# The Origin and Biomedical Relevance of Cannabigerol
## 5 Biological Activity of Cannabigerol  
Although cannabigerol is not one of the psychoactive compounds, it exhibits a number of therapeutic properties, including antibacterial, antifungal, and anti-inflammatory effects; it also prevents cell proliferation [40; 41]. Similar to cannabinoids, it is believed that cannabigerol's complex biological effects are the result of modifications of dependent redox and inflammatory processes, which in turn modulate cellular metabolism. Previously, cannabinoid has been shown to regulate redox balance by reducing the activity of one of the main pro-oxidant factors, i.e., iNOS--activating the membrane receptor PARP-\(\gamma\)--and by modulating the expression of the superoxide dismutase SOD-1, whose activity is increased by pro-inflammatory factors (e.g., lipopolysaccharide, LPS). Consequently, CBG contributes to the inhibition of cell death by shifting the redox balance in the direction of the antioxidant [42]. The phytocannabinoid can also modify inflammatory processes by significantly reducing Ix\(\beta\)-\(\alpha\) phosphorylation, thus reducing the transcriptional activity of the nuclear factor NF\(\kappa\)B, responsible for the transcription of pro-inflammatory cytokines [43], which results in reduced levels of cytokines, including TNF\(\alpha\) and IL-1\(\beta\) (Table 1) [42]. Based on previous analyses of biological activities of phytocannabinoids, some overlap is believed to exist with the activities of endocannabinoids, especially concerning their actions on G-protein-coupled membrane receptors and lipid mediators as well as phospholipid-metabolizing enzymes [44; 45]. Similar to endocannabinoids, phytocannabinoids belonging to the cannabinoid group also modify the activation of CB1 and CB2 cannabinoid receptors as agonists, with CBG also interacting with receptors such as TRPV1 and PPAR [36; 46; 47]. In addition, cannabinoid decreases the activity of FAAH, an enzyme that metabolizes anandamide, thus affecting its levels and biological effects. However, it should be noted that compared to CBD, CBG is less effective as an FAAH activity inhibitor [48; 49]. In contrast, phytocannabinoids from the cannabinoid group, e.g., CBG and CBGA, reduce the activity of DAGL, the enzyme responsible for the biosynthesis of 2-AG and the activities of COX-1 and COX-2, which metabolize PUFAs, mainly arachidonic acid, to lipid mediators [44; 50; 51]. This causes altered levels of both endocannabinoids and other lipid mediators, which by acting on receptors both directly and indirectly modify both redox balance and inflammation [44]. Consequently, chronic exposure to the bioactive constituents of cannabis leads to decreased CB1 receptor activation, resulting in decreased generation of ROS and TNF\(\alpha\)[45]. CBG has a low affinity for CB1 and CB2 receptors (\(\sim\)5-fold and 27-fold lower than \(\Delta^{9}\)-THC), with CBG showing a higher affinity for CB1 [36; 52]. The lower affinity of cannabinoid for CB1 compared to other phytocannabinoids explains the lack of psychotropic effect in the case of this particular phytocannabinoid [53]. Cannabigerol intermediates also show the ability to bind to cannabinoid receptors. It is known that CBGA, like CBG, is an agonist of CB1 and CB2 receptors [21], unlike Olivetol (OL) which acts as an antagonist of CB1 and CB2 receptors [54]. Cannabigerol exhibits a significant activity against several receptors from the TRP superfamily, including acting as a strong TRPA1 agonist (TRP ankyrin type 1) and a weak TRPV1 agonist (TRP vanilloid type 1), and an even weaker agonist of TRPV2 and TRPV4. It is also a potent inhibitor of TRPM8 (TRP melastatin type 8) [36; 49; 55]. In addition, CBG has been shown to act as a potent agonist of \(\alpha\)2 adrenergic receptor and to moderately block 5-HT1A receptors [52; 56], which may explain its biological activity considering its slight affinity for cannabinoid receptors [36].