Impact of chrysosplenetin, per se or in combination with artemisinin, on breast cancer resistance protein (Bcrp)/ABCG2 mRNA expression levels in mice small intestine

Antimalarial activity and sensitization of chrysosplenetin against artemisinin‐resistant genotype Plasmodium bergheiK173 potentially via dual‐mechanism of maintaining host P‐glycoprotein homeostasis mediated by NF‐κB p52 or PXR/CAR signaling pathways and regulating heme/haemozoin metabolism

“…Chrysosplenetin (CHR) is one of known polymethoxylated flavonoids in leaf of Artemisia annua L., artemisinin (ART)‐derived Traditional Chinese Medicine (Numonov et al, 2015). Previously, we investigated that CHR purified from ART industrial waste improved the bio‐availability and antimalarial efficiency of ART in combination ratio of 1:2 (optimized from combination proportions of 1:0.5, 1:1, 1:2, and 1:4 between ART and CHR) potentially through inhibiting CYP3a in vitro activity in rat liver microsomes in an un‐competitive manner (Wei et al, 2015) and in vivo or in vitro P‐gp efflux (Ma, Wei, et al, 2017; Yang et al, 2016) via reversing the up‐regulated P‐gp (Abcb1) or Bcrp (Abcg2) protein and mRNA levels by ART in healthy mice (Ma, Wei, et al, 2017; Ma, Zhang, & YL, Zhang CX, Wang JH, Ma LP, Yang B, Wu XL, Chen J., 2017). Here, we further design the experiments to explicit the efficacy and sensitization of CHR against ART‐resistant Plasmodium berghei K173 and the potential mechanism by which CHR blocks host ABC transporters and upstream transcript regulations through PXR/CAR and NF‐κB k52 signaling pathways.…”

Sensitization of Chrysosplenetin against Artemisinin Resistant Plasmodium berghei K173 via Blocking Host ABC Transporters Potentially Mediated by NF-κB p52 or PXR/CAR Signaling Pathway

“…Chrysosplenetin (CHR) is one of known polymethoxylated flavonoids in leaf of Artemisia annua L. (13). Previously, CHR purified from ART industrial waste improved the bioavailability and anti-malarial efficiency of ART in combination ratio of 1:2 (optimized from combination proportions of 1:0.5, 1:1, 1:2, and 1:4 between ART and CHR) through strongly inhibiting rat CYP3a activity in an un-competitive manner (14) and in vivo or in vitro P-gp efflux (15)(16) via reversing the up-regulated Pgp/ABCB1 or ABCG2 mRNA levels by ART in healthy mice (16)(17). Here, we further design this experiment to explicit the sensitization of CHR against ART resistant Plasmodium berghei K173 by blocking host ABC transporters and upstream transcript regulations by PXR/CAR and NF-κB k52.…”

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.…”