In Vitro and In Situ Characterization of the Intestinal Absorption of Capilliposide B and Capilliposide C from Lysimachia capillipes Hemsl

Abstract

The goal of this investigation was to determine the processes and mechanism of intestinal absorption for capilliposide B (CAPB) and capilliposide C (CAPC) from the Chinese herb, Lysimachia capillipes Hemsl. An analysis of basic parameters, such as drug concentrations, time, and behavior in different intestinal segments was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS). The susceptibility of CAPB and CAPC to various inhibitors such as P-glycoprotein (P-gp) inhibitor (verapamil); multidrug resistance-associated protein 2 (MRP2) inhibitor (indomethacin); cytochrome P450 protein 3A4 (CYP3A4) inhibitor (ketoconazole); and the co-inhibitor of P-gp, MRP2 and CYP3A4 (cyclosporine A) were assessed using both caco-2 cell monolayer and single-pass intestinal perfusion (SPIP) models. As a result, CAPB and CAPC are both poorly absorbed in the intestines and exhibited segment-dependent permeability. The intestinal permeability of CAPB and CAPC were significantly increased by the co-treatment of verapamil, indomethacin. In addition, the intestinal permeability of CAPB was also enhanced by ketoconazole and cyclosporine A. It can be concluded that the intestinal absorption mechanisms of CAPB and CAPC involve processes such as facilitated passive diffusion, efflux transporters, and enzyme-mediated metabolism. Both CAPB and CAPC are suggested to be substrates of P-gp and MRP2. However, CAPB may interact with the CYP3A4 system.

Analgesic and antiinflammatory activities of the capilliposide derived from Lysimachia capillipes Hemsl., a traditional Chinese medicinal herb

“…LCc, a natural compound extracted from the L. capillipes Hemsl. plant, exhibits an inhibitory effect on cell proliferation in various cancers [49]; however, its analgesic and antiinflammatory activities have not been sufficiently studied. In this paper, we show the analgesic and antiinflammatory activities of LCc in different animal models.…”

Approaches to minimize the effects of P‐glycoprotein in drug transport: A review

“…They suggest that for predicting human intestinal absorption of orally administered drugs, the rat model could be used but cannot be used to predict human drug metabolism or oral bioavailability (Cao et al, 2006). Indomethacin, Ketoconazole, Verapamil, and Cyclosporin enhanced the intestinal permeability as well as intestinal absorption of Capilliposide B and Capilliposide C (Zhang et al, 2019). When Digoxin co‐administered with Ledipasvir, it enhanced the intestinal absorption of Digoxin (Valentino et al, 2016).…”

Anti-Inflammatory Activity of Oxyresveratrol Tetraacetate, an Ester Prodrug of Oxyresveratrol, on Lipopolysaccharide-Stimulated RAW264.7 Macrophage Cells

“…The human epithelial colorectal adenocarcinoma cell line (Caco-2; HTB37) and murine macrophage cell line (RAW264.7; TIB71) were purchased from the American Type Culture Collection (Rockville, MD, USA). The Caco-2 cells (passage [25][26][27][28][29][30][31][32][33][34][35] were cultured in complete Dulbecco's Modified Eagle Medium (cDMEM; DMEM supplemented with 15% fetal bovine serum (FBS), 1% nonessential amino acid (v/v), 1% L-glutamine (v/v), 0.2% fungizone (v/v), and 1% penicillin and streptomycin (v/v). The RAW264.7 cells (passage 5-15) were cultured in cDMEM (DMEM containing 10% FBS and 1% penicillin and streptomycin (v/v).…”

“…The Caco-2 cells are often used to assess the epithelial permeation ability of compounds because they can form a monolayer with some components of the gut epithelium [29][30][31]. In this study, the determination of TEER value and phenol red analysis were used to investigate the monolayer integrity before and during the transport experiment [32]. The DMEM with phenol red was used as a medium on the apical side, while the DMEM without phenol red was added on the basolateral side to maintain pH and osmotic balance in the medium.…”