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Low Doses of β-Caryophyllene Reduced Clinical and Paraclinical Parameters of an Autoimmune Animal Model of Multiple Sclerosis: Investigating the Role of CB2 Receptors in Inflammation by Lymphocytes and Microglial

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Multiple Sclerosis (MS) is a prevalent inflammatory disease in which the immune system plays an essential role in the damage, inflammation, and demyelination of central nervous system neurons (CNS). The cannabinoid receptor type 2 (CB2) agonists possess anti-inflammatory effects against noxious stimuli and elevate the neuronal survival rate. We attempted to analyze the protective impact of low doses of β-Caryophyllene (BCP) in experimental autoimmune encephalomyelitis (EAE) mice as a chronic MS model. Immunization of female C57BL/6 mice was achieved through two subcutaneous injections into different areas of the hind flank with an emulsion that consisted of myelin Myelin oligodendrocyte glycoprotein (MOG)35–55 (150 µg) and complete Freund’s adjuvant (CFA) (400 µg) with an equal volume. Two intraperitoneal (i.p.) injections of pertussis toxin (300 ng) were performed on the animals on day zero (immunizations day) and 48 h (2nd day) after injection of MOG + CFA. The defensive effect of low doses of BCP (2.5 and 5 mg/kg/d) was investigated in the presence and absence of a CB2 receptor antagonist (1 mg/kg, AM630) in the EAE model. We also examined the pro/anti-inflammatory cytokine levels and the polarization of brain microglia and spleen lymphocytes in EAE animals. According to our findings, low doses of BCP offered protective impacts in the EAE mice treatment in a CB2 receptor-dependent way. In addition, according to results, BCP decreased the pathological and clinical defects in EAE mice via modulating adaptive (lymphocytes) and innate (microglia) immune systems from inflammatory phenotypes (M1/Th1/Th17) to anti-inflammatory (M2/Th2/Treg) phenotypes. Additionally, BCP elevated the anti-inflammatory cytokine IL-10 and reduced blood inflammatory cytokines. BCP almost targeted the systemic immune system more than the CNS immune system. Thus, a low dose of BCP can be suggested as a therapeutic effect on MS treatment with potent anti-inflammatory effects and possibly lower toxicity.

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

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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…

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A focused review on CB2 receptor-selective pharmacological properties and therapeutic potential of β-caryophyllene, a dietary cannabinoid

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The endocannabinoid system (ECS), a conserved physiological system emerged as a novel pharmacological target for its significant role and potential therapeutic benefits ranging from neurological diseases to cancer. Among both, CB1 and CB2R types, CB2R have received attention for its pharmacological effects as antioxidant, anti-inflammatory, immunomodulatory and antiapoptotic that can be achieved without causing psychotropic adverse effects through CB1R.

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