Table 1.
Inhibitory effects of key goldenseal alkaloids and goldenseal extract against selected transporters.
| Transporter | Berberine | (−)-β-Hydrastine | Hydrastinine | Goldenseal Extracta |
|---|---|---|---|---|
| IC50 (μM) | ||||
| NTCP | -- | -- | -- | -- |
| OAT1 | -- | 7.3 [1.9–28] | ||
| OAT3 | 79 [47–134] | 203 [169–243] | -- | 4.6 [2.6–8.0] |
| OATP1B1 | -- | 120 [85–165] | -- | 8.0 [6.8–9.5] |
| OATP1B3 | -- | -- | 1.3 [0.5–3.7] | |
| OATP2B1 | -- | -- | -- | |
| OCT1 | 19 [11–31] | 6.6 [5.3–8.1] | 2.6 [1.4–4.7] | |
| OCT2 | 45 [17–117] | 90 [38–214] | 95 [70–129] | 12 [5.6–25] |
| BSEP | -- | -- | -- | -- |
| BCRP | 180 [53–624] | 86.2 [19–391] | -- | 0.59 [0.43–0.78] |
| MATE1 | 0.73 [0.37–1.44] | 110 [90–131] | 82 [44–154] | 0.45 [0.27–0.76] |
| MATE2-K | 0.77 [0.41–1.48] | 0.47 [0.24–0.92] | ||
| MRP2 | -- | -- | -- | -- |
| MRP3 | -- | -- | -- | -- |
| P-gp | -- | -- | -- | -- |
Based on the concentration of berberine quantified in the extract. NTCP, sodium/taurocholate cotransporting polypeptide; OAT, organic anion transporter; OATP, organic anion transporting polypeptide; OCT, organic cation transporter; BSEP, bile salt export pump; BCRP, breast cancer resistant protein; MATE, multidrug and toxin extrusion protein; MRP, multidrug resistance-associated protein. P-gp, P-glycoprotein.
The goldenseal alkaloids berberine, (−)-β-hydrastine, and hydrastinine were screened as inhibitors of each transporters at 10 and 100 μM; the extract was tested at 1.75 and 17.5 μM (based on berberine concentration and solubility limit). --, inhibition not observed; ⬛, 20–50% inhibition; ⬛, 50–70% inhibition; or ⬛, >70% inhibition at the highest concentration tested. Subsequently, IC50 values were determined for test articles demonstrating ≥50% inhibition. Values denote mean IC50 [95% confidence interval] of three technical replicates.