Strawberry decreases intraluminal and intestinal wall hydrolysis of testosterone undecanoate

Zgair, Atheer; Dawood, Yousaf; Ibrahem, Suhaib M; Lee, Jong Bong; Feng, Wanshan; Fischer, Peter M.; Gershkovich, Pavel

Abstract

Male hypogonadism is often treated by testosterone (T) replacement therapy such as oral administration of the ester prodrug, testosterone undecanoate (TU). However, the systemic exposure to T following oral TU is very low due to esterase-mediated metabolism, particularly in the small intestine. The aim of this work was to examine the esterase-inhibitory effect of natural fruit extract of strawberry (STW) on the intestinal degradation of TU as a potential approach to increase the oral bioavailability of T. Herein, the hydrolysis of TU was assessed in fasted state simulated intestinal fluid with added esterase activity (FaSSIF/ES) and Caco-2 cell homogenates in the presence of STW extract. Noteworthy, STW has substantially inhibited the degradation of TU in FaSSIF/ES and Caco-2 cell homogenates at concentrations that could be achieved following oral consumption of less than one serving of STW fruit. This can significantly increase the fraction of unhydrolyzed TU in the intestinal lumen, as well as in enterocytes. In addition, it was demonstrated that TU has high intestinal lymphatic transport potential as the association of TU with plasma-derived human chylomicrons was in the range of 84%. Therefore, oral co-administration of TU with STW could potentially increase the intestinal stability of TU and consequently the contribution of lymphatically-delivered TU to the systemic exposure of T in vivo.

Citation

Zgair, A., Dawood, Y., Ibrahem, S. M., Lee, J. B., Feng, W., Fischer, P. M., & Gershkovich, P. (2021). Strawberry decreases intraluminal and intestinal wall hydrolysis of testosterone undecanoate. Molecules, 26(1), Article 233. https://doi.org/10.3390/molecules26010233

• Journal Article Type: Article
• Acceptance Date: Dec 31, 2020
• Online Publication Date: Jan 5, 2021
• Publication Date: Jan 5, 2021
• Deposit Date: Jan 24, 2021
• Publicly Available Date: Jan 25, 2021
• Journal: Molecules
• Electronic ISSN: 1420-3049
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 26
• Issue: 1
• Article Number: 233
• DOI: https://doi.org/10.3390/molecules26010233
• Keywords: Testosterone undecanoate; FaSSIF; intestinal degradation; first-pass metabolism
• Public URL: https://nottingham-repository.worktribe.com/output/5268236
• Publisher URL: https://www.mdpi.com/1420-3049/26/1/233