Effect of sample preparation on components and liver toxicity of Polygonum multiflorum

Lv, Guangping; Meng, Lan‐Zhen; Han, D.Q.; Li, H.Y.; Zhao, Jing; Li, S.P.

doi:10.1016/j.jpba.2015.02.029

Cited by 45 publications

(25 citation statements)

References 28 publications

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“…Some studies considered the toxic constituent to be emodin whereas some considered it to be the combined anthraquinones. Tannins, TSG and other components have also been considered (Yu et al, 2011; Lv et al, 2015; Li et al, 2017; Wang et al, 2017). There were substantial differences in the contents of the constituents among the different geographical areas/batches of PM (Lin et al, 2015c).…”

Section: Resultsmentioning

confidence: 99%

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: Resultsmentioning

confidence: 99%

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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“…Stilbenes have anti-aging effects and hepatoprotective activities [9] . However, many studies have also demonstrated that some quinones and stilbenes of PmT can lead to hepatotoxicity, especially emodin and rhein [10,11] . How these compounds produce these biphasic effects (liver injury and liver protection) remains to be determined.…”

Section: Introductionmentioning

confidence: 99%

Insights into the molecular mechanisms of Polygonum multiflorum Thunb-induced liver injury: a computational systems toxicology approach

Wang

et al. 2017

Acta Pharmacol Sin

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An increasing number of cases of herb-induced liver injury (HILI) have been reported, presenting new clinical challenges. In this study, taking Polygonum multiflorum Thunb (PmT) as an example, we proposed a computational systems toxicology approach to explore the molecular mechanisms of HILI. First, the chemical components of PmT were extracted from 3 main TCM databases as well as the literature related to natural products. Then, the known targets were collected through data integration, and the potential compound-target interactions (CTIs) were predicted using our substructure-drug-target network-based inference (SDTNBI) method. After screening for hepatotoxicity-related genes by assessing the symptoms of HILI, a compound-target interaction network was constructed. A scoring function, namely, Ascore, was developed to estimate the toxicity of chemicals in the liver. We conducted network analysis to determine the possible mechanisms of the biphasic effects using the analysis tools, including BiNGO, pathway enrichment, organ distribution analysis and predictions of interactions with CYP450 enzymes. Among the chemical components of PmT, 54 components with good intestinal absorption were used for analysis, and 2939 CTIs were obtained. After analyzing the mRNA expression data in the BioGPS database, 1599 CTIs and 125 targets related to liver diseases were identified. In the top 15 compounds, seven with Ascore values >3000 (emodin, quercetin, apigenin, resveratrol, gallic acid, kaempferol and luteolin) were obviously associated with hepatotoxicity. The results from the pathway enrichment analysis suggest that multiple interactions between apoptosis and metabolism may underlie PmT-induced liver injury. Many of the pathways have been verified in specific compounds, such as glutathione metabolism, cytochrome P450 metabolism, and the p53 pathway, among others. Hepatitis symptoms, the perturbation of nine bile acids and yellow or tawny urine also had corresponding pathways, justifying our method. In conclusion, this computational systems toxicology method reveals possible toxic components and could be very helpful for understanding the mechanisms of HILI. In this way, the method might also facilitate the identification of novel hepatotoxic herbs.

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“…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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Effect of sample preparation on components and liver toxicity of Polygonum multiflorum

Cited by 45 publications

References 28 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

Insights into the molecular mechanisms of Polygonum multiflorum Thunb-induced liver injury: a computational systems toxicology approach

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

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