Beta Caryophyllene

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The sesquiterpene β-caryophyllene is a major plant volatile found in large amounts in the essential oils of many different spice and food plants such as cloves (Syzygium aromaticum), oregano (Origanum vulgare L.), cinnamon (Cinnamomum spp.) and black pepper (Piper nigrum I.) (1,2,3).

β-Caryophyllene selectively binds to the CB2 receptor, resulting in anti-inflammatory effects in peripheral tissues (4,5). In vivo, CB receptors are activated by arachidonic acid-derived endocannabinoids, such as 2-arachidonoyl ethanolamine (anandamide or AEA) and 2-arachidonoylglycerol (2-AG) (6,7). CB2 receptor ligands have been shown to inhibit inflammation and fluid buildup (8), exhibit pain-killing effects (9), and play a protective role in the liver (10).

CB2 receptor agonists such as caryophyllene have been shown to reduce inflammation (11), cholesterol buildup (12) and bone weakening (13).

β-caryophyllene and medicinal plants containing β-caryophyllene have demonstrated a range of other useful properties (14), including anti-inflammatory (15), numbing (16), anti-proliferative (17), liver protective (18) and anti-stress (19) activities.

Pain-killing effects of β-caryophyllene have also been observed after local application (20,21,22).

β-Caryophyllene is a known agonist for the PPARγ protein which is protective of several biological systems including gastrointestinal, inflammatory and metabolic systems (23).

 

Beyond generalised gastrointestinal and related organ health, β-Caryophyllene has been found to be cytoprotective and to inhibit gastro-mucosal injuries and inflammation (36,37,38).

β-Caryophyllene has also been demonstrated to encourage bone mineralisation and suppress osteoclastogenesis, making bones more resistant to breakage (39).

β-Caryophyllene also enhances wound-healing by encouraging cell-migration to the damaged site (40,41).

 Key references:

  • CB2 Activity (4,5)

  • Anti-stress (19)

  • Anti-proliferative (17)

  • Anti-inflammatory (15)

  • Anti-bacterial

  • Numbing (16)

  • Gastroprotective (30,31,32)

  • Pain-reducing (9)

  • Liver protective (18,27,28,29)

  • Reduces gut inflammation (11,24,25,26)

  • Kidney protective (33,34,35)

  • Assists with wound repair (40,41)

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1 - Orav A, Stulova I, Kailas T, MQQrisepp M (2004) Effect of storage on the essential oil composition of Piper nigrum L. fruits of different ripening states. J Agric Food Chem 52:2582-2586

2 - Jayaprakasha GK, Jagan Mohan Rao L, Sakariah KK (2003) Volatile constituents from Cinnamomum zeylancium fruit stalks and their antioxidant activities. J Agric Food Chem 51:4344-4348.

3 - Mockute D, Bernotiene G, Judzentiene A (2001) The essential oil of Origanum vulgare L.ssp. vulgare growing wild in vilinius district (Lithuania). Phytochemistry 57:65-69

4 - Mackie K (2006) Cannabinoid receptors as therapeutic targets. Annu Rev Pharmacol Toxicol 46:101-122.

5 - Pertwee RG (2007) The diverse CB (1) and CB (2) receptor pharmacology of three plant cannabinoids: Delta (9)-tetrahydrocannabinol, cannabidiol and Delta (9)-tetrahydrocannabivarin. Br J Pharmacol 53: 199-215

6 - Devane WA, et al. (1992) Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258; 1946-1949

7 - Sugiura T, Waku K (2000) 2-Arachidonoyglycerol and the cannabinoid receptors. Chem Phys Lipids 108:89-106

8 - Iwamura H, Suzuki H, Kaya T, Inaba T (2001) In vitro and in vivo pharmacological characterization of JTE-907, a novel selective ligand for cannabinoid CB2 receptor. J Pharmacol Exp Ther 296:420-425

9 - Ibrahim MM, et al (2005) CB2 cannabinoid receptor activation produces antinociception by stimulating peripheral release of endogenous opiods. Proc Natl Acad Sci USA 102:3093-3098

10 - Batkai S, et al. (2007) Cannabinoid-2 receptor mediates protection against hepatic ischemia/reperfusion injury. FASEB J 21:1788-1800

11 - Kimball ES, Schneider CR, Wallace NH, Hornby PJ (2006) Agonists of cannabinoid receptor 1 and 2 inhibit experimental colitis induced by oil of mustard and by dextran sulfate sodium. Am J Physiol Gastrointest Liver Physiol 291: G364-371

12 - Steffens S, et al. (2007) Low dose oral cannabinoid therapy reduces progression of atherosclerosis in mice. Nature 434:782-786

13 - Ofek O, et al. (2006) Peripheral cannabinoid receptor, CB2, regulates bone mass. Proc Natl Acad Sci USA 103:696-701.

14 - Russo, E.B., 2011. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br. J. Pharmacol. 163,1344-1364

15 - Gertsch J., Leonti, M, Raduner, S., Racz, I., Chen, J.Z., Xie, X.Q., Altmann, K.H., Karsak, M., Zimmer, A., 2008. Beta-caryophyllene is a dietary cannabinoid. Pro. Natl: Acad. Sci. USA 105, 9099-9104.

16 - Ghelardini, C., Galeotti, N., Di Cesare Mannelli, L., Mazzanti, G., Bartolini, A., 2001. Local anaesthetic activity of beta-caryophyllene. Farmaco 56, 387-389.

17 - Legault, J., Pichette, A., 2007. Potentiating effect of beta caryophyllene on anticancer activity of a-humulene, isocaryophyllene and paclitaxel. J. Pharm. Pharmacol. 59, 1643-1647.

Loizzo, MR., Tundis, R., Menichini, F., Saab, A.M., Statti, G.A., Menichini, F., 2008. Antiproliferative effects of essential oils and their major constituents in human renal adenocarcinoma and amelanotic melanoma cells. Cell proliferation 41, 1002-1012.

18 - Calleja, M.A., Vieites, J.M., Montero-Meterdez, T., Torres, M.I., Faus, M.J., Gil, A., 2012. The antioxidant effect of beta caryophyllene protects rat liver from carbon tetrachloride-induced fibrosis by inhibiting hepatic stellate cell activation. Br. J. Nutr. 1, 1-8.

19 - Galdino, P.M., Nascimento, M.V.M., Florentino, I.F., Lino, R.C., Fajemiroye, J.O., Chaibub, B.A., de Paula, J.R., de Lima, T.C.M., Costa, E.A., 2012. The anxiolytic-like effect of an essential oil derived from Spiranthera odoratissima A. St. Hil. leaves and its major component, b-caryophyllene, in male mice. Prog. Neuropsychopharmacol. Biol. Psychiatry 38, 276-284.

20 - Katsuyama, S., Mizoguchi, H., Kuwahata, H., Komatsu, T., Nagaoka, K., Nakamura, H., Bagetta, G., Sakurada, T., Sakurada, S., 2012. Involvement of peripheral cannabinoid and opioid receptors in beta caryophyllene-induced antinociception. Eur. J. Pain 17, 664-675.

21 - Gertsch, J., Leonti, M., Raduner, S., Racz, I., Chen, J.Z., Xie, X.Q., Altmann, K.H., Karsak, M., Zimmer, A., 2008. Beta caryophyllene is a dietary cannabinoid. Proc. Natl. Acad. Sci. USA 105, 9099-9104.

Bento, A., Marcon, R., Dutra, R., Claudino, R., Cola, M., Leite, D., Calixto, J., 2011. Caryophyllene inhibits dextran sulfate sodium-induced colitis in mice through CB2 receptor activation and PPARy pathway. Am. J. Pathol. 178, 1153-1166.

Horvath, B., Mukhopadhyay, P., Kechrid, M., Patel, V., Tanchian, G., Wink, D.A., Gertsch, J., Pacher, P., 2012. B-caryophylllene ameliorates cisplatin-induced nephrotoxicity in a cannabinoid 2 receptor-dependant manner. Free Radic. Biol. Med. 52, 1325-1333.

22 - Katsuyama, S., Mizoguchi, H., Kuwahata, H., Komatsu, T., Nagaoka, K., Nakamura, H., & Sakurada, S. (2013). Involvement of peripheral cannabinoid and opioid receptors in β-caryophyllene-induced antinociception. European journal of pain, 17 (5), 664-675.

23 - Bento, A. F., Marcon, R., Dutra, R. C., Claudino, R. F., Cola, M., Leite, D. F. P., & Calixto, J. B. (2011). β-Caryophyllene inhibits dextran sulfate sodium-induced colitis in mice through CB2 receptor activation and PPARγ pathway. The American journal of pathology, 178 (3), 1153-1166.

24 - Cho, J. Y., Chang, H. J., Lee, S. K., Kim, H. J., Hwang, J. K., & Chun, H. S. (2007). Amelioration of dextran sulfate sodium-induced colitis in mice by oral administration of β-caryophyllene, a sesquiterpene. Life sciences, 80 (10), 932-939.

25 - Bento, A. F., Marcon, R., Dutra, R. C., Claudino, R. F., Cola, M., Leite, D. F. P., & Calixto, J. B. (2011). β-Caryophyllene inhibits dextran sulfate sodium-induced colitis in mice through CB2 receptor activation and PPARγ pathway. The American journal of pathology, 178 (3), 1153-1166.

26 - Cho, J. Y., Choi, E. H., Kang, J. I., Choi, C., & Chun, H. S. (2013). Supercritical fluid extract from maca alleviates colitis induced by dextran sulfate sodium in mice. Food Science and Biotechnology, 22 (3), 859-864.

27 - Chaieb, K., Hajlaoui, H., Zmantar, T., Kahla-Nakbi, A. B., Rouabhia, M., Mahdouani, K., & Bakhrouf, A. (2007). The chemical composition and biological activity of clove essential oil, Eugenia caryophyllata (Syzigium aromaticum L. Myrtaceae): a short review. Phytotherapy Research: An International Journal Devoted to Pharmacological and Toxicological Evaluation of Natural Product Derivatives, 21 (6), 501-506.

28 - Varga, Z. V., Matyas, C., Erdelyi, K., Cinar, R., Nieri, D., Chicca, A., ... & Hasko, G. (2018). β-Caryophyllene protects against alcoholic steatohepatitis by attenuating inflammation and metabolic dysregulation in mice. British journal of pharmacology, 175 (2), 320-334.

29 - Varga, Z. V., Matyas, C., Erdelyi, K., Cinar, R., Nieri, D., Chicca, A., ... & Hasko, G. (2018). β-Caryophyllene protects against alcoholic steatohepatitis by attenuating inflammation and metabolic dysregulation in mice. British journal of pharmacology, 175 (2), 320-334.

30 - Paiva, L. A. F., Rao, V. S. N., Gramosa, N. V., & Silveira, E. R. (1998). Gastroprotective effect of Copaifera langsdorffii oleoresin on experimental gastric ulcer models in rats. Journal of ethnopharmacology, 62 (1), 73-78.

31 - Sharma, C., M Al Kaabi, J., M Nurulain, S., N Goyal, S., Amjad Kamal, M., & Ojha, S. (2016). Polypharmacological properties and therapeutic potential of β-caryophyllene: a dietary phytocannabinoid of pharmaceutical promise. Current pharmaceutical design, 22 (21), 3237-3264.

32 - Lemos, M., Santin, J. R., Mizuno, C. S., Boeing, T., Sousa, J. P. B. D., Nanayakkara, D., ... & Andrade, S. F. D. (2015). Copaifera langsdorffii: evaluation of potential gastroprotective of extract and isolated compounds obtained from leaves. Revista Brasileira de Farmacognosia, 25 (3), 238-245.

33 - Horváth, B., Mukhopadhyay, P., Kechrid, M., Patel, V., Tanchian, G., Wink, D. A., ... & Pacher, P. (2012). β-Caryophyllene ameliorates cisplatin-inducednephrotoxicity in a cannabinoid 2 receptor-dependent manner. Free Radical Biology and Medicine, 52 (8), 1325-1333.

34 - Sharma, C., M Al Kaabi, J., M Nurulain, S., N Goyal, S., Amjad Kamal, M., & Ojha, S. (2016). Polypharmacological properties and therapeutic potential of β-caryophyllene: a dietary phytocannabinoid of pharmaceutical promise. Current pharmaceutical design, 22 (21), 3237-3264.

35 - Loizzo, M. R., Tundis, R., Menichini, F., Saab, A. M., Statti, G. A., & Menichini, F. (2008). Antiproliferative effects of essential oils and their major constituents in human renal adenocarcinoma and amelanotic melanoma cells. Cell Proliferation, 41 (6), 1002-1012.

36 - Tambe, Y., Tsujiuchi, H., Honda, G., Ikeshiro, Y., & Tanaka, S. (1996). Gastric cytoprotection of the non-steroidal anti-inflammatory sesquiterpene, β-caryophyllene. Planta medica, 62 (05), 469-470.

37 - Wright, K. L., Duncan, M., & Sharkey, K. A. (2008). Cannabinoid CB2 receptors in the gastrointestinal tract: a regulatory system in states of inflammation. British journal of pharmacology, 153 (2), 263-270.

38 - Boyar, K. Leaky Gut Syndrome: Cannabinoids and the Endocannabinoid System (ECS) as a therapeutic target.

39 - Yamaguchi, M., & Levy, R. M. (2016). β-Caryophyllene promotes osteoblastic mineralization, and suppresses osteoclastogenesis and adipogenesis in mouse bone marrow cultures in vitro. Experimental and therapeutic medicine, 12(6), 3602-3606.

40 - Koyama, S., Purk, A., Kaur, M., Soini, H. A., Novotny, M. V., Davis, K., & Mescher, A. (2019). Beta-caryophyllene enhances wound healing through multiple routes. PloS one, 14(12), e0216104.

41 - Koyama, S., Purk, A., Kaur, M., Soini, H. A., Novotny, M. V., Davis, K., & Mescher, A. (2019). Synergetic influence of beta-caryophyllene on wound healing. BioRxiv, 611046.