Erratum: Blood flow-improving activity of methyl jasmonate-treated adventitious roots of mountain ginseng / 한국실험동물학회지

In this article, So-Young Park is inadvertently omitted from the listed author names. In the Acknowledgement section, funding source is incorrectly cited and has been changed upon request of authors.

Blood flow-improving activity of methyl jasmonate-treated adventitious roots of mountain ginseng / 한국실험동물학회지

Ginsenosides from Panax ginseng are well known for their diverse pharmacological effects including antithrombotic activity. Since adventitious roots of mountain ginseng (ARMG) also contain various ginsenosides, blood flow-improving effects of the dried powder and extract of ARMG were investigated. Rats were orally administered with dried powder (PARMG) or ethanol extract (EARMG) of ARMG (125, 250 or 500 mg/kg) or aspirin (30 mg/kg, a reference control) for 3 weeks. Forty min after the final administration, carotid arterial thrombosis was induced by applying a 70% FeCl₃-soaked filter paper outside the arterial wall for 5 min, and the blood flow was monitored with a laser Doppler probe. Both PARMG and EARMG delayed the FeCl₃-induced arterial occlusion in a dose-dependent manner, doubling the occlusion time at high doses. In mechanism studies, a high concentration of EARMG inhibited platelet aggregation induced by collagen in vitro. In addition, EARMG improved the blood lipid profiles, decreasing triglyceride and cholesterol levels. Although additional action mechanisms remain to be clarified, it is suggested that ARMG containing high amount of ginsenosides such as Rg₃ improves blood flow not only by inhibiting oxidative thrombosis, but also by modifying blood lipid profiles.

Effects of neural stem cells and 5-fluorocytosine in canine metastatic lung tumor

This is the first case report to describe the tumor regressive effect of systemic human neural stem cell (NSC)/5-fluorocytosine (5-FC) therapy on canine metastatic lung tumor. The therapeutic effects appeared approximately two weeks after 5-FC administration. Thoracic radiographs revealed a reduced number of lung nodules and decreased nodule size. However, there were no significant antitumor effects on primary lesions in abdominal organs. In conclusion, human NSC/5-FC prodrug therapy can secure patient quality of life with the same or more therapeutic effects and fewer side effects than other recommended chemotherapies.

Withdrawal: Specific nephrotoxicity and cardiotoxicity of BT-CAL®, Sigma Anti-bonding Molecule Calcium Carbonate, in mice / 한국실험동물학회지

This article has been retracted.

Anti-atherosclerotic effects of perilla oil in rabbits fed a high-cholesterol diet / 한국실험동물학회지

Anti-atherosclerosis effects of perilla oil were investigated, in comparison with lovastatin, in rabbits fed a high-cholesterol diet (HCD). Hypercholesterolemia was induced in rabbits by feeding the HCD containing 0.5% cholesterol and 1% corn oil, and perilla oil (0.1 or 0.3%) was added to the diet containing 0.5% cholesterol for 10 weeks. HCD greatly increased blood total cholesterol and low-density lipoproteins, and caused thick atheromatous plaques, covering 74% of the aortic wall. Hyper-cholesterolemia also induced lipid accumulation in the liver and kidneys, leading to lipid peroxidation. Perilla oil not only attenuated hypercholesterolemia and atheroma formation, but also reduced fat accumulation and lipid peroxidation in hepatic and renal tissues. The results indicate that perilla oil prevents atherosclerosis and fatty liver by controlling lipid metabolism, and that it could be the first choice oil to improve diet-induced metabolic syndrome.

Extraction conditions of white rose petals for the inhibition of enzymes related to skin aging / 한국실험동물학회지

In order to assess inhibitory potentials of white rose petal extracts (WRPE) on the activities of enzymes related to dermal aging according to the extraction conditions, three extraction methods were adopted. WRPE was prepared by extracting dried white rose (Rosa hybrida) petals with 50% ethanol (WRPE-EtOH), Pectinex(R) SMASH XXL enzyme (WRPE-enzyme) or high temperature-high pressure (WRPE-HTHP). In the inhibition of matrix metalloproteinase-1, although the enzyme activity was fully inhibited by all 3 extracts at 100 microg/mL in 60 min, partial inhibition (50-70%) was achieved only by WRPE-EtOH and WRPE-enzyme at 50 microg/mL. High concentrations (> or =250 microg/mL) of all 3 extracts markedly inhibited the elastase activity. However, at low concentrations (15.6-125 microg/mL), only WRPE-EtOH inhibited the enzyme activity. Notably, WRPE-EtOH was superior to WRPE-enzyme and WRPE-HTHP in the inhibition of tyrosinase. WRPE-EtOH significantly inhibited the enzyme activity from 31.2 microM, reaching 80% inhibition at 125 microM. In addition to its strong antioxidative activity, the ethanol extract of white rose petals was confirmed to be effective in inhibiting skin aging-related enzymes. Therefore, it is suggested that WRPE-EtOH could be a good candidate for the improvement of skin aging such as wrinkle formation and pigmentation.

Erratum: Synergistic anti-inflammatory effects of Laminaria japonica fucoidan and Cistanche tubulosa extract / 한국실험동물학회지

As the request of the authors, one paragraph has been changed.

A Dunnione Compound MB12662 Improves Cisplatin-Induced Tissue Injury and Emesis

The present study was aimed to investigate the effects of MB12662, a synthetic dunnione compound, on cisplatin-induced vomiting reflexes and intestinal, renal, immune system, and hematopoietic toxicities in ferrets and mice, respectively. Male ICR mice were orally administered MB12662 (5, 10, 25 or 50 mg/kg) for 10 days, during which intraperitoneally challenged with cisplatin (3.5 mg/kg) from day 4 to 7, and sacrificed on day 10 for the pathological examination. Male ferrets were orally administered MB12662 (25, 50 or 100 mg/kg) for 7 days, subcutaneously challenged with cisplatin (5 mg/kg), and monitored for vomiting reflexes and survival of the animals. Four-day injection of cisplatin (3.5 mg/kg) to mice caused body weight loss and degeneration and atrophy of intestinal villi, reducing villi/crypt ratio to a half level of control animals. Cisplatin also induced renal and hepatic toxicities, and depletion of splenocytes and bone marrow progenitor cells. The systemic toxicities including decreased villi/crypt ratio, immune system atrophy, splenocyte depletion, and decreased cellularity in bone marrow were improved by MB12662. Cisplatin (5 mg/kg) induced retching and emetic responses of ferrets, which were remarkably attenuated by MB12662 in a dose-dependent manner. All the ferrets pretreated with MB12662 survived the challenge of cisplatin, in comparison with 40% mortality in vehicle-treated animals, and blood parameters of nephrotoxicity and hepatotoxicity were markedly recovered. It is expected that MB12662 could be a candidate for the body protection against burden, including emesis, of chemotherapeutic agents.

Erratum: In vitro and in vivo anti-Helicobacter pylori activities of FEMY-R7 composed of fucoidan and evening primrose extract / 한국실험동물학회지

As the request of the authors, Acknowledgments section has been changed.

Effectiveness of the combinational treatment of Laminaria japonica and Cistanche tubulosa extracts in hair growth / 한국실험동물학회지

Since scalp hair loss has increased recently even in young people, seriously affecting individual's quality of life, the hair growth-stimulating effects of Laminaria japonica extract (LJE) and Cistanche tubulosa extract (CTE) were investigated. After confirming anagen phase of follicles under shaving, male C57BL/6 mice were dermally applied with 3% Minoxidil or orally administered with the combinations of LJE and CTE for 21 days. Minoxidil promoted the hair regrowth and increased gamma-glutamyl transpeptidase (gamma-GTP) and alkaline phosphatase (ALP) activities. In addition, Minoxidil up-regulated epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) levels. Co-administration of LJE and CTE at 54 mg/kg LJE plus 162 mg/kg CTE exerted synergistic promoting effects on the hair regrowth, comparable to 3% Minoxidil. LJE preferentially enhanced ALP activity, while CTE increased both gamma-GTP and ALP activities as well as EGF and VEGF expressions. In vivo air pouch inflammation model, carrageenan-induced vascular exudation and increased nitric oxide and prostaglandin E2 concentrations in the exudates were synergistically suppressed by co-administration of LJE and CTE. In addition, inflammatory cell infiltration was substantially inhibited by the combinational treatment. The results suggest that combinational oral treatment with LJE and CTE in appropriate doses and ratios prevent hair loss and improve alopecia, which might be in part mediated by their anti-inflammatory activities.

Comparative analysis of anti-Helicobacter pylori activities of FEMY-R7 composed of Laminaria japonica and Oenothera biennis extracts in mice and humans / 한국실험동물학회지

Helicobacter pylori-eliminating effects of FEMY-R7, composed of Laminaria japonica and Oenothera biennis extracts, were investigated in mice and humans. Male C57BL/6 mice were infected with the bacteria by intragastric inoculation (1x10(9) CFU/mouse) 3 times at 2-day intervals, and simultaneously, orally treated twice a day with total 20, 64 or 200 mg/kg/day FEMY-R7 for 2 weeks. In Campylobcter-like organism (CLO)-detection tests on gastric mucosa and feces, FEMY-R7 reduced the urease-positive reactivity in a dose-dependent manner; i.e., the positivity ratios were decreased to 70, 20, and 10% for gastric mocosa and to 80, 50, and 20% for feces. In a clinical sudy, human subjects, confirmed to be infected with Helicobacter pylori, were orally administered twice a day with capsules containing total 100, 320 or 1,000 mg/man/day FEMY-R7 (matching doses for 20, 64 or 200 mg/kg/day, respectively, in mice from a body surface area-based dose translation) for 8 weeks. FEMY-R7 decreased the positivity ratios in feces to 70, 40, and 30%, respectively. In bacterial culture, H. pylori was identified from the CLO-positive stools of mice and humans. The bacterial identification ratios exhibited a good correlation between the matching doses in mice and humans. It is suggested that FEMY-R7 could be a promising functional food without tolerance as an adjunct to reduce the dosage of antibiotics for the treatment of recurrent H. pylori infection.

Perilla oil improves blood flow through inhibition of platelet aggregation and thrombus formation / 한국실험동물학회지

The inhibitory effects of perilla oil on the platelet aggregation in vitro and thrombosis in vivo were investigated in comparison with aspirin, a well-known blood flow enhancer. Rabbit platelet-rich plasma was incubated with perilla oil and aggregation inducers collagen or thrombin, and the platelet aggregation rate was analyzed. Perilla oil significantly inhibited both the collagen- and thrombin-induced platelet aggregations, in which the thromboxane B2 formation from collagen-activated platelets were reduced in a concentration-dependent manner. Rats were administered once daily by gavage with perilla oil for 1 week, carotid arterial thrombosis was induced by applying 35% FeCl3-soaked filter paper for 10 min, and the blood flow was monitored with a laser Doppler probe. Perilla oil delayed the FeCl3-induced arterial occlusion in a dose-dependent manner, doubling the occlusion time at 0.5 mL/kg. In addition, a high dose (2 mL/kg) of perilla oil greatly prevented the occlusion, comparable to the effect of aspirin (30 mg/kg). The results indicate that perilla oil inhibit platelet aggregation by blocking thromboxane formation, and thereby delay thrombosis following oxidative arterial wall injury. Therefore, it is proposed that perilla oil could be a good candidate without adverse effects for the improvement of blood flow.

In vitro and in vivo anti-Helicobacter pylori activities of FEMY-R7 composed of fucoidan and evening primrose extract / 한국실험동물학회지

Effects of FEMY-R7, composed of fucoidan and evening primrose extract, on the bacterial growth and intragastric infection of Helicobacter pylori as well as gastric secretion were investigated in comparison with a proton-pump inhibitor pantoprazole. For in vitro anti-bacterial activity test, H. pylori (1x10(8) CFU/mL) was incubated with a serially-diluted FEMY-R7 for 3 days. As a result, FEMY-R7 fully inhibited the bacterial growth at 100 microg/mL, which was determined to be a minimal inhibitory concentration. In addition, 6-hour incubation with H. pylori, FEMY-R7 inhibited urease activity in a concentration-dependent manner, showing a median inhibitory concentration of 1,500 microg/mL. In vivo elimination study, male C57BL/6 mice were infected with the bacteria by intragastric inoculation (5x10(9) CFU/mouse) 3 times at 2-day intervals, and simultaneously, orally treated twice a day with 10, 30 or 100 mg/kg FEMY-R7 for 7 days. In Campylobcter-like organism-detection test and bacterial identification, FEMY-R7 exerted a high bacteria-eliminating capacity at 30-100 mg/kg, comparably to 30 mg/kg pantoprazole. In contrast to a strong antacid activity of pantoprazole in a pylorus-ligation study, FEMY-R7 did not significantly affect gastric pH, free HCl, and total acidity, although it significantly decreased fluid volume at a low dose (10 mg/kg). The results indicate that FEMY-R7 eliminate H. pylori from gastric mucosa by directly killing the bacteria and preventing their adhesion and invasion, rather than by inhibiting gastric secretion or mucosal damage.

Clinicopathological Characteristics of Colon Cancer Diagnosed at Primary Health Care Institutions

BACKGROUND/AIMS: The purpose of this study was to evaluate the clinicopathologic characteristics of colon cancers detected at the SOK Sokpeynhan Internal Medical Network, a nationwide system of primary health care institutions. METHODS: We analyzed 579 colon cancer patients diagnosed using colonoscopy at the SOK network from January 2011 through December 2012. Cancers from the rectum to the splenic flexure were classified as left colon cancer. Patients over 65 were classified as senior. RESULTS: The mean age (+/-SD) of subjects was 60.9+/-10.5 years and 61.1% were men. More than one quarter (28.2%) of patients were asymptomatic. The prevalence of left colon cancer was higher (77.9%) than that for right colon cancer. The most frequent macroscopic and histologic types were depressed (58.9%) and moderately differentiated adenocarcinoma (52.2%), respectively. Asymptomatic subjects displayed protruding or well differentiated adenocarcinoma, while symptomatic patients were more likely to display depressed or moderately differentiated adenocarcinoma (P0.05). CONCLUSIONS: Study results indicated an increase of colon cancer amongst younger demographics in recent years. The effectiveness of colonoscopy screening was also evident, as asymptomatic patients demonstrated frequent findings of well differentiated adenocarcinomas. Study results also suggested a need for closer examination of older patients, as right colon cancer tended to increase with age.

Anti-Helicobacter pylori activities of FEMY-R7 composed of fucoidan and evening primrose extract in mice and humans / 한국실험동물학회지

Helicobacter pylori-eliminating effects of FEMY-R7, composed of fucoidan and evening primrose extract, were investigated in mice and humans. Male C57BL/6 mice were infected with the bacteria by intragastric inoculation (1x10(9) CFU/mouse) 3 times at 2-day intervals, and simultaneously, orally treated twice a day with 10 or 100 mg/kg FEMY-R7 for 2 weeks. In Campylobcter-like organism-detection test, FEMY-R7 markedly reduced the urease-positive reactivity. In a clinical sudy, human subjects, confirmed to be infected with Helicobacter pylori, were orally administered twice a day with a capsule containing 150 mg FEMY-R7 for 8 weeks. FEMY-R7 significantly decreased both the Delta over baseline-value in urea breath test and the serum pepsinogens I and II levels. The results indicate that FEMY-R7 not only eliminates H. pylori from gastric mucosa of animals and humans, but also improves gastric function.

Effects of anti-obesity drugs, phentermine and mahuang, on the behavioral patterns in Sprague-Dawley rat model / 한국실험동물학회지

According to WHO global estimates from 2008, more than 1.4 billion adults were overweight and among them, over 200 million men and 300 million women were obese. Although the main treatment modalities for overweight and obese individuals remain dieting and physical exercise, the synthetic anti-obesity medications have been increasingly used due to their perceived convenience. Generally, anti-obesity medications are classified as appetite suppressants or fat absorption blockers. In the present study, we examined the adverse side-effects in respect of behavior changes of phentermine and Ephedra sinica (mahuang) that are anti-obesity drugs currently distributed to domestic consumers. Phentermine is mainly classified as an anorexing agent and mahuang a thermogenic agent. Because phentermine and mahuang are considered to display effectiveness through the regulation of nerve system, their potential influences of on behavioral changes were examined employing animal experiments. From the results of experiments testing locomotor activity through the use of treadmill, rota-rod, and open field system, phentermine and mahuang were commonly revealed to induce behavioral changes of rats by reducing a motor ability, an ability to cope with an external stimulus, and a sense of balance or by augmenting wariness or excitement. These adverse effects of phenternime and mahuang in behavioral changes need to be identified in humans and anti-obesity medications such as phentermine and mahuang should be prescribed for only obesity where it is anticipated that the benefits of the treatment outweigh their potential risks.

An ethanolic extract of Angelica gigas improves atherosclerosis by inhibiting vascular smooth muscle cell proliferation / 한국실험동물학회지

The effects of an ethanolic extract of Angelica gigas (EAG) on the vascular smooth muscle cell (VSMC) proliferation and high-cholesterol diet-induced hypercholesterolemia and atherosclerosis were investigated. Rat aortic VSMCs were stimulated with platelet-derived growth factor-BB (25 ng/mL) for the induction of DNA synthesis and cell proliferation. EAG (1-10 microg/mL) significantly inhibited both the thymidine incorporation and cell proliferation in a concentration-dependent manner. Hypercholesterolemia was induced by feeding male New Zealand white rabbits with 0.5% cholesterol in diet for 10 weeks, during which EAG (1% in diet) was given for the final 8 weeks after 2-week induction of hypercholesterolemia. Hypercholesterolemic rabbits exhibited great increases in serum total cholesterol and low-density lipoproteins (LDL) levels, and finally severe atheromatous plaque formation covering 28.4% of the arterial walls. EAG significantly increased high-density lipoproteins (HDL), slightly decreased LDL, and potentially reduced the atheroma area to 16.6%. The results indicate that EAG attenuates atherosclerosis not only by inhibiting VASC proliferation, but also by increasing blood HDL levels. Therefore, it is suggested that EAG could be an alternative or an adjunct therapy for the improvement of hypercholesterolemia and atherosclerosis.

Nattokinase improves blood flow by inhibiting platelet aggregation and thrombus formation / 한국실험동물학회지

The effects of nattokinase on the in vitro platelet aggregation and in vivo thrombosis were investigated in comparison with aspirin. Rabbit platelet-rich plasma was incubated with nattokinase and aggregation inducers collagen and thrombin, and the platelet aggregation rate was analyzed. Nattokinase significantly inhibited both the collagen- and thrombin-induced platelet aggregations. Nattokinase also reduced thromboxane B2 formation from collagen-activated platelets in a concentration-dependent manner. Rats were orally administered with nattokinase for 1 week, and their carotid arteries were exposed. Arterial thrombosis was induced by applying 35% FeCl3-soaked filter paper for 10 min, and the blood flow was monitored with a laser Doppler probe. Nattokinase delayed the FeCl3-induced arterial occlusion in a dose-dependent manner, doubling the occlusion time at 160 mg/kg. In addition, a high dose (500 mg/kg) of nattokinase fully prevented the occlusion, as achieved with aspirin (30 mg/kg). The results indicate that nattokinase extracted from fermented soybean inhibit platelet aggregation by blocking thromboxane formation, and thereby delay thrombosis following oxidative arterial wall injury. Therefore, it is suggested that nattokinase could be a good candidate without adverse effects for the improvement of blood flow.

Neuroprotective Effects of a Butanol Fraction of Rosa hybrida Petals in a Middle Cerebral Artery Occlusion Model

The neuroprotective effects of a butanol fraction of white rose petal extract (WRPE-BF) were investigated in a middle cerebral artery occlusion (MCAO) model. Seven week-old male rats were orally administered WRPE-BF for 2 weeks and subjected to MCAO for 2 h, followed by reperfusion. Twenty-four h later, MCAO-induced behavioral dysfunctions were markedly improved in a dose-dependent manner by pretreatment with WRPE-BF. Moreover, higher dose of WRPE-BF not only decreased infarction area but also effectively reduced astrogliosis. The expression of inducible nitric oxide synthase, cyclooxygenase-2, and glial fibrillary acidic protein in MCAO model were markedly inhibited by WRPE-BF treatment. Notably, WRPE-BF decreased nitric oxide and malondialdehyde levels in the striatum and subventricular zone of stroke-challenged brains. These data suggested that WRPE-BF may exert its neuroprotective effects via anti-oxidative and anti-inflammatory activities against ischemia-reperfusion brain injury and could be a good candidate as a therapeutic target for ischemic stroke.

Inhibitory effects of a beta-dunnione compound MB12662 on gastric secretion and ulcers / 한국실험동물학회지

The effects of a beta-dunnione compound MB12662 on the gastric secretion and ulcers were investigated in rats. In order to assess the effects of MB12662 on the gastric secretion and acidity, rats were subjected to pylorus ligation operation, and 6 hours later, gastric fluid was collected. Treatment with MB12662 reduced the gastric fluid volume to 47.3% of control level and increased pH. In an alcohol-induced ulcer model, rats were orally administered 3 mL/kg of ethanol, and 1 hour later, the ulcer lesions ware measured under a stereomicroscope. MB12662 reduced ulcer index in a dose-dependent manner which was much stronger than a proton-pump inhibitor pantoprazole. In a stress-induced ulcer model, rats were subjected to water-immersion restraint stress, and 5 hours later, the ulcer lesions ware examined. MB12662 also attenuated the stress-induced gastric lesions, although the efficacy of MB12662 was lower than that of pantoprazole. Therefore, it is suggested that MB12662 could be a candidate compound for the prevention or treatment of gastric ulcers induced by gastric over-secretion and alcoholic hangover.