Bong Sik Yun

Glycation inhibitory activity and the identification of an active compound in Plantago asiatica extract

The glycation reaction involves a series of non‐enzymatic reactions between the carbonyl group on reducing sugars and the amino group on proteins leading to the formation of advanced glycation end‐products (AGEs), which are acknowledged to be involved in the pathogenesis of diabetic and aging‐related complications. Consequently, the development of AGE inhibitors is considered to have therapeutic potential in patients with diabetes or age‐related diseases. The preliminary results showed that a methanol extract (PAE) of Plantago asiatica, which is traditionally used as a folk medicine in Asian countries to treat fever, cough, wound etc., had strong glycation inhibitory activity. The effects of the extract on AGE fluorescence were dose‐dependent, reaching 41% inhibition at 0.1 µg/mL of extract. The purified principle from PAE was identified as plantamajoside. As well as antioxidant activities, in vitro glycation inhibitory activities with 10 and 25 mm plantamajoside were higher than those with 10 and 25 mm aminoguanidine. The results demonstrate that PAE and plantamajoside had significant effects on in vitro AGE formation, and the glycation inhibitory activity and antioxidant activity of plantamajoside were comparable to those obtained using millimolar concentrations of the standard antiglycation agent aminoguanidine, and the antioxidant ascorbate, respectively. Copyright

Hispidin analogue davallialactone attenuates carbon tetrachloride-induced hepatotoxicity in mice.

In this study the protective effects of davallialactone (1), isolated from Inonotus xeranticus, have been examined against carbon tetrachloride (CCl₄-induced acute liver injury. Mice received subcutaneous injection of 1 (2.5, 5, and 10 mg/kg) for three days before CCl₄ injection (1 mg/kg). Protection from liver injury by 1 was confirmed by the observation of decreased serum transaminases and diminished necrosis of liver tissue. Reduced hepatic injury was very similar to that observed with silymarin, a known hepatoprotective drug used in this work for comparison. The groups treated with 1 had reduced reactive oxygen species (ROS), reduced serum malonyldialdehyde levels, and increased levels of liver Cu/Zn superoxide dismutase, as compared to the CCl₄ control group. The expression of heme oxygenase-1 in the liver tissue was increased and the activity of liver cytochrome P4502E1 was restored in the mice treated with 1. In addition, levels of serum tumor necrosis factor-alpha (TNF-α), inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2), numbers of macrophage, and cleaved caspase-3-positive hepatocytes were reduced in the groups treated with 1. These findings suggest that davallialactone has protective effects against CCl₄-induced acute liver injury, and this protection is likely due to the suppression of ROS-induced lipid peroxidation and inflammatory response.

Neuroprotective activity of p-terphenyl leucomentins from the mushroom Paxillus panuoides.

The neuroprotective mechanism of p-terphenyl leucomentins from the mushroom Paxillus panuoides was studied. Leucomentins showed potent inhibition of lipid peroxidation and H2O2 neurotoxicity, but free from any role as reactive oxygen species (ROS) scavengers. Iron-mediated oxidative damage has been implicated in these processes, as a provider of ROS via iron. Leucomentins can chelate iron when DNA is present with iron and H2O2, and so inhibiting DNA single strand breakage. These results suggest that the neuroprotective action of leucomentins is dependent on their ability to chelate iron.

Complestatin antagonizes the AMPA/kainate-induced neurotoxicity in cultured chick telencephalic neurons.

Excitatory amino acids are known to induce considerable neurotoxicity in central nervous system. In the present study, the neurotoxicity was induced by application of kainate or AMPA in chick telencephalic neuron, and neuroprotective activity was tested with complestatin that was isolated from streptomyces species. In cultured telencephalic neurons exposed to 500 μM kainate for 2 days, the AMPA/kainate receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX, 5 μM) completely blocked kainate-induced neurotoxicity. Also, complestatin (0.5 μM) completely blocked kainate-induced neuronal injury at a concentration lower than that required for prototype AMPA/kainate receptor antagonist DNQX. In addition, complestatin blocked AMPA-induced neurotoxicity when the neurons were pretreated with cyclothiazide, a desensitization blocker of AMPA receptor. Surprisingly, when the onset of the treatment was delayed for 6 hours, complestatin led to a reduction in kainate-induced neuronal injury. While inhibition of protein kinase C (PKC) by staurosporin induced neurotoxicity, that was blocked by complestatin. Activation of PKC by phorbol dibutyrate partially inhibited the kainate-induced neurotoxicity. These results suggest that complestatin may be used as an anti-excitotoxic agent and involved in the PKC activation contributing to inhibition of neurotoxicity.