Chrysosplenetin

Chrysosplenetin is an orally active polymethoxyflavone. Chrysosplenetin exerts anticancer effects by inhibiting topoisomerase, protecting DNA and inducing apoptosis. Chrysosplenetin acts as an antimalarial sensitizer, reverses Artemisinin (HY-B0094) resistance by inhibiting and downregulating P-glycoprotein, and enhances the efficacy of Artemisinin. Chrysosplenetin promotes bone formation by activating the Wnt/β-catenin pathway and exerts anti-osteoporotic effects^[1][2][3][4]. In Vitro:Chrysosplenetin (6.06 μM) slightly enhances the transcriptional activities of PXR and CAR in human colorectal cancer LS174T cells^[1].
Chrysosplenetin (72 h) potently inhibits the proliferation of MCF-7 breast cancer cells, with an IC₅₀ of 0.3 μM after 72 h of incubation^[2].
Chrysosplenetin (12.5-100 μM; 1 h) protects supercoiled pBR322 plasmid DNA against Fenton reagent-induced oxidative damage in a concentration-dependent manner^[2].
Chrysosplenetin (20 μM; 6 h) inhibits P-gp-mediated artemisinin efflux in P-gp-overexpressing Caco-2 cells, increases the apical-to-basolateral permeability of artemisinin and reduces its efflux ratio^[3].
Chrysosplenetin (5-20 μM; 1-14 days) promotes the proliferation of hBMSCs in a time-dependent manner^[4].
Chrysosplenetin (5-20 μM; 14 days) promotes mineral deposition in hBMSCs^[4].
Chrysosplenetin (5-20 μM; 14 days) upregulates the expression of osteoblast marker genes (RUNX2, BGLAP, CTNNB1, BMP2) in hBMSCs after 14 days of treatment^[4].
Chrysosplenetin (10 μM; 3-14 days) activates the expression of Wnt/β-catenin pathway target genes (CTNNB1, TCF7, LEF1, CCND1, JUN, c-MYC) in hBMSCs^[4].
Chrysosplenetin (10 μM; 3-14 days) upregulates the expression of osteogenic downstream genes (RUNX2, DLX5, SPP1, COL1, BGLAP, BMP2) in human bone marrow mesenchymal stem cells (hBMSCs)^[4].
Chrysosplenetin (10 μM; 3-14 days) upregulates the expression level of total β-catenin protein and downregulates the expression of p-β-catenin protein in hBMSCs at a concentration of 10 μM^[4].
Chrysosplenetin (10 μM) promotes the nuclear translocation of β-catenin in hBMSCs^[4]. In Vivo:Chrysosplenetin (80 mg/kg, p.o., once daily for 7 consecutive days) exhibits direct antimalarial activity against artemisinin-resistant Plasmodium berghei K173; when administered in combination with artemisinin at a 1:2 ratio, it sensitizes artemisinin-resistant malaria parasites to artemisinin; it also exerts effects by regulating host P-glycoprotein homeostasis, hemozoin/heme metabolism and related signaling pathways^[1].
Chrysosplenetin (4-160 mg/kg, p.o., once daily for 7 consecutive days) reverses the artemisinin-induced upregulation of MDR1 mRNA and P-gp protein expression in the small intestine of mice, and exerts weak stimulatory effects on the ATPase activity associated with ABC transporters^[3].
Chrysosplenetin (3 mg/kg; i.p.; once every 2 days; for 6 consecutive weeks) significantly alleviates estrogen deficiency-induced bone loss in ovariectomized mice by improving bone microstructural parameters and increasing the number and activity of osteoblasts^[4].