Metabolism of Diterpenoids Derived from the Bark of Cinnamomum cassia in Human Liver Microsomes.

Su Min Choi,Sangkyu Lee,Jeong Ah Kim,Van Cong Pham

doi:10.3390/pharmaceutics13081316

Su Min Choi, Sangkyu Lee + Show 2 more

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https://doi.org/10.3390/pharmaceutics13081316

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Journal: Pharmaceutics	Publication Date: Aug 23, 2021
Citations: 4	License type: CC BY 4.0

Affiliation: Kyungpook National University

Abstract

Cinnamomum cassia L. is used as a spice and flavoring agent as well as a traditional medicine worldwide. Diterpenoids, a class of compounds present in C. cassia, have various pharmacological effects, such as anti-inflammatory, antitumor, and antibacterial activities; however, there are insufficient studies on the metabolism of diterpenoids. In this study, the metabolism of seven diterpenoids, namely, anhydrocinnzeylanol, anhydrocinnzeylanine (AHC), cinncassiol A, cinncassiol B, cinnzeylanol, cinnzeylanone, and cinnzeylanine, obtained from the bark of C. cassia was studied in human liver microsomes (HLMs). All studied diterpenoids, except for AHC, exhibited strong metabolic stability; however, AHC was rapidly metabolized to 3% in HLMs in the presence of β-NADPH. Using a high-resolution quadrupole-orbitrap mass spectrometer, 20 metabolites were identified as dehydrogenated metabolites (M1–M3), dehydrogenated and oxidated metabolites (M4–M10), mono-oxidated metabolites (M11–M13), or dioxidated metabolites (M14–M20). In addition, CYP isoforms involved in AHC metabolism were determined by profiling metabolites produced after incubation in 11 recombinant cDNA-expressed CYP isoforms. Thus, the diterpenoid compound AHC was identified in a metabolic pathway involving CYP3A4 in HLMs.

Highlights

Accepted: 20 August 2021Cinnamomum cassia L., which belongs to the family Lauraceae, is used as a spice and flavoring agent as well as a traditional medicine worldwide [1,2]
To examine the pharmacological properties of diterpenes isolated from C. cassia, we evaluated the metabolic stability of seven diterpenes and identified the metabolic pathway of AHC, which had the highest metabolic rate in human liver microsomes (HLMs)
Metabolic Stability of the Seven Diterpenoids in HLMs. To confirm their metabolic stability, seven diterpenoids (AHC, anhydrocinnzeylanol, cinncassiol A, cinncassiol B, cinnzeylanol, cinnzeylanone, and cinnzeylanine) derived from the bark of C. cassia were incubated with HLMs in the presence of the NADPH-regenerating system (NGS) for 60 min (Figure 1B)

Summary

Introduction

Cinnamomum cassia L., which belongs to the family Lauraceae, is used as a spice and flavoring agent as well as a traditional medicine worldwide [1,2]. Different parts of C. cassia are used for different therapeutic purposes [3]. The constituents of the treatments are well known, along with the various medicinal effects of phenylpropanoids, sesquiterpenoids, lignans, and diterpenoids isolated from. Diterpene compounds have been mainly identified in the leaves of C. cassia and were recently isolated from the bark [6,7]. Anhydrocinnzeylanol, anhydrocinnzeylanine (AHC), cinncassiol A, cinncassiol B, cinnzeylanol, cinnzeylanone, and cinnzeylanine have been extracted from the bark of C. cassia and classified as diterpenoids [2,8,9,10,11] (Figure 1)

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