Pharmacokinetics and Tissue Distribution of Aegeline after Oral Administration in Mice

Vamshi K. Manda; Mona H. Haron; Tahir M. Mir; Bharathi Avula; Mohammad K. Ashfaq; Saqlain Haider; Amar G. Chittiboyina; Ikhlas A. Khan; Shabana I. Khan

doi:10.1055/a-0851-6879

Planta Medica, Inhaltsverzeichnis

Planta Med 2019; 85(06): 491-495
DOI: 10.1055/a-0851-6879

Pharmacokinetic Investigations

Original Papers

Georg Thieme Verlag KG Stuttgart · New York

Pharmacokinetics and Tissue Distribution of Aegeline after Oral Administration in Mice

Vamshi K. Manda

¹National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, University, MS, USA

,

Mona H. Haron

¹National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, University, MS, USA

,

Tahir M. Mir

¹National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, University, MS, USA

,

Bharathi Avula

¹National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, University, MS, USA

,

Mohammad K. Ashfaq

¹National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, University, MS, USA

,

Saqlain Haider

¹National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, University, MS, USA

,

Amar G. Chittiboyina

¹National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, University, MS, USA

,

Ikhlas A. Khan

¹National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, University, MS, USA

²Division of Pharmacognosy, Department of BioMolecular Sciences, School of Pharmacy, The University of Mississippi, University, MS, USA

,

Shabana I. Khan

¹National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, University, MS, USA

²Division of Pharmacognosy, Department of BioMolecular Sciences, School of Pharmacy, The University of Mississippi, University, MS, USA

› Institutsangaben

Abstract

Aegeline is claimed to be a biologically active constituent of Aegle marmelos. Preclinical studies have reported possible therapeutic potential for aegeline against obesity and diabetes. In recent years, aegeline has been added to several weight loss products. However, the consumption of aegeline-containing supplements such as OxyELITE Pro and VERSA-1 has been linked to multiple cases of acute and chronic liver failure. This study was carried out to evaluate the pharmacokinetics and tissue distribution of aegeline in ND4 mice. Two doses of aegeline, a human equivalent dose (1×) 30 mg/kg and a 10× dose (300 mg/kg), were orally administered to the mice, and blood and tissue samples were collected over 8 h. The quantitative analysis of plasma and tissue homogenates (liver, kidney, and brain) was done by UHPLC-QTOF to determine aegeline concentrations. The peak plasma level of aegeline was achieved at a T_max of 0.5 h, indicating its rapid absorption from the gastrointestinal tract. Aegeline was not detected in the plasma at 8 h after oral administration, with a half-life of 1.4 ± 0.01 and 1.3 ± 0.07 h for the 30 and 300 mg/kg doses, respectively. The half-life of aegeline in the liver was 1.2 h and 1.7 h for 30 and 300 mg/kg doses, respectively, with a T_max of 1.9 h, which indicates relatively fast elimination of aegeline from the liver.

Key words

Aegeline - N-[2-Hydroxy-2(4-methoxyphenyl)ethyl]-3-phenyl-2-propenamide - Aegle marmelos - Rutaceae - pharmacokinetics

Volltext

Referenzen

References
1 Karmase A, Birari R, Bhutani KK. Evaluation of anti-obesity effect of Aegle marmelos leaves. Phytomedicine 2013; 20: 805-812
2 Karmase A, Jagtap S, Bhutani KK. Anti adipogenic activity of Aegle marmelos correa. Phytomedicine 2013; 20: 1267-1271
3 Gautam S, Ishrat N, Singh R, Narender T, Srivastava AK. Aegeline from Aegle marmelos stimulates glucose transport via Akt and Rac1 signaling, and contributes to a cytoskeletal rearrangement through PI3K/Rac1. Eur J Pharmacol 2015; 762: 419-429
4 Narender T, Shweta S, Tiwari P, Papi Reddy K, Khaliq T, Prathipati P, Puri A, Srivastava AK, Chander R, Agarwal SC, Raj K. Antihyperglycemic and antidyslipidemic agent from Aegle marmelos . Bioorg Med Chem Lett 2007; 17: 1808-1811
5 Govindachari TR, Premila MS. Some alkaloids from Aegle marmelos . Phytochemistry 1983; 22: 755-757
6 Manda VK, Avula B, Chittiboyina AG, Khan IA, Walker LA, Khan SI. Inhibition of CYP3A4 and CYP1A2 by Aegle marmelos and its constituents. Xenobiotica 2016; 46: 117-125
7 Baliga MS, Bhat HP, Pereira MM, Mathias N, Venkatesh P. Radioprotective effects of Aegle marmelos (L.) Correa (Bael): a concise review. J Altern Complement Med 2010; 16: 1109-1111
8 Kothari S, Minda M, Tonpay SD. Anxiolytic and antidepressant activities of methanol extract of Aegle marmelos leaves in mice. Indian J Physiol Pharmacol 2010; 54: 318-328
9 Heidemann LA, Navarro VJ, Ahmad J, Hayashi PH, Stolz A, Kleiner DE, Fontana RJ. Severe acute hepatocellular injury attributed to OxyELITE Pro: A case series. Dig Dis Sci 2016; 61: 2741-2748
10 Johnston DI, Chang A, Viray M, Chatham-Stephens K, He H, Taylor E, Wong LL, Schier J, Martin C, Fabricant D, Salter M, Lewis L, Park SY. Hepatotoxicity associated with the dietary supplement OxyELITE Pro – Hawaii, 2013. Drug Test Anal 2016; 8: 319-327
11 Roytman MM, Porzgen P, Lee CL, Huddleston L, Kuo TT, Bryant-Greenwood P, Wong LL, Tsai N. Outbreak of severe hepatitis linked to weight-loss supplement OxyELITe Pro. Am J Gastroenterol 2014; 109: 1296-1298
12 Chatham-Stephens K, Taylor E, Chang A, Peterson A, Daniel J, Martin C, Deuster P, Noe R, Kieszak S, Schier J, Klontz K, Lewis L. Hepatotoxicity associated with weight loss or sports dietary supplements, including OxyELITE Pro – United States, 2013. Drug Test Anal 2017; 9: 68-74
13 Foley S, Butlin E, Shields W, Lacey B. Experience with OxyELITE pro and acute liver injury in active duty service members. Dig Dis Sci 2014; 59: 3117-3121
14 U.S. Food and Drug Administration. Warning letter (USP labs 11/10/13), 11 October 2013. Available at: https://www.fda.gov/iceci/enforcementactions/warningletters/2013/ucm371203.htm Accessed December 12, 2018
15 U.S. Food and Drug Administration. OxyElite Pro Supplements Recalled. Available at: https://www.fda.gov/ForConsumers/ConsumerUpdates/UCM374742_F Accessed December 12, 2018
16 Kennedy ET, Luo H, Houser RF. Dietary supplement use pattern of US adult population in the 2007–2008 national health and nutrition examination survey (NHANES). Ecol Food Nutr 2013; 52: 76-84
17 Timbo BB, Ross MP, McCarthy PV, Lin CT. Dietary supplements in a national survey: Prevalence of use and reports of adverse events. J Am Diet Assoc 2006; 106: 1966-1974
18 Navarro VJ, Seeff LB. Liver injury induced by herbal complementary and alternative medicine. Clin Liver Dis 2013; 17: 715-735
19 Miousse IR, Skinner CM, Lin H, Ewing LE, Kosanke SD, Williams DK, Avula B, Khan IA, ElSohly MA, Gurley BJ, Koturbash I. Safety assessment of the dietary supplement OxyELITE Pro (New Formula) in inbred and outbred mouse strains. Food Chem Toxicol 2017; 109: 194-209
20 Davies B, Morris T. Physiological parameters in laboratory animals and humans. Pharm Res 1993; 10: 1093-1095
21 Avula B, Chittiboyina AG, Wang YH, Sagi S, Raman V, Wang M, Khan IA. Simultaneous determination of aegeline and six coumarins from different parts of the plant Aegle marmelos using UHPLC-PDA-MS and chiral separation of aegeline enantiomers using HPLC-ToF-MS. Planta Med 2016; 82: 580-588
22 Food and Drug Administration. Guidance for industry: estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers. Available at: https://www.fda.gov/downloads/Drugs/Guidances/UCM078932.pdf#search='guidekines+for+industry+sfe+starting' Accessed December 12, 2018
23 Madgula VL, Ashfaq MK, Wang YH, Avula B, Khan IA, Walker LA, Khan SI. Bioavailability, pharmacokinetics, and tissue distribution of the oxypregnane steroidal glycoside p57as3 (p57) from Hoodia gordonii in mouse model. Planta Med 2010; 76: 1582-1586
24 International Conference on Harmonisation. Validation of Analytical Procedures: Text and Methodology, ICH Harmonised Tripartite Guidelines, November 2005. Available at: http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q2_R1/Step4/Q2_R1__Guideline.pdf Accessed November 1, 2018