Lignans in schisandra have been linked to various effects including hepatoprotective (10), antiproliferative, and estrogenic activities (27). In vitro, schisantherins downregulated pro-inflammatory cytokines and mediators by blocking NF-κB and MAPK signaling (1). In animal toxicity models, pretreatment with schisandra lignans increased DT-diaphorase activity associated with enhanced menadione elimination (10), and provided hepatoprotection and improved Phase I metabolism 24 h after carbon tetrachloride exposure (28) (29). Other animal studies suggest that schisandra increases hepatic glutathione levels and glucose-6-phosphate and glutathione reductase activities (17). It also inhibits α-glucosidase activity, thereby lowering postprandial blood glucose levels (19), and can improve cardiac function after ischemic injury by downregulating inflammatory cytokines, activating the eNOS pathway, inhibiting apoptosis, and enhancing cell proliferation (12). In amyloid-beta-induced memory impairment, schisandra increased superoxide dismutase and glutathione peroxidase activities and glutathione levels in the cerebral cortex and hippocampus of mice while decreasing malondialdehyde and oxidized glutathione (14). It also enhanced endurance and metabolism in the skeletal muscle of exercised rats by upregulating PGC-1α expression (13).
α-iso-cubebenol in schisandra inhibited iNOS and COX-2 expression in lipopolysaccharide-stimulated macrophages (6) and reversed septic shock by triggering protective downstream signaling pathways in a mouse sepsis model (15).The anthocyanin cyanidin-3-O-xylosylrutinoside (Cya-3-O-xylrut) has been identified as responsible for its antioxidant activity (18).
In human renal cell carcinoma cells, a schisandra polysaccharide identified as SCP induced apoptosis via caspase-3 and -9 activation, increased PARP cleavage, and inactivation of the ERK pathway (8). Another polysaccharide known as SCPP11 exhibited antitumor effects in hepatic cancer models via increased thymus index as well as serum IL-2 and TNF-alpha levels, and enhanced phagocytosis and NO production (26). Pgp-mediated chemotherapy drug-resistance in various cancer cell lines was reversed by schisandrins through the inhibition of Pgp and total protein kinase C function/expression (20).
Schisandra coadministration increases oral bioavailability of tacrolimus via inhibition of Pgp-mediated efflux and cytochrome P450 3A-mediated metabolism, and reduction of intestinal first-pass effect (30).