• Title/Summary/Keyword: in vitro experiments

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Anti-Cancer Effect of Ginsenoside F2 against Glioblastoma Multiforme in Xenograft Model in SD Rats

  • Shin, Ji-Yon;Lee, Jung-Min;Shin, Heon-Sub;Park, Sang-Yong;Yang, Jung-Eun;KimCho, So-Mi;Yi, Tae-Hoo
    • Journal of Ginseng Research
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    • v.36 no.1
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    • pp.86-92
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    • 2012
  • The glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. Despite combination treatments of radiation and chemotherapy, the survival periods are very short. Therefore, this study was conducted to assess the potential of ginsenoside $F_2$ (F2) to treat GBM. In in vitro experiments with glioblastoma cells U373MG, F2 showed the cytotoxic effect with $IC_{50}$ of 50 ${\mu}g/mL$ through apoptosis, confirmed by DNA condensation and fragmentation. The cell population of cell cycle sub-G1 as indicative of apoptosis was also increased. In xenograft model in SD rats, F2 at dosage of 35 mg/kg weight was intravenously injected every two days. This reduced the tumor growth in magnetic resonance imaging images. The immunohistochemistry revealed that the anticancer activity might be mediated through inhibition of proliferation judged by Ki67 and apoptosis induced by activation of caspase-3 and -8. And the lowered expression of CD31 showed the reduction in blood vessel densities. The expression of matrix metalloproteinase-9 for invasion of cancer was also inhibited. The cell populations with cancer stem cell markers of CD133 and nestin were reduced. The results of this study suggested that F2 could be a new potential chemotherapeutic drug for GBM treatment by inhibiting the growth and invasion of cancer.

Strawberry, Garlic and Kale Consumption Increase Urinary Excretion of Dimethylamine and Trimethylamine in Humans

  • Chung, Mi-Ja;Lee, Soo-Jung;Shin, Jung-Hye;Sung, Nak-Ju
    • Preventive Nutrition and Food Science
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    • v.8 no.1
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    • pp.19-23
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    • 2003
  • Dimethylamine (DMA) is the immediate precursor of carcinogenic N-nitrosodimethylamine (NDMA). In vitro and in vivo experiments using whole strawberries, and garlic and kale juices were conducted to determine concentrations of DMA and trimethylamine (TMA) in foods and urine. Experimental diets [an amino-rich diet as nitrosatable precursors in combination with added nitrate-containing drinking water without (TD1) or with whole strawberries or garlic or kale juices (TD2, TD3 and TD4, respectively), or a diet of low in nitrate and amino (TD5) were incubated in simulated saliva and gastric juices at 37$^{\circ}C$ for 1 hour. We also studied the urinary excretion of DMA and TMA after consumption of the experimental diets (TD1~TD5). Urine samples were obtained for 18 hrs after consumption of experimental diets and concentrations of DMA and TMA were measured in the digested diet and urine. The DMA concentration after incubation in experimental diets (TD1~TD5) was 4.7$\pm$0.3, 6.7 $\pm$0.2, 7.9$\pm$0.2, 7.1$\pm$0.2 and 0.3$\pm$0.1 mg/kg, respectively. Urinary excretion of DMA (TD1~TD5) was 22.0$\pm$5.0, 28.3$\pm$4.3, 29.2$\pm$4.1, 27.4$\pm$4.5 and 20.4$\pm$3.1 mg/18 hr, respectively. Consumption diets with added strawberries or juices of kale or garlic increased urinary TMA and DMA, suggesting that those precursors were excreted and not converted to the carcinogen, NMDA.

Effect of $\beta$-Mercaptoethanol and Cysteamine With Bovine Oviduct Epithelial Cells on Development and Intracellular Glutathione Concentrations of Bovine IVM/IVF Embryos ($\beta$-Mercaptoethanol과 Cysteamine 첨가와 소 난관상피세포 공동배양이 소 체외수정란의 체외발육과 세포내 Glutathione 농도 변화에 미치는 영향)

  • 박동헌;양부근;김준국;정희태;박춘근;김종복;김정익
    • Journal of Embryo Transfer
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    • v.12 no.3
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    • pp.269-276
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    • 1997
  • The objective of this study was to investigate the effects of thiol compounds with bovine oviduct epithlial crlls(BOEC) co culture on development and intracellular glutathione(GSH) concentrations of bovine embryos derived from IVM /IVF oocytes. In experiment 1 and 2, embryos developed to 2~8 cell stage after in vitro fertilization were co-cultured with BOEC in CR$_1$aa with or without $\beta$-mercaptoethanol($\beta$-ME) and cysteamine. The percentage of embryos that developed to morulae and blastocysts in 0,10, 25 and 5O$\pi$M $\beta$-ME with BOEC was 48.1, 64.0, 72.9 and 75.9%, respectively. Twenty-five and 5O$\pi$M $\beta$-ME groups were significantly higher than in 0 and 1O$\pi$M $\beta$- -ME groups(P$\pi$M cysteamine with BOEC was 50.0, 53.2, 72.0 and 66.7%, respectively. Fifty $\pi$M cysteamine group was significantly higher than any other groups (P$_4$aa with 0 and 5O$\pi$M $\beta$-ME or cysteamine were 68.5, 77.8, 78.7 and 80.0pM, respectively. Fifty $\pi$M $\beta$-ME group was significantly higher than that of control(P<0.05), but cysteamine group was not. Cell numbers of blastocysts were not difference in all experimental groups. These experiments indicate that $\beta$-ME and cysteamine with BOEC co-culture can affect the development and intracellular GSH concentrations of bovine embryos produced by IVM /IVF docytes.

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DC23, a Triazolothione Resorcinol Analogue, Is Extensively Metabolized to Glucuronide Conjugates in Human Liver Microsomes

  • Shon, Jong Cheol;Joo, Jeongmin;Lee, Taeho;Kim, Nam Doo;Liu, Kwang-Hyeon
    • Mass Spectrometry Letters
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    • v.9 no.1
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    • pp.24-29
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    • 2018
  • DC23, a triazolothione resorcinol analogue, is known to inhibit heat shock protein 90 and pyruvate dehydrogenase kinase which are up-regulated in cancer and diabetes, respectively. This study was performed to elucidate the metabolism of DC23 in human liver microsomes (HLMs). HLMs incubated with DC23 in the presence of uridine 5'-diphosphoglucuronic acid (UDPGA) and/or ${\beta}$-nicotinamide adenine dinucleotide phosphate (NADPH) resulted in the formation of four metabolites, M1-M4. M1 was identified as DC23-N-Oxide, on the basis of LC-MS/MS analysis. DC23 was further metabolized to its glucuronide conjugates (M2, M3, and M4). In vitro metabolic stability studies conducted with DC23 in HLMs revealed significant glucuronide conjugation with a $t_{1/2}$ value of 1.3 min. The inhibitory potency of DC23 on five human cytochrome P450s was also investigated in HLMs. In these experiments, DC23 inhibited CYP2C9-mediated tolbutamide hydroxylase activity with an $IC_{50}$ value of $8.7{\mu}M$, which could have implications for drug interactions.

Water Extract of Taraxaci Radix Improves Rheumatoid Arthritis Induced by Type-II Collagen in Animal Models (민들레 뿌리 물 추출물의 류마티스 관절염 동물 모델에 대한 개선 효과)

  • Nho, Jong Hyun;Lee, Hyun Joo;Jang, Ji Hun;Yang, Beo Dul;Kim, A Hyeon;Woo, Kyeong Wan;Hwang, Tae Yeon;Seo, Jae Wan;Cho, Hyun Woo;Jung, Ho Kyung
    • Korean Journal of Medicinal Crop Science
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    • v.27 no.1
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    • pp.38-44
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    • 2019
  • Background: Taraxacum platycarpum has been used in traditional medicine in Korea to treat intoxication and edema and as a diuretic. According to previous reports, it has anti-cancer, anti-gastritis, and anti-inflammation effects. However, the improvement effect of T. platycarpum on rheumatoid arthritis has not been investigated. The anti-oxidative and anti-inflammation effects of the aerial parts of T. platycarpum are different from those of its subterranean parts. Thus, we evaluated the effect of the water extracts of Taraxaci radix (WTR) on type II collagen-induced rheumatoid arthritis (CIA) in animal models. Methods and Results: Rheumatoid arthritis was induced by type II collagen. WTR (100 mg/kg and 500 mg/kg) was administered to the animal models. Methotrexate was used as the positive control. The levels of interleukin-6, TNF-alpha, and type II collagen IgG in the animals were measured by using enzyme-linked immunosorbent assay. Treatment with 500 mg/kg WTR decreased the serum levels of interleukin-6, TNF-alpha, and collagen IgG in the CIA models. Moreover, treatment with WTR diminished the arthritisinduced swelling of the hind legs and monocyte infiltration in the bloodvessels of the animal models. Conclusions: These results indicate that WTR has the potential to improve rheumatoid arthritis by reducing the levels of inflammatory cytokines such as interleukin-6 and TNF-alpha. However, further experiments are required to elucidate the influence of WTR on signal transduction in vitro and in vivo.

Antitumor profiles and cardiac electrophysiological effects of aurora kinase inhibitor ZM447439

  • Lee, Hyang-Ae;Kwon, Miso;Kim, Hyeon-A;Kim, Ki-Suk
    • The Korean Journal of Physiology and Pharmacology
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    • v.23 no.5
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    • pp.393-402
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    • 2019
  • Aurora kinases inhibitors, including ZM447439 (ZM), which suppress cell division, have attracted a great deal of attention as potential novel anti-cancer drugs. Several recent studies have confirmed the anti-cancer effects of ZM in various cancer cell lines. However, there have been no studies regarding the cardiac safety of this agent. We performed several cytotoxicity, invasion and migration assays to examine the anti-cancer effects of ZM. To evaluate the potential effects of ZM on cardiac repolarisation, whole-cell patch-clamp experiments were performed with human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and cells with heterogeneous cardiac ion channel expression. We also conducted a contractility assay with rat ventricular myocytes to determine the effects of ZM on myocardial contraction and/or relaxation. In tests to determine in vitro efficacy, ZM inhibited the proliferation of A549, H1299 (lung cancer), MCF-7 (breast cancer) and HepG2 (hepatoma) cell lines with $IC_{50}$ in the submicromolar range, and attenuated the invasive and metastatic capacity of A549 cells. In cardiac toxicity testing, ZM did not significantly affect $I_{Na}$, $I_{Ks}$ or $I_{K1}$, but decreased $I_{hERG}$ in a dose-dependent manner ($IC_{50}$: $6.53{\mu}M$). In action potential (AP) assay using hiPSC-CMs, ZM did not induce any changes in AP parameters up to $3{\mu}M$, but it at $10{\mu}M$ induced prolongation of AP duration. In summary, ZM showed potent broad-spectrum anti-tumor activity, but relatively low levels of cardiac side effects compared to the effective doses to tumor. Therefore, ZM has a potential to be a candidate as an anti-cancer with low cardiac toxicity.

Extracellular Vesicles-Encapsulated miR-153-3p Potentiate the Survival and Invasion of Lung Adenocarcinoma

  • Cao, Hongli;Zhang, Ping;Yu, Hong;Xi, Jianing
    • Molecules and Cells
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    • v.45 no.6
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    • pp.376-387
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    • 2022
  • Extracellular vesicles (EVs) play an essential role in the communication between cells and the tumor microenvironment. However, the effect of tumor-derived EVs on the growth and metastasis of lung adenocarcinoma (LUAD) remains to be explored. This study aimed to elucidate the role of miR-153-3p-EVs in the invasion and migration capabilities of LUAD cells and explore its mechanism through in vivo and in vitro experiments. We found that miR-153-3p was specifically and highly expressed in LUAD and its secreted EVs. Furthermore, the expression of BANCR was negatively regulated by miR-153-3p and identified as a target gene of miR-153-3p using luciferase reporter assays. Through further investigation, we found that the downregulation of BANCR activates the PI3K/AKT pathway and accelerates the process of epithelial-mesenchymal transition (EMT), which ultimately leads to the aggravation of LUAD. The orthotopic xenograft mouse model was established to illustrate the effect of miR-153-3p-EVs on LUAD. Animal studies showed that miR-153-3p-EVs accelerated tumor growth in mice. Besides, we found that miR-153-3p-EVs could damage the respiratory ability of mice and produce a mass of inflammatory cells around the lung tissue of mice. Nevertheless, antagomir-153-3p treatment could inhibit the deterioration of respiratory function and inhibit the growth of lung tumors in mice. In conclusion, our study reveals the potential molecular mechanism of miR-153-3p-EVs in the development of LUAD and provides a potential strategy for the treatment of LUAD.

High fat diet-induced brain damaging effects through autophagy-mediated senescence, inflammation and apoptosis mitigated by ginsenoside F1-enhanced mixture

  • Hou, Jingang;Jeon, Byeongmin;Baek, Jongin;Yun, Yeejin;Kim, Daeun;Chang, Boyoon;Kim, Sungyeon;Kim, Sunchang
    • Journal of Ginseng Research
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    • v.46 no.1
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    • pp.79-90
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    • 2022
  • Background: Herbal medicines are popular approaches to capably prevent and treat obesity and its related diseases. Excessive exposure to dietary lipids causes oxidative stress and inflammation, which possibly induces cellular senescence and contribute the damaging effects in brain. The potential roles of selective enhanced ginsenoside in regulating high fat diet (HFD)-induced brain damage remain unknown. Methods: The protection function of Ginsenoside F1-enhanced mixture (SGB121) was evaluated by in vivo and in vitro experiments. Human primary astrocytes and SH-SY5Y cells were treated with palmitic acid conjugated Bovine Serum Albumin, and the effects of SGB121 were determined by MTT and lipid uptake assays. For in vivo tests, C57BL/6J mice were fed with high fat diet for 3 months with or without SGB121 administration. Thereafter, immunohistochemistry, western blot, PCR and ELISA assays were conducted with brain tissues. Results and conclusion: SGB121 selectively suppressed HFD-induced oxidative stress and cellular senescence in brain, and reduced subsequent inflammation responses manifested by abrogated secretion of IL-6, IL-1β and TNFα via NF-κB signaling pathway. Interestingly, SGB121 protects against HFD-induced damage by improving mitophagy and endoplasmic reticulum-stress associated autophagy flux and inhibiting apoptosis. In addition, SGB121 regulates lipid uptake and accumulation by FATP4 and PPARα. SGB121 significantly abates excessively phosphorylated tau protein in the cortex and GFAP activation in corpus callosum. Together, our results suggest that SGB121 is able to favor the resistance of brain to HFD-induced damage, therefore provide explicit evidence of the potential to be a functional food.

A Review of the Health Benefits of Kimchi Functional Compounds and Metabolites

  • Hyun Ju Kim;Min Sung Kwon;Hyelyeon Hwang;Ha-Sun Choi;WooJe Lee;Sang-Pil Choi;Haeun Jo;Sung Wook Hong
    • Microbiology and Biotechnology Letters
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    • v.51 no.4
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    • pp.353-373
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    • 2023
  • Kimchi is a traditional Korean dish made with salted fermented vegetables and contains various nutrients and functional substances with potential health benefits. The fermentation process used to make kimchi creates chemical changes in the food, developing nutrients and functional substances that are more easily absorbed and enhanced by the body. Recent studies have shown that several lactic acid bacteria strains isolated from kimchi exhibit probiotic properties and have several health benefiting properties such as such as anticancer, anti-obesity, and anti-constipation; they also promote colon health and cholesterol reduction in in vitro and in vivo experiments, as well as in epidemiological cohort studies. Kimchi contains prebiotics, non-digestible fibers that nourish beneficial gut bacteria; therefore, its intake effectively provides both probiotics and prebiotics for improved gut health and a fortified gut-derived immune system. Furthermore, fermentation of kimchi produces a variety of metabolites that enhance its functionality. These metabolites include organic acids, enzymes, vitamins, bioactive compounds, bacteriocins, exopolysaccharides, and γ-aminobutyric acid. These diverse health-promoting metabolites are not readily obtainable from single food sources, positioning kimchi as a valuable dietary option for acquiring these essential components. In this review, the health functionalities of kimchi ingredients, lactic acid bacteria strains, and health-promoting metabolites from kimchi are discussed for their properties and roles in kimchi fermentation. In conclusion, consuming kimchi can be beneficial for health. We highlight the benefits of kimchi consumption and establish a rationale for including kimchi in a balanced, healthy diet.

Studies on skin whitening efficacy and skin permeation using O/W Nanoemulsion system with Resorcinol Dipentyl Ether (레조시놀다이펜틸에터를 함유한 O/W 나노에멀젼의 경피흡수 및 미백 효능 효과 연구)

  • Cha, Young Kwon;Cho, Hyun Dae;Cho, Wan Goo;Byun, Sang Yo
    • Journal of the Korean Applied Science and Technology
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    • v.34 no.2
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    • pp.225-235
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    • 2017
  • In this study, we investigated the effect on the increase of In vitro skin permeation experiments and In-vivo skin whitening efficacy using a O/W nanoemulsion produced via PIC(Phase Inversion Composition) with 1,3-di(pentyloxyl)benzene. skin permeation experiments of RS-nanoemulsion formulated with selected condition was evaluated compared to mineral oil containing 1,3-di(pentyloxyl)benzene and normal O/W type RS-emulsion. Compared to mineral oil with 1,3-di(pentyloxyl)benzene and RS-emulsion. RS-Nanoemulsion has a statistically significant high percutaneous absorption in terms of index substance, which is 1,3-di(pentyloxyl)benzene. In vivo test were prepared in the system of O/W cream containing RS-nanoemulsion. There was no adverse reactions in both samples. After 8 weeks, the subjects was evaluated by a dermatologist's scoring and Chromameter. In conclusion, the testing product showed statistically improvement (p<0.05) compared to the controlled product and proved its whitening efficacy.