Permeability of rosmarinic acid from Prunella vulgaris and ursolic acid from sage extract across Caco‐2 cells

Abstract

We hypothesized that rosmarinic and ursolic acids would show similar permeability in Caco‐2 cells as pure compounds or from plant extracts (Prunella vulgaris and sage (Salvia officinalis)). The percentages of rosmarinic acid (RA) and ursolic acid (UA) in three ethanol extracts of P. vulgaris were 4.8±0.3 − 17.0 ±0.9% and 0.05±0.01 – 0.50±0.09%. Sage extract contained 26.0±4.0% UA. Concentrations ≥ 50 μM of pure RA and Prunella extracts containing ≥ 20 μM RA showed significant cytotoxicity to Caco‐2 cells whereas concentrations ≥ 20 μM of pure UA and sage extract were toxic to the Caco‐2 cells, measured by MTS assay. After incubation with β‐glucuronidase/sulfatase, 10.5±0.3% and 10.7±0.4 % of applied amounts of pure RA or RA from P. vulgaris extract were found in the cells. UA passed through the basolateral membrane without significant glucuronidation or sulfation. Apparent permeability of pure UA and UA from sage extract (5, 10 and 20 μM) was 3.5±0.8 cm/s. Extract matrix did not affect permeability of either compound. Apical recoveries of pure RA or RA from P. vulgaris were 81.5±4.6 – 93.7±9.3%. No RA was found basolaterally at transepithelial electrical resistance (TER) ≥ 250 Ωcm2. But 5.0±1.6% and 7.5±1.0% of 10 μM RA were recovered basolaterally at TERs of 150±10 and 210±10 Ωcm2. Modeling in vivo paracellular transfer in Caco‐2 cells may need TER < 250 Ωcm2. Supported by 95P50AT004155 NCCAM and ODS, NIH.