Cannabis compounds exhibit anti-inflammatory activity in vitro in COVID-19-related inflammation in lung epithelial cells and pro-inflammatory activity in macrophages

Abstract

Cannabis sativa is widely used for medical purposes and has anti-inflammatory activity. This study intended to examine the anti-inflammatory activity of cannabis on immune response markers associated with coronavirus disease 2019 (COVID-19) inflammation. An extract fraction from C. sativa Arbel strain (FCBD) substantially reduced (dose dependently) interleukin (IL)-6 and -8 levels in an alveolar epithelial (A549) cell line. FCBD contained cannabidiol (CBD), cannabigerol (CBG) and tetrahydrocannabivarin (THCV), and multiple terpenes. Treatments with FCBD and a FCBD formulation using phytocannabinoid standards (FCBD:std) reduced IL-6, IL-8, C–C Motif Chemokine Ligands (CCLs) 2 and 7, and angiotensin I converting enzyme 2 (ACE2) expression in the A549 cell line. Treatment with FCBD induced macrophage (differentiated KG1 cell line) polarization and phagocytosis in vitro, and increased CD36 and type II receptor for the Fc region of IgG (FcγRII) expression. FCBD treatment also substantially increased IL-6 and IL-8 expression in macrophages. FCBD:std, while maintaining anti-inflammatory activity in alveolar epithelial cells, led to reduced phagocytosis and pro-inflammatory IL secretion in macrophages in comparison to FCBD. The phytocannabinoid formulation may show superior activity versus the cannabis-derived fraction for reduction of lung inflammation, yet there is a need of caution proposing cannabis as treatment for COVID-19.

Comparative Investigation of Composition, Antifungal, and Anti-Inflammatory Effects of the Essential Oil from Three Industrial Hemp Varieties from Italian Cultivation

“…Regarding the Futura 75 variety, the inhibition of Bcl-2 and TGFβ was statistically significant at all tested concentrations, whereas the EOs of the other two cultivars did not significantly alter Bcl-2 and TGFβ gene expression. Recent studies explored the potential of industrial hemp polar extracts as anti-COVID-19 agents, with particular regards to the gene expression inhibition of ACE2 and TMPRSS2 [12,13], which, besides being co-expressed [33], are reputed to play master roles in mediating SARS-CoV-2 virus entry in the human host [15,16]. This is as also summarized by the pathway map hsa05171 deposited on the KEGG PATHWAY Database (https://www.genome.jp/kegg/pathway.html).…”

“…Although the inflorescences have long been considered as waste material to be sold in the dried form for the sole technical use [6], their inclusion as tonics in beverages or flavorings and nutraceuticals in certified foods has been suggested [7]. The valorization of hemp inflorescences is also supported by recent studies, pointing out the use of inflorescences as sources of bioactive extracts and biomolecules, including terpenes, terpenophenolics, and phenolic compounds [8][9][10][11][12][13]. In this regard, inflorescence essential oils (EOs) have been described as effective insecticide, antibacterial, and antiproliferative agents [8,14], whereas the water extracts displayed anti-inflammatory and antityrosinase properties together with intriguing inhibitory effects on the growth of multiple fungi strains, including Candida and dermatophytes species [9][10][11].…”

“…In this regard, inflorescence essential oils (EOs) have been described as effective insecticide, antibacterial, and antiproliferative agents [8,14], whereas the water extracts displayed anti-inflammatory and antityrosinase properties together with intriguing inhibitory effects on the growth of multiple fungi strains, including Candida and dermatophytes species [9][10][11]. Very recently, industrial hemp extracts characterized by different polarities have also been explored as anti-COVID-19 agents, with particular regards to the inhibitory effects on the gene expression of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) [12,13], which are reputed to play master roles in mediating SARS-CoV-2 virus entry in the human host [15,16]. Aiming to enlarge our comprehension about antimicrobial properties of industrial hemp by-products, in the present multidirectional study, we have tested the antimycotic properties of three industrial hemp varieties, namely, Futura 75, Carmagnola selezionata, and Eletta campana, toward several dermatophytes species (Trichophyton mentagrophytes, Trichophyton rubrum, Arthroderma crocatum, Arthroderma quadrifidum, Arthroderma gypseum, Arthroderma curreyi, and Arthroderma insingulare) which are reputed to be involved in skin inflammatory disorders, including hyperpigmentation [17][18][19].…”

“…In parallel, we have evaluated the inhibitory effects of the EOs against the activity of tyrosinase, an enzyme playing a master role in hyperpigmentation [20], and the production of prostaglandin E 2 in an ex vivo toxicity model constituted by isolated mouse skin specimens challenged with hydrogen peroxide [21]. Also considering the recent interest of scientific research toward hemp-deriving extracts as putative anti-COVID-19 agents [12,13], we investigated the influence of the aforementioned EOs on the gene expression of ACE-2 and TMPRSS2 in human H1299 lung adenocarcinoma cell line. In parallel, we studied the effects of the EOs on cell viability and the gene expression of apoptosis regulators, namely transforming growth factor (TGF)-β and B-cell lymphoma 2 (Bcl-2) [22,23], which could be targeted by hemp phytocompounds [24].…”

β-Caryophyllene, A Natural Dietary CB2 Receptor Selective Cannabinoid can be a Candidate to Target the Trinity of Infection, Immunity, and Inflammation in COVID-19

“…Many propositions have been made on the possible therapeutic potential of essential oils-derived phytochemicals, including many terpenes or terpeno-alcoholic compounds, in COVID-19 (Asif et al, 2020;Boukhatem and Setzer, 2020;da Silva et al, 2020;Diniz et al, 2021). Many of the terpene components present in cannabis are widely consumed in food and used in traditional medicine (Anil et al, 2021). Some of these compounds showed potential to modulate the endocannabinoid system, which represents one of the newest therapeutic targets in regard to regulation of innate and adaptive immunity and immunomodulatory and anti-inflammatory properties.…”