Table 10 Comparison of Predicted and Experimental ADMET properties of Palmatine and Berberine.
Parameter | Palmatine Predicted Value | Palmatine Experimental Value | Palmatine Agreement | Berberine Predicted Value | Berberine Experimental Value | Berberine Agreement |
|---|---|---|---|---|---|---|
GI Absorption | High | Low Bioavailability due to P-gp substrate | Moderate | High | Poor oral absorption and low bioavailability (Cmax = 0.411 µg/ml in rabbits after 50 mg/kg oral dose) | Moderate |
BBB Permeant | Yes | No Data | n/a | Yes | Limited information on BBB permeation | Uncertain |
P-gp Substrate | Yes | Palmatine is a P-gp substrate, no significant inhibition in Caco-2 cells | High | Yes | Berberine is a substrate for P-glycoprotein, contributing to low absorption in the intestine | High |
P-gp Interaction (Caco-2) | No Data | No significant inhibition of P-gp (1-100 µM) | n/a | No Data | No Data | n/a |
P-gp Interaction (LS 180) | No Data | Palmatine activated P-gp efflux and CYP3A4 function (10 µM) | n/a | No Data | No Data | n/a |
CYP1A2 Inhibitor | No | Metabolized by CYP1A2 | High | Yes | Increases CYP1A2 mRNA expression but is also metabolized by CYP1A2 (oxidative demethylation) | High |
CYP2C19 Inhibitor | No | No Data | n/a | No | No Data | n/a |
CYP2C9 Inhibitor | No | NP | n/a | No | No Data | n/a |
CYP2D6 Inhibitor | Yes | Weak inhibition of CYP2D6 (IC50 = 92.6 µM) | High | Yes | Decreases CYP2D6 enzyme activity after oral administration | High |
CYP3A4 Inhibitor | Yes | Palmatine activates CYP3A4 function | High | Yes | Decreases CYP3A4 enzyme activity in the liver | High |
