A novel method to analyze hepatotoxic components in Polygonum multiflorum using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry

Lin, Liwu; Lin, Hongmei; Zhang, Miao; Ni, Boran; Yin, Xingbin; Qu, Changhai; Ni, Jian

doi:10.1016/j.jhazmat.2015.06.014

Cited by 79 publications

(64 citation statements)

References 17 publications

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“…In the present study, PM was used as an example to analyze the relationship between the geographical areas/batches and toxicity and to speculate on the hepatotoxicity-inducing components in PM. Although the analytical procedure is consistent with the method we have previously used (Lin et al, 2015a), more attention was paid to the verification of the speculative results to reduce the false-positive results in this study. The experimental procedure is shown in Figure 1 .…”

Section: Introductionmentioning

confidence: 74%

A New Perspective on Liver Injury by Traditional Chinese Herbs Such As Polygonum multiflorum: The Geographical Area of Harvest As an Important Contributory Factor

Lin

et al. 2017

Front. Pharmacol.

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Herbal medicine has been widely used in the treatment of various diseases; however, the adverse reactions cannot be ignored. Most previous studies have ignored the relationship between the factors of geographical areas/batches and toxicity. This study used Polygonum multiflorum (PM) as an example to analyze the relationship between the geographical areas/batches and toxicity and speculated on the hepatotoxicity-inducing components in PM based on high content screening, UHPLC-Q-TOF/MS and Progenesis QI software analysis. The results of the study show that the toxicity of PM was obviously different among the different geographical areas, and the most toxic PM was from the Sichuan province. To obtain more accurate results and to reduce the false-positive rate, two methods were used to evaluate the speculative results. It was noteworthy that emodin was not the main hepatocyte toxicity constituent of PM. The analysis methods suggested that PM toxicity may be associated with tetrahydroxystilbene-O-(galloyl)-hex and emodin-O-hex-sulfate. The toxicity of these two components requires further study.

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Section: Introductionmentioning

confidence: 74%

A New Perspective on Liver Injury by Traditional Chinese Herbs Such As Polygonum multiflorum: The Geographical Area of Harvest As an Important Contributory Factor

Lin

et al. 2017

Front. Pharmacol.

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“…Besides, the present studies also have controversial issue (Wang et al, 2014). Several studies have demonstrated that anthraquinones, e.g., emodin, are the major hepatotoxins in Heshouwu (Yu et al, 2011; Lin et al, 2015; Ma et al, 2015). Westendorf (1993) concluded that the herb toxicity might be associated with anthraquinones that form highly reactive anthrones in the colon, thus resulting in hepatotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Metabolomic Study on Idiosyncratic Liver Injury Induced by Different Extracts of Polygonum multiflorum in Rats Integrated with Pattern Recognition and Enriched Pathways Analysis

Gao

et al. 2016

Front. Pharmacol.

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Currently, numerous liver injury cases related to a famous Chinese herb- Polygonum Multiflorum (Heshouwu in Chinese) have attracted great attention in many countries. Our previous work showed that Heshouwu-induced hepatotoxicity belonged to idiosyncratic drug-induced liver injury (IDILI). Unfortunately, the components and mechanisms attributed to IDILI of Heshouwu are difficult to determine and thus remain unknown. Attempts to explore puzzles, we prepared the chloroform (CH)-, ethyl acetate (EA)-, and residue (RE) extracts of Heshouwu to investigate IDILI constituents and underlying mechanisms, using biochemistry, histopathology, and metabolomics examinations. The results showed that co-treatment with non-toxic dose of lipopolysaccharide (LPS) and EA extract could result in evident liver injury, indicated by the significant elevation of plasma alanine aminotransferase and aspartate aminotransferase activities, as well as obvious liver histologic damage; whereas other two separated fractions, CH and RE extracts, failed to induce observable liver injury. Furthermore, 21 potential metabolomic biomarkers that differentially expressed in LPS/EA group compared with other groups without liver injury were identified by untargeted metabolomics, mainly involved two pathways: tricarboxylic acid cycle and sphingolipid metabolism. This work illustrated EA extract had close association with the idiosyncratic hepatotoxicity of Heshouwu and provided a metabolomic insight into IDILI of different extracts from Heshouwu.

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“…(Park et al, 2001; Mazzanti et al, 2004; Panis et al, 2005; Cárdenas et al, 2006; Laird et al, 2008; Zhang et al, 2009; Jung et al, 2011). So far, a broad spectrum of chemicals such as stilbenes, anthraquinones (AQs), flavonoids, and phospholipids have been isolated from PMR (Lin et al, 2015b). Among these compounds, AQs including emodin, physcion, rhein, aloe-emodin, and chrysophanol, are commonly and conveniently believed to be primarily responsible for the PMR-associated hepatotoxicity, especially emodin, a predominant AQs occurring in PMR, is assumed to be one of the leading hepatotoxic component (Zhang et al, 2010; Li et al, 2012; Lin et al, 2015b; Lv et al, 2015; Ma et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…So far, a broad spectrum of chemicals such as stilbenes, anthraquinones (AQs), flavonoids, and phospholipids have been isolated from PMR (Lin et al, 2015b). Among these compounds, AQs including emodin, physcion, rhein, aloe-emodin, and chrysophanol, are commonly and conveniently believed to be primarily responsible for the PMR-associated hepatotoxicity, especially emodin, a predominant AQs occurring in PMR, is assumed to be one of the leading hepatotoxic component (Zhang et al, 2010; Li et al, 2012; Lin et al, 2015b; Lv et al, 2015; Ma et al, 2015). Nevertheless, the specific mechanism of AQs-induced liver injury is still unclear, which limits the establishment of effective approaches for diagnosis and treatment of liver injury induced by PMR.…”

Section: Introductionmentioning

confidence: 99%

Detection of Emodin Derived Glutathione Adduct in Normal Rats Administered with Large Dosage of Polygoni Multiflori Radix

et al. 2017

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Polygoni Multiflori Radix (PMR) has been commonly used as a tonic in China for centuries. PMR-associated hepatotoxicity has been drawing increasingly more attention in recent years in parallel with its wide utilization. Anthraquinones (AQs) are recognized as the main hepatotoxic components in PMR. However, the exact underlying mechanism of AQs poisoning is still not fully understood. Herein, we proposed a hypothesis that metabolic activation of AQs such as emodin was involved in PMRinduced liver injury, AQs followed to generate the electrophilic reactive metabolites and subsequently formed covalent adduct with cellular nucleophiles in the liver to exert hepatotoxicity. In the present study, the link of cytotoxicity of PMR in primary human hepatocytes and the depletion of glutathione (GSH) was investigated by MTT assay and UHPLC-QqQ-MS/MS analysis. The results showed that PMR depleted GSH and therefore induced cytotoxicity. Then, emodin-GSH adduct was identified in bile of liver injured rats after intragastric administration of PMR or emodin with the aid of UHPLC-QTOF-MS/MS method. Our findings not only provided confirmative evidence that the mechanism of hepatotoxicity induced by AQs in PMR involved key metabolic steps, but also revealed that emodin-GSH adduct had potential to be further developed as a sensitive and traceable biomarker for the assessment of PMR-induced liver injury.

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A novel method to analyze hepatotoxic components in Polygonum multiflorum using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry

Cited by 79 publications

References 17 publications

A New Perspective on Liver Injury by Traditional Chinese Herbs Such As Polygonum multiflorum: The Geographical Area of Harvest As an Important Contributory Factor

A New Perspective on Liver Injury by Traditional Chinese Herbs Such As Polygonum multiflorum: The Geographical Area of Harvest As an Important Contributory Factor

Metabolomic Study on Idiosyncratic Liver Injury Induced by Different Extracts of Polygonum multiflorum in Rats Integrated with Pattern Recognition and Enriched Pathways Analysis

Detection of Emodin Derived Glutathione Adduct in Normal Rats Administered with Large Dosage of Polygoni Multiflori Radix

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