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.
Highlights
Caryophyllane sesquiterpenes are natural substances widely occurring in marine species, fungi, and especially in plants, where mixtures of β-caryophyllene, β-caryophyllene oxide, α-humulene, and isocaryophyllene with minor metabolites are usually found [1]
Out of the 231 records screened, none investigated the effects of isocaryophyllene on the immune system, while 135 papers were focused on essential oils or herbal extracts containing β-caryophyllene, β-caryophyllene oxide and/or α-humulene and 28 were on other substances: these latter papers were excluded as the selection criteria were not accomplished
Among the 67 eligible papers, 19 reports were excluded as other bioactivities of caryophyllane sesquiterpenes were evaluated or their immunomodulating effects were hypothesized (n = 2); 5 studies were excluded for lacking data, and 23 were excluded as they used caryophyllane sesquiterpenes of low purity (
Summary
Caryophyllane sesquiterpenes are natural substances widely occurring in marine species, fungi, and especially in plants, where mixtures of β-caryophyllene, β-caryophyllene oxide, α-humulene, and isocaryophyllene with minor metabolites are usually found [1]. Great attention has been devoted to their bioactivities, with β-caryophyllene being especially studied due to its analgesic, anti-inflammatory, antioxidant, neuroprotective, antidiabetic, and chemopreventive properties; its ability to modulate cannabinoid CB2 receptors has been highlighted too [1]. None of these sesquiterpenes is under clinical evaluation. Some studies have reported the ability of plant-derived caryophyllane sesquiterpenes to affect the immune system, suggesting that their immunomodulation can represent a mechanism that accounts for their bioactivities
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