Flavanol-hydroxytyrosol hybrids and diterpenoids with anti-neuroinflammatory activity by regulating the expressions of NF-κB and IL-1β in vitro from Tripterygium hypoglaucum rhizomes

The study aimed to identify the anti-neuroinflammatory compounds present in the rhizomes of Tripterygium hypoglaucum (Levl.) Hutch while simultaneously elucidating their mechanisms of action against neuroinflammation in vitro. Seven previously undescribed compounds, including a pair of flavanol-hydroxytyrosol hybrids (1–2) and three diterpenoids (5–7), were isolated from T. hypoglaucum rhizomes through sequential chromatographic methods under the guidance of LC-MS analyses. Their structures were determined by HRESIMS, NMR spectroscopic analysis combined with quantum-chemical ECD calculations. The anti-neuroinflammation activities of the isolates on LPS-induced BV-2 cells were evaluated that compounds 1–7 notably suppressed NO production to demonstrate anti-neuroinflammatory effects. Compounds 1–4 attenuated the expression of phosphorylated NF-κB, thereby mitigating NF-κB activation, whereas compounds 5–7 inhibited IL-1β expression to exhibit anti-neuroinflammatory activity. Compound 5 further inhibited the generation of inflammatory factors IL-6, IL-10, and COX-2. The results of molecular docking complemented the in vitro findings related to anti-neuroinflammation, demonstrating that all compounds exhibited strong binding affinity to the associated targets, characterized by high energy values, as well as favorable composite Log P values, NHBD, and NHBR. Collectively, these structurally diverse compounds expand the repertoire of candidate molecules for the development of drugs aimed at treating neurodegenerative diseases.