You-kyung Choi

Ethanol extract of Scutellaria baicalensis Georgi prevents oxidative damage and neuroinflammation and memorial impairments in artificial senescense mice

Aging is a progressive process related to the accumulation of oxidative damage and neuroinflammation. We tried to find the anti-amnesic effect of the Scutellaria baicalens Georgia (SBG) ethanol extract and its major ingredients. The antioxidative effect of SBG on the mice model with memory impairment induced by chronic injection of D-galactose and sodium nitrate was studied. The Y-maze test was used to evaluate the learning and memory function of mice. The activities of superoxide dismutase, catalase and the content of malondialdehyde in brain tissue were used for the antioxidation activities. Neuropathological alteration and expression of bcl-2 protein were investigated in the hippocampus by immunohistochemical staining. ROS, neuroinflammation and apoptosis related molecules expression such as Cox-2, iNOS, procaspase-3, cleaved caspase-3, 8 and 9, bcl-2 and bax protein and the products of iNOS and Cox-2, NO, PGE2, were studied using LPS-activated Raw 264.7 cells and microglia BV2 cells. The cognition of mice was significantly improved by the treatment of baicalein and 50 and 100 mg/kg of SBG in Y-maze test. Both SBG groups showed strong antioxidation, antiinflammation effects with significantly decreased iNOS and Cox-2 expression, NO and PGE2 production, increased bcl-2 and decreased bax and cleaved caspase-3 protein expression in LPS induced Raw 264.7 and BV2 cells. We also found that apoptotic pathway was caused by the intrinsic mitochondrial pathway with the decreased cleaved caspase-9 and unchanged cleaved caspase-8 expression. These findings suggest that SBG, especially high dose, 100 mg/kg, improved the memory impairments significantly and showed antioxidation, antiinflammation and intrinsic caspase-mediated apoptosis effects.

Selective Cytotoxic Effects on Human Cancer Cell Lines of Phenolic-Rich Ethyl-Acetate Fraction from Rhus verniciflua Stokes

Rhus verniciflua Stokes (RVS) is a plant with a long history of medicinal use in Eastern Asia. RVS has been widely used to treat gastritis, stomach cancer and atherosclerosis. The cytotoxic effects of different solvent fractions from an RVS ethanol extract were measured in 11 human cancer cell lines. The study showed that the ethyl-acetate (EtOAC) fraction was the most cytotoxic. This fraction contains a number of phenolic compounds, and this phenolic-rich EtOAC fraction was particularly effective against gastric and breast cancer cells. A purified phenolic-rich EtOAC fraction (PPEF) had a stronger apoptotic effect on these cells. Liquid chromatography-mass spectrometry (LC-MS) analysis showed that the PPEF contained gallic acid, protocatechuic acid, fisetin, sulfuretin, butein and 8 unknown compounds. There were only small amounts of flavonoids: fisetin, sulfuretin and butein. The results showed that PPEF induces apoptosis only in gastric and breast cancer cell lines, but not in lung, colon or liver cancer cell lines. Therefore, PPEF may have a significant potential as an organ-specific anti-cancer agent.

Protective effect of lanostane triterpenoids from the sclerotia of Poria cocos Wolf against cisplatin-induced apoptosis in LLC-PK1 cells

Cisplatin-induced nephrotoxicity is a serious adverse effect that limits the use of cisplatin in cancer patients. In the present study, we investigated the protective effect of lanostane triterpenoids (1-10) isolated from the ethanolic extract of Poria cocos Wolf against cisplatin-induced cell death in LLC-PK1 kidney tubular epithelial cells. Treatment of cisplatin induced significant cell death, which was suppressed by treatment with dehydroeburicoic acid monoacetate (1) and 3β-acetoxylanosta-7,9(11),24-trien-21-oic acid (9). Compound 1 exhibited the highest efficacy among the tested compounds and was thus subjected to further mechanistic studies. The increase in the percentage of apoptotic cells induced by cisplatin reduced by 4.3% after co-treatment of cells with compound 1 (50 and 100μM). Furthermore, phosphorylation of the mitogen-activated protein kinases JNK, ERK, and p38, and caspase-3, which characterize oxidative stress-mediated apoptosis, increased significantly after treatment with cisplatin, and decreased after treatment with compound 1. These results indicate that the renoprotective effects of compound 1 may be mediated by its anti-apoptotic activity.

Herbal Prescription, DSGOST, Prevents Cold-Induced RhoA Activation and Endothelin-1 Production in Endothelial Cells

Herbal prescription, Danggui-Sayuk-Ga-Osuyu-Saenggang-tang (DSGOST), has long been used to treat Raynauds phenomenon (RP) in traditional Chinese medicine (TCM). However, a biological mechanism by which DSGOST ameliorates RP is yet deciphered. In this study, we demonstrate that DSGOST inhibits cold-induced activation of RhoA, in both vascular smooth muscle cells (VSMC) and endothelial cells (EC), and blocks endothelin-1-mediated paracrine path for cold response on vessels. While cold induced RhoA activity in both cell types, DSGOST pretreatment prevented cold-induced RhoA activation. DSGOST inhibition of cold-induced RhoA activation further blocked α2c-adrenoreceptor translocation to the plasma membrane in VSMC. In addition, DSGOST inhibited endothelin-1-mediated RhoA activation and α2c-adrenoreceptor translocation in VSMC. Meanwhile, DSGOST inhibited cold-induced or RhoA-dependent phosphorylation of FAK, SRC, and ERK. Consistently, DSGOST inhibited cold-induced endothelin-1 expression in EC. Therefore, DSGOST prevents cold-induced RhoA in EC and blocks endothelin-1-mediated paracrine path between EC and VSMC. In conclusion, our data suggest that DSGOST is beneficial for treating RP-like syndrome.

Anti-Inflammatory Effect of Combination of Scutellariae Radix and Liriopis Tuber Water Extract

Scutellariae Radix and Liriopis Tuber have been used to treat the inflammatory diseases in traditional Korean medicine and anti-inflammatory effect of each herb has been shown partially in several articles. However, the combined extract of these medicinal herbs (SL) has not been reported for its anti-inflammatory effects. In this study, we investigated the effects of SL on the creation of several proinflammatory mediators in RAW 264.7 cell mouse macrophages induced by Lipopolysaccharide (LPS). SL inhibited significantly the increase of NO, the release of intracellular calcium, the increase of interleukin-6 (IL-6), macrophage inflammatory proteins (MIP-1α, MIP-1β, and MIP-2), and granulocyte colony-stimulating factor (G-CSF) in LPS-induced RAW 264.7 cell at the concentrations of 25, 50, and 100u2009μg/mL, and SL inhibited significantly the increase of macrophage colony-stimulating factor (M-CSF) at the concentrations of 25 and 50u2009μg/mL, and tumor necrosis factor (TNF) at the concentration of 25u2009μg/mL. These results implicate that SL has anti-inflammatory effects by suppressing the production of various inflammatory mediators in macrophages. But SL did not inhibit significantly the increase of granulocyte macrophage colony-stimulating factor (GM-CSF), leukemia inhibitory factor (LIF), and Regulated on Activation, Normal T cell Expressed and Secreted (RANTES); therefore, further study is demanded for the follow-up research to find out the possibility of SL as a preventive and therapeutic medicine for various inflammatory diseases.

Protective effect of casuarinin against glutamate-induced apoptosis in HT22 cells through inhibition of oxidative stress-mediated MAPK phosphorylation

Glutamate is the major excitatory neurotransmitter in the central nervous system and is involved in oxidative stress during neurodegeneration. In the present study, casuarinin prevented glutamate-induced HT22 murine hippocampal neuronal cell death by inhibiting intracellular reactive oxygen species (ROS) production. Moreover, casuarinin reduced chromatin condensation and annexin-V-positive cell production induced by glutamate. We also confirmed the underlying protective mechanism of casuarinin against glutamate-induced neurotoxicity. Glutamate markedly increased the phosphorylation of extracellular signal regulated kinase (ERK)-1/2 and p38, which are crucial in oxidative stress-mediated neuronal cell death. Conversely, treatment with casuarinin diminished the phosphorylation of ERK1/2 and P38. In conclusion, the results of this study suggest that casuarinin, obtained from natural products, acts as potent neuroprotective agent by suppressing glutamate-mediated apoptosis through the inhibition of ROS production and activation of the mitogen activated protein kinase (MAPK) pathway. Thus, casuarinin can be a potential therapeutic agent in the treatment of neurodegenerative diseases.

Inhibitory effect of ucha-shinki-hwan on cold-mediated response in human dermal microvascular endothelial cells

Raynauds phenomenon is characterized by prolonged vasoconstriction in cutaneous capillaries on cold stress. RhoA activity would be a therapeutic target for treating Raynauds phenomenon. A traditional herbal medicine, ucha‐shinki‐hwan, has been used to promote vasodilation, but the biological mechanism of ucha‐shinki‐hwan is still unclear. Thus, we hypothesized that ucha‐shinki‐hwan is able to be used for treatment of Raynauds phenomenon and that ucha‐shinki‐hwan inhibits cold‐induced vasoconstriction by targeting RhoA GTPase.

The definition and diagnosis of cold hypersensitivity in the hands and feet: Finding from the experts survey

Background Cold hypersensitivity in the hands and feet (CHHF) is a symptom patients usually feel cold in their hands and feet, but not dealt with a disease in western medicine. However, it is often appealed by patients at a clinic of Korean medicine (KM), considered to be a sort of key diagnostic indicator, and actively treated by physicians. Nevertheless, there is no standardized diagnostic definition for CHHF. Therefore, we surveyed KM experts’ opinions to address the clinical definition, diagnostic criteria, and other relevant things on CHHF. Methods We developed a survey to assess the definition, diagnosis, causes, and accompanying symptoms on CHHF. 31 experts who work at specialized university hospitals affiliated with KM hospitals consented to participation. Experts responded to survey questions by selecting multiple-choice answers or stating their opinions. Results Vast majority of experts (83.8%) agreed with our definition on CHHF (“a feeling of cold as a symptom; that ones hands or feet become colder than those of average people in temperatures that are not normally perceived as cold”). 77.4% of experts considered subjective symptoms on CHHF were more important than medical instrument results. Constitution or genetic factors (87.1%) and stress (64.5%) were the most common causes reported for CHHF. Conclusions This study offers an expert consensus regarding the themes, opinions, and experiences of practitioners with CHHF. Our results underscore the need for standardized definitions and diagnostic criteria for CHHF.