• Advances in Traditional Medicine
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• v.7 no.4
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• pp.336-340
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• 2007

Plants from the genus Centaurea (C.) (Family: Asteraceae alt. Compositae), widely distributed in Asia, Europe and North America, have traditionally been used in the treatment of various ailments. As a part of our on-going studies on the plants from the genus C. for their phytochemistry and biological activities, extracts of the seeds of Turkish endemic C. species, C. bornmuelleri and C. huber-morathii, were tested for their cytotoxicity towards the CaCo2 colon cancer cell line as well as for the toxicity towards the brine shrimps, using the MTT and the brine shrimp lethality assays, respectively. Among the extracts, the MeOH extract of these plants showed significant toxicity towards the brine shrimps ($LD_{50}=55.2{\times}10^{-2}\;and\;42.4{\times}10^{-2}mg/ml$, respectively). The MeOH extract of both C. species also inhibited the growth of CaCo2 colon cancer cells in the MTT assay ($IC_{50}$=29.9 and 33.0 g/ml, respectively). As the most prominent activities in both assays were observed with the MeOH extracts, it can be assumed that the compound(s) responsible for these activities are polar in nature.

• The Journal of Internal Korean Medicine
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• v.21 no.1
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• pp.46-54
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• 2000

Objectives : Talmyung-san(TMS) has been used for treatment of brain diseases in Chinese traditional medicine. However, little is known about the mechanism by which TMS rescues brain cells from ischemic damages. To elucidate the protective mechanisms of TMS, we execute experiments. Methods : The effects of TMS on ischemia/reperfusion-induced cytotoxicity and generation of nitric oxide(NO) are investigated in primary neonatal myocardial cells and A7rS, aortic smooth muscle cell line. Results : Ischemia/reperfusion itself induces severe myocardial cell death in vitro. However, treatment of the cells with TMS significantly reduces both ischemia/reperfusion-induced myocardial cell death and LDH release. In addition, pretreatment of TMS before reperfusion recovers the lose of beating rates alter ischemia/reperfusion. For a while, the water extract of TMS stimulates myocardial cells to produce NO in a dose dependent manner and it protects the damage of ischemia/reperfusion-induced myocardial cells. Furthermore, the protective effects of the water extract of TMS is mimicked by treatment of sodium nitroprusside, an exogenous NO donor. NG-monomethyl-L-arginine (NGMMA), a specific inhibitor of nitric oxide synthase(NOS), significantly blocks the protective effects of TMS on the cells after ischemia/reperfusion. In addition, on ischemia the water extract of TMS induce NO in A7r5 cell. Conclusions : Taken together, we suggest that the protective effects of TMS against ischemia/reperfusion-induced myocardial damages may be mediated by NO production of myocardial and vascular smooth muscle cell during ischemic condition.

• The Journal of Internal Korean Medicine
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• v.34 no.1
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• pp.14-30
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• 2013

Objectives : The aim of this study was to investigate whether the effects of extract from Saengkankunbi-tang and its composition that Artimisiae capillaris Herba, Crataegi Fructus, Alismatis Rhizoma, Hoelen and Raphani Semen could protect HepG2 cells from palmitic acid-induced lipotoxicity through lysosomal and mitochondrial pathways in an in vitro model. Methods : To examine the effects of the extracts from Saengkankunbi-tang and its composition that Artimisiae capillaris Herba, Crataegi Fructus, Alismatis Rhizoma, Hoelen and Raphani Semen on palmitic acid-induced lipotoxicity in HepG2 cells, we measured the contents of cell viability, cytotoxicity. Then to investigate the effects of the extract from Saengkankunbi-tang, Artimisiae capillaris Herba and Raphani Semen, we measured that triglyceride, reactive oxygen species, ATP levels, glutathione levels, cytochrome c and cathepsin B. Results : The extracts from Saengkankunbi-tang and its composition had a cell-protective function. The extracts from Saengkankunbi-tang, Artimisiae capillaris Herba and Raphani Semen controlled triglyceride over-accumulation in cells and reduced overproduction of reactive oxygen species. The extracts from Saengkankunbi-tang and Raphani Semen increased ATP and glutathione levels which had been decreased by lipotoxicity. The extracts from Saengkankunbi-tang, Artimisiae capillaris Herba and Raphani Semen reduced leakage of cytochrome c and the extracts from Saengkankunbi-tang and Raphani Semen reduced leakage of cathepsin B in lipotoxicity. Conclusions : These results show that the extracts from Saengkankunbi-tang and its composition that Artimisiae capillaris Herba and Raphani Semen have cell protective effects on palmitic acid-induced lipotoxicity through lysosomal and mitochondrial pathways.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5131-5136
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• 2012

Cancer is one of the major health problems worldwide and its current treatments have a number of undesired adverse side effects. Natural compounds may reduce these. Currently, a few plant products are being used to treat cancer. In this study, goniothalamin, a natural occurring styryl-lactone extracted from Goniothalamus macrophyllus, was investigated for cytotoxic properties against cervical cancer (HeLa), breast carcinoma (MCF-7) and colon cancer (HT29) cells as well as normal mouse fibroblast (3T3) using MTT assay. Fluorescence microscopy showed that GTN is able to induce apoptosis in HeLa cells in a time dependent manner. Flow cytometry further revealed HeLa cells treated with GTN to be arrested in the S phase. Phosphatidyl serine properties present during apoptosis enable early detection of the apoptosis in the cells. Using annexin V/PI double staining it could be shown that GTN induces early apoptosis on HeLa cells after 24, 48 and 72 h. It could be concluded that goniothalamin showing a promising cytotoxicity effect against several cancer cell lines including cervical cancer cells (HeLa) with apoptosis as the mode of cell death induced on HeLa cells by Goniothalamin was.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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• pp.89-94
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• 1998

Marine sponges are recognized as a plentiful source of diverse biologically active secondary metabolites. Recently, we have initiated a research to discover antitumor constituents from the marine sponges collected from Korean Waters. Marine sponges collected from the South Sea of Korea were screened for several biological activities including such as brine shrimp lethality and cytotoxicity. Significant brine shrimp lethality was detected in the crude extract of a two-sponge association of Poecillastra sp. and Jaspis sp. A cross-section of this sample showed two layers of morphologically distinct sponges. The thin and dirty yellow outer layer was identified as Poecillastra sp. (Pachastrellidae), the surface of which was very rough. The light-grey inner layer was identified as Jaspis sp. (Jaspidae), the surface of which was smooth. This two-sponge association appears to be consistent as these sponges were always found in associated form regardless of collection site or collection period. Investigation of the bioactive constituents monitored by brine shrimp lethality assay led to the isolation of pectenotoxin II (PTX2) and psammaplin A as causative compounds for the brine shrimp lethality. $^1$H- and $\^$13/C-nmr signals of PTX2 was fully assigned utilizing TOCSY, HETCOR, Long-range HETCOR, and Homonuclear J-resolved 2D experiments. PTX2 displayed very potent and selective cytotoxicities in the 60 cell line panel antitumor assay at the NCI. PTX2 has progressed to acute toxicity determination and in vivo antitumor assay at the NCI (Table 1). However, significant in vitro antitumor activity of PTX2 can not be affirmed in the in vivo assay.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.74-74
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• 1993

The in vitro cytotoxicity of SKI 2053R was evaluated against human tumor cell lines along with those of cisplatin and carboplatin using MTT assay. The cell lines tested were two human lung cancer cell lines and five human stomach cancer celt lines. The level of cytotoxic effects of SKI 2053R against two human lung cancer cell lines was located between cisplatin and carboplatin. However, the cytotoxic activity of SKI 2053R against five human stomach cancer cell lines was similar to that of cisplatin. SKI 2053R is considered to be selectively cytotoxic toward human stomach cancer cell lines. We carried out pharmacokinetic and ex vivo phrmacodynamic studies of SKI 2053R in beagle dogs to predict the clinical antitumor effect of SKI2053R, comparing with those of cisplatin and carboplatin. In ex vivo pharmacodynamics which used MTT assay as bioassay on the 2 lung and 5 stomach cancer cell, mean antitumor indexes (ATIs) of SKI 2053R were highest among three compounds in both lung and stomach cancer cell lines, especially in stomach cancer cell. Much higher ATI profile and maximal inhibition rates of SKI 2053R appeared in the stomach cancer cells will give desirable advantages to clinical trial s against gastric carcinoma. The anti tumor activity and target organ toxicity of SKI 2053R were compared with those of cisplatin on stomach cancer cell line, KATO III xenografted into nude BALB/c(nu/nu) mice. All groups of cisplatin and SKI 2053R showed active tumor regression. The inhibition rates(IR) of SKI 2053R were higher than that of cisplatin on the basis of mean IR. Though the loss of body weight was observed in all groups from the first week, the SKI 2053R group recovered it soon from the third week after the initiation of treatment, maintaining the most active anti tumor activity among three groups.

• Korean Journal of Plant Resources
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• v.19 no.6
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• pp.649-654
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• 2006

The objective of present study was to investigate the anti oxidative and hepatoprotective effects of tomato extracts. Total antioxidant capacity and total antioxidant response were 5.5 and $19.8{\mu}g$ Trolox equivalent per mg of tomato extract, respectively. DPPH radical scavenging activity of tomato extracts ($10mg\;ml^{-1}$) was 70% as compared to 100% by pyrogallol solution as a reference. The effect of the tomato extracts on lipid peroxidation was examined using rat liver mitochondria induced by iron/ascorbate. Tomato extracts at the concentration of $0.5mg\;ml^{-1}$ significantly decreased TBARS concentration. Tomato extracts prevented lipid peroxidation in a dose-dependent manner. The effect of the tomato extracts on reactive oxygen species (ROS) generation was examined using cell-free system induced by $H_2O_2/FeSO_4$. Addition of $1mg\;ml^{-1}$ of tomato extracts significantly reduced dichlorofluorescein (DCF) fluorescence. Tomato extracts caused concentration-dependent attenuation of the increase in DCF fluorescence, indicating that tomato extracts significantly prevented ROS generation in vitro. The effect of tomato extracts on cell viability and proliferation was examined using hepatocyte culture. Primary cultures of rat hepatocytes were incubated with 1mM tert-butyl hydroperoxide (t-BHP) for 90 min in the presence or absence of tomato extracts. MTT values by addition of tomato extracts at the concentration of 2, 10, and $20mg\;ml^{-1}$ in the presence of t-BHP were 13, 33 and 48%, respectively, compared to 100% as control. Tomato extracts increased cell viability in a dose-dependent manner. These results demonstrate that tomato extracts suppressed lipid peroxidation and t-BHP-induced hepatotoxicity and scavenged ROS generation. Thus antioxidant and hepatoprotective effects of tomato extracts seem to be due to, at least in part, the prevention from free radicals-induced oxidation, followed by inhibition of lipid peroxidation.

• Journal of Microbiology and Biotechnology
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• v.29 no.9
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• pp.1444-1452
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• 2019

The conventional prophylactic vaccines for human papillomavirus (HPV) efficiently prevent infection with high-risk HPV types, but they do not promote therapeutic effects against cervical cancer. Previously, we developed HPV16 E7-expressing Lactobacillus casei (L. casei-E7) as a therapeutic vaccine candidate for cervical cancer, which induces antitumor therapeutic effects in a TC-1 murine cancer model. To improve the therapeutic effect of L. casei-E7, we performed co-treatment with poly-gamma-glutamic acid (${\gamma}-PGA$), a safe and edible biomaterial naturally secreted by Bacillus subtilis. We investigated their synergistic effect to improve antitumor efficacy in a murine cancer model. The treatment with ${\gamma}-PGA$ did not show in vitro cytotoxicity against TC-1 tumor cells; however, an enhanced innate immune response including activation of dendritic cells was observed. Mice co-administered with ${\gamma}-PGA$ and L. casei-E7 showed significantly suppressed growth of TC-1 tumor cells and an increased survival rate in TC-1 mouse models compared to those of mice vaccinated with L. casei-E7 alone. The administration of ${\gamma}-PGA$ markedly enhanced the activation of natural killer (NK) cells but did not increase the E7-specific cytolytic activity of $CD8^+$ T lymphocytes in mice vaccinated with L. casei-E7. Overall, our results suggest that oral administration of ${\gamma}-PGA$ induces a synergistic antitumor effect in combination with L. casei-E7.

• Food Science of Animal Resources
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• v.42 no.5
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• pp.903-914
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• 2022

Probiotics are currently considered as one of tools to modulate immune responses under specific clinical conditions. The purpose of this study was to evaluate whether oral administration of three different probiotics (Lactiplantibacillus plantarum CJLP243, CJW55-10, and CJLP475) could evoke a cell-mediated immunity in immunodeficient mice. Before conducting in vivo experiments, we examined the in vitro potency of these probiotics for macrophage activation. After co-culture with these probiotics, bone marrow derived macrophages (BMDMs) produced significant amounts of proinflammatory cytokines including interleukin-6 (IL-6), IL-12, and tumor necrosis factor-α (TNF-α). Levels of inducible nitric oxide synthase (inos) and co-stimulatory molecules (CD80 and CD86) were also upregulated in BMDMs after treatment with some of these probiotics. To establish an immunocompromised animal model, we intraperitoneally injected mice with cyclophosphamide on day 0 and again on day 2. Starting day 3, we orally administered probiotics every day for the last 15 d. After sacrificing experimental mice on day 18, splenocytes were isolated and co-cultured with these probiotics for 3 d to measure levels of several cytokines and immune cell proliferation. Results clearly indicated that the consumption of all three probiotic strains promoted secretion of interferon-γ (IFN-γ), IL-1β, IL-6, IL-12, and TNF-α. NK cell cytotoxicity and proliferation of immune cells were also increased. Taken together, our data strongly suggest that consumption of some probiotics might induce cell-mediated immune responses in immunocompromised mice.

• Restorative Dentistry and Endodontics
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• v.48 no.1
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• pp.2.1-2.12
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• 2023

Objectives: In this study, natural substances were introduced as primary dental pulp caps for use in pulp therapy, and the antimicrobial and cytotoxic properties of these substances were investigated. Materials and Methods: In this in vitro study, the antimicrobial properties of calcium-enriched mixture (CEM) cement, propolis, and propolis individually combined with the extracts of several medicinal plants were investigated against Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. Then, the cytotoxicity of each substance or mixture against pulp stem cells extracted from 30 primary healthy teeth was evaluated at 4 concentrations. Data were gathered via observation, and optical density values were obtained using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) test and recorded. SPSS software version 23 was used to analyze the data. Data were evaluated using 2-way analysis of variance and the Tukey test. Results: Regarding antimicrobial properties, thyme alone and thyme + propolis had the lowest minimum inhibitory concentrations (MICs) against the growth of S. aureus, E. coli, and P. aeruginosa bacteria. For E. faecalis, thyme + propolis had the lowest MIC, followed by thyme alone. At 24 and 72 hours, thyme + propolis, CEM cement, and propolis had the greatest bioviability in the primary dental pulp stem cells, and lavender + propolis had the lowest bioviability. Conclusions: Of the studied materials, thyme + propolis showed the best results in the measures of practical performance as a dental pulp cap.