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.

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This article has been retracted.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.

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.

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.

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.

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.

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.

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.

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.

Specific nephrotoxicity and cardiotoxicity of BT-CAL(R), Sigma Anti-bonding Molecule Calcium Carbonate, in mice / 한국실험동물학회지

According to a high anti-osteoporotic efficacy of Sigma Anti-bonding Molecule Calcium Carbonate (SAC), repeated-dose toxicities of SAC were investigated to assess its feasibility as drug or functional food ingredient. Male ICR mice were given drinking water containing 0.006, 0.02 or 0.06% SAC for 4 weeks. SAC feeding decreased the body weights and feed and water consumptions of mice in a dose-dependent manner, especially, leading to severe emaciation and 70% death in 3 weeks in the high-dose (0.06%) group. Not only kidney and heart weights, but also the levels of blood urea nitrogen, creatinine, aspartate transaminase, and creatine phospokinase significantly increased after SAC administration, indicative of nephrotoxicity and cardiotoxicity. Such renal and cardiac toxicities were also confirmed by microscopic findings, exhibiting renal crystals and cardiac fibrosis, which may be due to the insoluble crystal formation and calcium overload, respectively. In conclusion, it is suggested that no observed adverse effect level of SAC is lower than 0.006% in mice, and that a long-term intake may cause serious adverse effects on renal and cardiac functions.

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.

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.

Anti-hypercholesterolemic and anti-atherosclerotic effects of polarized-light therapy in rabbits fed a high-cholesterol diet / 한국실험동물학회지

The effects of polarized-light therapy (PLT) on high-cholesterol diet (HCD)-induced hypercholesterolemia and atherosclerosis were investigated in comparison with that of lovastatin in rabbits. Hypercholesterolemia was induced by feeding male New Zealand white rabbits with 1% cholesterol in diet for 2 weeks and maintained with 0.5% cholesterol for 6 weeks, followed by normal diet for 2 weeks for recovery. Lovastatin (0.002% in diet) or daily 5-min or 20-min PLT on the outside surface of ears was started 2 weeks after induction of hypercholesterolemia. Hypercholesterolemic rabbits exhibited great increases in serum cholesterol and low-density lipoproteins (LDL) levels, and finally severe atheromatous plaques formation covering 57.5% of the arterial walls. Lovastatin markedly reduced both the cholesterol and LDL, but the reducing effect (47.5%) on atheroma formation was relatively low. By comparison, 5-min PLT preferentially decreased LDL, rather than cholesterol, and thereby potentially reduced the atheroma area to 42.2%. Notably, 20-min PLT was superior to lovastatin in reducing both the cholesterol and LDL levels as well as the atheromatous plaque formation (26.4%). In contrast to the increases in blood alanine transaminase and aspartate transaminase following lovastatin treatment, PLT did not cause hepatotoxicity. In addition, PLT decreased platelets and hematocrit level. The results indicate that PLT attenuates atherosclerosis not only by lowering blood cholesterol and LDL levels, but also by improving blood flow without adverse effects. Therefore, it is suggested that PLT could be a safe alternative therapy for the improvement of hypercholesterolemia and atherosclerosis.

Anti-Helicobacter pylori effects of IgY from egg york of immunized hens / 한국실험동물학회지

Effects of egg york containing IgY specific for Helicobacter pylori on the bacterial growth and intragastric infection were investigated in comparison with a proton-pump inhibitor pantoprazole. For in vitro anti-bacterial activity test, H. pylori (1x108 CFU/mL) was incubated with a serially diluted IgY for 3 days. As a result, IgY fully inhibited the bacterial growth at 16 mg/mL, which was determined to a minimal inhibitory concentration. In vivo elimination study, male C57BL/6 mice were infected with the bacteria by intragastric inoculation (1x108 CFU/mouse) 3 times at 2-day intervals, and 2 weeks later, orally treated twice a day with 50, 100, 200 or 500 mg/kg IgY for 18 days. After the final administration, biopsy sample of the gastric mucosa was assayed for the bacterial identification via urease, oxidase, catalase, nitrate reduction and H2S tests in addition to microscopic examination for mucosal inflammation. In CLO kit test, 75, 50, 12.5 and 12.5% of the animals revealed positive reaction following treatment with 50, 100, 200 and 500 mg/kg IgY, respectively, resulting in a superior efficacy at 200 mg/kg than 30 mg/kg pantoprazole that displayed 75% elimination. The CLO test results were confirmed by bacterial identification. Microscopic examination revealed that H. pylori infection caused severe gastric mucosal inflammation, which were not observed in the CLO-negative mice following treatment with IgY or pantoprazole. Taken together, IgY inhibited the growth of H. pylori, and improved gastritis and villi injuries by eliminating the bacteria from the stomach. The results indicate that IgY could be a good candidate overcoming tolerance of antibiotics for the treatment of H. pylori-mediated gastric ulcers.

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

The anti-inflammatory effects of fuciodan and Cistanche tubulosa (CT) extract were investigated in vitro macrophage culture system and in vivo carrageenan-induced air pouch inflammation model. CT extract inhibited nitric oxide production from activated RAW 264.7 macrophage cells, while fucoidan was inactive. 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 fucoidan or CT extract. Moreover, tissue inflammation was substantially attenuated by the combinational therapy. However, there was no synergistic effect against the inflammatory cell infiltration, although fucoidan and CT extract each markedly reduced the cell numbers. Therefore, it is suggested that fucoidan blocks infiltration of inflammatory cells, while CT extract inhibits activation of the cells, and that their combinational treatment could be a promising candidate for the relief of various types of inflammation.