New natural pro-inflammatory cytokines (TNF- α, IL-6 and IL-1β) and iNOS inhibitors identified from Penicillium polonicum through in vitro and in vivo studies

Int Immunopharmacol. 2023 Apr;117:109940. doi: 10.1016/j.intimp.2023.109940. Epub 2023 Mar 10.ABSTRACTOverexpression of pro-inflammatory cytokines and iNOS have been found to be concomitant with several chronic inflammatory diseases and hence targeting their inhibition would be a useful therapy for inflammation. In view of this, study on discovery of natural pro-inflammatory cytokines inhibitory lead molecules from Penicillium polonicum, an endophytic fungus isolated from the fresh fruits of Piper nigrum was performed. When the culture broth extract of P. polonicum (EEPP) was subjected to LPS-induced cytokines expression (ELISA in RAW 264.7 cells), it exhibited inhibition of TNF-α, IL-6 and IL-1β and this encouraged us to do chemical investigation on EEPP to explore the bioactive components. Four compounds isolated and characterised as 3,5-di-tert-butyl-4-hydroxy-phenyl propionic acid (1), 2,4-di-tert-butyl phenol (2), indole 3-carboxylic acid (3) and tyrosol (4) were tested for their effect on the production of TNF-α, IL-1β and IL-6 in RAW 264.7 cells (ELISA). All the compounds exhibited a highly significant (P < 0.0001) inhibition effect, particularly against IL-1β (IC50: 4-0.91 μM, 1-2.81 μM, 3-4.38 μM, and 2-5.54 μM). Tyrosol (4) was most active with IC50 values of 0.91, 2.67 and 4.60 μM against IL-1β, IL-6 and TNF-α, respectively. On observing the potential activity of the compounds, two compositions C1 and C2 were prepared by mixing equimolar concentratio...
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Source Type: research