January 1, 2021 Contact Author Assunta Tortora, Marida Bimonte and Annalisa Tito, Arterra Bioscience SpA, Naples, Italy; Claudia Zappelli, Vitalab srl, Naples, Italy Fabio Apone, Ph.D., Arterra Bioscience SpA and Vitalab srl, Naples, Italy
Originating from central Asia, Cannabis sativa is an annual herbaceous flowering plant. Although used medicinally for centuries,1, 2 it recently has experienced a significant resurgence in interest, becoming a buzzword in beauty.3 The main reasons behind this are the richness of chemical compounds produced by the plant and the significant opening up of regulatory markets.4
Cannabis plants contain more than 500 known compounds. In addition to phyto-cannabinoids, the plant contains saccharides, phenolic acids, flavonoids, stilbenes, lignans, fatty acids and terpenes.5-8 Several compounds of these classes are known to impart relevant biological activities in mammalian cells, including modulating appetite, pain sensation, mood, memory, inflammation and energy metabolism.9-10
In relation, plant cell and tissue cultures are an appropriate alternative to whole-plant cultivation both for studying and producing secondary metabolites of cosmetic interest. Moreover, plant cell cultures support the push toward sustainable sourcing methods to reduce land exploitation and minimize impact on the environment. At the same time, they represent a standardized, contaminant-free source of compounds for cosmetic applications on an industrial scale.11 Interestingly, many investigators have established callus cultures from the explants of different C. sativa organs (i.e., roots, hypocotyls, epicotyls, cotyledons, petioles, leaves and immature flower buds); however, scientific reports on secondary metabolite extraction and the biological properties of cannabis culture extracts are limited.
Taken together, this study examines and reports the properties and activities of a C. sativa cell culture extract. For example, cell suspension cultures of the botanical are prepared in a water/ethanol extract and tested for the capacity to modulate neurogenic inflammation in human cells. The term neurogenic inflammation describes the mechanism by which sensory nerves contribute to local inflammation by releasing inflammatory neuropeptides such as the Calcitonin Gene-Related Peptide (CGRP) and Substance P (SP).12 CGRP is the most abundant neuropeptide produced by the sensory nerves in the various skin layers13 and plays a striking role in the pathogenesis of inflammatory skin diseases such as psoriasis and atopic dermatitis.14-16
In the skin, the release of CGRP from the nerve fibers stimulates keratinocytes to produce pro-inflammatory cytokines including interleukins IL-1α, IL-6 and IL-8.17 In macrophages, it induces the release of the pro-inflammatory mediator histamine, which in turn triggers neuropeptide synthesis, thus establishing a bidirectional loop between sensory nerves and epidermis cells.18
While CGRP represents a pro-inflammatory neuropeptide, other types of neuropeptides such as β-endorphin produce an opposite effect, having analgesic and pain-relieving properties.19 β-Endorphins are mainly produced by nerve cells; however, a fully functional β-endorphins/receptor system is also present in skin keratinocytes, where it is involved in epithelization, tissue regeneration and pain relief.20, 21
Described herein are tests to assess the effects of C. sativa cell culture extract on CGRP in neuronal cells, and on histamine production in CGRP-treated macrophages. In addition, the extract’s activity is measured on the expression of genes involved in skin inflammation, such as those of the pro-inflammatory cytokines IL-1α, IL-8 and TNFα, and of the β-endorphin precursor POMC. Lastly, clinical studies examine its potential to soothe skin and reduce erythema.
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