Polyphenolics of purple devil fruits potentiate anti-inflammatory action by regulating the expression of inflammatory cytokines and apoptotic signaling molecules evident in extensive and combined experimental models

Abstract

This research investigated the anti-inflammatory effects of Purple Devil fruit’s chloroform extract (SAF-CFE) using LPS-stimulated RAW264.7 macrophage cells and in-vivo histamine- and carrageenan-induced paw edema models as well as membrane stabilization model. Writhing and licking tests for nociception and delayed-type hypersensitivity reaction (DTHR) for immunomodulation were accomplished. SwissADME, ProTox-II, and PASS tests assessed a ligand-receptor binding affinity, and network-pharmacological tests explored the modulatory linked-genes. The MCF-7 cells were strongly inhibited by SAF-CFE, which reduced LPS-induced PGE2, IL-6, TNF-α, and IL-1β expression. The upregulation of proapoptotic (p53 and Bax) and downregulation of antiapoptotic (Bcl-2) genes were observed by SAF-CFE. It significantly reduced inflammatory indexes in anti-inflammatory models. Tris (2,4-di-tert-butylphenyl) phosphate, a natural biometabolite from SAF-CFE, had the highest target receptor-binding and drug-likeness; while NOS2, PTGER1, TRPV1, HMGCR, and TBXAS1 hub genes were highly modulated by the SAF-CFE. The results demonstrate that SAF-CFE could be a functional food source for anti-inflammatory action.