Pyrrolizidine alkaloids and health risk of three Boraginaceae used in TCM

Objective: The aim of this study was to systematically explore the pyrrolizidine alkaloids (PAs) type, content and risk assessment in the three Boraginaceae used in TCM, involving Arnebia euchroma (AE), A. guttata (AG), and Lithospermum erythrorhizon (LE). Method: A UHPLC–MS/MS method was established to simultaneously determine eight pyrrolizidine alkaloids (PAs), namely intermedine, lycopsamine, intermedine N-oxide, lycopsamine N-oxide, 7-acetyllycopsamine, 7-acetyllycopsamine N-oxide, echimidine N-oxide, and echimidine in the three herbs. Based on these results, the risk assessment was explored using the routine margin of exposure (MOE) combined with relative potency (REP) for oral and external usage, respectively. Results and Conclusion: Imermedine and imermedine N-oxide were common components in the eight tested PAs. 7-acetyllycopsamine and its N-oxide were not detected in AE; echimidine and its N-oxide were not detected in AG; lycopsamine and its N-oxide, 7-acetyllycopsamine and its N-oxide were not detected in LE. The total contents of 8 PAs in 11 batches of AG was341.56–519.51 μg/g; the content in 15 batches of LE was 71.16–515.73 μg/g, and the content in 11 batches of AE was 23.35–207.13 μg/g. Based on these results, the risk assessment was explored using MOE combined with REP for oral and external usage, respectively. The findings of the risk assessment method of PAs based on MOE combined with the REP factor were consistent with the clinical toxicity results. As an oral herb, AE had low risk or no risk due to its low PA contents, and individual batches of LE were medium risk, while attention should be paid to their clinical use.AG was also low risk. The external use of the three Boraginaceae used in TCM was not associated with any risk. This study systematically explored the PA type and content of the three Boraginaceae used in TCM. Additionally, the refined risk assessment of PAs based on REP provided a more scientific basis for quality evaluation and rational use of the medicinal Boraginaceae used in TCM to improve public health.

[1]  J. Stanoeva,et al.  Assessment of Distribution and Diversity of Pyrrolizidine Alkaloids in the Most Prevalent Boraginaceae Species in Macedonia , 2022, Chemistry & biodiversity.

[2]  Xiangchun Zhang,et al.  Development, optimization, validation and application of ultra high performance liquid chromatography tandem mass spectrometry for the analysis of pyrrolizidine alkaloids and pyrrolizidine alkaloid N-oxides in teas and weeds , 2022 .

[3]  R. Teschke,et al.  Metabolic Toxification of 1,2-Unsaturated Pyrrolizidine Alkaloids Causes Human Hepatic Sinusoidal Obstruction Syndrome: The Update , 2021, International journal of molecular sciences.

[4]  S. Jeong,et al.  LC-ESI-MS/MS Simultaneous Analysis Method Coupled with Cation-Exchange Solid-Phase Extraction for Determination of Pyrrolizidine Alkaloids on Five Kinds of Herbal Medicines , 2021, Journal of AOAC International.

[5]  Siqi Ma,et al.  Determination of Toxic Pyrrolizidine Alkaloids in Traditional Chinese Herbal Medicines by UPLC-MS/MS and Accompanying Risk Assessment for Human Health , 2021, Molecules.

[6]  D. Schrenk,et al.  Pyrrolizidine alkaloids in food and phytomedicine: Occurrence, exposure, toxicity, mechanisms, and risk assessment - A review. , 2020, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[7]  Zhimin Luo,et al.  Development of UPLC-Q-TOF-MS coupled with cation-exchange solid-phase extraction method for the determination of ten pyrrolizidine alkaloids in herbal medicines. , 2019, Analytical sciences : the international journal of the Japan Society for Analytical Chemistry.

[8]  W. Jeong,et al.  Determination and Chemical Profiling of Toxic Pyrrolizidine Alkaloids in Botanical Samples with UPLC–Q-TOFMS , 2019, Chromatographia.

[9]  B. Steinhoff.  Pyrrolizidine alkaloid contamination in herbal medicinal products: Limits and occurrence. , 2019, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[10]  I. Rietjens,et al.  Risk assessment of intake of pyrrolizidine alkaloids from herbal teas and medicines following realistic exposure scenarios. , 2019, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[11]  Jianming Xu,et al.  Expert consensus on the clinical management of pyrrolizidine alkaloid‐induced hepatic sinusoidal obstruction syndrome , 2019, Journal of gastroenterology and hepatology.

[12]  D. Schrenk.  Toxicology of Pyrrolizidine Alkaloids. , 2019, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[13]  Yi He,et al.  Survey of pyrrolizidine alkaloids in the tribe Lithospermeae (Boraginaceae) from Pan-Himalaya and their chemotaxonomic significance , 2018, Biochemical Systematics and Ecology.

[14]  Heather M. Wallace,et al.  Risks for human health related to the presence of pyrrolizidine alkaloids in honey, tea, herbal infusions and food supplements , 2017, EFSA journal. European Food Safety Authority.

[15]  T. Mroczek,et al.  Comparative HILIC/ESI-QTOF-MS and HPTLC studies of pyrrolizidine alkaloids in flowers of Tussilago farfara and roots of Arnebia euchroma , 2017 .

[16]  D. Schrenk,et al.  Interim relative potency factors for the toxicological risk assessment of pyrrolizidine alkaloids in food and herbal medicines. , 2016, Toxicology letters.

[17]  C. Nam,et al.  Acute and 28-Day Subacute Toxicity Studies of Hexane Extracts of the Roots of Lithospermum erythrorhizon in Sprague-Dawley Rats , 2015, Toxicological research.

[18]  H. Takigami,et al.  Detection of glucocorticoid receptor agonists in effluents from sewage treatment plants in Japan. , 2015, The Science of the total environment.

[19]  C. Nam,et al.  Single- and Repeat-dose Oral Toxicity Studies of Lithospermum erythrorhizon Extract in Dogs , 2015, Toxicological research.

[20]  D. Schrenk,et al.  Application of the equivalency factor concept to the phototoxicity and -genotoxicity of furocoumarin mixtures. , 2014, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[21]  M. Wink,et al.  Diversity of Pyrrolizidine Alkaloids in the Boraginaceae Structures, Distribution, and Biological Properties , 2014 .

[22]  C. China Pharmacopoeia,et al.  Pharmacopoeia of the People's Republic of China , 2010 .

[23]  C. Tohyama,et al.  The 2005 World Health Organization reevaluation of human and Mammalian toxic equivalency factors for dioxins and dioxin-like compounds. , 2006, Toxicological sciences : an official journal of the Society of Toxicology.

[24]  E. Roeder,et al.  Pyrrolizidine alkaloids from Lithospermum erythrorhizon , 1990 .