Radical Scavenging Activity of the Essential Oil of Silver Fir ( <i>Abies alba</i> )

Yang, Seun-Ah,Jeon, Sang-Kyung,Lee, Eun-Jung,Im, Nam-Kyung,Jhee, Kwang-Hwan,Lee, Sam-Pin,Lee, In-Seon the Society for Free Radical Research Japan 2009 Journal of clinical biochemistry and nutrition Vol.44 No.3

<P>The essential oil of silver fir (<I>Abies alba</I>) is known to help respiratory system and have easing and soothing effect for muscle. In the present study, we investigated the chemical composition, cytotoxicity and its biological activities of silver fir (<I>Abies alba</I>) essential oil. The composition of the oil was analyzed by GC-MS and bornyl acetate (30.31%), camphene (19.81%), 3-carene (13.85%), tricyclene (12.90%), dl-limonene (7.50%), α-pinene (2.87%), caryophyllene (2.18%), β-phellandrene (2.13%), borneol (1.74%), bicyclo[2.2.1]hept-2-ene,2,3-dimethyl (1.64%) and α-terpinene (1.24%) were the major components in the oil. The results tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay indicated that the oil showed no cytotoxic effect, at concentrations of 1 and 5%, for as long as 24 and 3 h, respectively. The antiradical capacity was evaluated by measuring the scavenging activity of the essential oil on the 2,20-diphenylpicrylhydrazyl (DPPH) and 2,2'-azino-bis 3-ethyl benzothiazoline-6-sulfonic acid (ABTS) radicals. The oil was able to reduce the both radicals dose-dependently, and the concentration required for 50% reduction (RC<SUB>50</SUB>) against DPPH radicals (2.7 ± 0.63%) was lower than ABTS radicals (8.5 ± 0.27%). The antibacterial activity of the oil was also evaluated using disc diffusion method against <I>Staphylococcus aureus</I>, <I>Streptococcus mutans</I>, <I>Listeria monocytogenes</I>, <I>Acinetobacter baumannii</I>, <I>Escherichia coli</I>, and <I>Vibrio parahaemolyticcus</I>. The oil exhibited no antibacterial activity against all the bacterial strains tested except <I>S. aureus</I> of mild activity.</P>

Menthol Enhances an Antiproliferative Activity of 1α,25-Dihydroxyvitamin D ₃ in LNCaP Cells

Park, Eun-Jung,Kim, Su-Hwa,Kim, Byung-Joo,Kim, Sung-Young,So, Insuk,Jeon, Ju-Hong the Society for Free Radical Research Japan 2009 Journal of clinical biochemistry and nutrition Vol.44 No.2

<P>1α,25-dihydroxyvitamin D<SUB>3</SUB> [1α,25(OH)<SUB>2</SUB>D<SUB>3</SUB>], the most active form of vitamin D<SUB>3</SUB>, and its analogues have therapeutic benefits for prostate cancer treatment. However, the development of hypercalcemia is an obstacle to clinical applications of 1α,25(OH)<SUB>2</SUB>D<SUB>3</SUB> for cancer therapy. In this study, we provide evidence that menthol, a key component of peppermint oil, increases an anti-proliferation activity of 1α,25(OH)<SUB>2</SUB>D<SUB>3</SUB> in LNCaP prostate cancer cells. We found that menthol <I>per se</I> does not exhibit antiproliferative activity, but it is able to enhance 1α,25(OH)<SUB>2</SUB>D<SUB>3</SUB>-mediated growth inhibition in LNCaP cells. Fluorometric assays using Fura-2 showed that 1α,25(OH)<SUB>2</SUB>D<SUB>3</SUB> does not induce acute Ca<SUP>2+</SUP> response, whereas menthol evokes an increase in [Ca<SUP>2+</SUP>]<SUB>i</SUB>, which suggests that cross-talks of menthol-induced Ca<SUP>2+</SUP> signaling with 1α,25(OH)<SUB>2</SUB>D<SUB>3</SUB>-mediated growth inhibition pathways. In addition, Western blot analysis revealed that 1α,25(OH)<SUB>2</SUB>D<SUB>3</SUB> and menthol cooperatively modulate the expression of bcl-2 and p21 which provides the insight into the molecular mechanisms underlying the enhanced 1α,25(OH)<SUB>2</SUB>D<SUB>3</SUB>-mediated growth inhibition by menthol. Thus, our findings suggest that menthol may be a useful natural compound to enhance therapeutic effects of 1α,25(OH)<SUB>2</SUB>D<SUB>3</SUB>.</P>

Apoptotic Effect of Tolfenamic Acid in KB Human Oral Cancer Cells: Possible Involvement of the p38 MAPK Pathway

Kim, Jun-Hee,Jung, Ji-Youn,Shim, Jung-Hyun,Kim, Jin,Choi, Kyeong-Hee,Shin, Ji-Ae,Choi, Eun-Sun,Lee, Syng-Ook,Chintharlapalli, Sudhakar,Kwon, Ki Han,Leem, Dae-Ho,Cho, Nam-Pyo,Cho, Sung-Dae the Society for Free Radical Research Japan 2010 Journal of clinical biochemistry and nutrition Vol.47 No.1

<P>Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to inhibit cancer growth by inhibiting the activity of cyclooxygenase (COX). However, there is increasing evidence that the COX-independent pathway may be also involved in the inhibitory effect of NSAIDs against tumor progression. Tolfenamic acid is a NSAID that exhibits anticancer activity in pancreatic and colorectal cancer models. In the present study, the anti-tumor effect of tolfenamic acid in KB human oral cancer cells is investigated. The results showed that tolfenamic acid does not alter the expression of the COX proteins, but it inhibits cell growth and induces apoptosis as evidenced by the annexin V positivity, sub-G<SUB>1</SUB> population, nuclear fragmentation and the cleavage of poly ADP-ribose polymerase. In addition, tolfenamic acid also leads to a loss of the mitochondrial membrane potential in KB cells. These effects are related to the activation of p38 mitogen-activated protein kinase (MAPK) pathway. These results suggest that tolfenamic acid-induced apoptotic cell death inhibits cancer growth by activating the p38 MAPK pathway for cancer prevention.</P>

The Novel Acid Pump Antagonists for Anti-secretory Actions with Their Peculiar Applications Beyond Acid Suppression

Yeo, Marie,Kwak, Mi Sun,Kim, Dong Kyu,Chung, In Sik,Moon, Byoung Seok,Song, Keun Seog,Hahm, Ki-Baik The Society for Free Radical Research Japan 2006 Journal of clinical biochemistry and nutrition Vol.38 No.1

<P>The H<SUP>+</SUP>/K<SUP>+</SUP>-ATPase of gastric parietal cell exchanges luminal K<SUP>+</SUP> for cytoplasmic H<SUP>+</SUP>, of which outcome is gastric acidification with outflux of hydronium ion (H<SUB>3</SUB>O<SUP>+</SUP>). Secretion of gastric acid from the H<SUP>+</SUP>/K<SUP>+</SUP>-ATPase is stimulated by neuronal sensing and elaborately regulated various neuronal transmitters and hormones, consequently resulting in anchoring of the H<SUP>+</SUP>/K<SUP>+</SUP>-ATPase in canaliculi membrane of gastric parietal cell. Since hypersecretion of gastric acid or a defect of its barrier function is considered as a principal casual factor in the acid-related diseases such as duodenal and gastric ulcer, reflux esophagitis, and some types of gastritis, the development of anti-secretory agents including PPIs (proton pump inhibitors) and H2-RAs (histamine type 2 receptor antagonists) has revolutionized during the second millennium. Similar considerations applying to design of compounds substituting K<SUP>+</SUP> led to the development of acid pump antagonists (APAs), of which advantages are independent of secretory status, no lag time required, reversible in actions allowing “on-demand dosage”. Our recent studies revealed that these inhibitors of H<SUP>+</SUP>/K<SUP>+</SUP>-ATPase could be extensively applied for the selective induction of cancer cell apoptosis, a significant anti-inflammatory and gastroprotective action far beyond acid suppression. In the current review, we described the mechanistic regulation of gastric acid secretion with pump inhibitor, the difference and characteristics between PPI and APA based on the molecular mechanism, and their new applications beyond acid suppression.</P>

Ginsenoside Rg3 Suppresses Palmitate-Induced Apoptosis in MIN6N8 Pancreatic β-Cells

Kim, Kyong,Park, Min,Young Kim, Hye the Society for Free Radical Research Japan 2010 Journal of clinical biochemistry and nutrition Vol.46 No.1

<P>Chronic exposure to elevated levels of free fatty acids (FFA) causes β-cell dysfunction and may induce β-cell apoptosis in type 2 diabetes. The execution of β-cell apoptosis occurs through activation of mitogen-activated protein kinases (MAPKs). Ginsenoside Rg3 (Rg3), one of the active ingredients of ginseng saponins, has not been known about the effects on β-cell apoptosis mediated with FFA. The aims of this study were to investigate the <I>in vitro</I> protective effects of Rg3 on MIN6N8 mouse insulinoma β-cells against FFA-induced apoptosis, as well as the modulating effects on p44/42 MAPK activation. Our results showed that Rg3 inhibited the palmitate-induced apoptosis through modulating p44/42 MAPK activation. We conclude that Rg3 has the potential role in suppressing the progression of type 2 diabetes by inhibiting FFA-mediated loss of β-cells.</P>

Influence of Oryzanol and Ferulic Acid on the Lipid Metabolism and Antioxidative Status in High Fat-Fed Mice

Jin Son, Myoung,W. Rico, Catherine,Hyun Nam, Seok,Young Kang, Mi the Society for Free Radical Research Japan 2010 Journal of clinical biochemistry and nutrition Vol.46 No.2

<P>The comparative effects of oryzanol and ferulic acid on the lipid metabolism and antioxidative status of high fat-fed mice were investigated. The mice were given a diet containing 17% fat (HF), supplemented with oryzanol (HF-O) or ferulic acid for 7 weeks. The control mice (NC) were fed with normal diet. The HF mice exhibited increased body weight gain, plasma and hepatic total cholesterol and triglyceride concentrations, and lipid peroxidation rate, and reduced high-density lipoprotein cholesterol level. In general, they also showed lower hepatic antioxidant and higher lipid-regulating enzymes activities relative to that of NC group. Addition of oryzanol or ferulic acid in the diet counteracted these high fat-induced hyperlipidemia and oxidative stress via increased faecal lipid excretion and regulation of antioxidant and lipogenic enzymes activities. This study illustrates that oryzanol and ferulic acid have relatively similar hypolipidemic actions and could be effective in lowering the risk of high fat diet-induced obesity.</P>

Integrative Survival Response Evoked by Heme Oxygenase-1 and Heme Metabolites

Pae, Hyun-Ock,Kim, Eun-Cheol,Chung, Hun-Taeg the Society for Free Radical Research Japan 2008 Journal of clinical biochemistry and nutrition Vol.42 No.3

<P>Heme oxygenase (HO) catalyzes the rate-limiting step in heme degradation to produce carbon monoxide (CO), iron, and biliverdin. Biliverdin is subsequently converted to bilirubin by its reductase, and iron is recycled for heme synthesis. The inducible HO isoform, HO-1, is involved in the protection of multiple tissues and organs. The mechanism of protective actions of HO-1 has not been completely elucidated, but recent evidence suggests that one or more of heme metabolites can mediate the protective effects of HO-1. Particularly, CO mimics the antioxidant, anti-inflammatory, anti-apoptotic and antiproliferative actions of HO-1. Many of these effects of CO depend on the production of cyclic guanosine monophosphate (cGMP), and the modulation of mitogen-activated protein kinase (MAPK) pathways. The transcription factors, including nuclear factor E2-related factor-2 (Nrf2), and their upstream kinases, including MAPK pathway, play an important regulatory role in HO-1 expression by dietary antioxidants and drugs. This review attempts to concisely summarize the molecular and biochemical characteristics of HO-1, with a discussion on the mechanisms of signal transduction and gene regulation that mediate the induction of HO-1 by dietary antioxidants and drugs. In addition, the cytoprotective roles of HO-1 shall be discussed from the perspective of each of the metabolic by-products.</P>

Apigenin Induces Apoptosis through a Mitochondria/Caspase-Pathway in Human Breast Cancer MDA-MB-453 Cells

Choi, Eun Jeong,Kim, Gun-Hee The Society for Free Radical Research Japan 2009 Journal of clinical biochemistry and nutrition Vol.44 No.3

<P>In this study, we investigated the mechanistic role of the caspase cascade in extrinsic and intrinsic apoptosis induced by apigenin, which has been targeted as a candidate in the development of noncytotoxic anticancer medicines. Treatment with apigenin (1–100 μM) significantly inhibited the proliferation of MDA-MB-453 human breast cancer cells in a dose- and time-dependent manner with IC<SUB>50</SUB> values of 59.44 and 35.15 μM at 24 and 72 h, respectively. This inhibition resulted in the induction of apoptosis and the release of cytochrome <I>c</I> in cells exposed to apigenin at its 72 h IC<SUB>50</SUB>. Subsequently, caspase-9, which acts in mitochondria-mediated apoptosis, was cleaved by apigenin. In addition, apigenin activated caspase-3, which functions downstream of caspase-9. The apigenin-induced activation of caspase-3 was accompanied by the cleavage of capases-6, -7, and -8. These results are supported by evidence showing that the activity patterns of caspases-3, -8, and -9 were similar. The present study supports the hypothesis that apigenin-induced apoptosis involves the activation of both the intrinsic and extrinsic apoptotic pathways.</P>

Comparison of Prevention of NSAID-Induced Gastrointestinal Complications by Rebamipide and Misoprostol: A Randomized, Multicenter, Controlled Trial—STORM STUDY

Park, Soo-Heon,Cho, Chul-Soo,Lee, Oh-Young,Jun, Jae-Bum,Lin, San-Ren,Zhou, Li-Ya,Yuan, Yao-Zong,Li, Zhao-Shen,Hou, Xiao-Hua,Zhao, Hong-Chuan,Kachintorn, Udom,Kositchaiwat, Chomsri,Lertkupinit, Comson the Society for Free Radical Research Japan 2007 Journal of clinical biochemistry and nutrition Vol.40 No.2

<P>Nonsteroidal anti-inflammatory drugs (NSAIDs) have gastrointestinal side effects such as dyspepsia, peptic ulcer, hemorrhage, and perforation. Misoprostol and PPIs have been used to prevent NSAID-induced gastroduodenal injury. Rebamipide increases gastric mucus and stimulates the production of endogenous prostaglandins. The prophylactic effect of rebamipide on NSAID-induced gastrointestinal complications is unknown. The aim of this study was to compare NSAID-induced gastrointestinal complications in rebamipide- and misoprostol-treated groups. Patients were randomized to two groups and took a conventional NSAID plus rebamipide or misoprostol for 12 weeks. Gastric mucosal damage was evaluated by endoscopy at screening and the end of the study. The prevalences of active gastric ulcer were 7/176 (3.9%) in the rebamipide group and 3/156 (1.9%) in the misoprostol group. The prevalences of peptic ulcer were 8/176 (4.5%) in the rebamipide group and 7/156 (4.4%) in the misoprostol group. The cumulative incidences of peptic ulcer in the high-risk subgroup were 6/151 (4.0%) for rebamipide and 6/154 (3.9%) for misoprostol. In conclusion, rebamipide prevented NSAID-induced peptic ulcer as effectively as misoprostol in patients on long-term NSAID therapy. Rebamipide may be a useful therapeutic option for the prevention of NSAID-induced gastrointestinal ulcer because of its therapeutic effect and safety.</P>

Dietary inflammatory index and its relationship with high-sensitivity C-reactive protein in Korean: data from the health examinee cohort

Na, Woori,Kim, Misung,Sohn, Cheongmin the Society for Free Radical Research Japan 2018 Journal of clinical biochemistry and nutrition Vol.62 No.1

<P>Inflammation is associated with chronic disease. High-sensitivity C-reactive protein (hs-CRP) is a predictor of chronic disease. The dietary inflammatory index (DII) is used to determine the overall inflammatory potential of diet. A cross-sectional analysis of Health Examinee cohort data (2012–2014) from Korea was performed. Subjects were 40–79 years of age (8,332 males; 19,754 females). The DII was used to analyze the relationship between subject characteristics, nutrient intake, and the hs-CRP. Additionally, the relationship between DII and hs-CRP as a predictor of chronic disease was examined. The DII was divided into 4 quartile: Q1 = −7.21 to −1.88 (median: −3.020), Q2 = −1.87 to −0.02 (median: −0.410), Q3 = −0.01 to 1.87 (median = 0.870) and Q4 = 1.88 to 7.34 (median = 3.040). For each group, the carbohydrate/protein/fat intake ratio was Q1 = 66.7:16.6:19.2, Q2 = 67.2:15.6:18.7, Q3 = 67.3:15.1:18.4 and Q4 = 67.3:14.0:17.9. The odds of elevated hs-CRP were 1.241 times higher in participants with the most proinflammatory diets than those with the most anti-inflammatory diets [hs-CRP; odds ratio (95% confidence interval) for Q4 vs Q1: 1.241 (1.071, 1.438); <I>p</I> for trend = 0.002]. An association was found between a high DII and high levels of hs-CRP. The DII may be applied to measure the association between diet and chronic diseases.</P>