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Quantitative Determination and Toxicity Evaluation of Aristolochic Acid Analogues in Asarum heterotropoides F. Schmidt (Xixin) and Traditional Chinese Patent Medicines

Asarum (Xixin), which contains analogues of aristolochic acid (AA), is the only species of the genus Aristolochia included in the Chinese Pharmacopoeia 2020. However, the contents and nephrotoxic effects of AA analogs in Asarum (Xixin) and its formulations have not been clarified. An automatic, effe...

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Autores principales: Liu, Suyan, Xian, Zhong, Zhao, Yong, Wang, Lianmei, Tian, Jingzhuo, Pan, Chen, Han, Jiayin, Zhang, Yushi, Li, Chunying, Yi, Yan, Liu, Chenyue, Wang, Dunfang, Meng, Jing, Qin, Shasha, Wang, Fang, Liang, Aihua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8662950/
https://www.ncbi.nlm.nih.gov/pubmed/34899315
http://dx.doi.org/10.3389/fphar.2021.761593
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author Liu, Suyan
Xian, Zhong
Zhao, Yong
Wang, Lianmei
Tian, Jingzhuo
Pan, Chen
Han, Jiayin
Zhang, Yushi
Li, Chunying
Yi, Yan
Liu, Chenyue
Wang, Dunfang
Meng, Jing
Qin, Shasha
Wang, Fang
Liang, Aihua
author_facet Liu, Suyan
Xian, Zhong
Zhao, Yong
Wang, Lianmei
Tian, Jingzhuo
Pan, Chen
Han, Jiayin
Zhang, Yushi
Li, Chunying
Yi, Yan
Liu, Chenyue
Wang, Dunfang
Meng, Jing
Qin, Shasha
Wang, Fang
Liang, Aihua
author_sort Liu, Suyan
collection PubMed
description Asarum (Xixin), which contains analogues of aristolochic acid (AA), is the only species of the genus Aristolochia included in the Chinese Pharmacopoeia 2020. However, the contents and nephrotoxic effects of AA analogs in Asarum (Xixin) and its formulations have not been clarified. An automatic, effective solid phase extraction process and UPLC-MS/MS method were established for the pretreatment and quantitative detection of AA analogues in commercially available traditional Chinese patent medicines. The cytotoxicity and DNA damage induced by five analogues of AA were evaluated by CCK8 using human kidney cells (HK-2) and comet assays. HPLC was used to detect the analogues of AA in Asarum heterotropoides F. Schmidt (Xixin). The results showed that the contents of AA I, AA II, and AA IIIa were below the detection limit, while AA IVa and AL I presented relatively high contents of Asarum heterotropoides F. Schmidt (Xixin), within the range of 66.50–121.03 μg/g and 19.73–43.75 μg/g, respectively. The levels of AA analogues were in the nanogram-per-gram level in the main traditional Chinese patent medicines. AA I and AL I exhibited relatively high cytotoxicity at 48 h in CCK8 assays, while AA II, AA IIIa, and AA IVa showed weak cytotoxicity even at 800–1,000 μM. AA I induced significant pathological alterations and direct DNA damage at 40 mg/kg and 20 mg/kg, respectively. No distinct nephrotoxicity or hepatotoxicity was observed in mice treated with AA II, AA IIIa, AA IVa, or AL I at 40 mg/kg in this study. Consumption of Asarum heterotropoides F. Schmidt (Xixin) with controlled doses and periods is relatively safe as the contents of AA analogues in Asarum heterotropoides F. Schmidt (Xixin) and its formulations were far below those causing acute toxicity in this study. But, the long-term toxicity of Asarum heterotropoides F. Schmidt (Xixin) still needs further study.
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spelling pubmed-86629502021-12-11 Quantitative Determination and Toxicity Evaluation of Aristolochic Acid Analogues in Asarum heterotropoides F. Schmidt (Xixin) and Traditional Chinese Patent Medicines Liu, Suyan Xian, Zhong Zhao, Yong Wang, Lianmei Tian, Jingzhuo Pan, Chen Han, Jiayin Zhang, Yushi Li, Chunying Yi, Yan Liu, Chenyue Wang, Dunfang Meng, Jing Qin, Shasha Wang, Fang Liang, Aihua Front Pharmacol Pharmacology Asarum (Xixin), which contains analogues of aristolochic acid (AA), is the only species of the genus Aristolochia included in the Chinese Pharmacopoeia 2020. However, the contents and nephrotoxic effects of AA analogs in Asarum (Xixin) and its formulations have not been clarified. An automatic, effective solid phase extraction process and UPLC-MS/MS method were established for the pretreatment and quantitative detection of AA analogues in commercially available traditional Chinese patent medicines. The cytotoxicity and DNA damage induced by five analogues of AA were evaluated by CCK8 using human kidney cells (HK-2) and comet assays. HPLC was used to detect the analogues of AA in Asarum heterotropoides F. Schmidt (Xixin). The results showed that the contents of AA I, AA II, and AA IIIa were below the detection limit, while AA IVa and AL I presented relatively high contents of Asarum heterotropoides F. Schmidt (Xixin), within the range of 66.50–121.03 μg/g and 19.73–43.75 μg/g, respectively. The levels of AA analogues were in the nanogram-per-gram level in the main traditional Chinese patent medicines. AA I and AL I exhibited relatively high cytotoxicity at 48 h in CCK8 assays, while AA II, AA IIIa, and AA IVa showed weak cytotoxicity even at 800–1,000 μM. AA I induced significant pathological alterations and direct DNA damage at 40 mg/kg and 20 mg/kg, respectively. No distinct nephrotoxicity or hepatotoxicity was observed in mice treated with AA II, AA IIIa, AA IVa, or AL I at 40 mg/kg in this study. Consumption of Asarum heterotropoides F. Schmidt (Xixin) with controlled doses and periods is relatively safe as the contents of AA analogues in Asarum heterotropoides F. Schmidt (Xixin) and its formulations were far below those causing acute toxicity in this study. But, the long-term toxicity of Asarum heterotropoides F. Schmidt (Xixin) still needs further study. Frontiers Media S.A. 2021-11-26 /pmc/articles/PMC8662950/ /pubmed/34899315 http://dx.doi.org/10.3389/fphar.2021.761593 Text en Copyright © 2021 Liu, Xian, Zhao, Wang, Tian, Pan, Han, Zhang, Li, Yi, Liu, Wang, Meng, Qin, Wang and Liang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Liu, Suyan
Xian, Zhong
Zhao, Yong
Wang, Lianmei
Tian, Jingzhuo
Pan, Chen
Han, Jiayin
Zhang, Yushi
Li, Chunying
Yi, Yan
Liu, Chenyue
Wang, Dunfang
Meng, Jing
Qin, Shasha
Wang, Fang
Liang, Aihua
Quantitative Determination and Toxicity Evaluation of Aristolochic Acid Analogues in Asarum heterotropoides F. Schmidt (Xixin) and Traditional Chinese Patent Medicines
title Quantitative Determination and Toxicity Evaluation of Aristolochic Acid Analogues in Asarum heterotropoides F. Schmidt (Xixin) and Traditional Chinese Patent Medicines
title_full Quantitative Determination and Toxicity Evaluation of Aristolochic Acid Analogues in Asarum heterotropoides F. Schmidt (Xixin) and Traditional Chinese Patent Medicines
title_fullStr Quantitative Determination and Toxicity Evaluation of Aristolochic Acid Analogues in Asarum heterotropoides F. Schmidt (Xixin) and Traditional Chinese Patent Medicines
title_full_unstemmed Quantitative Determination and Toxicity Evaluation of Aristolochic Acid Analogues in Asarum heterotropoides F. Schmidt (Xixin) and Traditional Chinese Patent Medicines
title_short Quantitative Determination and Toxicity Evaluation of Aristolochic Acid Analogues in Asarum heterotropoides F. Schmidt (Xixin) and Traditional Chinese Patent Medicines
title_sort quantitative determination and toxicity evaluation of aristolochic acid analogues in asarum heterotropoides f. schmidt (xixin) and traditional chinese patent medicines
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8662950/
https://www.ncbi.nlm.nih.gov/pubmed/34899315
http://dx.doi.org/10.3389/fphar.2021.761593
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