Enhancement of biocompatibility and carbohydrate absorption control potential of rosmarinic acid through crosslinking into microparticles

Int J Biol Macromol. 2019 Sep 15;137:836-843. doi: 10.1016/j.ijbiomac.2019.07.032. Epub 2019 Jul 5.


Rosmarinic acid (RA), a bioflavonoid and antioxidant that exists in plants of the Lamiaceae family, was crosslinked into particles as poly(Rosmarinic Acid) (p(RA)) via an emulsion crosslinking method. The particles were characterized using scanning electron microscopy, Fourier transform infrared spectroscopy, solid state nuclear magnetic resonance 13C NMR spectroscopy, and thermal gravimetric analysis. The zeta potential values of p(RA) particles were determined at different pHs; the isoelectric point was estimated as pH 1.2. The release of monomeric RA from the particles at 37.5 °C was found to be similar at different pHs, 1.0, 7.4, and 11.0. The effects of p(RA) on hemolysis and coagulation were found to be minimal. The antioxidant activity of p(RA) particles and RA monomer were almost indistinguishable suggesting that p(RA) particles may be used as an antioxidant. On a per weight basis, p(RA) particles were ~66% less cytotoxic to mammalian cells that RA monomer, as assessed using COS-1 cells. In addition, p(RA) was an 8.6-fold stronger inhibitor of α-glycosidase than RA; the IC50s of the monomer and particles were 0.121 and 0.014 mg/mL, respectively. The strong inhibitory effect of p(RA) on α-glycosidase, coupled with its reduced cytotoxicity and antioxidant activity, provide new opportunities for the use of p(RA).

Keywords: Antioxidant microgel/nanogel; Inhibition of α-glucosidase activity; Rosmarinic acid particles.

MeSH terms

  • Absorption, Physicochemical*
  • Animals
  • Antioxidants / chemistry
  • Antioxidants / pharmacology
  • Benzothiazoles / chemistry
  • Biocompatible Materials / chemistry*
  • Biocompatible Materials / pharmacology*
  • COS Cells
  • Carbohydrates / chemistry*
  • Chlorocebus aethiops
  • Cinnamates / chemistry*
  • Cinnamates / pharmacology*
  • Depsides / chemistry*
  • Depsides / pharmacology*
  • Glycoside Hydrolase Inhibitors / chemistry
  • Glycoside Hydrolase Inhibitors / pharmacology
  • Humans
  • Microspheres*
  • Sulfonic Acids / chemistry


  • Antioxidants
  • Benzothiazoles
  • Biocompatible Materials
  • Carbohydrates
  • Cinnamates
  • Depsides
  • Glycoside Hydrolase Inhibitors
  • Sulfonic Acids
  • 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid
  • rosmarinic acid