Norsesquiterpenes from the stems and leaves of Pinellia pedatisecta Schott

A chemical investigation of the stems and leaves of Pinellia pedatisecta Schott afforded forty norsesquiterpenes, including eleven undescribed compounds (1-6, 10-13, and 23) and twenty-nine known analogues. Their structures were elucidated using detailed spectroscopic and comparative literature data analysis. The Mo₂(OAc)₄-induced ECD spectral analysis, DP4+ and ECD analysis were used to determine the absolute configuration of undescribed isolates. In addition, the results of the bioactivity evaluation indicated that components 3-6, 8-10, 12, 14, 15, 17-19, 21-22, 25-29, 33, and 39 significantly improved Aβ_25-35-induced PC-12 cell damage. The network pharmacology results showed that STAT3, NFKB1, HIF1A, EGFR, CASP3 were the correlated targets of compounds 3-6, 10, and 12 against AD, with Ras, PI3K-Akt, and MAPK as the potential signaling pathways. This study provided experimental basis for the treatment of Alzheimer's disease and we will further explore mechanisms in cells and mice to find accurate targets and pathways in the future.