This study aimed to identify the main chemical components of Panax notoginseng main root extract residues (PNMR-ER) by UPLC-Q-Exactive-Orbitrap-MS/MS technology, and figure out the whitening activity and its underlying molecular mechanism of PNMR-ER by network pharmacology and experimental verification. Based on UPLC-Q-Exactive-Orbitrap-MS/MS technology, 52 components were identified in PNMR-ER. Furthermore, by a visual "component target" network diagram established by network pharmacology, and the main active ingredients with whitening activity selected from PNMR-ER were patchouli alcohol, sucrose, citric acid, ginsenoside Re, ginsenoside F₁, ginsenoside Rh₁, isoquercitrin, ginsenoside Rh₇, 6'-malonyl ginsenoside Rd₁, ginsenoside Rh₄, and PNMR-ER may act on targets such as mitogen-activated protein kinase 3 (MAPK3), cAMP responsive element binding protein 1 (CREB1), and regulate the cAMP signaling pathway and MAPK signaling pathway to exert whitening activity. Finally, experimental verification showed that PNMR-ER and its active ingredients (such as patchouli alcohol, citric acid, ginsenoside Rh₁, isoquercitrin) could inhibit intracellular melanin synthesis and tyrosinase (TYR) activity (P < 0.05, P < 0.01) by using NaOH lysis and L-Dopa oxidation assay. Results of western blot showed that, compared with the model group, PNMR-ER could dose dependently inhibit the protein expression of microphthalmia-associated transcription factor (MITF), TYR, tyrosinase-related protein-1 (TRP-1) and tyrosinase-related protein-2 (TRP-2) in B16F10 cells (P < 0.05, P < 0.01), as well as the phosphorylation of CREB, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases (p38 MAPK) in B16F10 cells (P < 0.05, P < 0.01). Our findings provided research data support for the secondary development of PNMR-ER as a natural whitening substance for application in whitening cosmetics.

"> Panax notoginseng main root extract, residues, UPLC-QE-Orbitrap-MS /MS, Network pharmacology, whitening activity, mechanism of action