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(E)-β-Caryophyllene: A flavor agent with numerous bioactivities



β-Caryophyllene (C15H24) (Figure 1) with CAS # 87-44-5, chemically called by (1R,4E,9S)-4, 11, 11-trimethyl-8-methylidenebicyclo[7.2.0]undec-4-ene as the IUPAC name, is a natural bicyclic sesquiterpene hydrocarbon found in essential oils of many plant species. In nature, all-trans-β-caryophyllene is usually found together with small amounts of its isomers, cis-β-caryophyllene or iso-caryophyllene and α-caryophyllene or α-humulene, and β-caryophyllene oxide (Francomano et al., 2019). Table 1 shows relative contents of β-caryophyllene, its isomer and oxidation product from some plant species documented by PT Mitra Ayu Adipratama.


β-Caryophyllene has a sweet, woody, spice, clove, and dry odor as well as spicy, clove, woody, nut, skin, powdery and peppery flavor (The Good Scents Company, 2023). Gertsch (2008) and Gertsch et al. (2008) revealed that β-caryophyllene is used as additive or preservative and for aroma in food products and beverages. It is approved as flavoring agent and can be used in cosmetic (Fidyt et al., 2016, Machado et al., 2018). In addition, experimental result on oral sub-chronic toxicity revealed that β-caryophyllene is safe for use in the medical food products (Schmitt et al., 2016).


Figure 1. Molecular structure of (−)-β-caryophyllene


Table 1. Relative contents of (E)-β-caryophyllene, α-caryophyllene, and β-caryophyllene oxide from essential oils of several plant species (PT Mitra Ayu Adipratama)

Maffei (2020) has summarized the plant natural sources of β-caryophyllene with the percentage higher than 10%, extracted from 13 plant parts of 300 plant species and originating from 56 countries around the world. Essential oils from leaves of Scutellaria havanensis Jacg., and oleoresin of Copaifera langsdorffii contain the highest percentage of β-caryophyllene (75.6%) and yield of oil (28.0%), respectively. There are several plant species having percentage of β-caryophyllene ≥ 50% and yield of oil ≥ 2%, such as Spondias pinnata (Linn. F.) Kurz (leaves), Pimpinella kotschyana Boiss. (seeds), Bursera mircophylla A. Gray (oleo-gum-resin), Copaifera langsdorffii Desf. (oleoresins).


β-Caryophyllene is also a major component in the essential oil of Cannabis sativa L. with the relative content varied depending on the cultivar, namely 26–40% (Zheljazkov et al., 2020) and belongs to a class of cannabinoids, specifically phytocannabinoids (Fidyt et al., 2016). Cannabinoids have the ability to activate the cannabinoid receptors, i.e., type 1 (CB1) and type 2 (CB2), which play an important role in maintenance of energy balance, metabolism, neurotransmission, immune response, and pathological processes. Unlike the main cannabinoids which able to activate both receptors, β-caryophyllene is a pharmacologically selective agonist of the peripheral CB2 and exhibits no affinity to CB1 (Chicca et al, 2014). This specific lock and key model of receptor binding is due to the lipophilic nature of β-caryophyllene through ligand π-π stacking interaction (Gertsch et al., 2008). The activation of CB2 receptor is a potential therapeutic of β-caryophyllene for the treatment of inflammation, pain, atherosclerosis, osteoporosis (Gertsch et al., 2008) and has many biological activities, i.e., anticancer and analgesic activity (Fidyt et al., 2016), antioxidant, anti-inflammatory and re-epithelialization mechanisms (Gushiken et al., 2022), improve wound healing (Koyama et al., 2019), and antibacterial activity (Moo et al., 2022). Francomano et al. (2019) have reviewed the biological properties of β-caryophyllene in vitro and in vivo on animals demonstrating a great potential application for various pathological conditions. Further insights and clinical trials are requested for a future human application of β-caryophyllene.


Clove (Syzygium armaticum L.) is another plant species which has a relatively high yield of oil (8.58%) with 27.5% of β-caryophyllene from its flower buds. As in the previous article, clove is a native spice of Indonesia, the presence of β-caryophyllene in clove essential oils is sufficiently high with eugenol as the major compound. In addition, Indonesia is well known as the producer of clove essential oils. PT Mitra Ayu Adipratama produces natural isolate of β-caryophyllene purified by a fractional distillation from the essential oils of clove stems and and clove leaves. Contact PT Mitra Ayu Adipratama for specifications of this natural isolate. The highest grade of β-caryophyllene is achieved with the purity up to 95%.



References

1. Chicca, A., Caprioglio, D., Minassi, A., Petrucci, V., Appendino, G., Taglialatela-Scafati, O., and Gertcsch, J. (2014). Functionalization of β-caryophyllene generates novel polypharmacology in the endocannabinoid system. ACS Chemical Biology, 9: 1499–1507.

2. Fidyt, K., Fiedorowicz, A., Strządała, L., and Szumny, A. (2016). β-Caryophyllene and β-caryophyllene oxide-natural compounds of anticancer and analgesic properties. Cancer Medicine, 5: 3007–3017.

3. Francomano, F., Caruso, A., Barbarossa, A., Fazio, A., Torre, C.L., Ceramella, J., Mallamaci, R., Saturnino, C., Iacopetta, D., and Sinicropi, M.S. (2019). β-Caryophyllene: A sesquiterpene with countless biological properties. Applied Sciences, 9: 5420.

4. Gertsch, J. (2008). Anti-inflammatory cannabinoids in diet – towards a better understanding of CB2 receptor action? Communicative & Integrative Biology, 1: 26–28.

5. Gertsch, J., Leonti, M., Raduner, S., Racz, I., Chen, J.-Z., Xie, X.-Q., Altmann, K.-H., Karsak, M., and Zimmer, A. (2008). Beta-caryophyllene is a dietary cannabinoid. Proceedings of the National Academy of Sciences of the United States of America, 26: 9099–9104.

6. Gushiken, L.F.S., Beserra, F.P., Hussni, M.F., Gonzaga, M.T., Ribeiro, V.P., Souza, P.F., Campos, J.C.L., Massarom T.N.C., Hussni, C.A., Takahira, R.K., Marcato, P.D., Bastos, J.K., and Pellizzon, C.H. (2022). Beta-caryophyllene as an antioxidant, anti-inflammatory and re-epithelialization activities in a rat skin would excision model. Oxidative Medicine and Cellular Longevity, 2022: article ID 9004014.

7. Koyama, S., Purk., A., Kaur, M., Soini, H.A., Novotny, M.V., Davis, K., Kao, C.C., Matsunami, J., and Mescher, A. (2019). Beta-caryophyllene enhances wound healing through multiple routes. PLoS ONE, 14: e0216104.

8. Machado, K.D.C., Islam, M.T., Ali, E.S., Rouf, R., Uddin, S.J., Dev, S., Shilpi, J.A., Shill, M.C., Reza, H.M., Das, A.K., Shaw, S., Mubarak, M.S., Mishra, S.K., and Melo-Cavalcante, A.A.C. (2018). A systematic review on the neuroprotective perspectives of beta-caryophyllene. Phytotherapy Research, 32: 2376–2388.

9. Maffei, M.E. (2020). Plant natural sources of the endocannabinoid (E)-β-caryopjyllene: A systematic quantitative analysis of published literature. International Journal of Molecular Sciences, 21: 6540.

10. Moo, C.-L., Yang, S.-K., Osman, M.-A., Yuswan, M.H., Loh, J.-Y., Lim, W.-M., Lim, S.-H.-E., and Lai, K.-S. (2020). Antibacterial activity and mode of action of β-caryophyllene on Bacillus cereus. Polish Journal of Microbiology, 69: 49–54.

11. Schmitt, D., Levy, R., and Carroll, B. (2016). Toxicological evaluation of β-caryophyllene oil: Subchronic toxicity in rats. International Journal of Toxicology, 35: 558–567.

12. The Good Scents Company. (2023). Beta-caryophyllene. http://www.thegoodscentscompany.com/data/rw1060851.html (accessed at 5 February 2023).

13. Zheljazkov, V.D., Sikora, V., Dincheva, I., Kačániová, M., Astatkie, T., Semerdjieva, I.B., and Latkovic, D. (2020). Industrial, CBD, and wild hemp: How different are their essential oil profile and antimicrobial activity? Molecules, 25: 4631.

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