Abstract
(E)-β-caryophyllene (BCP) is a bicyclic sesquiterpene widely distributed in the plant kingdom, where it contributes a unique aroma to essential oils and has a pivotal role in the survival and evolution of higher plants. Recent studies provided evidence for protective roles of BCP in animal cells, highlighting its possible use as a novel therapeutic tool. Experimental results show the ability of BCP to reduce pro-inflammatory mediators such as tumor necrosis factor-alfa (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), thus ameliorating chronic pathologies characterized by inflammation and oxidative stress, in particular metabolic and neurological diseases. Through the binding to CB2 cannabinoid receptors and the interaction with members of the family of peroxisome proliferator-activated receptors (PPARs), BCP shows beneficial effects on obesity, non-alcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) liver diseases, diabetes, cardiovascular diseases, pain and other nervous system disorders. This review describes the current knowledge on the biosynthesis and natural sources of BCP, and reviews its role and mechanisms of action in different inflammation-related metabolic and neurologic disorders.
Highlights
The scientific interest for natural compounds as novel potential drugs has increased exponentially in the last few years, along with the number of trials and studies on nutraceuticals and herbal extracts, aimed to test their effects on many disorders, including obesity, type II diabetes (T2D), cardiovascular disease (CVD), NAFLD and cancer [1,2,3,4].The sesquiterpene hydrocarbon (E)-β-caryophyllene (BCP) is one of the most studied and promising natural compounds [5,6,7,8,9,10]
In the flowers of the model plant Arabidopsis thaliana, the expression of terpene synthases can be induced by the phytohormones gibberellin (GA) and JA, and their induction increases the expression of TPS21, which encodes an enzyme that converts farnesyl diphosphate into BCP [52,53]
The same in vitro model was already used to prove that dietary 5 or 10 μM BCP inhibits lipid accumulation in adipocytes and 0.15%–0.3% BCP dietary supplementation suppresses in vivo body weight gain and fasting blood glucose levels in high fat diet (HFD)-fed mice [134]. Another in vitro study tested the effects of 0.1–100 μM BCP on osteoblastic mineralization, osteoclastogenesis and adipogenesis in a bone marrow mesenchymal stem cells (MSC) model, demonstrating that BCP significantly suppresses the differentiation of bone marrow cells into adipocytes in a dose-dependent manner [85]
Summary
The scientific interest for natural compounds as novel potential drugs has increased exponentially in the last few years, along with the number of trials and studies on nutraceuticals and herbal extracts, aimed to test their effects on many disorders, including obesity, type II diabetes (T2D), cardiovascular disease (CVD), NAFLD and cancer [1,2,3,4]. The Japanese pepper (Zanthoxylum piperitum) produces BCP in the secretory cavities In this plant, the BCS ZpTPS1 accepts the substrate FPP and is responsible for the biosynthesis of BCP [51]. In the flowers of the model plant Arabidopsis thaliana, the expression of terpene synthases can be induced by the phytohormones gibberellin (GA) and JA, and their induction increases the expression of TPS21, which encodes an enzyme that converts farnesyl diphosphate into BCP [52,53]. The transcript level of PnTPS1 correlated with the predominant BCP biosynthesis in black pepper, defining it as a relevant source of BCP [57]
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