High-CBD Cannabis Extracts Inhibit the Expression of Proinflammatory Factors Via MiRNA-mediated Silencing in Human Small Intestinal Epithelial Cells

Overview

Journal Heliyon

Specialty Social Sciences

Date 2023 Sep 4

PMID 37664748

Authors

Bo Wang

Dongping Li

Anna Fiselier

Igor Kovalchuk

Olga Kovalchuk

Affiliations

Soon will be listed here.

Abstract

The incidence of chronic inflammatory disorders and autoimmune diseases is rapidly growing. To date, the COVID-19 pandemic caused by SARS-CoV-2 has killed over 6,209,000 people globally, while no drug has been proven effective for the disease. Screening natural anti-inflammatory compounds for clinical application has drawn much attention. In this study, we showed that high-CBD cannabis extracts #1, #5, #7, #169, and #317 suppressed the levels of expression of proinflammatory cyclooxygenase 2 (COX2) and increased the expression of the anti-inflammatory suppressor of cytokine signaling 3 (SOCS3) in human small intestinal epithelial cells (HSIEC) in TNFα/IFNγ-triggered inflammation. We revealed that these extracts, with the exception of extract #169, also profoundly attenuated induction of proinflammatory cytokines interleukin-6 (IL-6) and/or IL-8 proteins through miR-760- and miR-302c-3p-mediated silencing. The prevalent components in extracts #1 and #7 influenced the levels of IL-8 both individually as well as in combination with each other. However, the high-dose cannabis extracts displayed an inhibitory effect in the growth of HSIEC cells. These results show that our high-CBD cannabis extracts decrease the levels of proinflammatory molecules COX2, IL-6, and IL-8 via transcriptional suppression or miRNA-mediated silencing, highlighting their potential against COVID-19-associated cytokine storm syndrome.

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References

Pan H, Peto R, Henao-Restrepo A, Preziosi M, Sathiyamoorthy V, Abdool Karim Q . Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results. N Engl J Med. 2020; 384(6):497-511. PMC: 7727327. DOI: 10.1056/NEJMoa2023184. View

Roumier M, Paule R, Vallee A, Rohmer J, Ballester M, Brun A . Tocilizumab for Severe Worsening COVID-19 Pneumonia: a Propensity Score Analysis. J Clin Immunol. 2020; 41(2):303-314. PMC: 7666405. DOI: 10.1007/s10875-020-00911-6. View

Sun Y, Tang X, Half E, Kuo M, Sinicrope F . Cyclooxygenase-2 overexpression reduces apoptotic susceptibility by inhibiting the cytochrome c-dependent apoptotic pathway in human colon cancer cells. Cancer Res. 2002; 62(21):6323-8. View

Ghosn L, Chaimani A, Evrenoglou T, Davidson M, Grana C, Schmucker C . Interleukin-6 blocking agents for treating COVID-19: a living systematic review. Cochrane Database Syst Rev. 2021; 3:CD013881. PMC: 8406988. DOI: 10.1002/14651858.CD013881. View

Nugroho C, Suryantoro S, Yuliasih Y, Rosyid A, Asmarawati T, Andrianto L . Optimal use of tocilizumab for severe and critical COVID-19: a systematic review and meta-analysis. F1000Res. 2021; 10:73. PMC: 7953915. DOI: 10.12688/f1000research.45046.1. View

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

Coperchini F, Chiovato L, Croce L, Magri F, Rotondi M . The cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system. Cytokine Growth Factor Rev. 2020; 53:25-32. PMC: 7211650. DOI: 10.1016/j.cytogfr.2020.05.003. View

Gupta R, DuBois R . Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2. Nat Rev Cancer. 2002; 1(1):11-21. DOI: 10.1038/35094017. View

Wang B, Kovalchuk A, Li D, Rodriguez-Juarez R, Ilnytskyy Y, Kovalchuk I . In search of preventive strategies: novel high-CBD extracts modulate ACE2 expression in COVID-19 gateway tissues. Aging (Albany NY). 2020; 12(22):22425-22444. PMC: 7746344. DOI: 10.18632/aging.202225. View

10.

Chhabra J, Chattopadhyay B, Paul B . SOCS3 dictates the transition of divergent time-phased events in granulocyte TNF-α signaling. Cell Mol Immunol. 2013; 11(1):105-6. PMC: 4076751. DOI: 10.1038/cmi.2013.36. View

11.

Lopes Salles E, Khodadadi H, Jarrahi A, Ahluwalia M, Paffaro Jr V, Costigliola V . Cannabidiol (CBD) modulation of apelin in acute respiratory distress syndrome. J Cell Mol Med. 2020; 24(21):12869-12872. PMC: 7686987. DOI: 10.1111/jcmm.15883. View

12.

Dzobo K, Chiririwa H, Dandara C, Dzobo W . Coronavirus Disease-2019 Treatment Strategies Targeting Interleukin-6 Signaling and Herbal Medicine. OMICS. 2020; 25(1):13-22. DOI: 10.1089/omi.2020.0122. View

13.

Tian X, Liu H, Xiang F, Xu L, Dong Z . β-Caryophyllene protects against ischemic stroke by promoting polarization of microglia toward M2 phenotype via the TLR4 pathway. Life Sci. 2019; 237:116915. DOI: 10.1016/j.lfs.2019.116915. View

14.

Gupta S, Wang W, Hayek S, Chan L, Mathews K, Melamed M . Association Between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19. JAMA Intern Med. 2020; 181(1):41-51. PMC: 7577201. DOI: 10.1001/jamainternmed.2020.6252. View

15.

Nagarkatti P, Pandey R, Rieder S, Hegde V, Nagarkatti M . Cannabinoids as novel anti-inflammatory drugs. Future Med Chem. 2010; 1(7):1333-49. PMC: 2828614. DOI: 10.4155/fmc.09.93. View

16.

Wang B, Li D, Fiselier A, Kovalchuk I, Kovalchuk O . New AKT-dependent mechanisms of anti-COVID-19 action of high-CBD Cannabis sativa extracts. Cell Death Discov. 2022; 8(1):110. PMC: 8913855. DOI: 10.1038/s41420-022-00876-y. View

17.

Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y . Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis. 2020; 71(15):762-768. PMC: 7108125. DOI: 10.1093/cid/ciaa248. View

18.

Ruhaak L, Felth J, Karlsson P, Rafter J, Verpoorte R, Bohlin L . Evaluation of the cyclooxygenase inhibiting effects of six major cannabinoids isolated from Cannabis sativa. Biol Pharm Bull. 2011; 34(5):774-8. DOI: 10.1248/bpb.34.774. View

19.

Romano B, Pagano E, Orlando P, Capasso R, Cascio M, Pertwee R . Pure Δ-tetrahydrocannabivarin and a Cannabis sativa extract with high content in Δ-tetrahydrocannabivarin inhibit nitrite production in murine peritoneal macrophages. Pharmacol Res. 2016; 113(Pt A):199-208. DOI: 10.1016/j.phrs.2016.07.045. View

20.

Zagzoog A, Mohamed K, Kim H, Kim E, Frank C, Black T . In vitro and in vivo pharmacological activity of minor cannabinoids isolated from Cannabis sativa. Sci Rep. 2020; 10(1):20405. PMC: 7684313. DOI: 10.1038/s41598-020-77175-y. View