Chrysosplenetin, in the absence and presence of artemsininin, alters breast cancer resistance protein-mediated transport activity in Caco-2 cell monolayers using aristolochic acid I as a specific probe substrate

Nontargeted metabolomics integrated with1H NMR and LC–Q‐TOF–MS/MS methods to depict a more comprehensive metabolic profile in response to chrysosplenetin and artemisinin co‐treatment against artemisinin‐sensitive and ‐resistantPlasmodium bergheiK173

“…Our lab purified a polymethoxylated flavonol named chrysosplenetin (CHR) from ART industrial extraction waste using Artemisia annua L. leaves as raw materials and discovered that when the ratio between ART and CHR was 1:2, the anti‐malarial effects were enhanced significantly vs. ART alone (Li et al, 2019; Wei et al, 2015). Further studies in our laboratory indicated that CHR can improve the bioavailability of ART by inhibiting liver metabolic enzyme CYP3a, which plays a role in ART metabolism, and by downregulating P‐glycoprotein (P‐gp), a principal multidrug resistance protein, suggesting that CHR might be a potent small‐molecule inhibitor of ART multidrug resistance (Ma, Wei, et al, 2017; Ma, Zhang, et al, 2017; Zhang et al, 2020; Wei et al, 2015; Zhang et al, 2017; Yang et al, 2016). Recently, it was reported that CHR showed a good in vitro half‐maximum inhibitory concentration (IC 50 , 3.78 μ m ) and selectivity index (15.26), and was identified as a potential inhibitor of P. falciparum multiplication (Banzragchgarav et al, 2021), which is consistent with our previous work.…”