The distribution of these components in cannabis varies highly between species and between the different organs of the plant. For instance, the orientin content is higher in the leaves than in the seeds, without signifificant differences between male and female plants and cannabis varieties, whereas the presence of quercetin is higher in male flowers with important variation between male flowers of hemp and drug types . These differences are crucial, knowing that C. sativa can have female and male flowers on the same plant or on separate plants . As a result, cannabis flavonoids have been isolated and detected in different parts of the plant such as flowers, leaves, twigs, and pollen . Remarkable biological activities of cannflavins have been reported. These components can relieve pain up to thirty times more than aspirin . Flavonoids, being known as great antioxidant agents, appear to be responsible of the significant antioxidant potential of hemp oil .
Cannabis stilbenoids can be divided into three main types based on their structure: phenanthrenes, dihydrostilbenes, and spiroindans . These components have been isolated from the cannabis stem, leaves and flower heads . Despite their association with disease resistance and human health , only a few cannabis stilbenoids have been described in the literature with properties that may be beneficial to human health. However, denbinobin, one of the best characterized stilbenoids in cannabis, has been shown to have significant pro-oxidant and pro-apoptotic activity against human leukemia cell lines . Among the dihydrostilbenes, canniprene has attracted some attention as this compound unique to cannabis showed an anti-inflammatory activity. Cannabispirone and cannabispirenone A, the most recurrent spiroindans, have also been studied and antiinflammatory and anti-cancer activities have been reported. Furthermore, a competition in the formation of stilbenoids and flavonoids is suggested in C. sativa metabolism . The lignans isolated from C. sativa belong to two main groups: phenolic amides and lignanamides . Phenolic amides of C. sativa result from the reaction of a phenolic acid and an amine such as tyramine or octopamine. Three major phenolic amides have been recovered from cannabis.
These are, N-trans-coumaroyltyramine detected in the roots of C. sativa,N-trans-feruloyltyramine and N-trans-caffeoyltyramine isolated from cannabis seeds.N-trans-caffeoyloctopamine and N-trans-coumaroyloctopamine have also been identifified recently . Regarding lignanamides, the cannabisin molecules and grossamide have been extracted from cannabis. Lignanamides result from the oxidative coupling of phenolic amides, they also occur in Solanaceae and Papaveraceae families . Lignans are molecules of great interest where they can find applications in the pharmaceutical sector for their various properties. For example, N-trans-caffeoyltyramine and cannabisin A demonstrated a strong antioxidant activity, while anti-inflammatory proper-ties have been reported for grossamide and cannabisin F; cannabisin B showed a cytotoxic activity as well .Based on the articles identified, it can be said that most of the work that has been done using conventional solvent extraction has dealt with the characterization of PC in cannabis. Thus, studies essentially focused on determining the recovery potential of these molecules from cannabis by-products such as seed meals or leaves. The majority of the extractions were conducted at room temperature , though an increase in temperature leads to a higher PC recovery .
Only one study optimized the extraction temperature carried out with a new eco-friendly solvent, an aqueous solution of 2-hydroxypropyl-β- cyclodextrin . Cyclodextrines are hydrotropic agents which increase the solubility of hydrophobic solutes in water . During this work, the performances of absolute methanol, acetone, and their 50% aqueous mixture were compared using hemp leaves as plant material. Their results also demonstrated that acetone was more suitable than methanol for an extraction time of 2 h. However, by increasing the extraction time to 8 and 18 h, pure MeOH results in higher yields , giving 2 times more phenolic content than absolute acetone . Methanol was also found to be more efficient among pure solvent during long maceration of C. sativa leaves . Mourtzinos et al. used an innovative approach by extracting ground hemp meal with an aqueous solution of 2-hydroxypropyl-β-cyclodextrin . Optimal conditions gave a higher phenolic yield in comparison with methanol, ethanol and water. CD have the property to form inclusion complexes with PC resulting in increased contents. The effect of different concentrations of ethanol in water on the extraction yield, TPC and TFC of aerial parts of hemp has been examined by Dirini´c et al. . The results showed that 50% EtOH is the best solvent for PC recovery, with an extraction yield of 15.68 w%, a TPC of 17.05 mg GAE/g dry weight of plant material , and a TFC of 11.20 mg catechin equivalent /g. However, this optimal concentration ofEtOH in water could not be compared to the performance of other solvents such as acetone and MeOH. Cannabis roots have been briefly explored, where 0.01% DW of N–trans-coumaroyltyramine were isolated from an ethanolic extract . Likewise, stilbenoids have been extracted with polar and apolar solvents without any process optimization. A deeper investigation of the extraction might possibly lead to a better yield for these compounds. In most studies, the antioxidant activity of the extracts was evaluated using mainly in vitro assays.In general, PC where correlated to an antioxidant activity .
As a consequence, the extraction parameters had the same effect on the extraction of PC and the resulting antioxidants capacity of the extract. In addition, the extracts have been tested on diverse cell lines, bacteria and fungi, showing antioxidant activiy against human erythrocytes , antimicrobial activity and anti-inflammatory activity.The small number of studies identified demonstrates the need of additional work to assess the efficiency of CSE. Kinetic studies would enable a better definition of the minimum extraction time to reach equilibrium as well as the diffusion rate of the molecules into the solvent. The most used solvents for the extraction are acetone, MeOH, EtOH and their aqueous mixtures . The latter appear to be the most efficient for extracting phenolic compounds from hemp. However, optimization studies should be carried out to investigate the effects of the nature of the solvent, its concentration and the extraction temperature and their interactions on the yield of PC.