Isolation and characterization of neolignan derivatives with hepatoprotective and neuroprotective activities from the fruits of Citrus medica L. var. Sarcodactylis Swingle.

The fruit of Citrus medica L. var. sarcodactylis Swingle is a functional food with rich nutrients and medicinal values because of its content of bioactive compounds. A bioactivity-guided chemical investigation from the fruits of C. medica L. var. sarcodactylis Swingle afforded three new benzodioxane neolignans (1-3), three new phenanthrofuran neolignan glycosides (4-6), two new biphenyl-ketone neolignans (7-8), two new 1',7'-bilignan neolignans (9-10), as well as fourteen known neolignan derivatives (11-24), which were isolated and characterized from the fruits of C. medica L. var. sarcodactylis Swingle for the first time. These neolignan derivatives were determined by extensive and comprehensive analyzing NMR, HR-ESI-MS, UV, IR spectral data and compared with the data described in the literature. Among them, compounds 1-3 and 12-13 exhibited moderate hepatoprotective activities to improve the survival rates of HepG2 cells from 46.26 ± 1.90% (APAP, 10 mM) to 67.23 ± 4.25%, 62.87 ± 4.43%, 60.06 ± 6.34%, 56.75 ± 2.30%, 58.35 ± 6.14%, respectively. Additionally, compounds 7-8 and 21-22 displayed moderate neuroprotective activities to raise the survival rates of PC12 cells from 55.30 ± 2.25% to 66.94 ± 3.37%, 70.98 ± 5.05%, 64.64 ± 1.93%, and 62.81 ± 4.11% at 10 μM, respectively. The plausible biogenetic pathway and preliminary structure-activity relationship of the selected compounds were scientifically summarized and discussed in this paper.