Flavonoids are polyphenolic secondary metabolites commonly with a ketone group and usually yellow pigments from which their name comes (from the Latin flavus, “yellow”). Within flavonoids we can distinguish four main groups: flavonoids, isoflavonoids, neoflavonoids and anthocyanins, but in order not to complicate matters we will refer to them with the common term of flavonoids.
Carnivorous plants, such as Dionaea
muscipula, have a type of flavonoid
in their flowers and leaves that performs a
function of attracting the insects that
serve as food.
The biosynthesis of flavonoids follows the metabolic pathway of phenylpropane, in which coumaryl-SCoA is formed from the amino acid phenylalanine, which, conjugated with malonyl-CoA, creates a group of substances called chalcones that constitute the skeleton for the biosynthesis of all flavonoids and anthocyanins.
This reaction is catalyzed by the enzyme chalcone synthase, which belongs to the polyketide synthase (PKS) family. This PKS family also contains olivetol synthase, which is responsible for the synthesis of cannabinoids.
Flavonoids exert a wide spectrum of functions in plants, mainly as yellow colored pigments in flower petals with the function of attracting pollinating insects, or blue colors (anthocyanins) with the function of capturing certain wavelengths of light, allowing the plant to recognize the photoperiod. Many of these flavonoids are also involved in filtering ultraviolet rays protecting plants. At the cellular level, flavonoids have functions as regulators of the cell cycle. Certain flavonoids are synthesized in the roots of plants and play crucial roles in the establishment of symbiotic or mycorrhizal fungi and, at the same time, in fighting infections caused by pathogenic fungi.
Flavonoids have great pharmacological activities in “in vitro” models such as: antioxidants, anti-inflammatory, antiallergic, antibiotic, antidiarrheal and anticancer. In in vivo models it has not been possible to demonstrate the antioxidant activity, as well as they have not been directly related to the effectiveness against cancer. Some studies seem to indicate that a diet rich in flavonoids may decrease the risk of cancer, but no statistical significance has been found.
In the Cannabis plant we find various flavonoids such as Cannflavin A, Cannflavine B, Cannflavine C, Vitexin, Isovitexin, Apigenin, Kaempferol, Quercetin, Luteolin and Orientine. The distribution of these in the plant varies depending on the flavonoid in question, but flavonoids have not been found in the Cannabis roots. In Cannabis leaves and flowers the total content of flavonoids can be up to 2.5% of the dry weight, while in the seeds and roots it is almost nil. Some studies suggest that the distribution and concentration of flavonoids may be useful as a chemo-taxonomic character in Cannabis. Next we will give a brief description of the therapeutic properties of these flavonoids. Most of these compounds are soluble in water,
Cannflavinas A, B and C
They have anti-inflammatory activity because they exert an inhibitory action on the inflammatory pathway of prostaglandins. This mechanism of action is shared with other terpenes present in the Cannabis plant, providing greater synergy and an anti-inflammatory effect to that exerted by cannabinoids.
Vitexin and Isovitexin
Therapeutic applicability in gout disease by inhibiting thyroid peroxidase.
Kaempferol
It would appear to have antidepressant activity, and a diet rich in kamferol could reduce the risk of cancers and coronary heart disease. Although discussed, Cannabis seems to have some antidepressant action in some cases, so the presence of kaempferol in the plant could provide a synergistic effect with cannabinoids.
Apigenin
It has been shown to reduce the side effects of Cyclosporin A, an immunosuppressant that is administered during organ transplants to prevent organ rejection by the body. Apigenin has also been shown to be one of the few substances with the ability to stimulate the monoamine transporter by altering neurotransmitter levels. Apigenin has recently been shown to act on GABA receptors by exerting anxiolytic and sedative actions. This route of action is common with cannabinoids, so it could influence a possible synergy in the anxiolytic and sedative effects of Cannabis.
Quercytin
It inhibits viral enzymes and may have antiviral action, and it also inhibits the production of prostaglandins, exerting anti-inflammatory effects. Again, we see another compound that can produce synergy with cannabinoids increasing anti-inflammatory action. A recent study seems to provide data on the therapeutic applicability of quercetin in fibromyalgia due to its anti-inflammatory actions. As has been shown, Cannabis has therapeutic effects in cases of fibromyalgia and it is therefore possible that the conjunction of the action of quercetin with that of cannabinoids could be a source of synergy. Likewise, quercitin is an inhibitor of the enzyme Mono Amino Oxidase (MAO) that is involved in the metabolism of neurotransmitters and drugs;
Luteonin and Orientin (luteonin glycoside)
They have pharmacological activities demonstrated in preclinical studies as antioxidants, anti-inflammatories, antibiotics and to fight cancer. Two other compounds that can positively influence possible synergy with cannabinoids.
At the end of this article we have been able to verify that there are other classes of active substances in the Cannabis plant, and that the effects of this could be clearly influenced by the possible synergy provided by the combination of the effects of cannabinoids, terpenes and flavonoids. Thus, we see that the anti-inflammatory effect of the Cannabis plant is possibly the most affected by a probable synergy, because the three groups of compounds converge in similar or complementary mechanisms of action.