No abstract

Black mulberry is a widely acknowledged ancient traditional medicine. Its extract and constituents have been reported to exert various bioactivities including antimicrobial, hypotensive, analgesic etc. effects. While black mulberry preparations are also used as antispasmodic agents in folk medicine, no related studies are available on its isolated constituents. Through an extensive chromatographic purification, seven phenolic compounds were isolated from the methanol extract of Morus nigra root bark, including morusin (1), kuwanon U (2), kuwanon E (3), moracin P (4), moracin O (5), albanol A (6), and albanol B (7). A complete NMR signal assignment of moracin P and O was achieved, and related literature errors confusing the identity of moracin derivatives are hereby clarified. Compounds 2, 5 and 7 were identified as strong antispasmodic agents on isolated rat ileum and tracheal smooth muscles, while compound 3, a methoxy derivative of 2, was inactive. Moracin O (5) inhibited the ileal and tracheal smooth muscle contractions with Emax values of 85% and 302 mg, respectively. Those actions were superior as compared with papaverine. Our findings demonstrate that prenylated arylbenzofurans, geranylated flavonoids and Diels-Alder adducts from Morus nigra are valuable antispasmodic agents. Compounds 2, 5 and 7 are suggested as marker compounds for quality control of antispasmodic mulberry preparations. Moracin O (5) is a new lead compound for related drug development initiatives.

The ability of phenolic compounds from Morus nigra to modulate sarco-endoplasmic Ca 2+ -ATPase (SERCA1) activity was analyzed. Enzyme activity decrease correlated with the binding energy of agents to SERCA1. Results from theoretical and experimental approaches were coherent in identifying binding sites to SERCA1. Albanol A inhibited SERCA1 by immersion in the luminal gate at the site of Ca 2+ release. Kuwanon U exerted an inhibitory effect by preventing ATP binding in the cytosolic region of SERCA1, and this was associated with conformational alterations. On the basis of similarities of SERCA isoforms, the viability of beta-cells containing SERCA2b was analyzed. Both correlation of viability and negative correlation of SERCA2b expression with SERCA1 activity were found for agents with the highest binding energy to SERCA1. The compounds studied may regulate viability and apoptosis of pancreatic beta-cells via modulation of SERCA activity. Novel pharmacological interventions in diabetes may be realized via compounds restoring ER calcium levels.

No abstract