alt="Illustration of the tautomeric structures of Tetrahydrocannabinol and Cannabicitran."/> 2.19.2 Culture Conditions
Callus cultures were established in C. sativa by using the explants of seedlings and flowers. The fast synthesis of cannabinoids was observed in light, while slow response was achieved in dark. In suspension cultures, the cannabinoids could not be synthesized due to lack of polyketide synthase activity (Raharjo et al. 2006; Wang et al. 2009). By biotransformation, the cannabidiol biotransforms to cannabielsoin under normal growth culture conditions. The cannabidiol was converted to bound cannabielsoin and Δ-9-tetrahydrocannabinol to cannabicoumaronon (Braemer and Paris 1987). The cannabielsoin synthesis biologically catalyzed by the tissue culture technique for the first time was by Hartsel et al. (1983).
Besides the successful establishment of callus cultures of C. sativa by the various authors, the cell culture studies are facing several types of challenges, e.g. slow accumulation of secondary metabolites and improper supply of raw materials. By unifying the microbial and plant metabolic pathways for the production of isoquinoline alkaloids, these problems could be overcome (Sato and Kumagai 2013). By supplementing the culture medium with cadmium and nickel, the accumulation of isoquinoline alkaloids was enhanced by two to three times (Srivastava and Srivastava 2010). Both biotic and abiotic elicitors were used to increase the accumulation of isoquinoline alkaloids. For the enhancement of the production of isoquinoline alkaloids, the tetrahydrocannabinolic acid synthase gene signaling pathway was monitored (Flores-Sanchez et al. 2009). The production of isoquinoline alkaloids was optimized by developing the hairy root cultures. The hemp hypocotyls respond faster to the several strains of Agrobacterium rhizogenes for the increase of accumulation of isoquinoline alkaloids (Wahby et al. 2013).
The cannabinoid production was increased by the UV-B radiation treatment in the cells of C. sativa (Pate 1983). It is clear from findings that the genes of polyketide synthase catalyze the synthesis of olivetolic acid. This has strong similarity with chalcone synthase; it is considered as one of the important UV-B-regulated enzyme (Pacifico et al. 2008; Zhang and Björn 2009). Cannabidiol was synthesized from nonenzymatic decarboxylation of its precursor molecule, cannabidiolic acid. The cannabidiolic acid inhibits the growth of MDA-MB-231 human breast cancer cells. In this mechanism, the growth of these cancer cells was inhibited by cyclic adenosine monophosphate (AMP)-dependent protein kinase A, by clubbing of activated GTPase, Ras homolog gene family member A (RhoA). It was proposed that RhoA signaling pathway activation leads to the inhibition of the mobility of MDA-MB-231 cancer cells (Takeda et al. 2012). Cannabidiol was the most effective in the analgesic activity tested orally and was used topically to antagonize tetradecanoylphorbol acetate-induced erythema of skin. Actually, Δ1-tetrahydrocannabinol and cannabinol were not more effective in analgesic activity; it suggests a structural relationship between analgesic activity and anti-inflammatory activity among the cannabinoids related to their peripheral actions and separate from the central effects of Δ1-tetrahydrocannabinol (Formukong et al. 1988).
References
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