Effects of Schisandra Lignans on P-Glycoprotein-Mediated Drug Efflux in Human Intestinal Caco-2 Cells
Abstract
Schisandra fruits (Schisandraceae) are often used in traditional medicine and can be taken concomitantly with conventional medicine. In this study, the effects of dibenzocyclooctadiene lignans from Schizandra chinensis on P-gp-mediated efflux were examined to investigate a possible interaction with P-gp substrates. The cellular accumulation of rhodamine-123 in Caco-2 cells was measured with 12 Schisandra lignans. Most compounds resulted in slight or moderate increases of rhodamin-123 cellular uptake, indicating their P-gp inhibitory activity. Among them, deoxyschizandrin exhibited the most potent effect on the accumulation of rhodamine-123. Subsequently, bidirectional transports of digoxin and rhodamine-123 in Caco-2 cells were determined with deoxyschizandrin, the most active compound for the rhodamine-123 assay. In the bidirectional transport study, apical-to-basal (A-to-B) transports of digoxin and rhodamine-123 were increased, whereas basal-to-apical (B-to-A) transports were decreased by deoxyschizandrin in concentration- and time-dependent manners. At 50 microM of deoxyschizandrin, the transport ratios (B-A/A-B) for digoxin and rhodamine-123 were 2.2 and 2.1 compared with the control ratios of 15.2 and 12.2, respectively. These results demonstrated that deoxyschizandrin effectively inhibited the P-gp-mediated efflux in Caco-2 cells, suggesting they could potentially increase the absorption of drugs that can act as a P-gp substrate.
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Several studies reported that some lignans (gomisin A, gomisin G, schizandrin, and schisanhenol) possess antitumor bioactivities.
“Several studies reported that some lignans (gomisin A, gomisin G, schizandrin, and schisanhenol) possess antitumor bioactivities [94,95,96,97,98].”
From Plant Adaptogens—History and Future Perspectives (2021) · cites this paper as [95]
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- Authors
- Yoo, H., Lee, M., Lee, M., Lim, S., Shin, J., & Kim, D.-H.
- Affiliations
- Korea Institute of Science and Technology (KR)
- Seoul National University (KR)
- Venue
- Planta Medica
- Publisher
- Georg Thieme Verlag KG
- Published
- 2007-05
- Volume
- 73
- Issue
- 5
- Pages
- 444-450
- ISSN
- 0032-0943 (ISSN-L)
- 1439-0221
- OpenAlex
- W2085064931
- Cited by
- 49
- References
- 0
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 2 · 2021: 6 · 2020: 2 · 2019: 1 · 2017: 1 · 2016: 2 · 2014: 7 · 2013: 5 · 2012: 8
- FWCI
- 1.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Planta Medica (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Plant-derived Lignans Synthesis and Bioactivity
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- Schisandra chinensis, dibenzocyclooctadiene lignans, deoxyschizandrin, P-glycoprotein, drug efflux inhibition, intestinal drug absorption, Caco-2 cells, rhodamine 123 accumulation, bidirectional transport, digoxin, drug-drug interactions, traditional medicine
- MeSH terms
- Biological Transport, Digoxin, Humans, Polycyclic Compounds, Lignans, Caco-2 Cells, Rhodamine 123, ATP Binding Cassette Transporter, Subfamily B, Member 1, Schisandra, Cyclooctanes
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