Research on the Relationships between Endogenous Biomarkers and Exogenous Toxic Substances of Acute Toxicity in Radix Aconiti.

Haonan Zhou,Bin Yang,Jiabin Xie,Pengjie Zhang,Yuming Wang,Yubo Li,Yanyan Xu,Zhiguo Hou

doi:10.3390/molecules21121623

Abstract

Radix Aconiti, a classic traditional Chinese medicine (TCM), has been widely used throughout China for disease treatment due to its various pharmacological activities, such as anti-inflammatory, cardiotonic, and analgesic effects. However, improper use of Radix Aconiti often generated severe acute toxicity. Currently, research on the toxic substances of Radix Aconiti is not rare. In our previous study, acute toxic biomarkers of Radix Aconiti have been found. However, few studies were available to find the relationships between these endogenous biomarkers and exogenous toxic substances. Therefore, in this study, toxic substances of Radix Aconiti have been found using UPLC-Q-TOF-MS technology. Then, we used biochemical indicators as a bridge to find the relationships between biomarkers and toxic substances of Radix Aconiti through Pearson correlation analysis and canonical correlation analysis (CCA). Finally, the CCA results showed that LysoPC(22:5) is related to 14-acetyl-talatisamine, mesaconitine, talatisamine and deoxyaconitine in varying degrees; l-acetylcarnitine is negatively correlated with deoxyaconitine and demethyl-14-acetylkaracoline; shikimic acid has a good correlation with karacoline, demethyl-14-acetylkaracoline and deoxyaconitine; and valine is correlated with talatisamine and deoxyaconitine. Research on these relationships provides an innovative way to interpret the toxic mechanism of traditional Chinese medicine, and plays a positive role in the overall study of TCM toxicity.

Highlights

Radix Aconiti (Chuanwu in Chinese), the dried mother root of Aconitum carmichaeli Debx., has been widely used for thousands of years in clinical practice
Using metabolomic technology and canonical correlation analysis (CCA), we found the correlation between endogenous biomarkers and exogenous toxic substances
In this study, using biochemical indicators (CK, lactate dehydrogenase (LDH), ALT, AST, serum creatinine (Scr), and Urea) as the bridge, we developed a novel method to find the relationships between endogenous biomarkers and exogenous toxic substances of Radix Aconiti ethanol extraction by UPLC-Q-TOF-MS metabonomic method and CCA

Summary

Introduction

Radix Aconiti (Chuanwu in Chinese), the dried mother root of Aconitum carmichaeli Debx., has been widely used for thousands of years in clinical practice. As a famous and effective traditional Chinese medicine (TCM), it plays an important role in the treatment of diseases, such as rheumatoid joint pain, sciatica, paralysis and others [1]. The cardiotoxicity of this Chinese herbal medicine is severe, and the improper use of it will present highly toxicological risk and lead to fatal cardiac poisoning [2]. Mesaconitine, hypaconitine and other diester-type alkaloids are known to be the main toxic substances of Radix Aconiti [3]. Modern research showed that Radix Aconiti has an obvious toxicity caused by aconitine, and it usually produces abnormal heart function, fast respiratory rate, arrhythmia and other symptoms [4]. Biochemical tests and histopathological observation are used to evaluate the safety, but these methods are time-consuming, have low sensitivity, are a heavy workload and have other shortcomings, we can not find toxicity during the early stage

Results

Discussion

Conclusion