Dried Leaf Artemisia Annua Improves Bioavailability of Artemisinin via Cytochrome P450 Inhibition and Enhances Artemisinin Efficacy Downstream
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Artemisia annua L. and artemisinin, have been used for millennia to treat malaria. We used human liver microsomes (HLM) and rats to compare hepatic metabolism, tissue distribution, and inflammation attenuation by dried leaves of A. annua (DLA) and pure artemisinin. For HLM assays, extracts, teas, and phytochemicals from DLA were tested and IC50 values for CYP2B6 and CYP3A4 were measured. For tissue distribution studies, artemisinin or DLA was orally delivered to rats, tissues harvested at 1 h, and blood, urine and feces over 8 h; all were analyzed for artemisinin and deoxyartemisinin by GC-MS. For inflammation, rats received an intraperitoneal injection of water or lipopolysaccharide (LPS) and 70 mg/kg oral artemisinin as pure drug or DLA. Serum was collected over 8 h and analyzed by ELISA for TNF-α, IL-6, and IL-10. DLA-delivered artemisinin distributed to tissues in higher concentrations in vivo, but elimination remained mostly unchanged. This seemed to be due to inhibition of first-pass metabolism by DLA phytochemicals, as demonstrated by HLM assays of DLA extracts, teas and phytochemicals. DLA was more effective than artemisinin in males at attenuating proinflammatory cytokine production; the data were less conclusive in females. These results suggest that the oral consumption of artemisinin as DLA enhances the bioavailability and anti-inflammatory potency of artemisinin.
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In rats, artemisinin distributes in greater quantities to serum, tissues and organs when delivered from the plant than as the pure drug, resulting in greater downstream biological responses, e.g. reduction of inflammation markers TNF-α and IL-6.
“Indeed, Desrosiers et al. (2020) showed that in rats artemisinin distributes in greater quantities to serum, tissues and organs when delivered from the plant than as the pure drug, resulting in greater downstream biological responses, e.g. reduction of inflammation markers TNF-α and IL-6.”
From Enhancing artemisinin content in and delivery from Artemisia annua: a review of alternative, classical, and transgenic approaches (2021) · cites this paper as Desrosiers et al. 2020
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- Authors
- Desrosiers, M. R., Mittleman, A., & Weathers, P. J.
- Affiliations
- Worcester Polytechnic Institute (US)
- Corresponding author
- Weathers, Pamela J.
- Venue
- Biomolecules
- Publisher
- MDPI AG
- Published
- 2020-02-07
- Volume
- 10
- Issue
- 2
- Pages
- 254
- ISSN
- 2218-273X (ISSN-L)
- PMC
- PMC7072484
- OpenAlex
- W3004660097
- Cited by
- 46
- References
- 34
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 7 · 2023: 8 · 2022: 8 · 2021: 10 · 2020: 3
- FWCI
- 2.48
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Biomolecules (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (NIH-2R15AT008277-02)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Sesquiterpenes and Asteraceae Studies
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Phytochemical compounds biological activities
- Keywords
- Artemisia annua, artemisinin, bioavailability, CYP3A4 inhibition, first-pass metabolism, tissue distribution, anti-inflammatory activity, inflammatory cytokines, lipopolysaccharide-induced inflammation, malaria treatment, sex differences
- MeSH terms
- Animals, Biological Availability, Cytochrome P-450 Enzyme System, Female, Humans, Liver, Malaria, Male, Microsomes, Liver, Plant Extracts, Rats, Sprague-Dawley, Plant Leaves, Artemisia annua, Artemisinins, Rats, Cytochrome P-450 Enzyme Inhibitors
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