• 제목/요약/키워드: inhibitory mechanism

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Inhibitory Effect of Resveratrol on Lipopolysaccharide-induced p21 (WAF1/CIP1) and Bax Expression in Astroglioma C6 Cells (C6 신경교세포에서 lipopolysaccharide에 의한 p21 (WAF1/CIP1) 및 Bax의 발현증가에 미치는 resveratrol의 영향)

  • Kim, Young-Ae;Lim, Sun-Young;Rhee, Sook-Hee;Choi, Yung-Hyun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.1
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    • pp.124-129
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    • 2005
  • Resveratrol, a phytoalexin found at high levels in grapes and in grape products such as red wine, has been reported to possess a wide range of biological and pharmacological activities including anti-oxident, anti-inflammatory, anti-mutagenic, and anti-carcinogenic effects, but its molecular mechanism is poorly understood. In this study, we examined the effects of resveratrol on lipopolysaccharide (LPS)-induced growth inhibitory activity and cell growth-regulatory gene products in astroglioma C6 cells to elucidate its possible mechanism for anti-cytotoxicity. It is shown that LPS induced time-dependent growth inhibition and morphological changes of C6 cells, which were recovered by pre-treatment with resveratrol. The anti-proliferative effect of LPS was associated with the induction of tumor suppressor p53 and cyclin-dependent kinase (Cdk) inhibitor p21 (WAF1/CIP1) expression assessed by RT-PCR and Western blot analysis in time-dependent manner in C6 cells. In addition, the pro-apoptotic Bax expression was also up-regulated in LPS-treated C6 cells without alteration of anti-apoptotic Bcl-2 and Bcl-XL expression. However, resveratrol significantly inhibited LPS-induced p53, p21 and Bax levels, suggesting that the modulation of p53, p21 and Bax levels could be one of the possible pathways by which resveratrol functions as anti-cytotoxic agent.

Inhibitory Effects of β-Glycyrrhetinic Acid on Tumor Necrosis Factor-α Production in RAW 264.7 Cells

  • Park, Kyoung-Sik
    • Journal of Applied Biological Chemistry
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    • v.53 no.3
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    • pp.147-153
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    • 2010
  • $\beta$-glycyrrhetinic acid (GA), the active principle of licorice (Glycyrrhiza glabra L.) has been reported to exhibit anti-inflammatory properties in different animal models. In this study, the effects of GA on the production of inflammatory mediators including tumor necrosis factor (TNF)-$\alpha$, interleukin (IL)-6, nitric oxide (NO), and prostaglandin E (pGE)-2 were examined in RAW 264.7 cells in vitro. Furthermore, to elucidate a possible mechanism for the inhibitory effect of GA on the production of TNF-$\alpha$, it was investigated whether the treatment of GA affects the I-${\kappa}B{\alpha}$ degradation and subsequent nuclear translocation of NF-${\kappa}B$. Various inflammatory responses were induced in the culture system by treating with a lipopolysaccharide (LPS). GA showed anti-inflammatory activities in dose-dependant manner with $IC_{50}$ of $5.4{\mu}M$ by inhibiting the production of TNF-$\alpha$ in RAW 264.7 cells. In addition, the treatment of GA blocked both I-${\kappa}B{\alpha}$ degradation and the nuclear translocation of NF-${\kappa}B$ from cytosol to nucleus. However, it did not affect the production of IL-6, NO, and PGE-2, implying the direct blocking of the production of TNF-$\alpha$ resulting from both the I-${\kappa}B{\alpha}$ degradation and the nuclear translocation of NF-${\kappa}B$. This finding might provide the underlying mechanism to explain the reported anti-inflammatory activities of GA in animal models.

Kinetic Analysis of the Counter-transport Phenomenon in the Hepatic Transport of Organic Anionic Drugs (유기 음이온계 약물의 간수송과정에 있어서 대향수송현상에 관한 속도론적 연구)

  • Chung, Youn-Bok;Han, Kun;No, Jung-Ryul
    • Journal of Pharmaceutical Investigation
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    • v.22 no.4
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    • pp.289-300
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    • 1992
  • The counter-transport phenomena in the hepatic transport of 1-anilino-8-naphthalene sulfonate (ANS) were kinetically investigated by analyzing the plasma disappearance-time profiles and the transport into the isolated hepatocytes. In vivo "counter transport phenomena" were simulated based on the perfusion model which incorporated the carrier-mediated transport and the saturable intracellular binding. The condition that the mobility of carrier-ligand complex is greater than that of free carrier is not essential for the occurrence of counter-transport phenomenon. To examine the inhibitory effects on the initial uptake of a ligand by the liver, it is necessary to judge whether the true counter-transport mechanism (trans-stimulation) is working or not. The initial plasma disappearance curves of ANS were then kinetically analyzed based on a two-compartment model, in which the ligand is eliminated only from the peripheral compartment (liver compartment). No effects on the initial plasma disappearance rates of ANS were observed after preloading of bromophenol blue (BPB) or rose bengal (RB) in the liver. Inhibitory effect of BPB or RB on the initial uptake (or efflux) rates of ANS by the isolated hepatocytes were not observed, suggesting that the true counter transport mechanism is not working. In conclusion, checking the preloading effects of transstimulation on the initial uptake of a ligand by the liver could be a useful criterion for carrier cycling and common use of the same carrier between two ligands. However, one cannot exclude those possibilities even if the preloading effects cannot be observed.

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Kinetic Evidence for the Interactive Inhibition of Laccase from Trametes versicolor by pH and Chloride

  • Raseda, Nasrin;Hong, Soonho;Kwon, O Yul;Ryu, Keungarp
    • Journal of Microbiology and Biotechnology
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    • v.24 no.12
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    • pp.1673-1678
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    • 2014
  • The interactive inhibitory effects of pH and chloride on the catalysis of laccase from Trametes versicolor were investigated by studying the alteration of inhibition characteristics of sodium chloride at different pHs for the oxidation of 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid). At pH 3.0, the addition of sodium chloride (50 mM) brought about a 40-fold increase in $K{_m}^{app}$ and a 4-fold decrease in $V_{max}{^{app}}$. As the pH increased to 7.0, the inhibitory effects of sodium chloride became significantly weakened. The mixed-inhibition mechanism was successfully used to quantitatively estimate the competitive and uncompetitive inhibition strengths by chloride at two different pHs (pH 3.0 and 6.0). At pH 3.0, the competitive inhibition constant, $K_i$, was 0.35 mM, whereas the uncompetitive inhibition constant, $K{_i}^{\prime}$, was 18.1 mM, indicating that the major cause of the laccase inhibition by chloride is due to the competitive inhibition step. At a higher pH of 6.0, where the inhibition of the laccase by hydroxide ions takes effect, the inhibition of the laccase by chloride diminished to a great extent, showing increased values of both the competitive inhibition constant ($K_i=23.7mM$) and uncompetitive inhibition constant ($K{_i}^{\prime}=324mM$). These kinetic results evidenced that the hydroxide anion and chloride share a common mechanism to inhibit the laccase activity.

The Scavenging Effect on NO, DPPH and Inhibitory Effect on IL-4 in Schizandrae Fructus Herbal-Acupuncture Solution (오미자약침액(五味子藥鍼液)의 NO, DPPH 소거(消去) 및 IL-4에 대한 억제효과(抑制效果))

  • Cho Hyun-Yeul;Yoon Jong-Seok;Seo Bo-Myung;Lee Sea-Youn;Kim Sung-Woong;Baek Jung-Han;Park Chi-Sang;Seo Jeong-Chul;Han Sang-Won
    • Korean Journal of Acupuncture
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    • v.20 no.1
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    • pp.45-55
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    • 2003
  • Backgrounds : It has been investigated about ageing theory. However, ageing mechanism still remains to be unknown. Since Harman proposes that ageing and ageing related diseases might be due to oxidative damage and these are modifiable by genetic and environmental factors. For designing an optimal nutritional countermeasure against ageing and ageing related disease, it is necessary to understand the ageing mechanism and other reactive species. Objectives : Schizandra Chinesis has been clinically used to treat brain disease, respiratory or inflammatory disease etc. in Oriental medicine. The purpose of this study is to investigate the scavenging effect of Schizandrae Fructus herbal-acupuncture solution(SFHA) on NO, DPPH and IL-4. Results : The results are summarized as follows; (1) There is a significant scavenging effect of SFHA on NO in 0.1, 1, 10mg/ml group after 24hrs. (2) There is a significant scavenging effect of SFHA on DPPH in 1, $10{\mu}g/ml$ group. (3) There is a significant inhibitory effect of SFHA on IL-4 in 1, 10, $100{\mu}g/ml$ group. Conclusions : These findings indicate that SFHA can be used as antioxidant or antiimflammatory drug. But further study is needed about the effect of SFHA.

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Mechanism of Inhibitory Action of Anaphylaxis by Aqueous Extract of Poncirus trifoliata (즉시형(卽時型) 알레르기 반응(反應)에 있어서 물추출액(抽出液)의 억제작용기전(抑制作用機轉))

  • Hwang, Gwang-Ho;Lee, Eon-Jeong;Song, Bong-Keun;Kim, Hyeong-Kyun
    • The Journal of Korean Medicine
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    • v.18 no.1
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    • pp.316-325
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    • 1997
  • The dried unripe fruit of Poncirus trifoliata L. is widely used to treat urticaria, itch and indigestion in folk medicine. And recently it was reported the component of the fruit was found to exhibit an inhibitory effect on histamine release from mast cells. So to evaluate the effect of aqueous extract of Poncirus trifoliata L.(PTFE) on compound 48/80-induced histamine release, the study was carried out in rat peritoneal mast cell. PTFE $(10^{-3}{\sim}1mg/ml)$ inhibits the histamine release induced by compound 48/80 $(5{\mu}g/ml)$ in rat peritoneal mast cells. To clarify the mechanism of these inhibition, we investigated the effect of PTFE on cAMP and intracellular calcium content. The increase in cAMP content, when PTFE was added, was transient. At concentration of 1mg/ml, the cAMP content of mast cells was significantly increased at a rate of 53 times of basal cells at 10sec. PTFE inhibits histamine release by augmenting the cAMP content in mast cells. Moreover, PTFE inhibits intracellular calcium release induced by compound 48/80. This result suggests that PTFE may be useful for the prevention and treatment of allergy-related disease.

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The Effect of Essential Oils on Antimicrobial Activity (에센셜 오일이 항균 활성에 미치는 효과)

  • Park, Sang-Nam;Kang, Yun-Jung
    • Journal of Convergence for Information Technology
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    • v.10 no.4
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    • pp.104-114
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    • 2020
  • We investigated the best antibiotics using blending oils after screening 11 kinds of essential oil known as antibiotics from plants. The minimum inhibitory concentration (MIC) and the minimum killing concentration (MBC) were found to be essential for essential oils B and E to inhibit target bacteria. All gram-positive bacteria containing S. aureus used in this experiment were shown highly antibiotic activity. And only A. baumanii in gram-positive bacteria and C. albicans in fungi were shown highly antibiotic activity. The essential oils used in our experiments showed better antibiotic activity compared to major studies using natural antibiotics with excellent antibiotic activity and essential oils from natural medicine. It is not known what mechanism of antimicrobial activity the essential oil used in the test has, but it is interpreted as a synthetic inhibitory mechanism of cell wall compared with other previous studies. From these results, it is expected that some substances or functional products with antibiotic activity will be developed.

Inhibitory mechanism of ginsenoside Rh3 on granulocyte-macrophage colony-stimulating factor expression in UV-B-irradiated murine SP-1 keratinocytes

  • Park, Young Sun;Lee, Ji Eun;Park, Jong Il;Myung, Cheol hwan;Lim, Young-Ho;Park, Chae Kyu;Hwang, Jae Sung
    • Journal of Ginseng Research
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    • v.44 no.2
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    • pp.274-281
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    • 2020
  • Background: Ultraviolet (UV) goes through the epidermis and promotes release of inflammatory cytokines in keratinocytes. Granulocyte-macrophage colony-stimulating factor (GM-CSF), one of the keratinocyte-derived cytokines, regulates proliferation and differentiation of melanocytes. Extracellular signal-regulated kinase (ERK1/2) and protein kinase C (PKC) signaling pathways regulate expression of GM-CSF. Based on these results, we found that ginsenoside Rh3 prevented GM-CSF production and release in UV-B-exposed SP-1 keratinocytes and that this inhibitory effect resulted from the reduction of PKCδ and ERK phosphorylation. Methods: We investigated the mechanism by which ginsenoside Rh3 from Panax ginseng inhibited GM-CSF release from UV-B-irradiated keratinocytes. Results: Treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA) or UV-B induced release of GM-CSF in the SP-1 keratinocytes. To elucidate whether the change in GM-CSF expression could be related to PKC signaling, the cells were pretreated with H7, an inhibitor of PKC, and irradiated with UV-B. GM-CSF was decreased by H7 in a dose-dependent manner. When we analyzed which ginsenosides repressed GM-CSF expression among 15 ginsenosides, ginsenoside Rh3 showed the largest decline to 40% of GM-CSF expression in enzyme-linked immunosorbent assay. Western blot analysis showed that TPA enhanced the phosphorylation of PKCδ and ERK in the keratinocytes. When we examined the effect of ginsenoside Rh3, we identified that ginsenoside Rh3 inhibited the TPA-induced phosphorylation levels of PKCδ and ERK. Conclusion: In summary, we found that ginsenoside Rh3 impeded UV-B-induced GM-CSF production through repression of PKCδ and ERK phosphorylation in SP-1 keratinocytes.

Suppressive Effect of FARFARE FLOS Extracts on Oxidative Stress and Inflammatory Response through the Antioxidative Mechanism (FARFARE FLOS의 항산화 기전을 통한 산화적 스트레스 및 염증 반응 억제효과)

  • Shin, Seung-An;Lee, Min-Ja;Lee, Hye-Sook;Park, Won-Hwan
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.25 no.2
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    • pp.280-293
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    • 2011
  • There is currently increased interest in the identification of antioxidant compounds that are pharmacologically potent and have low or no side effects. Plants produce significant amounts of antioxidants to prevent the oxidative stress caused by photons and oxygen, therefore they represent a potential source of new compounds with antioxidant activity. FARFARE FLOS has been frequently used on the respiratory system including bronchitis, phthisis. In this study, the antioxidant activity of extract from FF was studied in vitro methods by measuring the antioxidant activity by TEAC, measuring the scavenging effects on reactive oxygen species (ROS) [superoxide anion, hydroxyl radical] and on reactive nitrogen species (RNS) [nitric oxide and peroxynitrite] as well as measuring the inhibitory effect on Cu2+-induced human LDL oxidation. The FF extracts were found to have a potent scavenging activity, as well as an inhibitory effect on LDL oxidation. And this study was designed to evaluate whether FFEA may ameliorate oxidative stress and inflammatory status through the antioxidative mechanism in LPS-stimulated RAW 264.7 murine macrophage cell line. Treatment of RAW 264.7 cells with FFEA significantly reduced LPS-stimulated inflammatory response in a dose-dependent manner. In conclusion, the FF extracts have anti-oxidative and anti-inflammatory effects in vitro system, which can be used for developing pharmaceutical drug against oxidative stress and atherosclerosis.

Study of ShengmaisanJiaweifang Extracts on the Inhibitory Effects of Melanin Synthesis and Superoxide Dismutase Activity (생맥산가미방 추출물이 멜라닌 생합성 저해 효과와 SOD 활성에 미치는 연구)

  • Jeong, Hyun Woo;Choi, Chan Hen
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.33 no.5
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    • pp.267-274
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    • 2019
  • This study aims to evaluate the effects of Shengmaisan (SMS) and three types of ShengmaisanJiaweifang on the inhibitory effect of melanin synthesis in B16F10 cells, the mechanism of action through tyrosinase, and the antioxidant effect through superoxide dismutase (SOD) activity. In this study, we used ShengmaisanJiaweifangs (SMS, SMSRR, SMSAD, SMSAR) to research the whitening effects in B16F10 cell lines. Shengmaisan (SMS) was a herbal medicine composed of Ginseng Radix, Liriopis Tuber, and Schisandrae Fructus. ShengmaisanJiaweifangs included SMSRR (SMS added with Rehmanniae Radix), SMSAD (SMS added with Asparagi Radix) and SMSAR (SMS added with Astragali Radix). We measured the cell viability, the inhibition rate of the melanin biosynthesis, and the activity of tyrosinase and SOD in malignant melanoma, B16F10 cells, to survey the whitening effect and the mechanism of the impact on the sample. As a result, SMSRR significantly suppressed the cell viability of B16F10 at more than $500{\mu}g/m{\ell}$ and significantly inhibited the generation of melanin induced by ${\alpha}$-MSH at more than $250{\mu}g/m{\ell}$. SMSRR ($500{\mu}g/m{\ell}$) decreased the activity of tyrosinase while increased the activity of SOD. Therefore, we considered that the SMSRR would be able to produce high value-added products more SMS if used as a commercial.