title: 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.
authors.affiliation: School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Reproductive Endocrinology Centre, Dongfang Hospital of Beijing University of Chinese Medicine, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Gong
authors.affiliation: School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lu
authors.affiliation: School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.
authors.forename: Shouying
authors.initials: S
authors.lastname: Du
authors.affiliation: Department of Psychiatry, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Yang
authors.affiliation: School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Bai
authors.affiliation: School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.
authors.forename: Pengyue
authors.initials: P
authors.lastname: Li
authors.affiliation: School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.
authors.forename: Huichao
authors.initials: H
authors.lastname: Wu
mesh_terms: D000199:Actins / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D001892:Camphanes / Q000633:toxicity*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003516:Cycloparaffins / Q000633:toxicity*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D039823:Iridoids / Q000032:analysis / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009297:Nasal Mucosa / Q000166:cytology*
chemical_list: D000199:Actins; D001892:Camphanes; D003516:Cycloparaffins; D039823:Iridoids; C007835:geniposide; C022871:isoborneol; C031021:muscone