Isoprenylated flavonoids from the root bark of Morus alba and their hepatoprotective and neuroprotective activities

A new isoprenylated flavonoid, 2S-5,7,2′,4′-tetrahydroxy-3′,5′-di-(γ,γ-dimethylallyl)flavanone, sanggenol Q (1), along with seven known isoprenylated flavonoids, sanggenol A (2), sanggenol L (3), kuwanon T (4), cyclomorusin (5), sanggenon F (6), sanggenol O (7), and sanggenon N (8), three known Diels-Alder type adducts, sanggenon G (9), mulberrofuran G (10), and mulberrofuran C (11), and a known benzofuran, moracin E (12), were isolated from the root bark of Morus alba using silica gel, ODS, and Sephadex LH-20 column chromatography. Chemical structures were determined based on spectroscopic data analyses including NMR, MS, CD, and IR. For the first time, compounds 1 and 7 were isolated from the root bark of M. alba. All compounds were evaluated for hepatoprotective activity on t-BHP-induced oxidative stress in HepG2 cells and neuroprotective activity on glutamate-induced cell death in HT22 cells. Compounds 1, 4, 8, 10, and 11 showed protective effects on t-BHP-induced oxidative stress with EC₅₀ values of 6.94 ± 0.38, 30.32 ± 6.82, 23.45 ± 4.72, 15.31 ± 2.21, and 0.41 ± 0.48 μM, respectively, and compounds 1, 2, 10, 11, and 12 showed protective effects on glutamate-induced cell death with EC₅₀ values of 5.54 ± 0.86, 34.03 ± 7.71, 19.71 ± 0.71, 16.50 ± 7.82, and 1.02 ± 0.13 μM, respectively.