Novel Insights into the Immunomodulatory Effects of Caryophyllane Sesquiterpenes: A Systematic Review of Preclinical Studies

Abstract

Immunomodulation is a key factor in the homeostasis of organisms, both for physiological and inflammatory conditions. In this context, great attention has been devoted to immunomodulant agents, which can boost or modulate the immune system, thus favoring disease relief. The present systematic review is focused on the immunomodulatory properties of plant-based caryophyllane sesquiterpenes, which are unique natural compounds widely studied due to their multiple and pleiotropic bioactivities. Despite lacking clinical evidence, the selected studies highlighted the ability of these substances, especially β-caryophyllene and α-humulene, to modulate the immune system of both in vitro and in vivo models of disease, such as neurodegenerative and inflammatory-based diseases, cancer, and allergies; moreover, some mechanistic hypotheses have been made too. The present overview suggests a further interest in immunomodulation by caryophyllane sesquiterpenes as a possible novel strategy for immune-based diseases or as an adjuvant treatment and encourages further high-quality studies, using high-purity compounds, to better clarify the mechanisms accounting for these properties and to support a further pharmaceutical development.

Anti-inflammatory effects of α-humulene and β-caryophyllene on pterygium fibroblasts

“…However, our findings are relevant because although the experimental model used presents disadvantages, such as limited cell-cycle divisions and expansion capacity, primary cell cultures show normal cell morphology and maintain many of the biological and functional features observed in vivo. Further studies can analyze β-caryophyllene oxide, in addition to β-caryophyllene and a-humulene, as these sesquiterpenes are frequently found associated in the nature, and there are relates that this compound can also contributes on immune system modulation [23] .…”

The Memory of Hops: Rural Bioculture as a Collective Means of Reimagining the Future

“…Clinical trials reveal that Humulus lupulus phytochemicals like 8-prenylnaringenin, kaempferol, β-caryophyllene, and isoxanthohumol have substantial health benefits, including anti-cancer, anti-inflammatory, and antioxidant effects, significantly influencing the nervous, digestive, and endocrine systems [52][53][54][55][56][57][58][59][60][61]. Hops, used for treating insomnia, menopause, and other conditions [62,63], involve key compounds like isoxanthohumol and β-caryophyllene, with the former, a xanthohumol isomer, acting as a potent agent against menstrual pain and potentially in cancer prevention by affecting oestrogen metabolism [64,65].…”