Journal
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
Volume 227, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.jpba.2023.115234
Keywords
Herb -herb interactions; Berberine; Organic cation transporter 1; 2; Multidrug and toxin extrusion transporter 1; Coptis chinensis Franch; rhizoma; Plantago asiatica L
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The combined efficacy of Plantago asiatica L. seed and Coptis chinensis Franch. rhizoma is better than either herb alone, likely due to herb-herb interactions affecting potency. The active components in Plantago, geniposidic acid (GPA), acteoside (ACT), and plantagoamidinic acid A (PLA), and the active component in Coptis, berberine (BBR), were found to have competitive interactions driven by transporters rOCT2 and rMATE1. These interactions affect the transport and excretion of compounds and lead to changes in efficacy after co-administration.
The combined efficacy in lowering serum lipid levels and increasing kidney protection of Plantago asiatica L. seed (Plantago) and Coptis chinensis Franch. rhizoma (Coptis) is far better than the effects of either herb alone. This finding suggests that there must be some degree of herb-herb interactions (HHI) affect potency. Here, we chose geniposidic acid (GPA), acteoside (ACT), and plantagoamidinic acid A (PLA) as active components in Plantago, and berberine (BBR) as the active component in Coptis, and, using transporter gene-transfected Madin-Darby canine kidney (MDCK) cells in combination with specific substrates and inhibitors, investigated Plantago-Coptis HHIs. We also established a UPLC-MS/MS analytical method to determine substrate content. Results showed that PLA in Plantago was a substrate of rOCT1/2 and rMATE1, and had inhibitory effects on rOCT2 and rMATE1. We also found that ACT is a substrate of rMATE1, but GPA was not a substrate of any transporter that we investi-gated. When BBR was used as the substrate, the inhibition rate of 10 mu M PLA was 53.6% on rOCT2 and 31.5% on rMATE1. The inhibition rates of 30 mu M ACT and 30 mu M GPA on rMATE1 were 47.0% and 31.0%, respectively. Thus, our findings suggest that GPA, ACT, PLA, and BBR have competitive interactions that are driven by the rOCT2 and rMATE1 transporters. These interactions affect the transport and excretion of compounds and result in efficacy changes after co-administration.
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