Intestinal Absorption of Triterpenoids and Flavonoids from Glycyrrhizae radix et rhizoma in the Human Caco-2 Monolayer Cell Model

Ultraviolet (UV) radiation, especially types A (UVA) and B (UVB), is one of the main causes of skin disorders, including photoaging and skin cancer. Ultraviolent radiation causes oxidative stress, inflammation, p53 induction, DNA damage, mutagenesis, and oxidation of various molecules such as lipids and proteins. In recent decades, the use of polyphenols as molecules with an antioxidant and anti-inflammatory capacity has increased. However, some of these compounds are poorly soluble, and information regarding their absorption and bioavailability is scarce. The main objective of this study was to compare the intestinal absorption and biological activity of apigenin and its more soluble potassium salt (apigenin-K) in terms of antioxidant and photoprotective capacity. Photoprotective effects against UVA and UVB radiation were studied in human keratinocytes, and antioxidant capacity was determined by different methods, including trolox equivalent antioxidant capacity (TEAC), ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) assays. Finally, the intestinal absorption of both apigenins was determined using an in vitro Caco-2 cell model. Apigenin showed a slightly higher antioxidant capacity in antioxidant activity assays when compared with apigenin-K. However, no significant differences were obtained for their photoprotective capacities against UVA or UVB. Results indicated that both apigenins protected cell viability in approximately 50% at 5 J/m2 of UVA and 90% at 500 J/m2 of UVB radiation. Regarding intestinal absorption, both apigenins showed similar apparent permeabilities (Papp), 1.81 × 10−5 cm/s and 1.78 × 10−5 cm/s, respectively. Taken together, these results suggest that both apigenins may be interesting candidates for the development of oral (nutraceutical) and topical photoprotective ingredients against UVA and UVB-induced skin damage, but the increased water solubility of apigenin-K makes it the best candidate for further development.

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The Evolving Role of the Caco-2 Cell Model to Estimate Intestinal Absorption Potential and Elucidate Transport Mechanisms

Drug Discovery and Development ◽

10.1201/9781315113470-17 ◽

2019 ◽

pp. 333-357

Author(s):

Jibin Li ◽

Ismael J. Hidalgo

Keyword(s):

Intestinal Absorption ◽

Cell Model ◽

Transport Mechanisms ◽

Absorption Potential

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Determination of intestinal absorption of the paralytic shellfish toxin GTX-5 using the Caco-2 human cell model

Environmental Science and Pollution Research ◽

10.1007/s11356-021-15342-y ◽

2021 ◽

Author(s):

Elsa T. Rodrigues ◽

Susana F. Nascimento ◽

Cristiana L. Pires ◽

Lia P. Godinho ◽

Catarina Churro ◽

...

Keyword(s):

Intestinal Absorption ◽

Human Cell ◽

Cell Model ◽

Paralytic Shellfish Toxin ◽

Paralytic Shellfish ◽

Shellfish Toxin

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The Evolving Role of the Caco-2 Cell Model to Estimate Intestinal Absorption Potential and Elucidate Transport Mechanisms

The Process of New Drug Discovery and Development, Second Edition ◽

10.1201/9781420004236.ch9 ◽

2006 ◽

pp. 161-186

Author(s):

Ismael Hidalgo ◽

Jibin Li

Keyword(s):

Intestinal Absorption ◽

Cell Model ◽

Transport Mechanisms ◽

Absorption Potential

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Elucidation of the Intestinal Absorption Mechanism of Loganin in the Human Intestinal Caco-2 Cell Model

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/8340563 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 5

Author(s):

Renjie Xu ◽

Yichu Yuan ◽

Jia Qi ◽

Jia Zhou ◽

Xiaowen Guo ◽

...

Keyword(s):

Intestinal Absorption ◽

Cell Model ◽

Iridoid Glycosides ◽

Cell Monolayer ◽

Efflux Transporter ◽

Cancer Resistance ◽

Absorption Mechanism ◽

Glycoprotein P ◽

Active Efflux ◽

Basolateral Side

Loganin, iridoid glycosides, is the main bioactive ingredients in the plant Strychnos nux-vomica L. and demonstrates various pharmacological effects, though poor oral bioavailability in rats. In this study, the intestinal absorption mechanism of loganin was investigated using the human intestinal Caco-2 cell monolayer model in both the apical-to-basolateral (A-B) and the basolateral-to-apical (B-A) direction; additionally, transport characteristics were systematically investigated at different concentrations, pHs, temperatures, and potential transporters. The absorption permeability (PappAB) of loganin, which ranged from 12.17 to 14.78 × 10−6cm/s, was high at four tested concentrations (5, 20, 40, and 80μM), while the major permeation mechanism of loganin was found to be passive diffusion with active efflux mediated by multidrug resistance-associated protein (MRP) and breast cancer resistance protein (BCRP). In addition, it was found that loganin was not the substrate of efflux transporter P-glycoprotein (P-gp) since the selective inhibitor (verapamil) of the efflux transporter exhibited little effects on the transport of loganin in the human intestinal Caco-2 cells. Meanwhile, transport from the apical to the basolateral side increased 2.09-fold after addition of a MRP inhibitor and 2.32-fold after addition of a BCRP inhibitor. In summary, our results clearly demonstrate, for the first time, a good permeability of loganin in the human intestinal Caco-2 cell model and elucidate, in detail, the intestinal absorption mechanism and the effects of transporters on iridoid glycosides compounds.

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