title: Simulated digestion of dried leaves of Artemisia annua consumed as a treatment (pACT) for malaria.
abstract: BACKGROUND
  Artemisinin (AN) is produced by Artemisia annua, a medicinal herb long used as a tea infusion in traditional Chinese medicine to treat fever; it is also the key ingredient in current artemisinin-based combination therapies (ACTs) effective in treating malaria. Recently we showed that dried leaves from the whole plant Artemisia annua that produces artemisinin and contains artemisinin-synergistic flavonoids seem to be more effective and less costly than ACT oral malaria therapy; however little is known about how digestion affects release of artemisinin and flavonoids from dried leaves.
  
  
  METHODS
  In the current study we used a simulated digestion system to determine how artemisinin and flavonoids are released prior to absorption into the bloodstream. Various delivery methods and staple foods were combined with dried leaves for digestion in order to investigate their impact on the bioavailability of artemisinin and flavonoids. Digestate was recovered at the end of the oral, gastric, and intestinal stages, separated into solid and liquid fractions, and extracted for measurement of artemisinin and total flavonoids.
  
  
  RESULTS
  Compared to unencapsulated digested dried leaves, addition of sucrose, various cooking oils, and rice did not reduce the amount of artemisinin released in the intestinal liquid fraction, but the amount of released flavonoids nearly doubled. When dried leaves were encapsulated into either hydroxymethylcellulose or gelatin capsules, there was >50% decrease in released artemisinin but no change in released flavonoids. In the presence of millet or corn meal, the amount of released artemisinin declined, but there was no change in released flavonoids. Use of a mutant Artemisia annua lacking artemisinin showed that the plant matrix is critical in determining how artemisinin is affected during the digestion process.
  
  
  CONCLUSIONS
  This study provides evidence showing how both artemisinin and flavonoids are affected by digestion and dietary components for an orally consumed plant delivered therapeutic and that artemisinin delivered via dried leaves would likely be more bioavailable if provided as a tablet instead of a capsule.
authors: Department of Biology and Biotechnology, Worcester Polytechnic Institute, 100 Institute Rd, Worcester, MA 01609, USA. Electronic address: weathers@wpi.edu.
authors: Pamela J
authors: PJ
authors: Weathers
authors: Department of Biology and Biotechnology, Worcester Polytechnic Institute, 100 Institute Rd, Worcester, MA 01609, USA.
authors: Nikole J
authors: NJ
authors: Jordan
authors: Department of Biology and Biotechnology, Worcester Polytechnic Institute, 100 Institute Rd, Worcester, MA 01609, USA.
authors: Praphapan
authors: P
authors: Lasin
authors: Department of Biology and Biotechnology, Worcester Polytechnic Institute, 100 Institute Rd, Worcester, MA 01609, USA.
authors: Melissa J
authors: MJ
authors: Towler
mesh_terms: D000962:Antimalarials / Q000008:administration & dosage / Q000493:pharmacokinetics*; D031172:Artemisia annua; D037621:Artemisinins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D002214:Capsules; D019587:Dietary Supplements; D004063:Digestion; D002523:Edible Grain; D005419:Flavonoids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018565:Food-Drug Interactions; D005753:Gastric Mucosa / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D008288:Malaria / Q000188:drug therapy / Q000378:metabolism; D018515:Plant Leaves; D010938:Plant Oils; D013395:Sucrose
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D002214:Capsules; D005419:Flavonoids; D010938:Plant Oils; D013395:Sucrose; C031327:artemisinin
keywords: AN; Antiprotozoal; Artemisinin; DW; Digestion; FLV; Flavonoids; GLS; Gastrointestinal system; Malaria; SD; artemisinin; dried A. annua leaves (SAM cultivar); dry weight; flavonoids; glandless A. annua null AN mutant; pACT; standard deviation