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Evaluation of drug interaction potential of Labisia pumila (Kacip Fatimah) and its constituents.

Manda VK, Dale OR, Awortwe C, Ali Z, Khan IA, Walker LA, Khan SI - Front Pharmacol (2014)

Bottom Line: The extract of L. pumila showed a significant time dependent inhibition (TDI) of CYP3A4, reversible inhibition of CYP2C9 and 2C19 and a weak inhibition of 1A2 and 2D6 as well as an inhibition of P-gp and rifampicin-induced PXR activation.The alkyl phenols inhibited CYP3A4 (TDI), CYP2C9, and 2C19 (reversible) while saponins inhibited P-gp and PXR.In conclusion, L. pumila and its constituents showed significant modulation of all three regulatory proteins (CYPs, P-gp, and PXR) suggesting a potential to alter the pharmacokinetic and pharmacodynamic properties of conventional drugs if used concomitantly.

View Article: PubMed Central - PubMed

Affiliation: National Center for Natural Products Research, School of Pharmacy, The University of Mississippi Oxford, MS, USA.

ABSTRACT
Labisia pumila (Kacip Fatimah) is a popular herb in Malaysia that has been traditionally used in a number of women's health applications such as to improve libido, relieve postmenopausal symptoms, and to facilitate or hasten delivery in childbirth. In addition, the constituents of this plant have been reported to possess anticancer, antioxidant, and anti-inflammatory properties. Clinical studies have indicated that cytochrome P450s (CYPs), P-glycoprotein (P-gp), and Pregnane X receptor (PXR) are the three main modulators of drug-drug interactions which alter the absorption, distribution, and metabolism of drugs. Given the widespread use of Kacip Fatimah in dietary supplements, the current study focuses on determining the potential of its constituents to affect the activities of CYPs, P-gp, or PXR using in vitro assays which may provide useful information toward the risk of herb-drug interaction with concomitantly used drugs. Six compounds isolated from the roots of L. pumila (2 saponins and 4 alkyl phenols) were tested, in addition to the methanolic extract. The extract of L. pumila showed a significant time dependent inhibition (TDI) of CYP3A4, reversible inhibition of CYP2C9 and 2C19 and a weak inhibition of 1A2 and 2D6 as well as an inhibition of P-gp and rifampicin-induced PXR activation. The alkyl phenols inhibited CYP3A4 (TDI), CYP2C9, and 2C19 (reversible) while saponins inhibited P-gp and PXR. In conclusion, L. pumila and its constituents showed significant modulation of all three regulatory proteins (CYPs, P-gp, and PXR) suggesting a potential to alter the pharmacokinetic and pharmacodynamic properties of conventional drugs if used concomitantly.

No MeSH data available.


Related in: MedlinePlus

Dose-response curves of P-gp inhibition by methanol extract (A) of Labisia pumila roots, its two saponin constituents (B–C) and positive control cyclosporin A (D), determined by calculating the basolateral to apical transport (%) of 3H-digoxin across hMDR1-MDCKII cell monolayers. The data are represented as mean ± SD of 3 independent experiments (n = 1 in each experiment).
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Figure 6: Dose-response curves of P-gp inhibition by methanol extract (A) of Labisia pumila roots, its two saponin constituents (B–C) and positive control cyclosporin A (D), determined by calculating the basolateral to apical transport (%) of 3H-digoxin across hMDR1-MDCKII cell monolayers. The data are represented as mean ± SD of 3 independent experiments (n = 1 in each experiment).

Mentions: The second probe used to determine the P-gp inhibition was radiolabelled digoxin [3H-digoxin]. Similar to the calcein-AM assay, the alkyl phenols had no effect on the basal to apical transport of digoxin in hMDR1-MDCKII cell monolayers, while the saponins and methanol extract showed strong inhibition. The IC50 values for primulanin, ardisimamilloside H, and methanol extract were 6.4 ± 2.3 μM, 4.2 ± 1.1 μM, and 8.5 ± 2.4 μg/mL, respectively, as compared to 1.1 ± 0.8 μM for cyclosporin A and 12 ± 2.1 μM for verapamil as shown in Figure 6. These results indicated that the extract of L. pumila and the two saponins inhibit P-gp strongly in terms of digoxin transport as compared to calcein-AM transport suggesting that these saponins may bind to the similar binding site as for digoxin.


Evaluation of drug interaction potential of Labisia pumila (Kacip Fatimah) and its constituents.

Manda VK, Dale OR, Awortwe C, Ali Z, Khan IA, Walker LA, Khan SI - Front Pharmacol (2014)

Dose-response curves of P-gp inhibition by methanol extract (A) of Labisia pumila roots, its two saponin constituents (B–C) and positive control cyclosporin A (D), determined by calculating the basolateral to apical transport (%) of 3H-digoxin across hMDR1-MDCKII cell monolayers. The data are represented as mean ± SD of 3 independent experiments (n = 1 in each experiment).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126480&req=5

Figure 6: Dose-response curves of P-gp inhibition by methanol extract (A) of Labisia pumila roots, its two saponin constituents (B–C) and positive control cyclosporin A (D), determined by calculating the basolateral to apical transport (%) of 3H-digoxin across hMDR1-MDCKII cell monolayers. The data are represented as mean ± SD of 3 independent experiments (n = 1 in each experiment).
Mentions: The second probe used to determine the P-gp inhibition was radiolabelled digoxin [3H-digoxin]. Similar to the calcein-AM assay, the alkyl phenols had no effect on the basal to apical transport of digoxin in hMDR1-MDCKII cell monolayers, while the saponins and methanol extract showed strong inhibition. The IC50 values for primulanin, ardisimamilloside H, and methanol extract were 6.4 ± 2.3 μM, 4.2 ± 1.1 μM, and 8.5 ± 2.4 μg/mL, respectively, as compared to 1.1 ± 0.8 μM for cyclosporin A and 12 ± 2.1 μM for verapamil as shown in Figure 6. These results indicated that the extract of L. pumila and the two saponins inhibit P-gp strongly in terms of digoxin transport as compared to calcein-AM transport suggesting that these saponins may bind to the similar binding site as for digoxin.

Bottom Line: The extract of L. pumila showed a significant time dependent inhibition (TDI) of CYP3A4, reversible inhibition of CYP2C9 and 2C19 and a weak inhibition of 1A2 and 2D6 as well as an inhibition of P-gp and rifampicin-induced PXR activation.The alkyl phenols inhibited CYP3A4 (TDI), CYP2C9, and 2C19 (reversible) while saponins inhibited P-gp and PXR.In conclusion, L. pumila and its constituents showed significant modulation of all three regulatory proteins (CYPs, P-gp, and PXR) suggesting a potential to alter the pharmacokinetic and pharmacodynamic properties of conventional drugs if used concomitantly.

View Article: PubMed Central - PubMed

Affiliation: National Center for Natural Products Research, School of Pharmacy, The University of Mississippi Oxford, MS, USA.

ABSTRACT
Labisia pumila (Kacip Fatimah) is a popular herb in Malaysia that has been traditionally used in a number of women's health applications such as to improve libido, relieve postmenopausal symptoms, and to facilitate or hasten delivery in childbirth. In addition, the constituents of this plant have been reported to possess anticancer, antioxidant, and anti-inflammatory properties. Clinical studies have indicated that cytochrome P450s (CYPs), P-glycoprotein (P-gp), and Pregnane X receptor (PXR) are the three main modulators of drug-drug interactions which alter the absorption, distribution, and metabolism of drugs. Given the widespread use of Kacip Fatimah in dietary supplements, the current study focuses on determining the potential of its constituents to affect the activities of CYPs, P-gp, or PXR using in vitro assays which may provide useful information toward the risk of herb-drug interaction with concomitantly used drugs. Six compounds isolated from the roots of L. pumila (2 saponins and 4 alkyl phenols) were tested, in addition to the methanolic extract. The extract of L. pumila showed a significant time dependent inhibition (TDI) of CYP3A4, reversible inhibition of CYP2C9 and 2C19 and a weak inhibition of 1A2 and 2D6 as well as an inhibition of P-gp and rifampicin-induced PXR activation. The alkyl phenols inhibited CYP3A4 (TDI), CYP2C9, and 2C19 (reversible) while saponins inhibited P-gp and PXR. In conclusion, L. pumila and its constituents showed significant modulation of all three regulatory proteins (CYPs, P-gp, and PXR) suggesting a potential to alter the pharmacokinetic and pharmacodynamic properties of conventional drugs if used concomitantly.

No MeSH data available.


Related in: MedlinePlus