SARS-CoV2 is known to induce cytokine storms. The exaggerated release of cytokines leads to acute respiratory distress syndrome (ARDS) and multiple organ damage. Recent studies have confirmed that the spike glycoprotein, S-1, is responsible for host immune responses. S-1 subunit causes enhanced release of pro-inflammatory cells and cytokines like interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-12 (IL-12), and tumour necrosis factor (TNFα). Various natural products are known to reduce inflammation. One such product is the edible seed of the plant Garcinia kola (bitter kola).
Garcinoic acid, an analogue of vitamin E, is isolated from G. kola seeds. G. kola and Garcinoic acid are known for their anti-inflammatory properties. The effect of crude seed extract of G. kola and garcinoic acid on S-1 stimulated PBMCs were studied. It was found that G. kola extract and garcinoic acid did not reduce the cell viability.
However, pre-treatment of PBMCs with G. kola for 60 min prior to spike protein S1 stimulation resulted in significant and concentration-dependent reduction in TNFα, IL-6, IL-1β, and IL-8 production. Garcinoic acid showed that spike protein S1-induced increased production of TNFα was significantly reduced by ~22%, 35% and 53% in cells pre-treated with 1.25, 2.5 and 5 µM of the compound. S1- induced increased production of IL-6, IL-1β and IL-8 were also significantly reduced in pre-treated cells. Stimulation of PBMCs with S1- proteins increases expressions of phospho-p65, and phospho-IBα.
However, pre-treating the cells with G. kola extract for 60 min prior to spike protein S1 stimulation resulted in significant reduction of phospho-p65, and phospho-IBα levels. G. kola also reduces the DNA binding capacity of p65 subunit. G.kola and garcinoic acid also reduce NF-𝛋B induced hyperinflammation. High concentrations of G.cola extracts reduced damage in A549 (human lung alveolar epithelial cells) cells when co-cultured with S-1 stimulated PBMCs. G.cola and garcinoic acid both reduced TNFα and IL-6 levels in A549 co-culture. Based on this, G.cola seed extracts and garcinoic acid can be potential anti-inflammatory molecules against SARS-CoV2 induced inflammation.
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