Undescribed Phyllocladane-Type Diterpenoids from Hesse ex Rehd. and Their Anti-Neuroinflammatory Activity.

Hesse ex Rehd. is an endemic plant in China and has long been used as a traditional medicine in several provinces. Although the plant has been reported to contain flavonoids, triterpenes, and alkaloids, this study represents the first report of the isolation of phyllocladane-type diterpenoids, a relatively rare class of compounds. In this study, 18 new phyllocladane-type diterpenoids (-) were isolated and structurally elucidated, including eight uncommon 3,4- phyllocladane-type diterpenoids (-) and two unusual phyllocladane-type diterpene dimers (-), along with six known analogues (-). Their structures were elucidated by a comprehensive analysis of 1D and 2D NMR, IR, and HRESIMS data. The absolute configurations were determined by single crystal X-ray diffraction experiments, DFT NMR calculations, and TDDFT ECD calculations. Based on the obtained and reported spectroscopic data, we refined a rule to distinguish phyllocladane-type diterpenoids from their diastereomeric -kaurane-type compounds. Additionally, the isolated compounds were evaluated for their in vitro anti-neuroinflammatory activity against lipopolysaccharide (LPS)-induced inflammation in BV-2 microglial cells. Compounds , , , , , and showed moderate inhibitory activity at the concentration of 20 μM, with compounds and markedly reducing the mRNA levels of the pro-inflammatory cytokines IL-1, IL-6, and TNF- at this concentration.