• Food Science and Preservation
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• v.20 no.3
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• pp.394-403
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• 2013

This study was performed to investigate the four-week repeated-dose toxicity of the crude antifungal compounds produced by Lactobacillus plantarum AF1 (Lb. plantarum AF1), a lactic acid bacterium isolated from kimchi, in male and female rats. Sprague-Dawley male and female rats were divided into four groups, with 10 animals in each group. The test article was administered once daily by gavage to rats at dosage levels of 0, 500, 1,000, and 2,000 mg/kg/day for four weeks. There were no test-article-related deaths or abnormal clinical signs in both the male and female rats during the observation period. Furthermore, no differences in the body weight changes, food intake and water consumption levels of the control and treatment groups were found. The hematological parameters, serum biochemical analysis results, histopathological examination results and all other findings also showed no significant or dose-dependent changes. There were also no changes in the organ weights upon the administration of the crude antifungal compounds produced by Lb. plantarum AF1. These results suggest that the oral administration of the crude antifungal compounds produced by Lb. plantarum AF1 had no adverse effects up to a dosage level of 2,000 mg/kg in both male and female rats.

• Journal of Ginseng Research
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• v.44 no.5
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• pp.725-737
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• 2020

Background: T-cell acute lymphoblastic leukemia (T-ALL) is a kind of aggressive hematological cancer, and the PI3K/Akt/mTOR signaling pathway is activated in most patients with T-ALL and responsible for poor prognosis. 20(S)-Ginsenoside Rh2 (20(S)-GRh2) is a major active compound extracted from ginseng, which exhibits anti-cancer effects. However, the underlying anticancer mechanisms of 20(S)-GRh2 targeting the PI3K/Akt/mTOR pathway in T-ALL have not been explored. Methods: Cell growth and cell cycle were determined to investigate the effect of 20(S)-GRh2 on ALL cells. PI3K/Akt/mTOR pathway-related proteins were detected in 20(S)-GRh2-treated Jurkat cells by immunoblotting. Antitumor effect of 20(S)-GRh2 against T-ALL was investigated in xenograft mice. The mechanisms of 20(S)-GRh2 against T-ALL were examined by cell proliferation, apoptosis, and autophagy. Results: In the present study, the results showed that 20(S)-GRh2 decreased cell growth and arrested cell cycle at the G1 phase in ALL cells. 20(S)-GRh2 induced apoptosis through enhancing reactive oxygen species generation and upregulating apoptosis-related proteins. 20(S)-GRh2 significantly elevated the levels of pEGFP-LC3 and autophagy-related proteins in Jurkat cells. Furthermore, the PI3K/Akt/mTOR signaling pathway was effectively blocked by 20(S)-GRh2. 20(S)-GRh2 suppressed cell proliferation and promoted apoptosis and autophagy by suppressing the PI3K/Akt/mTOR pathway in Jurkat cells. Finally, 20(S)-GRh2 alleviated symptoms of leukemia and reduced the number of white blood cells and CD3 staining in the spleen of xenograft mice, indicating antitumor effects against T-ALL in vivo. Conclusion: These findings indicate that 20(S)-GRh2 exhibits beneficial effects against T-ALL through the PI3K/Akt/mTOR pathway and could be a natural product of novel target for T-ALL therapy.

• Journal of Ginseng Research
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• v.44 no.2
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• pp.222-228
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• 2020

Background: 20(S)-ginsenoside-Rg3 (C₄₂H₇₂O₁₃), a natural triterpenoid saponin, is extracted from red ginseng. The increasing use of 20(S)-ginsenoside Rg3 has raised product safety concerns. Methods: In acute toxicity, 20(S)-ginsenoside Rg3 was singly and orally administrated to Kunming mice and Sprague-Dawley (SD) rats at the maximum doses of 1600 mg/kg and 800 mg/kg, respectively. In the 26-week toxicity study, we used repeated oral administration of 20(S)-ginsenoside Rg3 in SD rats over 26 weeks at doses of 0, 20, 60, or 180 mg/kg. Moreover, a 4-week recovery period was scheduled to observe the persistence, delayed occurrence, and reversibility of toxic effects. Results: The result of acute toxicity shows that oral administration of 20(S)-ginsenoside Rg3 to mice and rats did not induce mortality or toxicity up to 1600 and 800 mg/kg, respectively. During a 26-week administration period and a 4-week withdrawal period (recovery period), there were no significant differences in clinical signs, body weight, food consumption, urinalysis parameters, biochemical and hematological values, or histopathological findings. Conclusion: The mean oral lethal dose (LD₅₀) of 20(S)-ginsenoside Rg3, in acute toxicity, is above 1600 mg/kg and 800 mg/kg in mice and rats, respectively. In a repeated-dose 26-week oral toxicity study, the no-observed-adverse-effect level for female and male SD rats was 180 mg/kg.

• Journal of Life Science
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• v.16 no.7 s.80
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• pp.1174-1180
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• 2006

The present study was sought to clarify whether the combination of mental activity with subway noise affects hematological variables. Fifty-six healthy volunteers participated in this experiment and underwent a stress task consisting of combination_of mental activity (mental arithmetic) with subway noise for 50 min and 60min of recovery after the end of the stress task. Venous blood samples were collected for measuring CBC, prothrombin time (PT), activated partial thromboplastin time (aPTT), erythrocyte sedimentation rate (ESR), fibrinogen concentration, D-dimer and high sensitive C-reactive protein (H-CRP) levels before (baseline), 50min of stress task (S-50m), and 60 min of recovery (R-60m). Total leukocyte, neutrophil and lymphocyte counts significantly increased at R-60m compared with baselines. RBC count at S-50m was higher, while monocyte counts at S-50m and R-60m were lower than those of baselines. aPTTs shortened at S-50m and R-60m, but PT reduced at R-60m as compared with baselines. D-dimer and H-CRP levels at S-50m and R-60m were significantly higher than those of baselines. These findings imply that a combination of mental activity with subway noise nay cause leukocytosis, homo-concentration, shortened PT and aPTT, decreased ESR, and raised D-dimer and H-CRP levels, suggesting possible development of inflammation and prothrombogenic reaction attributable to a subway environment.

• Journal of Life Science
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• v.24 no.6
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• pp.700-706
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• 2014

Doxorubicin (trade name adriamycin), an anthracycline antibiotic, is commonly used in the treatment of a wide range of cancers, including hematological malignancies, many types of carcinoma, and soft tissue sarcomas. It is closely related to the natural product daunomycin, and like all anthracyclines, it works by intercalating DNA. Its most serious adverse effect is life-threatening heart damage. Its anti-metastatic mechanisms in human prostate carcinomas are not fully understood. In this study, we used LNCap human prostate carcinoma cells to investigate the inhibitory effects of doxorubicin on cell motility and invasion, two critical cellular processes that are often deregulated during metastasis. Doxorubicin treatment inhibited cell migration and invasiveness of LNCap cells without showing any toxicity. Doxorubicin treatment also suppressed the activity and expression of matrix metalloproteinase (MMP)-2 and MMP-9, which were associated with up-regulated expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in LNCap cells. Doxorubicin treatment also attenuated the expression levels of claudin family members (claudin-1, -2,-3 and -4), major components of tightening of tight junctions (TJs) and increased the tightening of TJs, as demonstrated by an increase in transepithelial electrical resistance. The present findings demonstrate that doxorubicin reduces the migration and invasion of prostate carcinomas LNCap cells by modulating the activity of TJs and MMPs.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.5
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• pp.612-620
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• 2012

This study was performed to investigate the 4-week repeated-dose toxicity of $Lactobacillus$ $plantarum$ AF1 ($Lb.$ $plantarum$ AF1), a lactic acid bacteria isolated from kimchi, in male and female rats. Sprague-Dawley male and female rats were divided into four groups, with 10 animals in each group. The test article was administered once daily by gavage to rats at dosage levels of 0, 0.5, 1.0, and 2.0 g/kg/day for 4-weeks. There were no test articlerelated deaths or abnormal clinical signs in either gender of rat during the observation period. Furthermore, no differences were found between the control and treatment groups in terms of body weight changes, food intake, and water consumptions. Hematological parameters, serum biochemical analysis, and any other findings also showed no significant or dose-dependent alterations. There were no alterations in organ weights upon administration of $Lb.$ $plantarum$ AF1. These results suggest that there were no adverse effects of oral application of $Lb.$ $plantarum$ AF1 up to a dosage level of 2.0 g/kg in both male and female rats.

• The Journal of Internal Korean Medicine
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• v.27 no.3
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• pp.664-676
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• 2006

Objective : Although chronic non-bacterial prostatitis is a common disease, it is very difficult to treat effectively. Lygodium japonicum has been traditionally used in treatment of urinary tract inflammation and voiding disturbance. In this study, we investigated the therapeutic effects and action mechanism of Lygodium japonicum in the rat model of non-bacterial prostatitis induced by castration and testosterone treatment. Methods : Five-month-old rats were treated with 17$\beta$-estradiol after castration for induction of experimental non-bacterial prostatitis, which is similar to human chronic prostatitis in histopathological profiles. Lygodium japonicum and testosterone were administered as an experimental specimen and a positive control. respectively. The prostates were evaluated by histopathological parameters including the epithelial score and epithelio-stromal ratio for glandular damage. PCNA labeling index for cyto-proliferation and a TUNEL(deoxyuridine triphosphate biotin nick end-labeling) assay for cell apoptosis. Results : While prostates of control rats revealed severe acinar gland atrophy and stromal proliferation, the rats treated with Lygodium japonicum showed a diminished range of tissue damage. Epithelial score was improved in the Lygodium japonicum group over that of the control (P<0.05). The epithelio-stromal ratio was lower in the Lygodiutn japonicum group when compared to that of the control (P<0.05). Although there was no difference in PCNA and TUNEL positive cells of the glandular epithelia. we found an decreased number of PCNA positive cell and concurrent increase of TUNEL positive cells in the stroma of Lygodium japonicum treated rats (P<0.01). Conclusions : These findings suggest that Lygodium japonicum may protect the glandular epithelial cells and also inhibit stromal proliferation in association with suppression of cyto-proliferation and stimulation of apoptosis. We concluded that Lygodium japonicum could be a useful remedy agents for treating chronic non-bacterial prostatitis.

• Korean Journal of Food Science and Technology
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• v.50 no.6
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• pp.629-635
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• 2018

In this study, the safety aspect of Maesil-cheongs with reduced amygdalin levels was investigated in terms of toxicokinetics and repeated oral toxicity. Plasma or UVC treatment was utilized to obtain Maesil-cheongs with reduced amygdalin levels. The toxicokinetic study demonstrated that the oral absorption of amygdalin decreased remarkably after a single-dose oral administration of both plasma- and UVC-treated Maesil-cheongs. The fourteen-day repeated oral toxicity study revealed that plasma- or UVC-treated Maesil-cheongs did not cause changes in body weight, food intake, water consumption, and absolute and relative organ weights. No significant effects on hematological and serum biochemical parameters were found. Histopathological examination showed no abnormality or toxicological change. These findings suggest that plasma- and UVC-treated Maesil-cheongs have no toxicity potential, and these processes will be useful to obtain products with safe, reduced amygdalin levels.

• Herbal Formula Science
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• v.29 no.3
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• pp.127-145
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• 2021

Objectives : The purpose of this study was to evaluate the effects of Daeganghwal-tang on knee cartilage in monosodium iodoacetate(MIA)-induced osteoarthritis rats. Methods : Forty SD rats were randomly divided into five groups(n=8/group): normal group was SD rats group injected with normal saline at left knee joint and administrated orally distilled water, control group was MIA-induced osteoarthritis SD rats group administrated orally distilled water, Indomethacin group was MIA-induced osteoarthritis SD rats group administrated orally indomethacin 2 mg/kg, DGHT(L) group was MIA-induced osteoarthritis SD rats group administrated orally 1280 mg/kg of Daeganghwal-tang, and DGHT(H) group was MIA-induced osteoarthritis SD rats group administrated orally 2560 mg/kg of Daeganghwal-tang. After orally administration of drugs for 4 weeks, gross appearance and histological analysis were used to evaluate the degree of knee cartilage damage. In addition, pro-inflammatory cytokines, bone degrade factor and bone defence factors were analyzed to investigate the anti-inflammatory and cartilage protection effects of Daeganghwal-tang. Also, hematological test, biochemical test, and liver and kidney tissue were analyzed to determine the safety of Daeganghwal-tang. Results : Daeganghwal-tang inhibited the damage of the knee cartilage, and significantly prevented the reduction in cartilage thickness. In addition, the pro-inflammatory cytokines and the bone degrade factor significantly decreased, and the bone defence factors significantly increased. In the safety assessment of Daeganghwal-tang, there were no significant differences among the experimental groups and no abnormal findings were observed. Conclusions : Daeganghwal-tang has anti-inflammatory effect, inhibits cartilage damage, and protects cartilage in MIA-induced osteoarthritis rats.

• Journal of Pharmacopuncture
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• v.26 no.1
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• pp.27-37
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• 2023

Objectives: Moroccan Arbutus unedo is an essential medicinal plant; however, little is known about the biological properties of its leaves mentioned in Moroccan traditional medicine. Methods: Various standard experiments were performed to evaluate the phytochemical, antidiabetic, antioxidant, antibacterial, and acute and sub-chronic toxicity characteristics of A. unedo leaves. Results: Phytochemical screening led to the identification of several phytochemical classes, including tannins, flavonoids, terpenoids, and anthraquinones, with high concentrations of polyphenols (31.83 ± 0.29 mg GAEs/g extract) and flavonoids (16.66 ± 1.47 mg REs/g extract). Further, the mineral analysis revealed high levels of calcium and potassium. A. unedo extract demonstrated significant antioxidant and anti-diabetic activities by inhibiting α-amylase (1.350 ± 0.32 g/mL) and α-glucosidase (0.099 ± 1.21 g/mL) compared to the reference drug Acarbose. Also, the methanolic extract of the plant exhibited significantly higher antibacterial activity than the aqueous extract. Precisely, three of the four examined bacterial strains exhibited substantial susceptibility to the methanolic extract . Minimum bactericidal concentration (MBC)/minimum inhibitory concentration (MIC) values indicated that A. unedo harbor abundant bactericidal compounds. For toxicological studies, mice were administered with A. unedo aqueous extract at single doses of 2,000 and 5,000 mg/kg. They did not exhibit significant abnormal behavior, toxic symptoms, or death during the 14-day acute toxicity test and the 90-day sub-chronic toxicity test periods. The general behavior, body weight, and hematological and biochemical status of the rats were assessed, revealing no toxicological symptoms or clinically significant changes in biological markers observed in the mice models, except hypoglycemia, after 90 days of daily dose administration. Conclusion: The study highlighted several biological advantages of A. unedo leaves without toxic effects in short-term application. Our findings suggest that conducting more comprehensive and extensive in vivo investigations is of utmost importance to identify molecules that can be formulated into pharmaceuticals in the future.