Comprehensive studies of the anti-inflammatory effect of tetraprenyltoluquinone, a quinone from Garcinia cowa Roxb

Garcinia cowa Roxb. is called asam kandis in West Sumatra. This plant contains several quinone compounds, including tetraprenyltoluquinone (TPTQ). The bioactivity of this compound has been tested as an anticancer agent. However, reports regarding its anti-inflammatory effects are still limited, especially against coronavirus disease (Covid-19).

This study explores the anti-inflammatory effect of TPTQ in silico, in vitro, and in vivo.

In silico testing used the Gnina application, opened via Google Colab. The TPTQ structure was docked with the nuclear factor kappa B (NF-ĸB) protein (PDB: 2RAM). In vitro testing began with testing the cytotoxicity of TPTQ against Raw 264.7 cells, using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) method. A phagocytic activity test was carried out using the neutral red uptake method, and interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) secretion tests were carried out using the enzyme-linked immunosorbent assay (ELISA) method. In vivo, tests were carried out on mice by determining cluster of differentiation 8+ (CD8⁺), natural killer cell (NK cell), and IL-6 parameters, using the ELISA method.

TPTQ has a lower binding energy than the native ligand and occupies the same active site as the native ligand. TPTQ decreased the phagocytosis index and secretion of IL-6 and TNF-α experimentally in vitro. TPTQ showed significant downregulation of CD8⁺ and slightly decreased NK cells and IL-6 secretion in vivo.

The potent inhibitory effect of TPTQ on the immune response suggests that TPTQ can be developed as an anti-inflammatory agent, especially in the treatment of Covid-19.