6,8-Di-C-methyl-flavonoids with neuroprotective activities from Rhododendron fortunei

Abstract Six 6,8-di- C -methyl-flavonoids, (2 R ,3 R )-6,8-di- C -methyl-5,7,4′-trihydroxyflavanonol 7- O - β - d -gluco-pyranoside ( 1 ), (2 R ,3 R )-6,8-di- C -methyl-5,7,4′-trihydroxyflavanonol 7- O - β - d -xylopyranosyl(1 → 6)- β - d -glucopyranoside ( 2 ), 6,8-di- C -methylkaempferol 7- O - β - d -glucopyranoside ( 3 ), (2 R )-farrerol ( 4a ), (2 R/ 2 S )-farrerol 7- O - β - d -glucopyranoside ( 5 ), and (2 R/ 2 S )-farrerol 7- O - β - d -xylopyranosyl(1 → 6)- β - d -glucopyranoside ( 6 ), and four known analogues, farrerol ( 4b ), (2 R ,3 R )-6,8-di- C -methyldihydrokae-mpferol ( 7 ), 6,8-di- C -methylkaempferol 7- O - β - d -glucopyranoside ( 8 ), and 6,8-di- C -methylkaempferol ( 9 ), were isolated from the twigs and leaves of Rhododendron fortunei . The structures of compounds 1 – 9 were determined by spectroscopic analyses (HRESIMS, 1D and 2D NMR, and CD) and chemical methods. Compounds 1 – 9 were evaluated for their neuroprotective effects on the human neuroblastoma SH-SY5Y cells apoptosis induced by hydrogen peroxide (H 2 O 2 ) and amyloid β peptide (A β ), respectively. Compounds 1 – 3 and 5 – 9 exhibited significant neuroprotective effects against H 2 O 2 -induced SH-SY5Y cell apoptosis, and compound 8 exhibited the strongest activity with a improvement of cell viability by about 30% at the concentration of 10 μM. Compounds 1 – 9 showed significant neuroprotective effects against A β -induced SH-SY5Y cell apoptosis.