Identification of sesquiterpenes from Curcuma longa and its potential for alcoholic liver disease based on FBMN strategy and network pharmacology

To explore the hepaprotective sesquiterpenes from Curcuma longa L., the Feature-Based Molecular Networking (FBMN) strategy was used to annotate the sesquiterpenes in the ethyl acetate fraction of C. longa (EAC) and their MS/MS fragmentation patterns. A total of 30 sesquiterpenes (1−30) were identified from the EAC based on ultra performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) data. Network pharmacology and molecular docking elucidated procurcumenol (24) may targeted the key genes protein kinase B alpha (AKT1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) through regulating the PI3K/AKT signaling pathway in the prevention of alcoholic liver disease (ALD). Furthermore, compound 24, as the main constituent of EAC, exerted anti-inflammatory effects in ALD by downregulating inflammatory factors, such as TNF-α, IL-6. Western blotting analysis showed that it can up-regulate the phosphoinositol-3-kinase (p-PI3K) and p-AKT levels. Taken together, our findings suggested that 24 exerts therapeutic effects on ALD in NCTC1469 cells by suppressing inflammatory and modulating the PI3K/AKT signaling pathway.