Discovery and mechanistic exploration of anti-colorectal cancer bioactive compounds from Perilla frutescens leaf volatile oil by integrating GC-MS, network pharmacology, and pathway validation

Thirty chemical components were identified in the volatile oil of Perilla frutescens leaves. The results of network pharmacology showed that the volatile oil from Perilla frutescens leaves regulates phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) and mitogen activated protein kinase (mitogen activated protein kinase) by acting on targets such as heat shock protein 90 alpha family class A member 1 (HSP90AA1), proto oncogene tyrosine kinase src (SRC), phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA), etc.

The protein kinase (MAPK) signaling pathway plays an anti CRC role. Molecular docking revealed that representative components (perilla aldehyde, celery brain, trans orange blossom tertiary alcohol) have strong affinity for potential anti CRC targets. The cell experiment results showed that trans orange blossom tertiary alcohol and celery brain had significant inhibitory effects on the proliferation of HCT116 cells.

Perilla leaf volatile oil inhibited EGFR mRNA expression (P<0.05) and reduced the phosphorylation of PI3K, Akt, and mechanical target of rapamycin (mTOR) (P<0.05, 0.01, 0.001). In summary, perilla leaves contain abundant volatile oil components and exert anti CRC effects in a dose-dependent manner, which may be related to the inhibition of PI3K/Akt/mTOR.