Abstract:
ETHNOPHARMACOLOGICAL RELEVANCE:Labisa pumila (LP), popularly known with its local name, Kacip Fatimah, is a well known herb grown in Indochina and Southeast Asia and is traditionally used to regain energy after giving birth in women. The propensity of LP to cause drug-herb interaction via cytochrome P450 (CYP) enzyme system has not been investigated. AIM OF THE STUDY:To evaluate the in vitro inhibitory effects of various LP extracts (aqueous, ethanol, dichloromethane (DCM) and hexane) on cytochrome P450 2C8 (CYP2C8), CYP2C9, CYP2C19 and CYP3A4 activities. MATERIALS AND METHODS:Probe substrate-based high performance liquid chromatography (HPLC) methods were established for CYP2C9, CYP2C19 and CYP3A4 whereas a fluorescence-based enzyme assay was established for CYP2C8. The metabolite formations were examined after incubation of probe substrate with respective CYP isoform in the present or absent of LP extracts. The inhibitory effect of LP was characterized with kinetic parameters IC(50) and K(i) values. RESULTS:LP extracts showed differential effect of CYP activities with the order of inhibitory potency as follows: dichloromethane>hexane>ethanol>aqueous. This differential effect was only observed in CYP2C isoforms but not CYP3A4. Both the hexane and DCM extracts exhibited moderate to potent inhibition towards CYP2C activities in different modes including non-competitive, competive and mixed-type. The DCM effect was notably strong for CYP2C8 and CYP2C9 showing K(i) values of below 1 μg/ml. The selectivity of LP for CYP2C isoforms rather than CYP3A4 may be attributed to the presence of relatively small, lipophilic yet slightly polar compounds within the LP extracts. CONCLUSIONS:The results of our study revealed that phytoconstituents contained in LP, particularly in hexane and dichloromethane extracts, were able to selectively inhibit CYP2C isoforms. The inactivation was characterized by low K(i) values, in particular, in CYP2C8 and CYP2C9. These in vitro data indicate that LB preparations contain constituents that can potently inhibit CYP2C activities and suggest that this herb should be examined for potential pharmacokinetic drug interactions in vivo.
journal_name
J Ethnopharmacoljournal_title
Journal of ethnopharmacologyauthors
Pan Y,Tiong KH,Abd-Rashid BA,Ismail Z,Ismail R,Mak JW,Ong CEdoi
10.1016/j.jep.2012.07.024subject
Has Abstractpub_date
2012-09-28 00:00:00pages
586-91issue
2eissn
0378-8741issn
1872-7573pii
S0378-8741(12)00493-Xjournal_volume
143pub_type
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
pub_type: 杂志文章,评审
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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journal_title:Journal of ethnopharmacology
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