Effects of the extracts and derived fractions of four medicinal plants on hepatic microsomal enzymes: an in-vitro study
Main Article Content
Abstract
Background: The use of medicinal plants for treatment of diverse ailments has continued to increase worldwide,
especially in developing countries. The concurrent use of herbal medicines and conventional drugs is common.
Herb-drug interaction through the inhibition/induction of cytochrome (CYP) P450 metabolizing enzymes could
result in pharmacotoxicity/therapeutic failure.
Objective: This study investigated the extracts and fractions of four medicinal plants (Crinum glaucum, Baphia
nitida, Byrsocarpus coccineus, and Sanseviera liberica) for possible effects on hepatic microsomal enzymes in-
vitro.
Methods: The benzyloxy-4-[trifluoromethyl]-coumarin O-debenzyloxylase (BFCOD; CYP3A4) and
benzyloxyresorufin O-debenzylase (BROD; CYP2B1/2) assays were used.
Results: The ethyl acetate:methanol and ethanol:water extracts of the plants demonstrated significant (p < 0.05)
inhibitory effect on CYP activity, pronouncedly at the highest concentration (1 mg/ml) in the BROD assay. The
aqueous extracts and fractions of all the plants did not significantly affect CYP activity in both assays. The same
trend of observation was recorded in the BFCOD assay except that the ethyl acetate:methanol extract of C.
glaucum did not significantly affect CYP activity. The ethyl acetate:methanol extract of B. nitida and B. coccineus
elicited significant stimulatory effect at 0.01 and 0.1 mg/ml in the BROD assay. The hexane and n-butanol
fractions of the extracts showed varying tendency to cause stimulation of CYP activity at lower doses and
inhibition at the highest dose.
Conclusion: Findings suggest that the aqueous extracts/fractions of the plants investigated have little or no
tendency to significantly affect CYP activity. Other organic solvent extracts/fractions possess the ability to inhibit
CYP activity, especially at high doses
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References
Leonti M, Casu L (2013). Traditional medicines and globalization: current and future perspectives in ethnopharmacology. Frontiers in Pharmacology 4:92. doi:10.3389/fphar.2013.00092
The Lismore Clinic (2015). Integrated medicine. Available at http://herbalmedicine.ie/integrated- medicine. Accessed on 14th November, 2016.
Duru CB, Diwe KC, Uwakwe KA, Duru CA, Merenu IA, Iwu AC, Oluoha UR, Ohanle I (2016). Combined orthodox and traditional medicine use among households in Orlu, Imo State, Nigeria: prevalence and determinants. World Journal of Preventive Medicine 4(1):5-11.
Gilani AH, Rahman AU (2005). Trends in ethnopharmacology. Journal of Ethnopharmacology 100:43-49.
Fasinu PS, Bouic PJ, Rosenkranz B (2012). An overview of the evidence and mechanisms of herb-drug interactions. Frontiers in Pharmacology 3:69. doi: 10.3389/fphar.2012.000696.
Cho H-J, Yoon I-S (2015). Pharmacokinetic interactions of herbs with cytochrome P450 and P-glycoprotein. Evidence-Based Complementary and Alternative Medicine 2015: 2015. doi:10.1155/2015/736431
Busti AJ (2015). Herbal or Natural Supplements Known to Inhibit Cytochrome P450 (CYP) 3A4. EBM Consult. Available at http://www.ebmconsult.com/articles/herbal- natural-medicines-inhibitors-cyp3a4-enzyme.
Accessed on 14th November, 2016.
Houghton PJ, Agbedahunsi JM, Adegbulugbe A (2004). Choline esterase inhibitory properties of alkaloids from two Nigerian Crinum species. Phytochemistry 65:2893-2896.
Duri ZJ, Scovill JP, Huggins JW (1994). Activity of a methanolic extract of Zimbabwean Crinum macowanii against exotic RNA viruses in vitro. Phytotherapy Research 8:121-122.
Okpo SO, Adeyemi OO (1998). Effects of Crinum glaucum aqueous extract on intestinal smooth muscle activity. Phytotherapy Research 12:413- 416.
Okpo SO, Fatokun F, Adeyemi OO (2001). Analgesic and anti-inflammatory activity of Crinum glaucum aqueous extract. Journal of Ethnopharmacology 78:207-211.
Okpo SO, Adeyemi OO (2002). The antianaphylactic effects of Crinum glaucum aqueous extract. Journal of Ethnopharmacology 81:187-190.
Ishola IO, Olayemi SO, Idowu AR (2013). Anticonvulsant, anxiolytic and hypnotic effects of aqueous bulb extract of Crinum glaucum A. Chev (Amaryllidaceae): role of GABAergic and nitrergic systems. Pakistan Journal of Biological Sciences 16:701-710.
Lawal U, Ibrahim H, Agunu A, Abdulahi Y (2010). Anti-inflammatory and analgesic activity of water extract from Ipomoea asarifolia Desr (Convolvulaceae). African Journal of Biotechnology 9:8877-8880.
Onwukaeme DN (1995). Anti-inflammatory activities of flavonoids of Baphia nitida Lodd (Leguminosae) on mice and rats. Journal of Ethnopharmacology 462:121-124.
Okungbowa FI, Okpako OE (2011). Plants used for treating human fungal skin diseases in three Urhobo rural communities in Delta State, Nigeria: Implication for conservation. Plant Archives 11:1155-1158.
Roger KG, Christelle AN, Akhanovna MBJ, Yves-Alain B (2011). CCM D'extraits selectifs de 10 plantes utilisees dans le traitement traditionnel du cancer du sein en Côte d'Ivoire. European Journal of Scientific Research 63:592-603.
Kone-Bamba D, Pelissier Y, Ozoukou ZF, Kouao D (1987). Hemostatic activity of 216 plants used in traditional medicine in the Ivory Coast. Plant Medicines and Phytotherapy 21:122-130.
Adeyemi OO (1992). Effects of aqueous extract of Baphia nitida on isolated cardiac tissues. Phytotherapy Research 6:318-321.
Adeyemi OO, Yemitan OK, Taiwo AE (2006). Neurosedative and muscle relaxant activities of ethyl acetate extract of Baphia nitida AFZEL. Journal of Ethnopharmacology 106:312-316.
Adeyemi OO, Akindele AJ (2008). Antidiarrhoeal activity of the ethyl acetate extract of Baphia nitida (Papilionaceae). Journal of Ethnopharmacology 116:407-412.
Irié-N'guessan G, Champy P, Kouakou-Siransy G, Koffi A, Kablan BJ, Leblais V (2011). Tracheal relaxation of five Ivorian anti-asthmatic plants: role of epithelium and K? channels in the effect of the aqueous-alcoholic extract of Dichrostachys cinerea root bark. Journal of Ethnopharmacology 138:432-438.
Burkill HM (1985). The Useful Plants of West Tropical Africa, Vol. 1. Kew: Royal Botanic Gardens.
Okunji CO, Iwu MM (1988). Control of Schistosomiasis using Nigerian medicinal plants as molluscicides. International Journal of Crude Drug Research 26:246-252.
Amos S, Binda L, Kunle OF, Wambebe C, Gamaniel K (2002). Uterotonic properties of the ethanolic extract of Byrsocarpus coccineus. Pharmaceutical Biology 40:33-38.
Oke JM, Hamburger MO (2002). Screening of some Nigerian medicinal plants for antioxidant activity using 2,2, diphenyl-picryl-hydrazyl radical. African Journal of Biomedical Research 5:77-79.
Ahmadu AA, Akpulu IN, Hassan HS, Sule MI, Pateh UU (2006). Antibacterial and anti-inflammatory activity of Byrsocarpus coccineus and its constituents. Planta Medica 72:203.
Ahmadu AA, Akpulu IN, Hassan HS, Sule MI, Pateh UU (2006). Preliminary phytochemical and antimicrobial screening of the leaves of Byrsocarpus coccineus Schum. and Thonn. (Connaraceae). Journal of Pharmacy & Bioresources 3:107-110.
Akindele AJ, Ezenwanebe KO, Anunobi CC, Adeyemi OO (2010). Hepatoprotective and in vivo antioxidant effects of Byrsocarpus coccineus Schum. and Thonn. (Connaraceae). Journal of Ethnopharmacology 129:46-52.
Akindele AJ, Adeyemi OO (2010). Anxiolytic and sedative effects of Byrsocarpus coccineus Schum. and Thonn. (Connaraceae) extract. International Journal of Applied Research in Natural Products 3:28-36.
Akindele AJ, Iyamu EA, Dutt P, Satti NK, Adeyemi OO (2014). Ameliorative effect of hydroethanolic leaf extract of Byrsocarpus coccineus in alcohol- and sucrose-induced hypertension in rats. Journal of Traditional and Complementary Medicine 4:177-188.
Dada OK, Akindele AJ, Morakinyo OA, Sofidiya MO, Ota D (2013). Hypoglycemic and antioxidant activities of the hydroethanolic leaf extract of Byrsocarpus coccineus Schum. and Thonn. (Connaraceae). Chinese Journal of Natural
Medicines 11:0628-0637.
Bero J, Hannaert V, Chataigne G, Herent MF, Quetin-Leclercq J (2011). In vitro antitrypanosomal and antileishmanial activity of plants used in Benin in traditional medicine and bioguided fractionation of the most active extract. Journal of Ethnopharmacology 137:998- 1002.
Watt JM, Breyer-Brandwiijk MJ (1962). Medicinal and Poisonous Plants of South and Eastern Africa, 2nd edition. Churchill Livingstone.
Adeyemi OO, Yemitan OK, Adebiyi OO (2007). Sedative and anticonvulsant activities of the aqueous root extract of Sanseviera liberica Gerome & Labroy (Agavaceae). Journal of Ethnopharmacology 113:111-114.
Umukoro S, Ashorobi RB (2008). Effects of the methanol leaf extract of Sansevieria liberica on the central nervous system in mice. Journal of Natural Remedies 8:242-246.
Adeyemi OO, Akindele AJ, Ogunleye EA (2009). Evaluation of the antidiarrhoeal effect of Sanseviera liberica Gerome & Labroy (Agavaceae) root extract. Journal of Ethnopharmacology 123:459-463.
Bero J, Ganfon H, Jonville MC, Frédérich M, Gbaguidi F, DeMol P, Moudachirou M, Quetin- Leclercq J (2009). In vitro antiplasmodial activity of plants used in Benin in traditional medicine to treat malaria. Journal of Ethnopharmacology 122:439-444.
Ikewuchi JC, Ikewuchi CC, Igboh NM, Mark-Balm T (2011). Protective effect of aqueous extract of the rhizomes of Sansevieria liberica Gerome and Labroy on carbon tetrachloride induced hepatotoxicity in rats. EXCLI Journal 10:312-321.
Chinasa EC, Ifeoma IA , Obodoike EC, Chukwuemeka ES (2011). Evaluation of anti- inflammatory property of the leaves of Sansevieria liberica Ger. and Labr. (fam: Dracaenaceae). Asian Pacific Journal of Tropical Medicine 4:791-795.
Akindele AJ, Wani ZA, Sharma S, Mahajan G, Satti NK, Adeyemi OO, Mondhe DM, Saxena AK (2015). In-vitro and in-vivo anticancer activity of root extracts of Sansevieria liberica Gerome and Labroy (Agavaceae). Evidence-Based Complementary and Alternative Medicine 2015: 560404, 11pages. http://dx.doi.org/10.1155/2015/560404
He M, Jiang J, Qiu F, Liu S, Peng P, Gao C, Miao P (2013). Inhibitory effects of gypenosides on seven human cytochrome P450 enzymes in vitro. Food and Chemical Toxicology 57:262-265.
Mekjaruskul C, Jay M, Sripanidkulchai B (2012). Modulatory effects of Kaempferia parviflora extract on mouse hepatic cytochrome P450 enzymes. Journal of Ethnopharmacology 141(3): 831-839.
Johnson SS, Oyelola FT, Ari T, Juho H (2013). In vitro inhibitory activities of the extract of Hibiscus sabdariffa L. (family Malvaceae) on selected cytochrome P450 isoforms. African Journal of Traditional, Complementary and Alternative
Medicines 10(3):533-540.
Pekthong D, Martin H, Abadie C, Bonet A, Heyd B, Mantion G, Richert L (2008). Differential inhibition of rat and human hepatic cytochrome P450 by Andrographis paniculata extract and andrographolide. Journal of Ethnopharmacology
: 432-440.
Huber WW, Rossmanith W, Grusch M, Haslinger E, Prustomersky S, Peter-Vorosmarty B, Parzefall W, Scharf G, Schulte-Hermann R (2008). Effects of coffee and its chemopreventive components kahweol and cafestol on cytochrome P450 and sulfotransferase in rat liver. Food and Chemical Toxicology 46:1230-1238.
Stresser DM, Blanchard AP, Turner SD, Erve JCL, Dandeneau AA, Miller VP, Crespi CL (2000). Substrate-dependent modulation of CYP3A4 catalytic activity: analysis of 27 test compounds with four fluorometric substrates. Drug
Metabolism and Disposition 28:1440-1448.
Akindele AJ, Eksioglu EA, Kwan JC, Adeyemi OO, Liu C, Luesch H, James MO (2011). Biological effects of Byrsocarpus coccineus Schum. and Thonn. (Connaraceae) in vitro. Pharmaceutical Biology 49:152-160.
James MO, Altman AH, Morris K, Kleinow KM, Tong Z (1997). Dietary modulation of phase 1 and phase 2 activities with benzo(a)pyrene and related compounds in the intestine but not the liver of channel catfish, Ictalurus punctatus. Drug
Metabolism and Disposition 25:346-354.
Renwick AB, Surry D, Price RJ, Lake BG, Evans DC (2000). Metabolism of 7-benzyloxy-4- trifluoromethylcoumarin by human hepatic cytochrome P450 isoforms. Xenobiotica 30:955- 969.
Prough RA, Burke MD, Mayer RT (1978). Direct fluorometric methods for measuring mixed- function oxidase activity. Methods in Enzymology 52: 372-377.
Pohl RJ, Fouts JR (1980). A rapid method for assaying the metabolism of 7-ethoxyresorufin by microsomal subcellular fractions. Analytical Biochemistry 107:150-155.
Girennavar B, Jayaprakasha GK, Patil BS (2007). Potent inhibition of human cytochrome P450 3A4, 2D6, and 2C9 isoenzymes by grapefruit juice and its furocoumarins. Journal of Food Science 72: C417-421.
Pekthong D, Desbans C, Martin H, Richert L (2012). Bupropion hydroxylation as a selective marker of rat CYP2B1 catalytic activity. Drug Metabolism and Disposition 40:32-38.
Mazzari AL, Prieto JM (2014). Herbal medicines in Brazil: pharmacokinetic profile and potential herb-drug interactions. Frontiers in Pharmacology 5: 162. doi:10.3389/fphar.2014.00162
Zhou SF, Liu JP, Chowbay B (2009). Polymorphism of human cytochrome P450 enzymes and its clinical impact. Drug Metabolism Reviews 41:89- 295.
Cowan MM (1999). Plant products as antimicrobial agents. Clinical Microbiology Reviews 12:564-582.
Low Dog T (2009). Smart talk on supplements and botanicals. Alternative and Complementary Therapies 15:101-102.
Wendakoon C. Evaluation of selected medicinal plants extracted in different ethanol concentrations for antibacterial activity against human pathogens. Journal of Medicinally Active Plants 2012;1:60-68.