Neuroprotective effect of undecylenic acid extracted from Ricinus communis L. through inhibition of µ-calpain.

The key neuropathological features of Alzheimer's disease are abnormal deposition of Aß plaques and insoluble Aß peptides in extracellular brain and intracellular neurofibril tangles induced by abnormal tau hyperphosphorylation. µ-Calpain is one of the factors that bridge these Aß- and hyperphosphorylated tau-mediated pathological pathways. Undecylenic acid (UDA), a naturally occurring unsaturated fatty acid, was discovered as a µ-calpain inhibitor by screening a chemical library using a substrate specific µ-calpain assay method. UDA inhibited Aß oligomerization and Aß fibrillation and reversed Aß-induced neuronal cell death. In addition, UDA scavenged ROS and reversed the levels of proapoptotic proteins induced by ROS in SH-SY5Y cells. UDA inhibited µ-calpain activity with better potency than the known peptide-like µ-calpain inhibitor, MDL28170, in SH-SY5Y and HEK293T cells transfected with the catalytic subunit of µ-calpain. These results suggest that UDA is a novel non-peptide-like µ-calpain inhibitor with good cell permeability and potent neuroprotective effect.

Compounds with tyrosinase inhibition, elastase inhibition and DPPH radical scavenging activities from the branches of Distylium racemosum Sieb. et Zucc.

Twenty compounds were isolated from the ethanol extract of Distylium racemosum branches and their inhibitory activities on tyrosinase, elastase and free radicals evaluated. The isolated compounds were identified as dibenzofurans (1-4), abscisic acid (5), 6'-O-galloylsalidroside (6), catechin derivatives (7-11), gallic acid derivatives (12-14), tyrosol (15), flavonoids (16-18), lupeol (19) and 1,2,3,6-tetragalloylglucose (20). For study of tyrosinase inhibition activities, when compared with arbutin (IC(50) 48.8 µg/mL), four compounds (8, 11, 13, 17) showed higher activities, with IC(50) values of 4.8, 30.2, 40.5 and 37.7 µg/mL, respectively. For the elastase inhibition test, dibenzofuran 1 showed greater activity than the positive control, oleanolic acid (IC(50) 9.7 µg/mL), with an IC(50) of 7.7 µg/mL. In the studies on DPPH radical scavenging activities, five compounds (11, 12, 13, 14, 15) showed higher activities than ascorbic acid (IC(50) 5.0 µg/mL), with IC(50) values of 4.6, 3.9, 2.9, 3.8 and 4.7 µg/mL, respectively.

Tyrosinase inhibitory constituents from the stems of Maackia fauriei.

Bioassay-guided investigation of the stems of Maackia fauriei led to the isolation of seven flavonoid constituents, formononetin (1), genistein (2), daidzein (3), texasin (4), tectorigenin (5), odoratin (6) and mirkoin (7). Their structures were elucidated on the basis of spectral studies as well as by comparison with literature data. Tyrosinase inhibition activities were carried out on the isolated compounds. Among these, mirkoin (7) was identified as a potent tyrosinase inhibitor. It inhibited mushroom tyrosinase with an IC(50) value of 0.005 mm, which is ten times more active than kojic acid (IC(50) = 0.045 mm). The inhibition kinetics, analysed by Lineweaver-Burk plots, indicated mirkoin (7) to be a competitive inhibitor of tyrosinase when L-tyrosinase was used as a substrate. The results suggest that hydroxyl groups at C-4' in the B ring of flavonoids play an important role in the tyrosinase inhibition activities. Interestingly, compounds 4-7 were isolated for the first time from this plant.