Table 3.
Effect of small molecule inhibitors on host factors as well as on different cytokines (immunomodulatory functions)
| Sl no | Compound/plant | Properties | Biological/immune-action | Studies in In-vivo models | References |
|---|---|---|---|---|---|
| 01 | Quercetin | Impacts on ACE2 and Furin | a) Gene silencing b) Expression studies c) Transgenic mouse models |
Quercetin affected ACE2 expression. In addition, it was found that it could alter the expression of 98 of 332 (30%) genes which encode human proteins that serve as target for the SARS-CoV-2 | [29] |
| 02 | citral and lemon grass | anti-inflammatory action | Inhibits IL-6, IL-10, TNF-α, IL-4, IFNϒ and IL-1β, either release or production and NLRP3 inflammasome activation via blocking activites of proteins, NF-kB,p65, ATP-induced caspase-1 | In macrophages challenges with LPS-induced mouse ASLN model | [[98], [104]] |
| 03 | Ginsenoside | anti-inflammatory action | Down-regulates IL-6, TNF-α, mRNA expression via blocking the activation of NF-kB | II/R induced lung injury in-vivo | [102] |
| 04 | Withaferin-A | Immunosuppressant | Affect the release of TNF-α, IL-1α, IL-1β, IL-5, IL-3, IL-6, IL-8, IP-10, CCL2, MCP-1, SDF-1α, MIP-1α, MIP-1β and GM-CSF. | ATP-stimulated monocyte-derived THP-1 cells. Also mouse and human islet cells – in vitro. | [77,99] |
| 05 | Kaempferol | anti-inflammatory action | TNF-α, IL-1β, IL-6, IL-8 via inhibiting the activation of PKC θ | human mast cells | [105] |
|
06 |
EGCG |
Regulation of cytokine driven signaling pathways |
Downregulating the IL-6 and IL-6 driven JAK-STAT pathway Similarly by affecting IL-1 driven MAPK pathway Reduced the protein levels of the receptors including CD11a, CXCR3, and CCR2 in human T-lymphocyte cells |
Primary human melanocytes, human T cells or purified CD8+ T cells from PBMC |
[18,60] |
| – | Prevents the cytokine storm and mucous hypersecretion in COVID-19 | [81] | |||
| 07 | Cannabidol | anti-inflammatory and immunosuppressive | These effects are mediated by inhibition of pro-inflammatory cytokine release (e.g. tumor necrosis factor-a, Interferon-gamma, IL-1b, IL-6, and IL-17) and stimulation of several anti-inflammatory cytokine production (e.g. IL-4, IL-5, IL-10, and IL-13). | COVID 19 Patients | https://clinicaltrials.gov/ct2/show/NCT04731116 |
| 08 | FTHC | Only low anti-inflammatory activity | Epithelial cancer cell lines (A549) | [6] | |
| 09 | FCBD | showed reduction of IL-6 and IL-8 secretion levels from lung epithelial cells with an IC50 values of 3.45 and 3.49 μg/mL respectively. | Epithelial cancer cell lines (A549) | [6] |