Comparative Analysis of Aristolochic Acids in <i>Aristolochia</i> Medicinal Herbs and Evaluation of Their Toxicities

Aristolochic acids (AAs) are a group of nitrophenanthrene carboxylic acids present in many medicinal herbs of the <i>Aristolochia</i> genus that may cause irreversible hepatotoxicity, nephrotoxicity, genotoxicity and carcinogenicity. However, the specific profile of AAs and their toxicit...

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Main Authors: Shu-Han Zhang, Yun Wang, Jing Yang, Dan-Dan Zhang, Yan-Lei Wang, Shu-Hui Li, Ying-Ni Pan, Hua-Min Zhang, Yi Sun
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:Toxins
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Online Access:https://www.mdpi.com/2072-6651/14/12/879
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author Shu-Han Zhang
Yun Wang
Jing Yang
Dan-Dan Zhang
Yan-Lei Wang
Shu-Hui Li
Ying-Ni Pan
Hua-Min Zhang
Yi Sun
author_facet Shu-Han Zhang
Yun Wang
Jing Yang
Dan-Dan Zhang
Yan-Lei Wang
Shu-Hui Li
Ying-Ni Pan
Hua-Min Zhang
Yi Sun
author_sort Shu-Han Zhang
collection DOAJ
description Aristolochic acids (AAs) are a group of nitrophenanthrene carboxylic acids present in many medicinal herbs of the <i>Aristolochia</i> genus that may cause irreversible hepatotoxicity, nephrotoxicity, genotoxicity and carcinogenicity. However, the specific profile of AAs and their toxicity in <i>Aristolochia</i> plants, except for AAs Ι and ΙΙ, still remain unclear. In this study, a total of 52 batches of three medicinal herbs belonging to the Aristolochia family were analyzed for their AA composition profiles and AA contents using the UPLC-QTOF-MS/MS approach. The studied herbs were <i>A. mollissima</i> Hance (AMH), <i>A. debilis Sieb</i>.etZucc (ADS), and <i>A. cinnabaria</i> C.Y.Cheng (ACY). Chemometrics methods, including PCA and OPLS-DA, were used for the evaluation of the <i>Aristolochia</i> medicinal herbs. Additionally, cytotoxicity and genotoxicity of the selected AAs and the extracts of AMH and ADS were evaluated in a HepG2 cell line using the MTT method and a Comet assay, respectively. A total of 44 AAs, including 23 aristolochic acids and 21 aristolactams (ALs), were detected in <i>A. mollissima</i>. Moreover, 41 AAs (23 AAs and 18 ALs) were identified from <i>A. debilis Sieb</i>, and 45 AAs (29 AAs and 16 ALs) were identified in <i>A. cinnabaria.</i> Chemometrics results showed that 16, 19, and 22 AAs identified in AMH, ADS, and ACY, respectively, had statistical significance for distinguishing the three medicinal herbs of different origins. In the cytotoxicity assay, compounds AL-BΙΙ, AAΙ and the extract of AMH exhibited significant cytotoxicities against the HepG2 cell line with the IC<sub>50</sub> values of 0.2, 9.7 and 50.2 μM, respectively. The results of the Comet assay showed that AAΙ caused relatively higher damage to cellular DNA (TDNA 40–95%) at 50 μM, while AAΙΙ, AMH and ADS extracts (ranged from 10 to 131 μM) caused relatively lower damage to cellular DNA (TDNA 5–20%).
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spelling doaj.art-e2fb29c8527f498da1796763af36a9032023-11-24T18:27:23ZengMDPI AGToxins2072-66512022-12-01141287910.3390/toxins14120879Comparative Analysis of Aristolochic Acids in <i>Aristolochia</i> Medicinal Herbs and Evaluation of Their ToxicitiesShu-Han Zhang0Yun Wang1Jing Yang2Dan-Dan Zhang3Yan-Lei Wang4Shu-Hui Li5Ying-Ni Pan6Hua-Min Zhang7Yi Sun8Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaExperimental Research Center, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaSchool of Traditional Chinese Materia Medica, Shengyang Pharmaceutical University, Shenyang 110016, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaInstitute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, ChinaAristolochic acids (AAs) are a group of nitrophenanthrene carboxylic acids present in many medicinal herbs of the <i>Aristolochia</i> genus that may cause irreversible hepatotoxicity, nephrotoxicity, genotoxicity and carcinogenicity. However, the specific profile of AAs and their toxicity in <i>Aristolochia</i> plants, except for AAs Ι and ΙΙ, still remain unclear. In this study, a total of 52 batches of three medicinal herbs belonging to the Aristolochia family were analyzed for their AA composition profiles and AA contents using the UPLC-QTOF-MS/MS approach. The studied herbs were <i>A. mollissima</i> Hance (AMH), <i>A. debilis Sieb</i>.etZucc (ADS), and <i>A. cinnabaria</i> C.Y.Cheng (ACY). Chemometrics methods, including PCA and OPLS-DA, were used for the evaluation of the <i>Aristolochia</i> medicinal herbs. Additionally, cytotoxicity and genotoxicity of the selected AAs and the extracts of AMH and ADS were evaluated in a HepG2 cell line using the MTT method and a Comet assay, respectively. A total of 44 AAs, including 23 aristolochic acids and 21 aristolactams (ALs), were detected in <i>A. mollissima</i>. Moreover, 41 AAs (23 AAs and 18 ALs) were identified from <i>A. debilis Sieb</i>, and 45 AAs (29 AAs and 16 ALs) were identified in <i>A. cinnabaria.</i> Chemometrics results showed that 16, 19, and 22 AAs identified in AMH, ADS, and ACY, respectively, had statistical significance for distinguishing the three medicinal herbs of different origins. In the cytotoxicity assay, compounds AL-BΙΙ, AAΙ and the extract of AMH exhibited significant cytotoxicities against the HepG2 cell line with the IC<sub>50</sub> values of 0.2, 9.7 and 50.2 μM, respectively. The results of the Comet assay showed that AAΙ caused relatively higher damage to cellular DNA (TDNA 40–95%) at 50 μM, while AAΙΙ, AMH and ADS extracts (ranged from 10 to 131 μM) caused relatively lower damage to cellular DNA (TDNA 5–20%).https://www.mdpi.com/2072-6651/14/12/879Aristolochiaceaearistolochic acidaristolactamultra performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS)orthogonal partial least squares-discriminant analysis (OPLS-DA)cytotoxicity
spellingShingle Shu-Han Zhang
Yun Wang
Jing Yang
Dan-Dan Zhang
Yan-Lei Wang
Shu-Hui Li
Ying-Ni Pan
Hua-Min Zhang
Yi Sun
Comparative Analysis of Aristolochic Acids in <i>Aristolochia</i> Medicinal Herbs and Evaluation of Their Toxicities
Toxins
Aristolochiaceae
aristolochic acid
aristolactam
ultra performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS)
orthogonal partial least squares-discriminant analysis (OPLS-DA)
cytotoxicity
title Comparative Analysis of Aristolochic Acids in <i>Aristolochia</i> Medicinal Herbs and Evaluation of Their Toxicities
title_full Comparative Analysis of Aristolochic Acids in <i>Aristolochia</i> Medicinal Herbs and Evaluation of Their Toxicities
title_fullStr Comparative Analysis of Aristolochic Acids in <i>Aristolochia</i> Medicinal Herbs and Evaluation of Their Toxicities
title_full_unstemmed Comparative Analysis of Aristolochic Acids in <i>Aristolochia</i> Medicinal Herbs and Evaluation of Their Toxicities
title_short Comparative Analysis of Aristolochic Acids in <i>Aristolochia</i> Medicinal Herbs and Evaluation of Their Toxicities
title_sort comparative analysis of aristolochic acids in i aristolochia i medicinal herbs and evaluation of their toxicities
topic Aristolochiaceae
aristolochic acid
aristolactam
ultra performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS)
orthogonal partial least squares-discriminant analysis (OPLS-DA)
cytotoxicity
url https://www.mdpi.com/2072-6651/14/12/879
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