• The Korean Journal of Physiology and Pharmacology
• /
• v.14 no.6
• /
• pp.435-440
• /
• 2010

Valproic acid (VPA) is a well-known anti-epileptic and mood stabilizing drug. A growing number of reports demonstrate that VPA is neuroprotective against various insults. Despite intensive efforts to develop new therapeutics for stroke over the past two decades, all treatments have thus far failed to show clinical effect because of treatment-limiting side effects of the drugs. Therefore, a safety-validated drug like VPA would be an attractive candidate if it has neuroprotective effects against ischemic insults. The present study was undertaken to examine whether pre- and post-insult treatments with VPA protect against brain infarct and neurological deficits in mouse transient (tMCAO) and permanent middle cerebral artery occlusion (pMCAO) models. In the tMCAO (2 hr MCAO and 22 hr reperfusion) model, intraperitoneal injection of VPA (300 mg/kg, Lp.) 30 min prior to MCAO significantly reduced the infarct size and the neurological deficit. VPA treatment immediately after reperfusion significantly reduced the infarct size. The administration of VPA at 4 hr after reperfusion failed to reduce the infarct size and the neurological deficit. In the pM CAO model, treatment with VPA (300 mg/kg, i.p.) 30 min prior to MCAO significantly attenuated the infarct size, but did not affect the neurological deficit. Western blot analysis of acetylated H3 and H4 protein levels in extracts from the ischemic cortical area showed that treatment with VPA increased the expression of acetylated H3 and H4 at 2 hrs after MCAO. These results demonstrated that treatment with VPA prior to ischemia attenuated ischemic brain damage in both mice tMCAO and pMCAO models and treatment with VPA immediately after reperfusion reduced the infarct area in the tMCAO model. VPA could therefore be evaluated for clinical use in stroke patients.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.16
• /
• pp.6893-6898
• /
• 2014

Curcumin and its analogues have been reported to exert anti-cancer activity against a variety of tumors. Here, we reported A501, a new curcumin analogue. The effect of A501 on cell viability was detected by MTT assay, the result showed that A501 had a better inhibiting effect on the four non-small cell lung cancer (NSCLC) cells than that of curcumin. Moreover, Colony forming experiment showed A501 significant restrained cell proliferation. Flow cytometry displayed A501 can cause G2/M arrest and induce apoptosis. Western blotting showed that A501 decreased the expression of cyclinB1, cdc-2, bcl-2, while increased the expression of p53, cleaved caspase-3 and bax. In conclusion, curcumin analogues A501 played antitumor activity by inhibiting cell proliferation and inducing apoptosis of NSCLC cells. And it was likely to be a promising starting point for the development of curcumin-based anticancer drugs.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.6
• /
• pp.2619-2623
• /
• 2014

Aim: To investigate signaling pathways for reversal of EGF-mediated multi-drug resistance (MDR) in hepatocellular carcinoma (HCC) models. Materials and Methods: HCC MDR cell strain HepG2/adriamycin (ADM) and SMMC7721/ADM models were established using a method of exposure to medium with ADM between low and high concentration with gradually increasing concentration. Drug sensitivity and reversal of multi-drug resistance by EGF were determined and the cell cycle distribution and apoptosis were analyzed by flow cytometry. Phosphorylation of ERK1, ERK2, ERK5 and expression of Bim were detected by Western blotting. Results: The results showed that HepG2/ADM and SMMC7721/ADM cells were resistant not only to ADM, but also to multiple anticancer drugs. When used alone, EGF had no anti-tumor activity in HepG2/ADM and SMMC7721/ADM cells in vitro, while it increased the cytotoxicity of ADM. EGF induced cell apoptosis and G0/G1 phase cell cycle arrest in HepG2/ADM And SMMC7721/ADM cells, while enhancing activity of p-ERKs and up-regulated expression of BimEL. Conclusions: EGF might enhance the chemosensitivity of HepG2/ADM and SMMC7721/ADM cells via up-regulating p-ERKs and BimEL protein.

• Journal of Pharmacopuncture
• /
• v.17 no.3
• /
• pp.70-73
• /
• 2014

Sexual dysfunction (SD) is a health problem which occurs during any phase of the sexual response cycle that keeps the individual or couple from experiencing satisfaction from the sexual activity. SD covers a wide variety of symptoms like in men, erectile dysfunction and premature or delayed ejaculation, in women, spasms of the vagina and pain with sexual intercourse, in both sexes, sexual desire and response. And pharmacopuncture, i.e. injection of subclinical doses of drugs, mostly herb medicine, in acupoints, has been adopted with successful results. This case report showed the effect of bee venom on SD. A 51-year-old male patient with SD, who had a past history of taking Western medication to treat his SD and who had previously undergone surgery on his lower back due to a herniated disc, received treatments using pharmacopuncture of sweet bee venom (SBV) at Gwanwon (CV4), Hoeeum (CV1), Sinsu (BL23), and Gihaesu (BL24) for 20 days. Objectively, the patient showed improvement on most items on the International Index for Erectile Dysfunction (IIEF) like 28 to 29 out of perfect score 30 for erectile function, 10 to 10 out of perfect score 10 for orgasmic function, 6 to 8 out of perfect score 10 for sexual desire, 10 to 13 out of perfect score 15 for satisfaction with intercourse, and 6 to 8 out of perfect score 10 for overall satisfaction; subjectively, his words, the tone of his voice and the look of confidence in his eyes all indicated improvement. Among the variety of effects of SBV pharmacopuncture, urogenital problems such as SD may be health problems that pharmacopuncture can treat effectively.

• Nutrition Research and Practice
• /
• v.12 no.4
• /
• pp.298-306
• /
• 2018

BACKGROUND/OBJECTIVES: Obesity is a global health problem of significant importance which increases mortality. In place of anti-obesity drugs, natural products are being developed as alternative therapeutic materials. In this study, we investigated the effect of Brassica juncea L. leaf extract (BLE) on fat deposition and lipid profiles in high-fat, high-cholesterol diet (HFC)-induced obese rats. MATERIALS/METHODS: Male Sprague-Dawley rats were divided into four groups (n = 8 per group) according to diet: normal diet group (ND), high-fat/high-cholesterol diet group (HFC), HFC with 3% BLE diet group (HFC-A1), and HFC with 5% BLE diet group (HFC-A2). Each group was fed for 6 weeks. Rat body and adipose tissue weights, serum biochemical parameters, and tissue lipid contents were determined. The expression levels of mRNA and proteins involved in lipid and cholesterol metabolism were determined by reverse transcription polymerase chain reaction and western blot analysis, respectively. RESULTS: The HFC-A2 group showed significantly lower body weight gain and food efficiency ratio than the HFC group. BLE supplementation caused mesenteric, epididymal, and total adipose tissue weights to decrease. The serum levels of triglyceride, total cholesterol, and low-density lipoprotein cholesterol were significantly reduced, and high-density lipoprotein cholesterol was significantly increased in rats fed BLE. These results were related to lower glucose-6-phosphate dehydrogenase, acetyl-coA carboxylase, and fatty acid synthase mRNA expression, and to higher expression of the cholesterol $7{\alpha}$-hydroxylase and low density lipoprotein-receptor, as well as increased protein levels of peroxisome proliferator-activated receptor ${\alpha}$. Histological analysis of the liver revealed decreased lipid droplets in HFC rats treated with BLE. CONCLUSIONS: Supplementation of HFC with 3% or 5% BLE inhibited body fat accumulation, improved lipid profiles, and modulated lipogenesis- and cholesterol metabolism-related gene and protein expression.

• The Korean Journal of Physiology and Pharmacology
• /
• v.13 no.1
• /
• pp.33-37
• /
• 2009

Anti-inflammatory factor(AIF) is a water soluble extract of three herbs, Panax notoginseng(Burk.) F. H. Chen, Rehmannia glutinosa Libosch and Eleutherococcus senticosus. The present study aimed to investigate the safety and efficacy of herb extracts, AIF, on Korean knee osteoarthritis patients for six weeks. Fifty seven patients with knee osteoarthritis, ranging from 43 to 73 years of age, who fulfilled the "American College of Rheumatology"(ACR) classification of idiopathic osteoarthritis of knee and radiographic criteria were randomly selected and enrolled for the study. After initial screening and resting period, two capsules each of AIF(Each capsule contains; 400 mg) and similar identical placebo were administered twice a day to both groups. Pain intensity at second, fourth, and sixth weeks of study as well as one week after discontinuation of drugs was assessed by using 100 mm visual analogue scale(VAS). Changes in the Korean version of the Western Ontario and McMaster Universities(K-WOMAC) index score were compared at the initiation and completion of the study. VAS assessed by patients were significantly reduced(at visit 2; $54.64{\pm}14.72$, at visit 4, $37.32{\pm}16.58$, p<0.001) after AIF administration. Results showed an improvement in the physical function of K-WOMAC scale which was significantly higher(p=0.013) in AIF than placebo group, and decreases of total K-WOMAC score were also significantly higher(p=0.030) in AIF groups than placebo group. No serious adverse effect was observed, and there was no difference in incidence of adverse effect between AIF and placebo groups. In this population of Korean patients with knee osteoarthritis, AIF was found to be safe, tolerable and effective for symptomatic improvement of pain and physical function.

• Journal of Haehwa Medicine
• /
• v.20 no.1
• /
• pp.91-104
• /
• 2011

Background : Although chronic non-bacterial prostatitis is increasing, it is hard to treat effectively. In western medicine, antimicrobials drug, ${\alpha}$-adreno-ceptor antagonists, anti-inflammatory drugs, tricyclic antidepressants and anticholinergic agents are used commonly, but chronic prostatitis/chronic pelvic pain syndromes is confusing and frustrating for urologist. IDS(Indongsoyeom-bang) is used in treatment of chronic prostatitis/chronic pelvic pain syndromes. And it is reported that GLS(Gleditsiae spina) and TOF(Toosendan fructus) components of IDS have significant effect on protection of the glandular epithelial cells. Objective : In this study was conducted to investigate the therapeutic effects and action machanism of IDS in the rat model of non-bacterial prostatitis induced by castration and testosterone treatment. Methods : We observed six experimental objects of normal group, control group, testosterone group, and IDS 50 mg/kg, 200mg/kg, 400mg/kg group. Rats were treated with 17 ${\beta}$-estradiol after castration for induction of experimental non-bacterial prostatitis, which is similar to human chronic prostatitis in histophatological profiles. IDS and testosterone were administered as an experimental specimen and a positive control, respectively. The prostates were evaluated by histological parameters including the epithelial score and epithelio-stromal ratio for glandular damage. Also, the prostates were observed by Hematological alterations of WBC, RBC, hemoglobin and platelet. Results : While prostates of control rats revealed severe acinar gland atrophy and stromal proliferation, the rats treated with IDS-50 showed a diminished range of the tissue damage. Epithelial score was improved in IDS than that of the control. The epithelio-stromal ratio was lower in IDS when compared to that of the control. Also, the examination of bloods were not observed hematological change. Conclusion : These finding suggests that IDS may protects the glandular epithelial cells. We concluded that IDS could be a useful remedy agent for treating chronic non-bacterial prostatitis.

• The Korea Journal of Herbology
• /
• v.21 no.4
• /
• pp.51-58
• /
• 2006

Objectives : In this study, we investigate that Ulmi cortex extract contributes to growth inhibitory effect and anti-cancer activity on the HT-29 human colon cancer cells. Methods : Ulmi cortex was extracted from the leaves of the plant using water. The Ulmi cortex extract was treated to different concentrations for 24 hr. Growth inhibitory effect was analyzed by measuring FACS study and MTT assay. Cell cycle inhibition was confirmed by kinases assay. Cell apoptosis was confirmed by surveying caspases cascades activation using Western blot. Results : Exposure to Ulmi cortex extract (0.4mg/ml) results in an inhibitory effect on cell growth in HT-29 cells. Growth inhibition by Ulmi cortex extract in HT-29 cells was related with the inhibition of proliferation and induction of apoptosis. The Ulmi cortex extract induces G1-cell cycle arrest and DNA fragmentation in HT-29 cells. Furthermore, Ulmi cortex extract induces cell apoptosis through the activation of caspases-3 and PARP cleavage. Conclusion : Ulmi cortex extract induces apoptosis in human colon cancer cells, therefore, we suggest that Ulmi cortex extract can be used as a novel class of anti-cancer drugs.

• BMB Reports
• /
• v.35 no.4
• /
• pp.377-383
• /
• 2002

Arsenic trioxide ($As_O_3$) was recently demonstrated to be an effective inducer of apoptosis in patients with relapsed acute promyelocytic leukemia (APL) as well as patients with APL in whom all-trans-retinoic acid and conventional chemotherapy failed. Chronic myelogenous leukemia cells are highly resistant to chemotherapeutic drugs. To determine if $As_O_3$ might be useful for the treatment of chronic myelogenous leukemia, we examined the ability of $As_O_3$ to induce apoptosis in K562 cells. In vitro cytotoxicity of $As_O_3$ was evaluated in K562 cells by a MTT assay: the $IC_50$ value for $As_O_3$ was determined to be $10\;{\mu}m$. When analyzed by agarose gel electorphoresis, the DNA fragments became evident after incubation of the cells with $20\;{\mu}m$ $As_O_3$ for 24 h. We also found morphological changes and chromatin condensation of the cells undergoing apoptosis. Activation of caspase-3 was observed 6 h after treatment with $20\;{\mu}m$ $As_O_3$ by a Western blot analysis. Next, we examined the MAP kinase-signaling pathway of $As_O_3$-induced apoptosis in K562 cells. $As_O_3$ at $10\;{\mu}m$ strongly induced the activation of p38, inhibited $As_O_3$ induced apoptotic cell death. These results suggest that $As_O_3$ is able to induce the apoptotic activity in K562 cells, and its apoptotic mechanism may be associated with the activation of p38.

• BMB Reports
• /
• v.40 no.6
• /
• pp.853-860
• /
• 2007

Resistance to anticancer drugs is a major obstacle in the effective treatment of tumors. To understand the mechanisms responsible for multidrug resistance (MDR), a proteomic approach was used to identify proteins that were expressed in different levels by the adriamycinresistant human gastric cancer cell line, SGC7901/ADR, and its parental cell line, SGC7901. Two-dimensional gel electrophoresis (2-DE) and image analysis was used to determine which protein spots were expressed in different levels by the two cell lines. These spots were then partially identified using ESI-Q-TOF mass spectrometry, and the differential expressional levels of the partially identified proteins were then determined by western blot analysis and real-time RT-PCR. Additionally, the association of Nucleophosmin (NPM1), a protein that was highly expressed by SGC7901/ADR, with MDR was analyzed using siRNA. As a result of this study, well-resolved, reproducible 2-DE patterns of SGC7901/ADR and SGC7901 were established, and 16 proteins that may playa role in the development of thermo resistance were identified. Additionally, suppression of NPMl expression was found to enhance adriamycin chemosensitivity in SGC7901/ADR. These results provide a fundamental basis for the elucidation of the molecular mechanism of MDR, which may assist in the treatment of gastric cancer.