Patchouli oil and its main component patchouli alcohol inhibit colorectal cancer by activating ectopic olfactory...

Growing evidence suggests that ectopic olfactory receptors are involved in regulating various physiological functions, including the progression of colorectal cancer (CRC). Patchouli oil, the primary bioactive volatile fraction of Pogostemon cablin (Blanco) Benth (P. cablin), demonstrates potent anti-colorectal cancer activity, though its precise mechanism of action remains incompletely understood.

This project aims to investigate the anti-CRC effects of patchouli oil, with a focus on elucidating its regulatory mechanisms involving the ectopic olfactory receptor OR13G1, the CaMKK2/AMPK signaling pathway, and ferroptosis, and to identify its crucial active constituents.

An AOM/DSS-induced CRC mouse model was used to evaluate patchouli oil's effects on tumor development, inflammation, and pathological changes. Differential protein expression and pathways were analyzed via 4D-FastDIA proteomics. Mechanisms related to OR13G1, CaMKK2/AMPK, and ferroptosis were further examined in CT26 and HCT116 cell lines. Chemical constituents were identified via GC-MS, followed by the quantification of anti-tumor bioactive components. Patchouli alcohol was subsequently identified as the key active ingredient through screening in HCT116 cell models. The in vivo and in vitro efficacy and mechanisms were validated using a mouse model in conjunction with inhibitors/agonists of ferroptosis or relevant signaling pathways.

Patchouli oil significantly improved survival, suppressed tumor growth, attenuated inflammation, and alleviated pathological damage. It up-regulated OR13G1, activated the CaMKK2/AMPK pathway, and induced ferroptosis. In vitro, it inhibited proliferation, migration, and colony formation while promoting ferroptosis. Patchouli alcohol was identified as the crucial anti-CRC constituent, exerting effects through OR13G1-CaMKK2/AMPK axis modulation and ferroptosis induction.

Patchouli oil inhibits CRC progression by upregulating OR13G1, modulating CaMKK2/AMPK signaling, and inducing ferroptosis, with patchouli alcohol as its primary active constituent.