1.New targeted compounds-biosynthesis of phytocannabinoids.
Ping GAO ; Yuxian CHEN ; Chongrong KE ; Xinwei YANG ; Jianzhong HUANG
Chinese Journal of Biotechnology 2021;37(6):1968-1985
Phytocannabinoids are bioactive terpenoids that are exclusive to Cannabis sativa L. The main pharmacologically active phytocannabinoids are Δ9-tetrahydrocannabinol and cannabidiol, both target endogenous cannabinoid receptors. Δ9-tetrahydrocannabinol and cannabidiol have extensive therapeutic potential due to their participation in many physiological and pathological processes in human body by activating the endocannabinoid system. At present, Δ9-tetrahydrocannabinol, cannabidiol and their analogues or combination preparations are used to treat epilepsy, vomiting in patients with cancer chemotherapy, spasticity in multiple sclerosis and relieve neuropathic pain and pain in patients with advanced cancer. With the further exploration of the application value of Δ9-tetrahydrocannabinol and cannabidiol as well as the increasing demand for standardization of pharmaceutical preparations, it is imminent to achieve large-scale production of Δ9-tetrahydrocannabinol and cannabidiol in the pharmaceutical industry. In this article, pharmacological research progress of phytocannabinoids in recent years, biosynthetic pathways of phytocannabinoids and the mechanism of key enzymes as well as various product development strategies of cannabinoids in pharmaceutical industry are reviewed. By exploring the potential of synthetic biology as an alternative strategy for the source of phytocannabinoids, it will provide a theoretical basis for the research and development of microbial engineering for cannabinoids synthesis, and promote the large-scale production of medicinal cannabinoids.
Cannabidiol
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Cannabinoids/biosynthesis*
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Cannabis
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Humans
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Receptors, Cannabinoid
2.Cannabinoids increase mechanosensitivity of trigeminal ganglion neurons innervating the inner walls of rat anterior chambers via activation of TRPA1.
Yun LING ; Zhuang-Li HU ; Qing-Li MENG ; Peng FANG ; Hai-Xia LIU
Journal of Huazhong University of Science and Technology (Medical Sciences) 2016;36(5):727-731
Our previous study found that some trigeminal ganglion (TG) nerve endings in the inner walls of rat anterior chambers were mechanosensitive, and transient receptor potential ankyrin 1 (TRPA1) was an essential mechanosensitive channel in the membrane. To address the effect of cannabinoids on the mechanosensitive TG nerve endings in the inner walls of anterior chambers of rat eye, we investigated the effect of the (R)-(+)-WIN55, 212-2 mesylate salt (WIN), a synthetic cannabinoid on their cell bodies in vitro. Rat TG neurons innervating the inner walls of the anterior chambers were labeled by 1,1'-dilinoleyl-3,3,3',3'-tetramethylindocarbocyanine, 4-chlorobenzenesulfona (FAST DiI). Whole cell patch clamp was performed to record the currents induced by drugs and mechanical stimulation. Mechanical stimulation was applied to the neurons by buffer ejection. WIN evoked inward currents via TRPA1 activation in FAST DiI-labeled TG neurons. WIN enhanced mechanosensitive currents via TRPA1 activation in FAST DiI-labeled TG neurons. Our results indicate that cannabinoids can enhance the mechanosensitivity of TG endings in the inner walls of anterior chambers of rat eye via TRPA1 activation.
Action Potentials
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drug effects
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Animals
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Anterior Chamber
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drug effects
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innervation
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Cannabinoids
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administration & dosage
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Eye
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drug effects
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innervation
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Neurons
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drug effects
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Patch-Clamp Techniques
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Rats
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Rats, Sprague-Dawley
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TRPA1 Cation Channel
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TRPC Cation Channels
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biosynthesis
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genetics
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Trigeminal Ganglion
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drug effects
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physiology