Wang Bo, Li Dongping, Fiselier Anna, Kovalchuk Igor, Kovalchuk Olga
Department of Biological Sciences, University of Lethbridge, Lethbridge, Alberta, T1K 3M4, Canada.
Pathway Rx Inc., Calgary, Alberta, T3H 4Z2, Canada.
Heliyon. 2023 Aug 5;9(8):e18817. doi: 10.1016/j.heliyon.2023.e18817. eCollection 2023 Aug.
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.
慢性炎症性疾病和自身免疫性疾病的发病率正在迅速上升。截至目前，由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的新冠疫情已在全球造成超过620.9万人死亡，而尚无药物被证明对该疾病有效。筛选用于临床的天然抗炎化合物备受关注。在本研究中，我们发现高CBD大麻提取物#1、#5、#7、#169和#317在肿瘤坏死因子α/干扰素γ引发的炎症中，可抑制人小肠上皮细胞（HSIEC）中促炎环氧化酶2（COX2）的表达水平，并增加抗炎细胞因子信号传导抑制因子3（SOCS3）的表达。我们还发现，除提取物#169外，这些提取物还通过miR-760和miR-302c-3p介导的沉默作用，显著减弱促炎细胞因子白细胞介素-6（IL-6）和/或白细胞介素-8蛋白的诱导。提取物#1和#7中的主要成分单独或相互组合均会影响IL-8水平。然而，高剂量大麻提取物对HSIEC细胞的生长具有抑制作用。这些结果表明，我们的高CBD大麻提取物通过转录抑制或miRNA介导的沉默作用降低了促炎分子COX2、IL-6和IL-8的水平，凸显了它们对抗新冠相关细胞因子风暴综合征的潜力。
