Dalbergioidin

Human neutrophil elastase inhibitory potential of flavonoids from Campylotropis hirtella and their kinetics.[Pubmed:27558014]

J Enzyme Inhib Med Chem. 2016;31(sup1):16-22.

Campylotropis hirtella is used as a food supplement in the subtropical region of China. In an intensive hunt for human neutrophil elastase inhibitors, we isolated eight flavonoids from C. hirtella three of which (1-3) emerged to be elastase inhibitors. Geranylated flavonoids (1-3) displayed significant inhibitory activity with IC50s between 8.5 and 30.8 muM. The most striking example was geranylated isofavanone 3 that inhibited elastase significantly (IC50 = 30.8 muM) but its parent compound (Dalbergioidin) and isoflavone analog (5) were inactive (IC50 > 200 muM). Compounds (1-3) displayed different kinetic mechanisms (noncompetitive, competitive, and mixed type, respectively) that were dependent upon the parent skeleton. The competitive inhibitor, isoflavan-3-ol-4-one 2 manifested an inhibition of isomerization profile for elastase with kinetic parameters K5 = 0.0386 M(-1)S(-1), K6 = 0.0244 muM(-1)S(-1) and Ki(app) = 16.3427 muM. The specific identification of metabolites was accomplished by LC-DAD-ESI/MS that was also used to analyze abundance of active components (1-3) within the plant.

Dalbergioidin (DAL) protects MC3T3-E1 osteoblastic cells against H2O2-induced cell damage through activation of the PI3K/AKT/SMAD1 pathway.[Pubmed:28374099]

Naunyn Schmiedebergs Arch Pharmacol. 2017 Jul;390(7):711-720.

Reactive oxygen species (ROS) is a pivotal pathogenic factor in the development of osteoporosis. Dalbergioidin (DAL) can be isolated from Uraria crinite, an edible herb used as a natural food for childhood skeletal dysplasia. Recent research has implicated DAL as having an antiosteoporosis effect, although the mechanism of this is unclear. We used an effective oxidative stress model, induced by hydrogen peroxide (H2O2) in osteoblastic MC3T3-E1 cells, to investigate the protective effects of DAL in osteoporosis and the underlying molecular mechanisms. The results indicated that treatment with DAL maintained redox balance, reduced MC3T3-E1 cell apoptosis, improved alkaline phosphatase activity, and elevated the osteogenic-related protein expression of Runx2, Osterix, and BMP2 against oxidative damage induced by H2O2. The potential molecular mechanism involved in the protective effect of DAL against H2O2-induced cell death in MC3T3-E1 cells may lie in the activation of the PI3K/AKT/SMAD1 cell signal pathway. Taken together, the results indicated that the potential protective effects of DAL against osteoporosis were linked to a reduction in oxidative damage, suggesting that DAL may be useful in bone metabolism diseases, particularly osteoporosis.

Dalbergioidin Ameliorates Doxorubicin-Induced Renal Fibrosis by Suppressing the TGF-beta Signal Pathway.[Pubmed:28100935]

Mediators Inflamm. 2016;2016:5147571.

We investigated the effect of Dalbergioidin (DAL), a well-known natural product extracted from Uraria crinita, on doxorubicin- (DXR-) induced renal fibrosis in mice. The mice were pretreated for 7 days with DAL followed by a single injection of DXR (10 mg/kg) via the tail vein. Renal function was analyzed 5 weeks after DXR treatment. DXR caused nephrotoxicity. The symptoms of nephrotic syndrome were greatly improved after DAL treatment. The indices of renal fibrosis, the phosphorylation of Smad3, and the expression of alpha-smooth muscle actin (alpha-SMA), fibronectin, collagen III (Col III), E-cadherin, TGF-beta, and Smad7 in response to DXR were all similarly modified by DAL. The present findings suggest that DAL improved the markers for kidney damage investigated in this model of DXR-induced experimental nephrotoxicity.