Jong-Hyeong Park

Inhibition of the PI3K-Akt/PKB survival pathway enhanced an ethanol extract of Rhus verniciflua Stokes-induced apoptosis via a mitochondrial pathway in AGS gastric cancer cell lines

Rhus verniciflua Stokes (RVS) has been used in traditional Eastern Asia medicine for the treatment of gastritis and stomach cancer, although the mechanism for its biological activity remains to be elucidated. We previously established that an ethanol extract of RVS-induced G(1)-cell cycle arrest via accumulation of p27(Kip1) controlled by Skp2 reduction and apoptosis in AGS human gastric cancer cells. Here, we showed that an ethanol extract of RVS-induced apoptosis via caspase-9 activation (mitochondrial death pathway) is mediated by the loss of mitochondrial membrane potential (MMP, Deltapsi(m)) and the release of cytochrome C from the mitochondrial intermembrane space. In addition, an ethanol extract of RVS inactivated PI3K-Akt/PKB kinase in a time-dependent manner. Moreover, combined treatment of an ethanol extract of RVS and LY294002 (a PI3K inhibitor) markedly increased apoptosis compared to treatment with an ethanol extract of RVS alone. The role of PI3K-Akt/PKB in this process was confirmed by constitutive expression of inactive mutants of this kinase in AGS cells. Finally, siRNA-mediated knockdown of Akt/PKB expression resulted in a significant reduction in AGS cell proliferation. Taken together, these results suggest that an ethanol extract of RVS induces apoptosis via a mitochondrial death pathway in human gastric cancer cells, but not in normal cells, and inhibition of the PI3K-Akt/PKB pathway enhanced the mitochondrial death pathway.

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.

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.

Effect of oriental medicine music therapy on patients with Hwa-byung: a study protocol for a randomized controlled trial

BackgroundHwa-byung, a Korean culture-bound syndrome with both psychological and somatic symptoms, is also known as ‘anger syndrome’. It includes various physical symptoms including anxiety, a feeling of overheating, a sensation of pressure on the chest, heart palpitations, respiratory stuffiness, insomnia, and anxiety.Methods/designThe proposed study is a single-center, double-blind, randomized, controlled trial with two parallel arms: an oriental medicine music therapy (OMMT) group and a control music therapy (CMT) group. In total, 48 patients will be enrolled into the trial. The first visit will be the screening visit. At baseline (visit 2), all participants fulfilling both the inclusion and the exclusion criteria will be split and randomly divided into two equal groups: the OMMT and the CMT (n = 24 each). Each group will receive treatment sessions over the course of 4 weeks, twice per week, for eight sessions in total. The primary outcome is the State-Trait Anxiety Inventory (STAI), and the secondary outcomes are the Hwa-byung scale (H-scale), the Center for Epidemiologic Studies Depression Scale (CES-D), the Hwa-byung visual analogue scale (H-VAS) for primary symptoms, the World Health Organization Quality of Life scale, brief version (WHOQOL-BREF), and levels of salivary cortisol. Patients will be asked to complete questionnaires at the baseline visit (visit 2), after the last treatment session (visit 9), and at 4 weeks after the end of all trial sessions (visit 10). From the baseline (visit 2) through the follow-up (visit 10), the entire process will take a total of 53 days.DiscussionThis proposed study targets patients with Hwa-byung, especially those who have exhibited symptoms of anxiety. Therefore, the primary outcome is set to measure the level of anxiety. OMMT is music therapy combined with traditional Korean medicinal theories. Unlike previously reported music therapies, for which patients simply listen to music passively, in OMMT, patients actively move their bodies and play the music. Because Hwa-byung is caused by an accumulation of blocked emotions and anger inside the body, OMMT, because of its active component, is expected to be more efficacious than pre-existing music therapies.Trial registrationCurrent Controlled Trials ISRCTN11939282

Adenoviral gene transfer of acetylcholinesterase T subunit in the hypothalamus potentiates electroacupuncture analgesia in rats

Our previous studies, using cDNA microarray and real‐time reverse transcription‐polymerase chain reaction, showed that acetylcholinesterase T subunit (AChET) gene was more abundantly expressed in the hypothalamus of the responder rats that were sensitive to electroacupuncture (EA) in the tail flick latency (TFL) test than in that of the non‐responder rats that were insensitive to EA. In this study, we hypothesized that the expression of the AChET gene in the hypothalamus modulates EA analgesia in rats. To explore the hypothesis, we constructed an AChET‐encoding adenovirus and a control virus expressing only green fluorescence protein, either of which was then injected into the hypothalamus of Sprague‐Dawley rats. The hypothalamic activity of acetylcholinesterase was significantly higher in rats that were injected with the AChET virus than in rats that were injected with the control virus. The basal pain threshold measured by a TFL test was not changed by microinjection of AChET or control virus into the hypothalamus when EA treatment was not conducted. However, the analgesic effect of EA was significantly enhanced from 7 days after microinjection of the AChET virus into the hypothalamus but not after injection of the control virus. Furthermore, expression of the AChET in the hypothalamus did not affect body core temperature, body weight, motor function or learning and memory ability. Taken together, these results suggest that adenoviral expression of the AChET gene in the hypothalamus potentiates EA analgesia in rats without apparent side‐effects.

A relationship between Stroke and Sasang Constitution in Korean

Experts of Sasang Constitution Medicine of Traditional Korean Medicine have classified stroke patients with four types of Sasang constitutions in their clinical practice and some types of Sasang constitutions have been regarded as risk factors of stroke, but this is uncertain because there were no evidences by large scale of prospective studies. The purpose of this was to study the association between strokes and Sasang constitutions. Case-control study has been conducted to the patients admitted to the research hospitals. The patients were confirmed stroke by brain MRI or CT scans and recruited from May 2003 to August 2005. The subjects who met the requirement of inclusion and exclusion criteria were 108 patients as the cases and 107 as healthy controls. Data collection has been performed by the trained specialists majoring neurologists through interviews, physical examinations, and laboratory testes. No statistical significance was obtained between the strokes and Sasang constitutions, yet Taeumin, and Soyangin types showed a trend of increase in the incidence of strokes as compared with Soeumin. To acquire more concrete data on this theme, we need further and large scale of prospective researches.

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.