and Paotianxiong (PTX). A novel +dp/dtmax assay for acute heart failure in rats was developed to evaluate the cardiac activity. It was found that all eight processed products had cardiac effects, with Shengfupian showing the strongest cardiotonic effect and the ability to restore damaged cardiac function to normal within 15 minutes of injection. Heishunpian, Baifupian and the three other products displayed moderate activity, while Paofuzi and Paotianxiong were the weakest. An LC-MS/MS method was utilized to determine the content of 13 alkaloids in water extracts. The results demonstrated that hypertoxic aconitine, mesaconitine, and hypaconitine could not be detected, higenamine was only present in Shengfupian, and salsolinol was about 4-56 times higher in Shengfupian than in other products. A correlation analysis showed that salsolinol had the best correlation with the cardiotonic index, with a correlation coefficient as high as 0.817, while the three monoester alkaloids failed to correlate with the cardiotonic effect. Higenamine and salsolinol were cardiotonic, while the 11 other components had no cardiotonic activity. This study establishes methods for precise evaluation of cardiotoxicity and cardiac activity, reveals the toxicity and efficacy of common processed products, and identifies the key quality markers for cardiac activity, providing scientific support for the quality evaluation and clinical application of processed products of aconite.