Berberine as a chemical and pharmacokinetic marker of the butanol-extracted Food Allergy Herbal Formula-2

•Berberine is the major component in both FAHF-2 and B-FAHF-2 formula.•Berberine alone did not protect peanut-allergic mice from anaphylaxis reaction in vivo, while the B-FAHF-2 formula did.•Berberine showed very poor bioavailability in mice, while the B-FAHF-2 formula increased the berberine absorption rate.•7 out of 9 herbal constituents in B-FAHF-2 formula showed enhanced absorption of berberine by Caco-2 cells in vitro.

RationaleFood Allergy Herbal Formula-2 (FAHF-2) provided protection against peanut anaphylaxis in a murine model and induced beneficial immune-modulation in humans. Butanol-refined FAHF-2, B-FAHF-2, retained safety and efficacy in the peanut allergic murine model at only 1/5 of FAHF-2 dosage. One compound, berberine, was isolated and identified in vitro as a bioactive component present in FAHF-2 and B-FAHF-2. The aim of this study was to investigate berberine as a chemical and pharmacokinetic marker of B-FAHF-2.MethodsThe consistency of constituents between B-FAHF-2 and FAHF-2 was tested. Peanut allergic C3H/HeJ mice were orally administered with 1 mg of berberine or B-FAHF-2 containing an equivalent amount of berberine, and the ability to protect against peanut anaphylaxis and pharmacokinetic parameters were determined. Human intestinal epithelial cells (Caco-2) were cultured with berberine with or without the nine individual herbal constituents in B-FAHF-2, and the absorbed berberine levels were determined.ResultsBerberine is one of the major components in B-FAHF-2 and FAHF-2 formula. In a peanut allergic mouse model, B-FAHF-2, but not berberine, protected mice from anaphylaxis reactions. Pharmacokinetic profiles showed that the Cmax of B-FAHF-2 fed mice was 289.30 ± 185.40 ng/mL; whereas berberine alone showed very low bioavailability with Cmax value of 35.13 ± 47.90 ng/mL. Caco-2 cells influx assay showed that 7 of 9 herbal constituents in B-FAHF-2 increased berberine absorption at rates ranging from 18 to 205%.ConclusionsB-FAHF-2 remarkably increased the bioavailability of berberine. Berberine can be used as chemical and pharmacokinetic marker of B-FAHF-2. Other herbal components in B-FAHF-2 may facilitate the absorption of berberine.