Ionones are a small group of terpenoid ketones found in rose essential oil. Among these are alpha and beta ionone, isomers with related but distinct physiological effects.
Alpha ionone has been shown to activate the PKA-CREB pathway and in turn stimulate myogenesis and prevent muscular atrophy in response to a high-fat diet, leading to increased skeletal muscle mass and strength (1). Further, in models of solar UVB-induced skin damage, alpha ionone is able to increase hyaluronic acid and collagen synthesis via enhanced fibroblast activity, thus protecting against sun-damage and wrinkles (12).
Beta ionone by comparison has demonstrated an anti-proliferative role, particularly via regulating MAPKs in breast tissue, with up to 84% inhibition of deleterious cell proliferation (2,3). This effect is quite specific, not relying on typical pathways such as HMG-CoA reductase inhibition (4). Beta ionone has also been demonstrated to inhibit the deleterious proliferation of other cell types via upregulation of tissue inhibitors of metalloproteinases (5). Metalloproteinases are required to break down extracellular matrix, making room for the formation of new blood vessels, and as such their inhibition induced by beta ionone limits deleterious cell replication (6).
The anti-proliferative effect of beta ionone also extends to the liver, where the compound protects against DNA damage (7), and in over-proliferating gastric cells where apoptosis (programmed cell recycling) is induced in response to beta ionone (8).
Beta ionone is also anti-inflammatory, significantly attenuating lipopolysaccharide-induced nitric oxide, prostaglandin E2 and tumor necrosis factor-α release (9).
Beta ionone's anti-proliferative effect, particularly in prostate tissue, is also linked to its activation of the OR51E2 olfactory receptor, further exemplifying the importance of odorant compounds on affecting the physiology of tissues other than those used for smelling, as discussed in the cedrine article (10). This effect is further enhanced via beta ionone's activation of the 'prostate-specific G protein-coupled receptor', which specifically blocks the androgen receptor from translocating to the nucleus in prostate tissue (11).
Key references:
Alpha Ionone
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Protects skeletal muscle (1)
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Protects collagen and hyaluronic acid against sun damage in skin, reducing wrinkle formation (12)
Beta Ionone
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Antiproliferative in many tissues, especially breast and prostate (2,3,4,5,8,10,11)
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Protects DNA from damage (7,8)
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Anti-inflammatory (9)
Alpha Ionone
Beta Ionone
1 - Tong, T., Kim, M., & Park, T. (2019). α-Ionone attenuates high-fat diet-induced skeletal muscle wasting in mice via activation of cAMP signaling. Food & function, 10(2), 1167-1178.
2 - Liu, J. R., Yang, Y. M., Dong, H. W., & Sun, X. R. (2005). Effect of beta-ionone in human mammary cancer cells (Er-) by MAPK pathway. Wei sheng yan jiu= Journal of hygiene research, 34(6), 706.
3 - Liu, J. R., Sun, X. R., Dong, H. W., Sun, C. H., Sun, W. G., Chen, B. Q., & Yang, B. F. (2008). β‐Ionone suppresses mammary carcinogenesis, proliferative activity and induces apoptosis in the mammary gland of the Sprague‐Dawley rat. International journal of cancer, 122(12), 2689-2698.
4 - Duncan, R. E., Lau, D., El-Sohemy, A., & Archer, M. C. (2004). Geraniol and β-ionone inhibit proliferation, cell cycle progression, and cyclin-dependent kinase 2 activity in MCF-7 breast cancer cells independent of effects on HMG-CoA reductase activity. Biochemical pharmacology, 68(9), 1739-1747.
5 - Liu, J. R., Yang, B. F., Chen, B. Q., Yang, Y. M., Dong, H. W., & Song, Y. Q. (2004). Inhibition of β-ionone on SGC-7901 cell proliferation and upregulation of metalloproteinases-1 and-2 expression. World journal of gastroenterology, 10(2), 167.
6 - Quintero-Fabián, S., Arreola, R., Becerril-Villanueva, E., Torres-Romero, J. C., Arana-Argáez, V. E., Lara-Riegos, J., & Alvarez Sanchez, M. E. (2019). Role of matrix metalloproteinases in angiogenesis and cancer. Frontiers in oncology, 9, 1370.
7 - de Moura Espíndola, R., Mazzantini, R. P., Ong, T. P., de Conti, A., Heidor, R., & Moreno, F. S. (2005). Geranylgeraniol and β-ionone inhibit hepatic preneoplastic lesions, cell proliferation, total plasma cholesterol and DNA damage during the initial phases of hepatocarcinogenesis, but only the former inhibits NF-κB activation. Carcinogenesis, 26(6), 1091-1099.
8 - Liu, Q., Dong, H. W., Sun, W. G., Liu, M., Ibla, J. C., Liu, L. X., & Liu, J. R. (2013). Apoptosis initiation of β-ionone in SGC-7901 gastric carcinoma cancer cells via a PI3K-AKT pathway. Archives of toxicology, 87(3), 481-490.
9 - Kang, C. H., Jayasooriya, R. G. P. T., Choi, Y. H., Moon, S. K., Kim, W. J., & Kim, G. Y. (2013). β-Ionone attenuates LPS-induced pro-inflammatory mediators such as NO, PGE2 and TNF-α in BV2 microglial cells via suppression of the NF-κB and MAPK pathway. Toxicology in Vitro, 27(2), 782-787.
10 - Neuhaus, E. M., Zhang, W., Gelis, L., Deng, Y., Noldus, J., & Hatt, H. (2009). Activation of an olfactory receptor inhibits proliferation of prostate cancer cells. Journal of Biological Chemistry, 284(24), 16218-16225.
11 - Xie, H., Liu, T., Chen, J., Yang, Z., Xu, S., Fan, Y., & He, D. (2019). Activation of PSGR with β-ionone suppresses prostate cancer progression by blocking androgen receptor nuclear translocation. Cancer letters, 453, 193-205.
12 - Tong, T., Park, J., Moon, Y., Kang, W., & Park, T. (2019). α-Ionone protects against UVB-induced photoaging in human dermal fibroblasts. Molecules, 24(9), 1804.