Schadich Ermin, Kaczorová Dominika, Béres Tibor, Džubák Petr, Hajdúch Marián, Tarkowski Petr, Ćavar Zeljković Sanja
Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czech Republic.
Czech Advanced Technology and Research Institute (CATRIN), Palacký University, Olomouc, Czech Republic.
Arch Pharm (Weinheim). 2025 Jan;358(1):e2400607. doi: 10.1002/ardp.202400607. Epub 2024 Nov 14.
This study deals with the comprehensive phytochemical composition and antiviral activity against SARS-CoV-2 of acidic (non-decarboxylated) and neutral (decarboxylated) ethanolic extracts from seven high-cannabidiol (CBD) and two high-Δ-tetrahydrocannabinol (Δ-THC) Cannabis sativa L. genotypes. Their secondary metabolite profiles, phytocannabinoid, terpenoid, and phenolic, were determined by LC-UV, GC-MS, and LC-MS/MS analyses, respectively. All three secondary metabolite profiles, cannabinoid, terpenoid, and phenolic, varied significantly among cannabinoid extracts of different genotypes. The dose-response analyses of their antiviral activity against SARS-CoV-2 showed that only the single predominant phytocannabinoids (CBD or THC) of the neutral extracts exhibited antiviral activity (all IC < 10.0 μM). The correlation matrix between phytoconstituent levels and antiviral activity revealed that the phenolic acids, salicylic acid and its glucoside, chlorogenic acid, and ferulic acid, and two flavonoids, abietin, and luteolin, in different cannabinoid extracts from high-CBD genotypes are implicated in the genotype-distinct antagonistic effects on the predominant phytocannabinoid. On the other hand, these analyses also suggested that the other phytocannabinoids and the flavonoid orientin can enrich the extract's pharmacological profiles. Thus, further preclinical studies on cannabinoid extract formulations with adjusted non-phytocannabinoid compositions are warranted to develop supplementary antiviral treatments.
本研究涉及七种高含量大麻二酚(CBD)和两种高含量Δ-四氢大麻酚(Δ-THC)的大麻(Cannabis sativa L.)基因型的酸性(非脱羧)和中性(脱羧)乙醇提取物的综合植物化学成分及其对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的抗病毒活性。分别通过液相色谱-紫外(LC-UV)、气相色谱-质谱(GC-MS)和液相色谱-串联质谱(LC-MS/MS)分析确定了它们的次生代谢产物谱,包括植物大麻素、萜类化合物和酚类化合物。在不同基因型的大麻素提取物中,大麻素、萜类化合物和酚类这三种次生代谢产物谱均有显著差异。它们对SARS-CoV-2的抗病毒活性的剂量反应分析表明,只有中性提取物中的单一主要植物大麻素(CBD或THC)表现出抗病毒活性(所有IC<10.0μM)。植物成分水平与抗病毒活性之间的相关矩阵显示,来自高CBD基因型的不同大麻素提取物中的酚酸、水杨酸及其糖苷、绿原酸和阿魏酸,以及两种黄酮类化合物枞皮素和木犀草素,与对主要植物大麻素的基因型特异性拮抗作用有关。另一方面,这些分析还表明,其他植物大麻素和黄酮类化合物东方蓼黄素可以丰富提取物的药理特性。因此,有必要对非植物大麻素成分经过调整的大麻素提取物配方进行进一步的临床前研究,以开发辅助抗病毒治疗方法。