Fenchone: Natural Occurrence, Metabolism and Bioactivity

General Description

Fenchone, a compound with a pleasant aroma, is primarily sourced from sweet fennel essential oil but can also be found in other plants like anise. Its natural origin makes it popular in perfumery and food industries. In metabolism studies, fenchone was found to undergo oxidation in the liver, involving enzymes like CYP2A6 and CYP2B6. These enzymes play a key role in producing hydroxylated metabolites. Additionally, fenchone exhibits diverse bioactivities such as antioxidant, antimicrobial, and cytotoxic properties. Overall, fenchone's natural origin, metabolic pathways, and bioactivities make it a valuable ingredient with various applications.

Figure 1. Fenchone

Natural Occurrence

Fenchone, a compound known for its distinct and pleasant aroma, primarily originates from the essential oil extracted from sweet fennel. Sweet fennel, utilized widely in herbal medicine and culinary practices, serves as the primary natural source of this compound. However, Fenchone can also be found in smaller quantities in other plants, including anise and star anise, contributing to their unique fragrances. Renowned for its refreshing and sweet scent, Fenchone finds extensive applications in perfumery and as a flavoring agent in various food products. Its natural origin assures both safety and purity, rendering it a preferred choice in the cosmetic and food industries. The reliance on natural sources for Fenchone underscores its appeal to consumers seeking natural and authentic ingredients. The utilization of Fenchone from sweet fennel and other botanical sources highlights the significance of sustainable and environmentally friendly practices in obtaining natural compounds for various applications. Overall, Fenchone's natural origins, along with its versatile applications and pleasant aroma, make it a valuable ingredient in industries ranging from perfumery to culinary arts. ¹

Metabolism

The metabolism of fenchone, a compound found in human liver microsomes, was investigated using gas chromatography-mass spectrometry. It was observed that fenchone undergoes oxidation to produce metabolites such as 6-exo-hydroxyfenchone, 6-endo-hydroxyfenchone, and 10-hydroxyfenchone, with the involvement of P450 enzymes present in human liver microsomes. Among the various enzymes tested, CYP2A6 and CYP2B6 were identified as the major catalysts for the hydroxylation of fenchone. This conclusion was drawn based on several lines of evidence, including the inhibition of fenchone oxidation by specific inhibitors, as well as the correlation between the levels of CYP2A6 and CYP2B6 and the hydroxylation activities of fenchone in liver microsomes. Further kinetic analysis revealed specific values for the catalytic activity of CYP2A6 and CYP2B6 in metabolizing fenchone. For instance, CYP2A6 exhibited higher catalytic activity towards fenchone 6-exo-hydroxylation compared to CYP2B6. Additionally, the apparent Km and Vmax values provided insights into the substrate specificity and efficiency of these enzymes in metabolizing fenchone. Overall, the metabolism of fenchone involves the enzymatic activity of CYP2A6 and CYP2B6, which play crucial roles in the oxidation of fenchone to produce various hydroxylated metabolites. This study enhances our understanding of the metabolic pathways involved in the biotransformation of (-)-fenchone in human liver microsomes. ²

Bioactivity

Fenchone, a natural monoterpene abundant in fennel essential oil, exhibits diverse biological activities, as elucidated through in silico structural similarity analysis and experimental validation. Using an approach of virtual structural similarity searching, fenchone's bioactivity was explored comprehensively. Firstly, fenchone demonstrated high structural similarity with camphor, suggesting potential overlapping biological effects. Molecular docking studies further supported this, revealing analogous binding modes between fenchone and camphor against the protein Cytochrome CYP101D1. Experimental assays confirmed several biological activities of fenchone. It exhibited potent antioxidant properties, as evidenced by its ability to scavenge DPPH free radicals with an IC50 value of 3.32±0.008mM. Additionally, fenchone displayed antimicrobial activity with a minimum inhibitory concentration (MIC) of 0.49mM and strong antifungal activity. Moreover, fenchone demonstrated protective effects against H2O2-induced cytotoxicity in yeast cells and exhibited cytotoxicity against cancerous Hela cells, with an IC50 value of 12.63±0.12 μM. Furthermore, fenchone treatment led to reduced activity of antioxidant enzymes such as glutathione-S-transferase, catalase, and lipid peroxidase. In conclusion, this study represents the first comprehensive exploration of fenchone's bioactivity using virtual structural similarity searching, highlighting its antioxidant, antimicrobial, antifungal, and cytotoxic properties. These findings contribute to a better understanding of the pharmacological potential of fenchone. ³

Reference

1. El Omari N, Balahbib A, Bakrim S, Benali T, Ullah R, Alotaibi A, Naceiri El Mrabti H, Goh BH, Ong SK, Ming LC, Bouyahya A. Fenchone and camphor: Main natural compounds from Lavandula stoechas L., expediting multiple in vitro biological activities. Heliyon. 2023; 9(11): e21222.

2. Miyazawa M, Gyoubu K. Metabolism of (-)-fenchone by CYP2A6 and CYP2B6 in human liver microsomes. Xenobiotica. 2007; 37(2): 194-204.

3. Singh S, Gupta P, Gupta J. Virtual Structural Similarity Elucidates Bioactivity of Fenchone: A Phytochemical Enriched in Fennel Essential Oil. Curr Drug Discov Technol. 2020; 17(5): 619-630.