Enhancing Effect of Borneol and Muscone on Geniposide Transport across the Human Nasal Epithelial Cell Monolayer

Abstract

Geniposide is widely used in the treatment of cerebral ischemic stroke and cerebrovascular diseases for its anti-thrombotic and anti-inflammatory effects. Recent studies demonstrated that geniposide could be absorbed promptly and thoroughly by intranasal administration in mice and basically transported into the brain. Here, we explored its transport mechanism and the effect of borneol and muscone on its transport by human nasal epithelial cell (HNEC) monolayer. The cytotoxicity of geniposide, borneol, muscone and their combinations on HNECs was evaluated by the MTT assay. Transcellular transport of geniposide and the influence of borneol and muscone were studied using the HNEC monolayer. Immunostaining and transepithelial electrical resistance were measured to assess the integrity of the monolayer. The membrane fluidity of HNEC was evaluated by fluorescence recovery after photobleaching. Geniposide showed relatively poor absorption in the HNEC monolayer and it was not a P-gp substrate. Geniposide transport in both directions significantly increased when co-administrated with increasing concentrations of borneol and muscone. The enhancing effect of borneol and muscone on geniposide transport across the HNEC may be attributed to the significant enhancement on cell membrane fluidity, disassembly effect on tight junction integrity and the process was reversible. These results indicated that intranasal administration has good potential to treat cerebrovascular diseases.

Review on the Applications and Molecular Mechanisms ofXihuangPill in Tumor Treatment

“…Though muscone has not been reported to have any effects on tumors, there are potential mechanisms for tumor therapy. Muscone could significantly enhance cell membrane fluidity and improve the effect of geniposide transport across the human nasal epithelial cell monolayer [ 95 ]. Therefore, we hypothesize that facilitating the metabolism and absorption of antitumor drugs might be a mechanism of muscone.…”

Drug resistance reversal in ovarian cancer cells of paclitaxel and borneol combination therapy mediated by PEG-PAMAM nanoparticles

“…and Blumea balsamifera DC , or chemically synthesized from camphor and turpentine oil. Previous studies reported that BNL could improve the intestinal absorption [ 10 ] and blood brain barrier permeability [ 11 ] of some drugs, owing to its P-gp suppression effect. Similarly, BNL was also demonstrated to improve anticancer efficacy by means of enhancing cellular uptake related to P-gp suppression [ 12 ].…”

Borneol Depresses P-Glycoprotein Function by a NF-κB Signaling Mediated Mechanism in a Blood Brain Barrier in Vitro Model

“…Borneol ( Figure 1 ), Chinese materia medica monomer (molecular weight 154.24), is extracted from Dryobalanops aromatica Gaertn f. and Blumea balsamifera DC , and is widely used for the treatment of cardiovascular and cerebrovascular diseases in China. Previous studies showed that borneol was able to improve the permeability of BBB by a physiological process, enhance penetration and accumulation of some drugs into the brain such as tetramethylpyrazine phosphate, gastrodin, puerarin, geniposide, kaempferol and nimodipine, and increase the brain bioavailability of these drugs [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. The mechanisms of borneol opened BBB focused on loosening the endothelial tight junctions, increasing the number and volume of pinocytosis, and decreasing the mdr1a and mdr1b expression in hippocampus and hypothalamus [ 20 , 21 , 22 ].…”