Background: The raw and processed roots of Polygonum multiflorum Thunb (PM) are commonly used in clinical practice to treat diverse diseases; however, reports of hepatotoxicity induced by Polygoni Multiflori Radix (PMR) and Polygoni Multiflori Radix Praeparata (PMRP) have emerged worldwide. Thus, it is necessary for researchers to explore methods to improve quality standards to ensure their quality and treatment effects. Methods: In the present study, an ultra-high performance liquid chromatography triple quadrupole mass spectrometry (UHPLC-QQQ-MS/MS) method was optimized and validated for the determination of dianthrones in PMR and PMRP using bianthronyl as the internal standard. Chromatographic separation with a gradient mobile phase [A: acetonitrile and B: water containing 0.1% formic acid (v/v)] at a flow rate of 0.25 mL/min was achieved on an Agilent ZORBAX SB-C₁₈ column (2.1 mm × 50 mm, 1.8 μm). The triple quadrupole mass spectrometer (TQMS) was operated in negative ionization mode with multiple reaction monitoring for the quantitative analysis of six dianthrones. Moreover, compounds 5 and 6 were further evaluated for their cytotoxicity in HepaRG cells by CCK-8 assay. Results: The UHPLC-QQQ-MS/MS method was first developed to simultaneously determine six dianthrones in PMR and PMRP, namely, polygonumnolides C1–C4 (1–4), trans-emodin dianthrones (5), and cis-emodin dianthrones (6). The contents of 1–6 in 90 batches of PMR were in the ranges of 0.027–19.04, 0.022–13.86, 0.073–15.53, 0.034–23.35, 0.38–83.67 and 0.29–67.00 µg/g, respectively. The contents of 1–6 in 86 batches of commercial PMRP were in the ranges of 0.020–13.03, 0.051–8.94, 0.022–7.23, 0.030–12.75, 0.098–28.54 and 0.14–27.79 µg/g, respectively. Compounds 1–4 were almost completely eliminated after reasonable processing for 24 h and the contents of compounds 5 and 6 significantly decreased. Additionally, compounds 5 and 6 showed inhibitory activity in HepaRG cells with IC₅₀ values of 10.98 and 15.45 μM, respectively. Furthermore, a systematic five-step strategy to standardize TCMs with endogenous toxicity was proposed for the first time, which involved the establishment of determination methods, the identification of potentially toxic markers, the standardization of processing methods, the development of limit standards and a risk–benefit assessment. Conclusion: The results of the cytotoxicity evaluation of the dianthrones indicated that trans-emodin dianthrones (5) and cis-emodin dianthrones (6) could be selected as toxic markers of PMRP. Taking PMR and PMRP as examples, we hope this study provides insight into the standardization and internationalization of endogenous toxic TCMs, with the main purpose of improving public health by scientifically using TCMs to treat diverse complex diseases in the future.

Arsenic is a common toxic heavy metal contaminant that is widely present in the ocean, and seaweeds have a strong ability to concentrate arsenic, posing a potential risk to human health. This study first analyzed the arsenic content in two different seaweeds and then used an innovative method to categorize the seaweeds into low-arsenic and high-arsenic groups based on their arsenic exposure levels. Finally, a non-targeted metabolomic analysis based on mass spectrometry was conducted on seaweed from different arsenic exposure groups. The results indicated that as the arsenic concentration increased in the seaweeds, linolenic acid, tyrosine, pheophorbide a, riboflavin, and phenylalanine were upregulated, while arachidonic acid, eicosapentaenoic acid (EPA), betaine, and oleamide were downregulated. The following four key metabolic pathways involving unsaturated fatty acids and amino acids were identified: isoquinoline alkaloid biosynthesis, tyrosine metabolism, phenylalanine metabolism, and riboflavin metabolism. The identification of biomarkers and the characterization of key metabolic pathways will aid in the selection and breeding of low-arsenic-accumulating seaweed varieties, providing insights into the metabolic and detoxification mechanisms of arsenic in seaweeds.

In recent years, global consumption of seaweed has been on the rise, yet there is a lack of accurate methods for assessing the health risks associated with its consumption. This gap could pose a threat to public safety or lead to wasted resources by government regulatory bodies. In this study, animal models and an innovative PBET (IPBET) were used to determine the bioavailability and bioaccessibility of arsenic (As) and cadmium (Cd) in various seaweeds, followed by an in vivo-in vitro correlation (IVIVC) analysis. The results indicated that the bioaccessibility of As and Cd was strongly correlated with As-RBA and Cd-RBA, highlighting the method's significant potential for predicting As-RBA and Cd-RBA in seaweeds. Additionally, the study explored the impact of mineral elements on the bioaccessibility of As and Cd in seaweed, finding a significant influence. In vivo metabolism experiments in mice revealed that different As species undergo several biochemical transformations in the body, including oxidation, reduction, methylation, and demethylation, all of which should not be overlooked. Building on previous studies, we have developed a new perspective for risk assessment of combined As and Cd exposure in seaweed. Calculations of the target hazard quotient (THQ) and total risk (TR) indicated that factoring in the bioavailability of heavy metals, As species, and biotransformation rates (BR) substantially reduces the health risks associated with seaweed consumption. However, for populations consuming seaweed over the long term, there still remains a certain level of risk to human health.

Seaweeds are one of the major marine foods with high values. The diversity of seaweed species significantly impacts their quality and is closely linked to their purity and safety. For the first time, this study established a model to discriminate seaweed species using a multi-element fingerprinting approach for species identification. Twenty-nine elements derived from seaweeds were analyzed. Chemometrics showed that seaweed samples could be well separated by the established multi-element fingerprints, of which Ag, Mn, Sr, and K were the most important variables for discrimination. Furthermore, the present study proposed an innovative risk–benefit assessment strategy for seaweeds that considers both risks and benefits, developing a novel risk–benefit assessment model from both dietary and medicinal perspectives for the first time. Our innovative strategy was well-conceived to accurately and effectively differentiate seaweeds based on species and scientifically evaluate both benefits and risks associated with seaweeds. This strategy is poised to offer invaluable insights into the sustainable growth of the seaweed sector and to bolster public health initiatives, ensuring a robust and forward-looking approach to both industry and healthcare advancements.

Objective: This study aimed to provide data for the type and content of linear furocoumarins (FCs) in Angelica dahurica (AD) in order to assess their cumulative risks and provide a scientific basis for the rational use and quality evaluation of the medicinal AD to improve public health. Methods: A UPLC method was developed for the simultaneous determination of nine FCs initially by using imperatorin (Im) as the internal standard substance, including Im, phellopterin (Ph), isoimperatorin (Is), oxypeucedanin hydrate (Oh), byakangelicin (Bn), xanthotoxin (8-MOP), bergapten (5-MOP), byakangelicol (Bl), and oxypeucedanin (Op) in two species of Angelica dahurica (AD). And, the risk assessment for the total FCs in AD was explored using the hazard index combined with the toxic equivalency factor (TEF-HI) strategy for the first time. Results: The established method revealed acceptable applicability, and there were no significant differences compared with the external standard method (ESM). The quantitative results demonstrated that the total content of FCs in Angelica dahurica (BZ) were higher than that in Angelica dahurica var. formosana (HBZ), and there was a great difference between the Bl and Op. Moreover, the risk assessment data revealed that the risk of total FCs in AD to human health was low. Conclusions: The established UPLC method that determined nine FCs in AD using a single marker could solve the problem of difficulty in obtaining a chemical reference substance with high purity and requiring a long determination time. And, the TEF-HI risk assessment approach associated with FCs in ADs could guide the rational utilization of toxic FCs in ADs in the progress of improving public health safety. In short, the whole systematic strategy provides a scientific basis for rational quality evaluation and the healthy use of related herbal medicines.