Pharmacokinetics, Tissue Distribution, and Human Serum Albumin Binding Properties of Delicaflavone, a Novel Anti-Tumor Candidate

Abstract

Delicaflavone (DF), a natural active ingredient from Selaginella doederleinii Hieron, has been reported to have favorable anticancer effects and is thus considered a potential anticancer agent. However, its pharmacokinetics and plasma protein binding properties remain unknown. Here, we investigated the pharmacokinetic profile of DF in rats using a validated HPLC-MS/MS methods, as well as its human serum albumin (HSA) binding properties through multi-spectroscopic and in silico methods. The results showed that DF was rapidly eliminated and had a widespread tissue distribution after intravenous administration. DF showed linear dynamics in the dose range of 30–60 mg/kg and poor oral bioavailability. The major distribution tissues of DF were the liver, lungs, and kidneys. Ultraviolet and fluorescence spectroscopy and molecular docking demonstrated that DF had a static quenching effect on HSA, with one binding site, and relatively strong binding constants. Thermodynamic analysis of the binding data revealed that hydrogen bonding and van der Waals interactions played major roles in binding. The results of this study further our understanding of the pharmacokinetic and plasma protein binding properties of the potential anticancer agent DF and shed light on pharmacological strategies that may be useful for the development of novel cancer therapeutics.

Anti-tumor effect and mechanism of the total biflavonoid extract from S doederleinii on human cervical cancer cells in vitro and in vivo

“…Currently, it is still an attention spot for screening natural active ingredients [ 3 , 4 ], especially for anti-cancer candidates from herbal medicines [ 5 ]. Selaginella doederleinii Hieron, an anticancer Chinese herb medicine and belonging to the Selaginella genus of the Selaginellaceae family [ [6] , [7] , [8] ], has been recognized recently as a research topic by researchers due to its anti-cancer potentials [ [9] , [10] , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] ]. According to the reports [ 7 , 8 ], S .…”

Tissue Distribution, Excretion, and Interaction With Human Serum Albumin of Total Bioflavonoid Extract From Selaginella doederleinii

“…Analysis of tissue distribution of delicaflavone after intravenous administration has illustrated distribution predominantly in the livers, lungs, and kidneys, followed by rapid elimination. However, to the best of our knowledge, there are no specific reports on the tissue distribution, excretion, and plasma protein binding of TBESD (Chen et al, 2021).…”

Advances in the Anti-Tumor Activity of Biflavonoids in Selaginella

“…The anticancer immunological response mediated by delicaflavone was reversed in tumor-bearing mice by overexpression of the N6-methyladenosine (m6A) transferase Mettl3/Mettl14 [151]. In addition, the pharmacokinetic profile of delicaflavone in rats was also examined by Chen et al [155] using a validated HPLC-MS/MS method, including its binding characteristics to human serum albumin utilizing multispectral and computer simulation approaches. The results showed that delicaflavone was rapidly eliminated after intravenous administration, with wide tissue distribution.…”