Sun-Ho Shin

Quercetin protects the hydrogen peroxide-induced apoptosis via inhibition of mitochondrial dysfuntion in H9c2 cardiomyoblast cells

Quercetin possesses a broad range of pharmacological properties, including protection of LDL from oxidation. However, little is known about the mechanism by which quercetin rescues cardiomyoblasts from oxidative damage. This study was designed to investigate the protective mechanism of quercetin on H(2)O(2)-induced toxicity of H9c2 cardiomyoblasts. Oxidative stress, such as H(2)O(2), ZnCl(2), and menadione, significantly decreased the viability of H9c2 cells, which was accompanied with apparent apoptotic features, including fragmentation of genomic DNA as well as activation of caspase protease. However, quercetin markedly inhibited the apoptotic characteristics via reduction of intracellular reactive oxygen species generation. Also, it prevented the H(2)O(2)-mediated mitochondrial dysfunction, including disruption of mitochondria membrane permeability transition as well as an increase in expression of apoptogenic Bcl-2 proteins, Bcl-2 and Bcl-X(L). Furthermore, pretreatment of quercetin inhibited the activation of caspase-3, thereby both cleavage of poly(ADP-ribose) polymerase and degradation of inhibitor of caspase-activated DNase/DNA fragmentation factor by H(2)O(2) were completely abolished. Taken together, these data suggest that protective effects of quercetin against oxidative injuries of H9c2 cardiomyoblasts may be achieved via modulation of mitochondrial dysfunction and inhibition of caspase activity.

Inhibitory effects of the stem bark of Catalpa ovata G. Don. (Bignoniaceae) on the productions of tumor necrosis factor-α and nitric oxide by the lipopolisaccharide-stimulated RAW 264.7 macrophages

In order to validate the use of the stem bark of Catalpa ovata G. Don. (Bignoniaceae) as an anti-inflammatory drug in the traditional Korean medicine, we have investigated the effects of the methanol extract of this folk medicine on the productions of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) on RAW 264.7 macrophages activated with the endotoxin lipopolysaccharide. The extract inhibited the productions of TNF-alpha and NO with significant decreases in mRNA levels of TNF-alpha and inducible NO synthase, suggesting that the stem bark of Catalpa ovata may have therapeutic potential in the control of inflammatory disorders.

Samul extract protects against the H2O2-induced apoptosis of H9c2 cardiomyoblasts via activation of extracellular regulated kinases (Erk) 1/2.

Samul extract, containing Radix Rehmanniae, Radix Angelicae Gigantis, Radix Paeoniae, and Rhizoma Cnidii, has been traditionally used for treatment of ischemic heart and brain damages in Oriental medicine. However, little is known about the mechanism by which Samul rescues cells from cytotoxic damage. This study was designed to investigate the protective mechanisms of Samul on H(2)O(2)-induced death of H9c2 cells. Treatment with H(2)O(2) markedly decreased the viability of H9c2 cells in a dose- and time-dependent manner, which was significantly prevented by pre-treatment with Samul. The nature of death of H9c2 cells by H(2)O(2) was demonstrated by apoptotic features, including ladder-pattern fragmentation of genomic DNA and chromatin condensation, which were markedly abolished by pretreatment of Samul in H(2)O(2)-treated cells. We further demonstrated that MEK inhibitor, PD98059, dose-dependently attenuated the protective effects of Samul against H(2)O(2), whereas inhibitors of Jnk and p38 did not. Consistently, Samul induced the early phosphorylation of Erk, p44, in H(2)O(2)-treated cells. In addition, treatment with Samul also resulted in an increase of expression of anti-apotogenic Bcl2 protein, which was decreased by H(2)O(2). However, it inhibited the expression of apotogenic Bax protein in H(2)O(2)-treated cells. Taken together, these results suggest that the protective effects of Samul against oxidative damage may be achieved via activation of MAP kinase, Erk as well as Bcl2 family proteins.