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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2022-12-01
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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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