ANTIOXIDANT PROPERTIES OF GYNURA PROCUMBENS EXTRACTS AND THEIR INHIBITORY EFFECTS ON TWO MAJOR HUMAN RECOMBINANT CYTOCHROME P450S USING A HIGH THROUGHPUT LUMINESCENCE ASSAY.

Authors

  • Atiqah Afandi Centre for Drug Research, Universiti Sains Malaysia, Penang, Malaysia
  • Halimhilmi Zulkiffli M
  • Amirin Sadikun
  • Sabariah Ismail

Abstract

 

 Objective: Gynura procumbens is an evergreen herb traditionally used to treat various diseases such as fever, kidney disease, and diabetes. Despite various studies conducted on the pharmacological activities of G. procumbens, the interaction between this herb with drug-metabolizing enzymes is still unknown.

Methods: This study investigates the effects of ethanol, methanol, and aqueous extracts of G. procumbens on CYP3A4 and CYP1A2 enzyme activities along with its antioxidant capacity using high throughput luminescence assay.

Results: The content of phenolic compounds in G. procumbens extracts can be ranked in decreasing order as follows: Methanol extract > ethanol extract > aqueous extract, whereas the content of flavonoid compounds in G. procumbens extracts can be ranked in decreasing order as follows: Ethanol extract > methanol extract > aqueous extract. The methanol extract of G. procumbens exhibited the most active free radical scavenger compared to the other extracts. Ethanol extract of the G. procumbens exhibited strong inhibitory effect on CYP3A4 and CYP1A2 enzyme with IC50 values of 32.01±1.11 μg/mL and 7.87±1.22 μg/mL, respectively. The methanol extract exhibited weak inhibitory effect on CYP3A4 and CYP1A2 enzymes with IC50 values more than 100 μg/mL. The aqueous extract, on the other hand, demonstrated no inhibitory effect on both enzymes.

Conclusion: The inhibition of CYP3A4 and CYP1A2 in this study follows the rank order of total flavonoid content (ethanol extract > methanol extract > aqueous extract) in which the higher the total flavonoid content in the extract, the higher would be the inhibition of drug metabolizing enzymes studied.

Keywords: Gynura procumbens, Antioxidant properties, CYP3A4, CYP1A2.

Downloads

Download data is not yet available.

References

Hansen TS, Nilsen OG. In vitro CYP3A4 metabolism: Inhibition by Echinacea purpurea and choice of substrate for the evaluation of herbal inhibition. Basic Clin Pharmacol Toxicol 2008;103(5):445-9.

Ernst E. Herb-drug interactions: Potentially important but woefully under-researched. Eur J Clin Pharmacol 2000;56(8):523-4.

Zhou S, Koh HL, Gao Y, Gong ZY, Lee EJ. Herbal bioactivation: The good, the bad and the ugly. Life Sci 2004;74(8):935-68.

Wang X, Cheung CM, Lee WY, Or PM, Yeung JH. Major tanshinones of Danshen (Salvia miltiorrhiza) exhibit different modes of inhibition on human CYP1A2, CYP2C9, CYP2E1 and CYP3A4 activities in vitro. Phytomedicine 2010;17(11):868-75.

Iwata H, Tezuka Y, Kadota S, Hiratsuka A, Watabe T. Identification and characterization of potent CYP3A4 inhibitors in Schisandra fruit extract. Drug Metab Dispos 2004;32(12):1351-8.

Guengerich FP. Cytochromes P450, drugs, and diseases. Mol Interv 2003;3(4):194-204.

Guengerich FP. In vitro techniques for studying drug metabolism. J Pharmacokinet Pharmacodyn 1996;24(5):521-33.

Gonzalez FJ, Gelboin HV. Role of human cytochromes P450 in the metabolic activation of chemical carcinogens and toxins. Drug Metab Rev 1994;26(1-2):165-83.

Slaga TJ, Gleason GL, DiGiovanni J, Sukumaran KB, Harvey RG. Potent tumor-initiating activity of the 3,4-dihydrodiol of 7,12-dimethylbenz(a) anthracene in mouse skin. Cancer Res 1979;39:1934-6.

Kim H, Choi HK, Jeong TC, Jahng Y, Kim DH, Lee SH, et al. Selective inhibitory effects of mollugin on CYP1A2 in human liver microsomes. Food Chem Toxicol 2013;51:33-7.

Bhore S, Vaishana K. Comparison of three plant tissue culture media for efficient micropropagation of an important tropical medicinal plant, Gynura procumbens (Lour) Merr. Am Eurasia J Agric Environ Sci 2010;8(4):474-81.

Saiman MZ, Mustafa NR, Schulte AE, Verpoorte R, Choi YH. Induction, characterization, and NMR-based metabolic profiling of adventitious root cultures from leaf explants of Gynura procumbens. Plant Cell Tissue Organ Cult 2012;109(3):465-75.

Kim MJ, Lee HJ, Wiryowidagdo S, Kim HK. Antihypertensive effects of Gynura procumbens extract in spontaneously hypertensive rats. J Med Food 2006;9(4):587-90.

Rosidah, Yam MF, Sadikun A, Ahmad M, Akowuah GA, Asmawi MZ. Toxicology evaluation of standardized methanol extract of Gynura procumbens. J Ethnopharmacol 2009;123(2):244-9.

Hassan Z, Yam MF, Ahmad M, Yusof AP. Antidiabetic properties and mechanism of action of Gynura procumbens water extract in streptozotocin-induced diabetic rats. Molecules 2010;15(12):9008-23.

Lee HW, Hakim P, Rabu A, Sani HA. Antidiabetic effect of Gynura procumbens leaves extracts involve modulation of hepatic carbohydrate metabolism in streptozotocin-induced diabetic rats. J Med Plants Res 2012;6(5):796-812.

Zahra A, Kadir F, Mahmood A, Al Hadi A, Suzy S, Sabri S, et al. Acute toxicity study and wound healing potential of Gynura procumbens leaf extract in rats. J Med Plants Res 2011;5(12):2551-8.

Iskander MN, Song Y, Coupar IM, Jiratchariyakul W. Antiinflammatory screening of the medicinal plant Gynura procumbens. Plant Foods Hum Nutr 2002;57(3-4):233-44.

Yam M, Sadikun A, Asmawi M. Antioxidant potential of Gynura procumbens. Pharm Biol 2008;46(9):616-25.

Zhai S, Dai R, Friedman FK, Vestal RE. Comparative inhibition of human cytochromes P450 1A1 and 1A2 by flavonoids. Drug Metab Dispos 1998;26(10):989-92.

Ho PC, Saville DJ, Wanwimolruk S. Inhibition of human CYP3A4 activity by grapefruit flavonoids, furanocoumarins and related compounds. J Pharm Pharm Sci 2001;4(3):217-27.

Juan MY, Chou CC. Enhancement of antioxidant activity, total phenolic and flavonoid content of black soybeans by solid state fermentation with Bacillus subtilis BCRC 14715. Food Microbiol 2010;27(5):586 91.

Shimada K, Fujikawa K, Yahara K, Nakamura T. Antioxidative properties of xanthan on the autoxidation of soybean oil in cyclodextrin emulsion. J Agric Food Chem 1992;40(6):945-8.

Sun T, Ho CT. Antioxidant activities of buckwheat extracts. Food Chem 2005;90(4):743-9.

Algariri K, Meng KY, Atangwho IJ, Asmawi MZ, Sadikun A, Murugaiyah V, et al. Hypoglycemic and anti-hyperglycemic study of Gynura procumbens leaf extracts. Asian Pac J Trop Biomed 2013;3(5):358-66.

Pourmorad F, Hosseinimehr S, Shahabimajd N. Antioxidant activity, phenol and flavonoid contents of some selected Iranian medicinal plants. Afr J Biotechnol 2006;5(11):1142-5.

Pekthong D, Martin H, Abadie C, Bonet A, Heyd B, Mantion G, et al. Differential inhibition of rat and human hepatic cytochrome P450 by Andrographis paniculata extract and andrographolide. J Ethnopharmacol 2008;115(3):432-40.

Krippendorff BF, Lienau P, Reichel A, Huisinga W. Optimizing classification of drug-drug interaction potential for CYP450 isoenzyme inhibition assays in early drug discovery. J Biomol Screen 2007;12(1):92-9.

Appiah-Opong R, Commandeur JN, van Vugt-Lussenburg B, Vermeulen NP. Inhibition of human recombinant cytochrome P450s by curcumin and curcumin decomposition products. Toxicology 2007;235(1-2):83 91.

Guengerich FP. Roles of cytochrome P-450 enzymes in chemical carcinogenesis and cancer chemotherapy. Cancer Res 1988;48(11):2946 54.

Tsyrlov IB, Mikhailenko VM, Gelboin HV. Isozyme- and species-specific susceptibility of cDNA-expressed CYP1A P-450s to different flavonoids. Biochim Biophys Acta 1994;1205(2):325-35.

Strandell J, Neil A, Carlin G. An approach to the in vitro evaluation of potential for cytochrome P450 enzyme inhibition from herbals and other natural remedies. Phytomedicine 2004;11(2-3):98-104.

Published

01-11-2014

How to Cite

Afandi, A., H. Zulkiffli M, A. Sadikun, and S. Ismail. “ANTIOXIDANT PROPERTIES OF GYNURA PROCUMBENS EXTRACTS AND THEIR INHIBITORY EFFECTS ON TWO MAJOR HUMAN RECOMBINANT CYTOCHROME P450S USING A HIGH THROUGHPUT LUMINESCENCE ASSAY”. Asian Journal of Pharmaceutical and Clinical Research, vol. 7, no. 5, Nov. 2014, pp. 36-41, https://mail.innovareacademics.in/journals/index.php/ajpcr/article/view/1162.

Issue

Section

Original Article(s)