title: Artemisia dracunculus L. polyphenols complexed to soy protein show enhanced bioavailability and hypoglycemic activity in C57BL/6 mice.
abstract: OBJECTIVE
  Scientifically validated food-based interventions are a practical means of addressing the epidemic of metabolic syndrome. An ethanolic extract of Artemisia dracunculus L. (PMI-5011) containing bioactive polyphenols, such as 2', 4'-dihydroxy-4-methoxydihydrochalcone (DMC-2), improved insulin resistance in vitro and in vivo. Plant polyphenols are concentrated and stabilized when complexed to protein-rich matrices, such as soy protein isolate (SPI), which act as effective food-based delivery vehicles. The aim of this study was to compare the bioaccessibility, bioavailability, and efficacy of polyphenols extracted from A. dracunculus and delivered as PMI-5011 (ethanolic extract alone), formulated with the non-food excipient Gelucire(®), (5011- Gelucire), or sorbed to SPI (5011-Nutrasorb(®)).
  
  
  METHODS
  PMI-5011, 5011-Gelucire or 5011-Nutrasorb each containing 162 μg of DMC-2 was delivered to the TNO intestinal model-1 of the human upper gastrointestinal tract to compare the effect of delivery vehicle on DMC-2 bioaccessibility. C57BL6/J mice were orally administered 5011-Nutrasorb or PMI-5011 to compare effects of polyphenol-protein complexation on acute hypoglycemic activity and bioavailability of DMC-2 in serum.
  
  
  RESULTS
  At 500 mg/kg, 5011-Nutrasorb and PMI-5011 had similar hypoglycemic activity in a high-fat diet-induced diabetes mouse model despite the fact that 5011-Nutrasorb delivered 15 times less DMC-2 (40 versus 600 μg/kg). This can be partially explained by eight times greater DMC-2 absorption into serum from 5011-Nutrasorb than from PMI-5011. TNO intestinal model-1 experiments confirmed higher total bioaccessibility of DMC-2 in vitro when delivered in 5011-Nutrasorb (50.2%) or Gelucire-5011 (44.4%) compared with PMI-5011 (27.1%; P = 0.08).
  
  
  CONCLUSIONS
  Complexation with soy protein makes antidiabetic A. dracunculus polyphenols more bioavailable and bioaccessible.
authors.affiliation: Rutgers, The State University of New Jersey, School of Environmental and Biological Sciences, New Brunswick, New Jersey, USA. Electronic address: Ribnicky@aesop.rutgers.edu.
authors.forename: David M
authors.initials: DM
authors.lastname: Ribnicky
authors.affiliation: Rutgers, The State University of New Jersey, School of Environmental and Biological Sciences, New Brunswick, New Jersey, USA.
authors.forename: Diana E
authors.initials: DE
authors.lastname: Roopchand
authors.affiliation: Rutgers, The State University of New Jersey, School of Environmental and Biological Sciences, New Brunswick, New Jersey, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Poulev
authors.affiliation: Rutgers, The State University of New Jersey, School of Environmental and Biological Sciences, New Brunswick, New Jersey, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Kuhn
authors.affiliation: Rutgers, The State University of New Jersey, School of Environmental and Biological Sciences, New Brunswick, New Jersey, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Oren
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
authors.forename: William T
authors.initials: WT
authors.lastname: Cefalu
authors.affiliation: Rutgers, The State University of New Jersey, School of Environmental and Biological Sciences, New Brunswick, New Jersey, USA.
authors.forename: Ilya
authors.initials: I
authors.lastname: Raskin
mesh_terms: D000818:Animals; D019306:Artemisia / Q000737:chemistry*; D001682:Biological Availability; D047188:Chalcones / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D059305:Diet, High-Fat; D016503:Drug Delivery Systems; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D007408:Intestinal Absorption; D051379:Mice; D008810:Mice, Inbred C57BL; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D059808:Polyphenols / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D030262:Soybean Proteins / Q000737:chemistry
chemical_list: C514624:2',4'-dihydroxy-4-methoxydihydrochalcone; D047188:Chalcones; D007004:Hypoglycemic Agents; C541449:PMI-5011; D010936:Plant Extracts; D059808:Polyphenols; D030262:Soybean Proteins
keywords: Artemisia dracunculus; Bioaccessibility; Bioavailability; Chalcones; Metabolic syndrome; PMI-5011; Polyphenols; Russian tarragon; TIM-1; Type 2 diabetes