Terpenoids From Leaves of Diospyros kaki and Their Neuroprotective Effects

Ischemic stroke (IS) is a major global cause of morbidity and mortality, highlighting the need for safe and effective treatments. Diospyros kaki leaves are a key ingredient in the clinical drug NaoXinQing and the health beverage persimmon leaf tea, yet their active components remain poorly defined. In this study, 16 compounds, including two new terpenoids (1, 3) and 14 known monoterpenoids (2, 4-16), were isolated from D. kaki leaves using an MS/MS molecular networking approach. Their structures were elucidated via NMR, quantum chemical NMR, and ECD calculations. Neuroprotective screening in OGD/R-injured HT22 cells showed that compounds 7 and 14 exhibited significant activity. They reduced apoptosis and intracellular ROS accumulation. Mechanistic studies, including network pharmacology, molecular docking, molecular dynamics, and Western blotting, confirmed that 7 and 14 protect neurons by inhibiting the JAK2/STAT3 signaling pathway. This work reveals terpenoids from D. kaki leaves as potential anti-ischemic agents, clarifies the active material basis of NaoXinQing and persimmon leaf tea, and supports further development of this medicinal resource.