Anti-hyperglycemic constituents from the leaves of Cinnamomum macrostemon

Glucose transport and metabolism are tightly associated with diseases including diabetes. Sodium-coupled glucose co-transporters (SGLTs), SGLT1 and SGLT2, are important for intestinal absorption and renal reabsorption of glucose, respectively. The previous study reported that dual SGLT1/SGLT2 inhibitor as an adjunct therapy to insulin in type 1 diabetes could improve glycemic control and overcome the side effect, such as hypoglycemia and weight loss.

Approximately 60 species of Lauraceae plants have been screened for the SGLT inhibitory activity and Cinnamomum macrostemon Hay. (Lauraceae) was shown as the most active species. The methanolic extract of the leaves of C. macrostemon was partitioned into the water-soluble and ethyl acetate layers. Water-soluble layer showed the potent activity toward SGLT inhibitory. Till now, the chemical constituents of water-soluble layer and bioactivity from C.macrostemon have never been investigated. Bioassay-guided fractionation of the active water-soluble layer from the leaves of C. macrostemon led to the isolation of one new megastigmane, cinnamacroside (1), along with 14 known compounds, including one benzenoid, one coumarin, 11 flavonoid glycosides, and one lignan. Twenty-one known compounds were also isolated from the ethyl acetate layer of the leaves of C. macrostemon.

Among the isolates, kaempferol 3-O-β-D-glucopyranosyl-(1→4)-α-L-rhamnopyranosyl-7-O-α-L-rhamnopyranoside and kaempferol 3-O-(2''-β-D-glucopyranosyl)-α-L-rhamnopyranoside showed potent inhibitory activity toward SGLT, which IC₅₀ values 475 ± 34.2 and 123 ± 11.6 nM for SGLT1, and 68.8 ± 14.2 and 12.5 ± 2.95 nM for SGLT2, respectively.