4.6 Article

In vitro nephrotoxicity and quantitative UPLC-MS analysis of three aristololactams in Houttuynia cordata

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DOI: 10.1016/j.jpba.2023.115289

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Aristololactams; Houttuynia cordata; HK-2 cells; Cytotoxicity; Quantitative analysis; UPLC-MSn

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This study isolated three analogues of aristololactam I from Houttuynia cordata and evaluated their toxicity on human proximal tubular epithelial cells. The distribution of these compounds in H. cordata was also investigated to estimate the safety of the plant.
Three analogues of aristololactam I (AL I), AL AII, AL FI and AL BII, had been isolated from Houttuynia cordata, a commonly used medicinal and edible plant with heat-removing and toxin-removing functions. Considering the significant nephrotoxicity of AL I, this study evaluated the toxicity of these three aristololactams (ALs) on human proximal tubular epithelial cells (HK-2) by MTT assay, ROS assay, ELISA tests and cytologic morphology observation. Furthermore, the distribution of the three ALs in H. cordata were investigated by UPLC-MSn recognition and quantitation in SIM mode, so as to estimate primarily the safety of the plant. The results showed that all the three ALs in H. cordata had comparative cytotoxicity as AL I with the IC50 values from 3.88 mu M to 20.63 mu M, caused high levels of cellular levels of reactive oxygen species (ROS) in HK-2 cells, exhibited the potential to cause renal fibrosis by remarkably increasing the levels of transforming growth factor-13 (TGF-131) and fibronectin (FN), and induced fibrous changes in morphology of HK-2 cells. The contents of the three ALs varied significantly in 30 batches of H. cordata from different regions and parts. Overall, the aerial part contained much more ALs (3.20 - 108.19 mu g/g) than the underground part (0.95 - 11.66 mu g/g), and flowers had the highest contents. Besides, no ALs were detected in the water extract of any part of H. cordata. This work revealed that the aristololactams in H. cordata had similar in vitro nephrotoxicity as AL I and were mainly distributed in the aerial part of the plant.

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