Evaluation of the Intestinal Permeability of Rosmarinic Acid from Thunbergia laurifolia Leaf Water Extract in a Caco-2 Cell Model

Abstract

Thunbergia laurifolia (TL) has been traditionally used as an antidote and an antipyretic drug by folk healers for centuries in Thailand. Rosmarinic acid (RA) is major compound in TL extract and has attracted great interest due to its potential broad pharmacological effects. Herein, the permeability of RA was investigated in TL extract and as a pure compound in a Caco-2 cell model by using high-performance liquid chromatography with a photodiode array detector (HPLC-PDA). The results reveal that the apparent permeability coefficient (Papp) values of RA in TL extracts and pure RA significantly increased after deconjugation by β-glucuronidase/sulfatase enzymes. Our findings exhibit possible saturable biotransformation of RA and/or membrane transport while penetrated through Caco-2 cells. The cumulative amounts of RA as pure compounds and in TL extracts increased with the exposure time, and the efflux ratio (ER) was 0.27–1.14. RA in the TL extract has a similar absorption in the conjugated form and in the pure compound. The intestinal absorption of them is through passive diffusion. Therefore, our findings conclude that the intestinal transport of RA in TL extracts was mainly penetrated as conjugated forms with glucuronic acid and/or sulfate across Caco-2 cells and transported via passive diffusion.

Cyclodextrin Derivatives as Promising Solubilizers to Enhance the Biological Activity of Rosmarinic Acid

“…RA [ 40 ] is usually described as slightly/poorly soluble [ 8 ]. There are few studies and literature reports on RA solubility because it is a biologically active substance, often studied as an extract component.…”

“…There are few studies and literature reports on RA solubility because it is a biologically active substance, often studied as an extract component. Its water solubility was estimated in silico as 0.041 g/L (ALOGPS) [ 8 ]. The aqueous solubility of the RA in pH 1.2 was determined as close to 5 mM [ 16 ], while at pH 7.2 in PBS, the solubility was approx.…”

“…The intestinal permeability of RA in Thunbergia laurifolia extract was determined as better than pure RA. Moreover, P app values were increased after deconjugation by β-glucuronidase/sulfatase enzymes [ 8 ]. Additionally, RA undergoes degradation within GIT.…”

“…Its extraordinary preventive and therapeutic potential is hampered by its limited solubility. Most of the compounds of rosemary extract are assigned to the III or IV class of the Biopharmaceutics Classification System (BCS) due to ambiguous solubility and low permeability [ 8 ]. RA is believed to have slight solubility and low permeability, subsequently impacting low absorption.…”

“…Unfortunately, during studies, the presence of RA after the oral administration of Melissa officinalis extract containing 100 mg of RA in almost all healthy volunteers was not determined [ 10 ]. Moreover, the LLOQ and LLOD failed to detect RA in plasma samples for the majority of the volunteers after the administration of the Thunbergia laurifolia leaf extract [ 8 ].…”