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Background: Radix Aconiti Lateralis (Fuzi), a mono‐herbal preparation of Aconitum herbs in the genus Aconitum, is commonly used in traditional Chinese medicine (TCM) to treat critical illnesses. The curative effect of Fuzi is remarkable. However, the toxic effects of Fuzi are still a key clinical focus, and the substances inducing nephrotoxicity are still unclear. Therefore, this study proposes a research model combining "in vitro and in vivo component mining‐virtual multi‐target screening‐active component prediction‐literature verification" to screen potential nephrotoxic substances rapidly. Method: The UHPLC‐Q‐Exactive‐Orbitrap MS analysis method was used for the correlation analysis of Fuzi's in vitro–in vivo chemical substance groups. On this basis, the key targets of nephrotoxicity were screened by combining online disease databases and a protein–protein interaction (PPI) network. The computer screening technique was used to verify the binding mode and affinity of Fuzi's components with nephrotoxic targets. Finally, the potential material basis of Fuzi‐induced nephrotoxicity was screened. Results: Eighty‐one Fuzi components were identified. Among them, 35 components were absorbed into the blood. Based on the network biology method, 21 important chemical components and three potential key targets were screened. Computer virtual screening revealed that mesaconine, benzoylaconine, aconitine, deoxyaconitine, hypaconitine, benzoylhypaconine, benzoylmesaconine, and hypaconitine may be potential nephrotoxic substances of Fuzi. Conclusions: Fuzi may interact with multiple components and targets in the process of inducing nephrotoxicity. In the future, experiments can be designed to explore further. This study provides a reference for screening Fuzi nephrotoxic components and has certain significance for the safe use of Fuzi. The study screened 21 components of Fuzi for potential nephrotoxicity. These components induce renal injury in rats by acting on multiple targets. [ABSTRACT FROM AUTHOR]

Background: Fuzi-Gancao herb couple is one of the commonly used herb couples involved in the traditional Chinese medicine formulations, with radix aconiti lateralis (Fuzi in Chinese) and radix glycyrrhizae (Gancao in Chinese) as a ratio of 1:1. Alkaloids and flavonoids were considered as the main active ingredients of Fuzi-Gancao herb couple. However, no analytical methods have been reported to quantitatively analyze these activity ingredients in Fuzi-Gancao herb couple simultaneously. Objective: To develop a simple, rapid, and sensitive UHPLC-MS/MS method for simultaneous quantitation of six alkaloid and three flavonoid compounds, namely, aconitine (AC), mesaconitine (MA), hypaconitine (HA), benzoylaconitine (BAC), benzoylmesaconitine (BMA), benzoylhypaconitine (BHA), liquiritin, isoliquiritin, and licochalcone A (LCA) in Fuzi-Gancao herb couple. Materials and Methods: The chromatographic separation was achieved using a reversed phase C18 column and a mobile phase consisted of water (0.1% formic acid in water, v/v) and acetonitrile. The detection was achieved in multiple reaction monitoring modes. The optimal mass transition ion pairs (m/z) for quantitation were 646.3/586.5 for AC, 632.4/572.5 for MA, 616.3/556.4 for HA, 604.5/572.5 for BAC, 590.4/540.4 for BMA, 574.1/542.5 for BHA, 419.4/257.1 for liquiritin, 419.4/257.1 for isoliquiritin, and 339.2/121.1 for LCA. Results: Good linearity was observed in validated concentration range for each analyte (r > 0.9992), and the intra- and inter-day precisions were <3.12% and 3.65%, respectively. The recovery ranged from 85.36% to 110.14%. Conclusions: The results demonstrated that the method developed was reliable, rapid, and specific. Moreover, this method was successfully applied to control the quality of Fuzi-Gancao herb couple. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Radix Aconiti Lateralis (Fuzi in Chinese, derived from the lateral roots of Aconitum Carmichaeli Debx.) is widely used for the treatment of heart failure, internal cold, arthralgia, diarrhea and edema for thousands of years. It was usually prescribed in combination with Rhizoma Zingiberis (Ganjiang in Chinese, derived from the dry rhizome of Zingiber officinale Rosc.) to decrease toxicity and increase efficacy. Aim of the study: In order to investigate the influence of Rhizoma Zingiberis on pharmacokinetics of six Aconitum alkaloids, i.e. aconitine (AC), hypaconitine (HA), mesaconitine (MA), benzoylaconine (BAC), benzoylhypaconine (BHA) and benzoylmesaconine (BMA), in Fuzi−Ganjiang herb couple, the comparative pharmacokinetics of six Aconitum alkaloids after oral administration of Fuzi and Fuzi−Ganjiang aqueous extract was carried out. Materials and methods: A sensitive, specific and rapid LC−MS/MS method was developed to determine the six analytes in plasma. Then the rats were randomly divided into two groups and orally administered with Fuzi and Fuzi−Ganjiang aqueous extract. At designated time points after oral administration, the concentrations of the six Aconitum alkaloids in rat plasma were determined, and main pharmacokinetic parameters were investigated using 3P97 (Practical Pharmacokinetics Program Version 1.0). Results: Comparing with Fuzi group, both T 1/2 and AUC0−t of AC and HA decreased (P<0.05), while T 1/2, AUC0−t and C max of BAC, BHA increased (P<0.05) in Fuzi−Ganjiang group, which indicated that Ganjiang could promote the elimination of AC and HA and enhance the absorption of BAC, BHA and BMA. Conclusion: The differences of pharmacokinetics of Aconitum alkaloids in rat plasma could support those of pharmacologics and toxicity in previous reports between Fuzi and Fuzi−Ganjiang herb couple. The results might be helpful in explaining the mechanism of combination of Fuzi−Ganjiang to decrease toxicity and increase efficacy. [Copyright &y& Elsevier]

The type and content change of alkaloids of Radix Aconiti Lateralis (Lateral root of Aconitum carmichaeli Debx, an important and popular medicinal herb in Traditional Chinese Medicine) in processing were studied using high performance liquid chromatography-electrospray ionization-multi-stage mass spectrometry (HPLC-ESI-MSn). Extract containing alkaloids, which were known to be the main bioactive components of the herb, was prepared by 1% ( v/v) hydrochloric acid solution. An HPLC method which can simultaneously separate these alkaloids was established with gradient elution mode. Forty-eight compounds were structurally identified by employing LC-MSn techniques; the MSn spectra of most alkaloids displayed a characteristic behaviour of loss of CH3COOH (60 u), CH3OH (32 u), C6H5COOH (122 u), CO (28 u) and H2O (18 u). Among them, the fragmentation ion C6H5COOH (122 u) was reported for the first time. By comparison, 22 compounds were found both in the crude materials and the processed products; 17 alkaloids were only found in the processed products and 9 alkaloids,which existed in crude material, could not be detected after processing. In the process of identification, we found new kinds of alkaloids, with protonated molecules at m/z 452, 468, and 482. We called these compounds dehydra-hypaconine, dehydra-mesaconine, and dehydra-aconine, respectively. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

This study established a new, rapid, and accurate method for bioactive compound screening by the combination of serum pharmacochemistry and serum pharmacology based on a spectrum-effect relationship model. HPLC/ESI-Q-TOF-MS was used for the chemical profiling of samples of dosed plasma, control plasma, and Radix Aconiti Lateralis decoction. A comparison was made of the resulting chemical profiles, which totaled 20 compounds including 16 prototype compounds and 4 metabolites derived from SF decoction that were detected as potential bioactive components. Using MS/MS analysis and accurate molecular weight assessments of TOF, 17 components in 20 potential bioactive compounds were structurally identified. Moreover, the pretreated plasma samples were injected into venous sinus of isolated toad hearts to investigate the cardio-toxicity according to heart ratio (HR) situation and electrocardiograph (ECG) parameters, including PR interval, QRS interval, and QT interval. Finally, 4 compounds in these 20 potential bioactive components that had closest correlation with 4 cardio-toxic experimental indexes respectively were investigated by spectrum-effect relationship model for the first time. The 4 compounds were considered as the real cardio-toxic components. This study proposed a series of potential bioactive components in Radix Aconiti Lateralis and provided a general research pattern to identify the potential bioactivity compounds in Chinese herbs or natural pharmacy. [ABSTRACT FROM AUTHOR]

Background: Fuzi ( Radix aconiti lateralis)- Gancao ( Radix glycyrrhizae ) is one of the most classical drug pairs of traditional Chinese medicine. In clinical practice, decoctions containing Fuzi-Gancao (F-G) are often used in the treatment of liver diseases such as hepatitis and liver failure., Aim: To investigate the metabolomics of F-G in CCl 4 induced acute liver injury in rats and its regulatory effect on the bile acid profile., Methods: The pharmacodynamic effect of F-G on CCl 4 induced acute liver injury in rats was evaluated, and an ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous determination of 92 metabolites from multiple pathways was established to explore the protective metabolic mechanism of F-G in serum on the liver., Results: Twenty-four differential metabolites were identified in serum samples. The primary bile acid biosynthetic metabolic pathway was the major common pathway in the model group and F-G group. Subsequently, a UPLC-MS/MS method for simultaneous determination of 11 bile acids, including cholic acid, ursodeoxycholic acid, glycochenodeoxycholic acid, glycochenodeoxycholic acid, taurocholic acid, glycocholic acid, chenodeoxycholic acid, deoxycholic acid, taurochenodeoxycholic acid, taurocholic acid, and glycinic acid, was established to analyze the regulatory mechanism of F-G in serum. F-G decreased the contents of these 11 bile acids in serum in a dose-dependent manner compared with those in the model control group., Conclusion: F-G could protect hepatocytes by promoting the binding of free bile acids to glycine and taurine, and reducing the accumulation of free bile acids in the liver. F-G could also regulate the compensatory degree of taurine, decreasing the content of taurine-conjugated bile acids to protect hepatocytes., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to disclose., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Radix aconiti lateralis (Fuzi) is widely used in China as a traditional Chinese medicine for the treatment of asthenia, pain and inflammation. However, its toxic alkaloids often lead to adverse reactions. Currently, most of the toxicity studies on Fuzi are focused on the heart and nervous system, and more comprehensive toxicity studies are needed. In this study, based on the previous reports of Fuzi hepatotoxicity, serum pharmacochemistry and network toxicology were used to screen the potential toxic components of Heishunpian(HSP), a processed product of Fuzi, and to explore the possible mechanism of HSP-induced hepatotoxicity. The results obtained are expressed based on the toxicological evidence chain (TEC). It was found that 22 potential toxic components screened can affect Th17 cell differentiation, Jak-STAT signaling pathway, glutathione metabolism, and other related pathways by regulating AKT1, IL2, F2, GSR, EGFR and other related targets, which induces oxidative stress, metabolic disorders, cell apoptosis, immune response, and excessive release of inflammatory factors, eventually inducing liver damage in rats. This is the first study on HSP-induced hepatotoxicity based on the TEC concept, providing references for further studies on the toxicity mechanism of Fuzi. Image 1 • The first systematic study of HSP-induced hepatotoxicity based on the TEC concept. • 22 candidate potential hepatotoxic components of HSP were obtained. • Inflammation, oxidative stress, metabolic disorders, and apoptosis are closely related to HSP-induced hepatotoxicity. [ABSTRACT FROM AUTHOR]

Background: Fuzi-Gancao herb couple is one of the commonly used herb couples involved in the traditional Chinese medicine formulations, with radix aconiti lateralis (Fuzi in Chinese) and radix glycyrrhizae (Gancao in Chinese) as a ratio of 1:1. Alkaloids and flavonoids were considered as the main active ingredients of Fuzi-Gancao herb couple. However, no analytical methods have been reported to quantitatively analyze these activity ingredients in Fuzi-Gancao herb couple simultaneously., Objective: To develop a simple, rapid, and sensitive UHPLC-MS/MS method for simultaneous quantitation of six alkaloid and three flavonoid compounds, namely, aconitine (AC), mesaconitine (MA), hypaconitine (HA), benzoylaconitine (BAC), benzoylmesaconitine (BMA), benzoylhypaconitine (BHA), liquiritin, isoliquiritin, and licochalcone A (LCA) in Fuzi-Gancao herb couple., Materials and Methods: The chromatographic separation was achieved using a reversed phase C18 column and a mobile phase consisted of water (0.1% formic acid in water, v/v) and acetonitrile. The detection was achieved in multiple reaction monitoring modes. The optimal mass transition ion pairs (m/z) for quantitation were 646.3/586.5 for AC, 632.4/572.5 for MA, 616.3/556.4 for HA, 604.5/572.5 for BAC, 590.4/540.4 for BMA, 574.1/542.5 for BHA, 419.4/257.1 for liquiritin, 419.4/257.1 for isoliquiritin, and 339.2/121.1 for LCA., Results: Good linearity was observed in validated concentration range for each analyte ( r > 0.9992), and the intra- and inter-day precisions were <3.12% and 3.65%, respectively. The recovery ranged from 85.36% to 110.14%., Conclusions: The results demonstrated that the method developed was reliable, rapid, and specific. Moreover, this method was successfully applied to control the quality of Fuzi-Gancao herb couple., Summary: A simple, rapid, and sensitive UHPLC-MS/MS method for simultaneous quantitation of six alkaloid and three flavonoid compounds in Fuzi-Gancao herb couple has been developed. Abbreviations used: UHPLC-ESI-MS/MS: Ultra High Performance Liquid Chromatography-electrospray ionization-mass spectrometry; RSD: Relative standard deviations; LOD: Limit of detection; LOQ: Limit of quantification; MRM: Multiple reaction monitor; TCMs: Traditional Chinese medicines., Competing Interests: There are no conflicts of interest.