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Programmed cell death protein 1 (PD-1) is one of the immune checkpoints and is known to be involved with immunological self-tolerance. PD-1 plays a suppressive role toward T cell activity in peripheral tissues and in the tumor microenvironment. Cytokines from the tumor microenvironment such as interferon-gamma (IFN-γ) induce PD-1 ligand-1 (PD-L1), and the PD-1 ligands are found on most cancers. Interaction of PD-1 and PD-L1 is closely associated with impaired T cell functions, allowing cancer cells to escape immune surveillance. Therefore, reversal of T cell dysfunction through blocking of PD-1/PD-L1 is considered an important strategy for enhancing immunity to cancer.
Geranii Herba extract (GHE) is a novel candidate agent for PD-1/PD-L1 inhibition. GHE was reported to contain various phytochemicals including flavonoids and phenolic compounds. Among them, kaempferitrin (KI, kaempferol-3,7-dirhamnoside) was identified as one of the abundant compounds of GHE. KI has been known to be hydrolyzed to kaempferol (KO) and kaempferol 7-O-rhamnoside (KR) in the human intestine by the gut microbiome.