Comparative Analysis of Aristolochic Acids in Aristolochia Medicinal Herbs and Evaluation of Their Toxicities

• Published in: Toxins Vol. 14; no. 12; p. 879
• Main Authors: Zhang, Shu-Han, Wang, Yun, Yang, Jing, Zhang, Dan-Dan, Wang, Yan-Lei, Li, Shu-Hui, Pan, Ying-Ni, Zhang, Hua-Min, Sun, Yi
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 16.12.2022; MDPI
• Subjects: Acids; aristolactam; Aristolochia; Aristolochiaceae; aristolochic acid; Aristolochic Acids - toxicity; Bioassays; Carbon dioxide; Carboxylic acids; Carcinogenicity; Carcinogens; Chemometrics; Comet assay; Comparative analysis; Cytotoxicity; Damage detection; DNA damage; Drugs, Chinese Herbal; Genotoxicity; Hepatotoxicity; Herbal medicine; Herbs; Medicinal herbs; Medicinal plants; Nitrogen dioxide; orthogonal partial least squares-discriminant analysis (OPLS-DA); Plants, Medicinal; Provinces; Tandem Mass Spectrometry - methods; Toxicity; ultra performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS); China; genotoxicity; orthogonal partial least squares-discriminant analysis (OPLS-DA); aristolactam; ultra performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS); Aristolochiaceae; cytotoxicity; aristolochic acid
• ISSN: 2072-6651; 2072-6651
• DOI: 10.3390/toxins14120879

Aristolochic acids (AAs) are a group of nitrophenanthrene carboxylic acids present in many medicinal herbs of the genus that may cause irreversible hepatotoxicity, nephrotoxicity, genotoxicity and carcinogenicity. However, the specific profile of AAs and their toxicity in 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 Hance (AMH), .etZucc (ADS), and C.Y.Cheng (ACY). Chemometrics methods, including PCA and OPLS-DA, were used for the evaluation of the 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 . Moreover, 41 AAs (23 AAs and 18 ALs) were identified from , and 45 AAs (29 AAs and 16 ALs) were identified in 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 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%).