Eleven new chromane meroterpenoids (1-11), along with 24 known ones (12-35) were isolated from Rhododendron capitatum, a Tibetan medicine. Their structures were determined via extensive spectroscopic methods. The absolute configurations of 1 and 2 were determined by comparison of the experimental and theoretically calculated ECD data. For compounds 3-9, the absolute configurations at the C-2 were assigned according to the empirical chromane helicity rule. The stereochemistry of the chiral alcohols at C-13 in 3 and C-15 in 4 were determined using the Rh2(OCOCF3)4-induced ECD spectra based on the bulkiness rule. Additionally, the absolute configurations of secondary alcohols at C-13 in 8 and 9 were unambiguously established by Mosher's method. Neuroprotection evaluations in vitro and in vivo revealed that compounds 1, 18, and 21 can significantly inhibit the inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) protein expressions. Compound 21 also down-regulated MAPK signal pathway in BV-2 cells. The PC-12 cell damage induced by H2O2 and 6-hydroxydopamine (6-OHDA) was attenuated by compounds 1, 21, and 22, especially for 22. Moreover, compounds 3, 6, 22, 23, and 28 significantly enhanced NGF-induced neurite growth in PC-12 cells. Notably, compound 6 demonstrated the most potent neurite growth promotion with a rate of 22.93 ± 2.24 % at 10 μM, which was approximately 3-fold higher than that induced by nerve growth factor (NGF). In AD Caenorhabditis elegans CL4176 model, compounds 1 and 21 delayed Aβ-induced paralysis and reduced ROS expression levels. These studies provide new potential neuroprotective agents for the prevention and treatment of neurodegenerative diseases.
