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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 profiles of reversible and TDI of CYP2C19 enzyme by Labisia pumila root extract (A) and its alkyl phenolic constituents (B–E). The data are represented as mean ± SD of 3 independent experiments (n = 2 in each experiment).
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Figure 4: Dose response profiles of reversible and TDI of CYP2C19 enzyme by Labisia pumila root extract (A) and its alkyl phenolic constituents (B–E). The data are represented as mean ± SD of 3 independent experiments (n = 2 in each experiment).

Mentions: The methanolic extract and alkyl phenolic compounds showed dose dependent inhibition of CYP3A4, 2C9, and 2C19 (Figures 2–4) while saponins did not affect the activity of these enzymes. Out of the alky phenols, 5-[10(Z)-pentadecenyl]-resorcinol was effective in inhibiting CYP3A4 and 2C9 with IC50 values of 4.1 ± 0.2 and 11 ± 0.8 μM, respectively, while belamcandol B inhibited CYP2C19 with an IC50 value of 2.2 ± 0.6 μM.


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 profiles of reversible and TDI of CYP2C19 enzyme by Labisia pumila root extract (A) and its alkyl phenolic constituents (B–E). The data are represented as mean ± SD of 3 independent experiments (n = 2 in each experiment).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Dose response profiles of reversible and TDI of CYP2C19 enzyme by Labisia pumila root extract (A) and its alkyl phenolic constituents (B–E). The data are represented as mean ± SD of 3 independent experiments (n = 2 in each experiment).
Mentions: The methanolic extract and alkyl phenolic compounds showed dose dependent inhibition of CYP3A4, 2C9, and 2C19 (Figures 2–4) while saponins did not affect the activity of these enzymes. Out of the alky phenols, 5-[10(Z)-pentadecenyl]-resorcinol was effective in inhibiting CYP3A4 and 2C9 with IC50 values of 4.1 ± 0.2 and 11 ± 0.8 μM, respectively, while belamcandol B inhibited CYP2C19 with an IC50 value of 2.2 ± 0.6 μM.

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