• 제목/요약/키워드: Pharmacological mechanisms

검색결과 289건 처리시간 0.022초

수종 한약제의 위암세포에 대한 항암작용 효능 검색 및 약리작용에 관한 분자생물학적 연구 (Molecular analysis on the pharmacological actions of oriental medicines in stomach cancer cells)

  • 김진성;이지향;류봉하;박재훈;지성길;유진화
    • 대한한방종양학회지
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    • 제5권1호
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    • pp.47-60
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    • 1999
  • Traditional oriental medicines have been used for treatment of various kinds of human cancers for long times and some of them proven to be effective clinically. However, the pharmacological actions and mechanisms related to cancer treatment are generally unknown. In an effort to clarify the action mechanisms of several oriental medicines used for cancer treatments, we planned this experimental procedures. We selected Cordyceps sinensis (冬蟲下草), Punellae Herba (夏枯草), Rehmanniae Radix (熟地黃), Paeoniae Radix (白芍藥), Oldenlandiae Herba (白花蛇舌草), Partulaceae Herba (馬齒? ), Scdopendra subspinipes mutilans (蜈蚣), Mylabris Phalerara (班蟄), Phellinus igniarius(桑黃), Ganodermae Lignum(靈芝) for evaluation, which have been used for patients of gastric cancers. The twenty grams of medicines were boiled in 100ml of water for 1 hour and filtered with $0.2\;{\mu}m$ pore-sized filter unit to remove insoluble particles. Initially we evaluated the effects oriental medicines on growth inhibition in stomach cancer cells. The gastric cancer cell line, AGS, was cultured in RPMI 1640 supplemented with l0% heat-inactivated fetal bovine serum and treated with $10{\mu}l$ oriental medicines per 1ml of medium up to 48 hours. The specimens were subjected to MTT assay for evaluation of growth inhibition. We found mat Mylabris phalerata (班蟄) markedly suppressed the growth of cancer cells as shown in results. Next, we checked the effects of oriental medicines on cancer on cell cycles and apptosis. Mylabrls phalerata (班蟄) inhibited cell cycle progression of cancer cells a compared with control cells and cells treated with other medicines. In addition, Mylabri phalerata (班蟄) induced apoptosis in 30-40% of stomch cancer cells within 24 hours. Other oriental medicines used for this experiments did not show apoptosis-inducing effects on cancer cells. Finally, we determined the expression levels of genes associated with cell cycle and apoptosis. The expressions of Bcl-2 and bcl-XL were downregulated by the treatment of Mylabris phalerata (班蟄). However, the expression levels of genes related to cell cycles were not altered significantly. In conclusion, we found that Mylabris phalerata (班蟄) has in vivo gowth-inhibiting and apptosis-inducing effects on stomach cancer cells. However, we think that at least animal experiments are necessay for evduations.

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인삼의 약리작용 (Pharmacological Action of Ginseng)

  • 홍사악;임정규;박찬웅;차인준
    • Journal of Ginseng Research
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    • 제3권1호
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    • pp.66-93
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    • 1979
  • Panax ginseng C. A. Meyer, which has been known for more than EWO years. occupies a Particular prince in folk medicine as so called tonic remedy. The pharmacolgical investigations of ginseng, based on the scientific concepts and methodology, have been performed by many researchers through the past 50∼60 years at different parts of the world. The pharmacological action of Panax ginseng compiled from the numerous reports can be summarized as follows: 1. On central nervous system, the effect of Panax ginseng is timulatory in smaller doses and somewhat depressive in larger doses. From the psychopharmacological aspect, ginseng seems to increase the mental efficiency of man. 2. Ginseng has the effect tending to Protect organism from various physical and chemical stresses. 3. The growth and basal metabolic rates of experimental animals are stimulated by ginseng. Ginseng also prolongs the survival time of animals under adverse influences. 4. Increasing the physical and mental efficiency, ginseng postpones the onset of fatigue and increases the working capacities. 5. In the case of the intravenous administration of ginseng, a transitory and slight hypotensive effect is observed. These hypotensive effects seems to include that of a direct action and actions related to the release of histamine and/or serotonin by ginseng. 6. It is Presumed that ginseng lowers the elevated bleed ingar and cholesterol level. 7. Ginseng tends to increase the gastrointestinal motizity and tone 8. It is presumed that ginseng Promotes the iron metabolism and activates the hematopoietic factors. 9. Ginseng tends to stimulate the biosynthesis of nucleic acid and release of histamine and serotonin. 10. The toxicity end adverse reactions of ginseng appear to be nothing that warrants apprehension. 11. Anticancer erects of ginseng seem to be due to indirect action rather than direct action on cancer cell, by improving the host condition 12. Recent clinical trials of ginseng harts obtained sent good results, but Present trial is still limited in its range, so it is necessary to broaden the scope of trial covering many kinds of organs and diseases. From the above, although it appears that substantial advancements have been achieved in the studies on the Pharmacological actions of Panax ginseng there are many discrepancies noticed in the reported data. Furthermore the precise mechanisms of actions of ginseng are sometimes obscure, even unknown in other actions as the students stand now. The main reasons for this are considered to be that even though saponin has been identified at one of the active substances of ginseng, other components have not fully been identified and that the experimental approaches of the investigations varied with different researchers. Thus a thorough analysis of the chemical components and newer standardized concepts and metohds appear to be the pre-requisites for further study of the pharmacolgical effects and mechaisms of Panax ginseng.

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비만 환경 내 면역세포 활성화 표현형의 변화 (Phenotype Changes in Immune Cell Activation in Obesity)

  • 박주휘;남주옥
    • 생명과학회지
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    • 제33권3호
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    • pp.295-303
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    • 2023
  • 면역 체계와 대사 체계는 항상성을 유지하는데 중요한 요소이다. 면역 반응과 대사 조절은 연관성이 높아, 정상적인 대사가 교란되면 대사 질환이 발생하며, 면역 반응에도 변화가 발생하였다. 마찬가지로, 비만은 면역 반응과 높은 관련이 있다. 에너지 대사의 불균형으로 발생하는 비만은 인슐린 저항성, 제2형 당뇨병, 지방간 질환, 동맥경화증, 고혈압 등의 대사 질환과 관련이 있다. 알려진 바로는, 비만은 낮은 수준의 염증이 만성화된 상태가 특징이다. 비만 환경에서, 면역세포의 미세 환경은 대식세포, 자연살해세포, T세포 같은 면역세포의 독특한 활성화 표현형에 의해 염증성이 되었다. 또한, 면역 세포는 세포 간의 기전, 사이토카인을 매개하는 기전을 통해 상호작용하여 비만으로 인한 염증 반응을 강화한다. 이러한 현상은 기존의 췌장 리파아제나 알파-아밀라아제 같은 체내 효소의 억제나 지방전구세포의 분화를 억제를 표적으로 하는 일반적인 비만의 약리학적 치료 외에 면역세포 활성화 조절을 표적으로 하는 비만의 약리학적 치료 전략을 시사한다. 본 논문에서는 대식세포, 자연살해세포, T세포의 활성화 표현형과 비만 환경 내이들의 양상에 대해 정리하였다. 또한, 본 논문에서는 현재까지 확인된 면역세포의 활성화 조절을 통한 비만을 완화하는 약리학적 물질에 대해서 정리하였다.

Acacia Honey Exerts Anti-Inflammatory Activity through Inhibition of NF-κB and MAPK/ATF2 Signaling Pathway in LPS-Stimulated RAW264.7 Cells

  • Kim, Ha Na;Park, Su Bin;Kim, Jeong Dong;Jeong, Hyung Jin;Jeong, Jin Boo
    • 한국자원식물학회:학술대회논문집
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    • 한국자원식물학회 2018년도 추계학술대회
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    • pp.97-97
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    • 2018
  • Honey used as conventional medicine has various pharmacological properties. In the honey and anti-inflammatory effect, Gelam honey and Manuka honey has been reported to exert anti-inflammatory activity. However, the anti-inflammatory effect and potential mechanisms of acacia honey (AH) are not well understood. In this study, we investigated anti-inflammatory activity and mechanism of action of AH in LPS-stimulated RAW264.7 cells. AH attenuated NO production through inhibition of iNOS expression in LPS-stimulated RAW264.7 cells. AH also decreased the expressions of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ as pro-inflammatory cytokines, and MCP-1 expression as a pro-inflammatory chemokine. In the elucidation of the molecular mechanisms, AH decreased LPS-mediated $I{\kappa}B-{\alpha}$ degradation and subsequent nuclear accumulation of p65, which resulted in the inhibition of $NF-{\kappa}B$ activation in RAW264.7 cells. AH dose-dependently suppressed LPS-mediated phosphorylation of ERK1/2 and p38 in RAW264.7 cells. In addition, AH significantly inhibited ATF2 phosphorylation and nuclear accumulation of ATF2 in LPS-stimulated RAW264.7 cells. These results suggest that AH has an anti-inflammatory effect, inhibiting the production of pro-inflammatory mediators such as NO, iNOS, $TNF-{\alpha}$, IL-6, $IL-1{\beta}$ and MCP-1 via interruption of the $NF-{\kappa}B$ and MAPK/ATF2 signaling pathways.

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Suppression of Human Prostate Cancer Cell Growth by β-Lapachone via Down-regulation of pRB Phosphorylation and Induction of Cdk Inhibitor p21WAF1/CIP1

  • Choi, Yung-Hyun;Kang, Ho-Sung;Yoo, Mi-Ae
    • BMB Reports
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    • 제36권2호
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    • pp.223-229
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    • 2003
  • The product of a tree (Tabebuia avellanedae) from South America, $\beta$-lapachone, is known to exhibit various pharmacological properties, the mechanisms of which are poorly understood. The aim of the present study was to further elucidate the possible mechanisms by which $\beta$-lapachone exerts its anti-proliferative action in cultured human prostate cancer cells. We observed that the proliferation-inhibitory effect of $\beta$-lapachone was due to the induction of apoptosis, which was confirmed by observing the morphological changes and cleavage of the poly(ADP-ribose) polymerase protein. A DNA flow cytometric analysis also revealed that $\beta$-lapachone arrested the cell cycle progression at the G1 phase. The effects were associated with the down-regulation of the phosphorylation of the retinoblastoma protein (pRB) as well as the enhanced binding of pRB and the transcription factor E2F-1. Also, $\beta$-lapachone suppressed the cyclindependent kinases (Cdks) and cyclin E-associated kinase activity without changing their expressions. Furthermore, this compound induced the levels of the Cdk inhibitor $p21^{WAF1/CIP1}$ expression in a p53-independent manner, and the p21 proteins that were induced by $\beta$-lapachone were associated with Cdk2. $\beta$-lapachone also activated the reporter construct of a p21 promoter. Overall, our results demonstrate a combined mechanism that involves the inhibition of pRB phosphorylation and induction of p21 as targets for $\beta$-lapachone. This may explain some of its anticancer effects.

Herbal Remedies for Combating Irradiation: a Green Anti-irradiation Approach

  • Lachumy, Subramanion Jothy;Oon, Chern Ein;Deivanai, Subramanian;Saravanan, Dharmaraj;Vijayarathna, Soundararajan;Choong, Yee Siew;Yeng, Chen;Latha, Lachimanan Yoga;Sasidharan, Sreenivasan
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권10호
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    • pp.5553-5565
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    • 2013
  • Plants play important roles in human life not only as suppliers of oxygen but also as a fundamental resource to sustain the human race on this earthly plane. Plants also play a major role in our nutrition by converting energy from the sun during photosynthesis. In addition, plants have been used extensively in traditional medicine since time immemorial. Information in the biomedical literature has indicated that many natural herbs have been investigated for their efficacy against lethal irradiation. Pharmacological studies by various groups of investigators have shown that natural herbs possess significant radioprotective activity. In view of the immense medicinal importance of natural product based radioprotective agents, this review aims at compiling all currently available information on radioprotective agents from medicinal plants and herbs, especially the evaluation methods and mechanisms of action. In this review we particularly emphasize on ethnomedicinal uses, botany, phytochemistry, mechanisms of action and toxicology. We also describe modern techniques for evaluating herbal samples as radioprotective agents. The usage of herbal remedies for combating lethal irradiation is a green anti-irradiation approach for the betterment of human beings without high cost, side effects and toxicity.

Tricyclic antidepressant amitriptyline inhibits 5-hydroxytryptamine 3 receptor currents in NCB-20 cells

  • Park, Yong Soo;Myeong, Seok Ho;Kim, In-Beom;Sung, Ki-Wug
    • The Korean Journal of Physiology and Pharmacology
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    • 제22권5호
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    • pp.585-595
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    • 2018
  • Amitriptyline, a tricyclic antidepressant, is commonly used to treat depression and neuropathic pain, but its mechanism is still unclear. We tested the effect of amitriptyline on 5-hydroxytryptamine 3 ($5-HT_3$) receptor currents and studied its blocking mechanism because the clinical applications of amitriptyline overlapped with $5-HT_3$ receptor therapeutic potentials. Using a whole-cell voltage clamp method, we recorded the currents of the $5-HT_3$ receptor when 5-HT was applied alone or co-applied with amitriptyline in cultured NCB-20 neuroblastoma cells known to express $5-HT_3$ receptors. To elucidate the mechanism of amitriptyline, we simulated the $5-HT_3$ receptor currents using Berkeley $Madonna^{(R)}$ software and calculated the rate constants of the agonist binding and receptor transition steps. The $5-HT_3$ receptor currents were inhibited by amitriptyline in a concentration-dependent, voltage-independent manner, and a competitive mode. Amitriptyline accelerated the desensitization of the $5-HT_3$ receptor. When amitriptyline was applied before 5-HT treatment, the currents rose slowly until the end of 5-HT treatment. When amitriptyline was co-applied with 5-HT, currents rose and decayed rapidly. Peak current amplitudes were decreased in both applications. All macroscopic currents recorded in whole cell voltage clamping experiments were reproduced by simulation and the changes of rate constants by amitriptyline were correlated with macroscopic current recording data. These results suggest that amitriptyline blocks the $5-HT_3$ receptor by close and open state blocking mechanisms, in a competitive manner. We could expand an understanding of pharmacological mechanisms of amitriptyline related to the modulation of a $5-HT_3$ receptor, a potential target of neurologic and psychiatric diseases through this study.

홍삼의 약리와 독성 기전에 대한 고찰 (Review of Red Ginseng in terms of Mechanisms for Pharmacodynamics and Toxicity)

  • 박영철;임정대;김종봉;이선동
    • 대한한의학회지
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    • 제33권3호
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    • pp.200-230
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    • 2012
  • Objectives: Ginseng, Panax ginseng C. A., white ginseng, has been used for thousands of years in Traditional Korean Medicine. Red ginseng can be made by a steaming process of white ginseng changing a variety of ginsenosides and ingredients such as dencichine. This article reviews red ginseng for mechanisms for pharmacodynamics and toxicity based on the content of ginseng's active ingredients, ginsenoside changed by steaming. Methods: The following electronic databases were searched: PubMed, Science Direct and Chinese Scientific Journals full text database (CQVIP), and KSI (Korean Studies Information) from their respective inceptions to June 2012. Results: Compared with unsteamed ginseng, the content of ginsenosides Rg2, Rg3, Rg5, Rh1, Rh2 and Rk1 called red ginseng-specific ginsenosides increased after the steaming process. Different ginsenosides have shown a wide variety of effects such as lowering or raising blood sugar and blood pressure or stimulating or sedating the nervous system. Especially, the levels of Rg2, Rg3, Rg5, Rh1, Rh2 and Rk1 were increased by the steaming process, showing a variety of pharmacodynamics in biological systems. Also, various processing methods such as puffing and fermentation have been developed in processing crude ginseng or red ginseng, affecting the content of ginseng's ingredients. The safety issue could be the most critical, specifically, on changed ginseng's ingredients such as dencichine. The level of dencichine was significantly reduced in red ginseng by the steaming process. In addition, the possible toxicity for red ginseng was affected by cytochrome P450, a herbal-drug interaction. Conclusions: The variety of pharmacological and toxicological properties should be changed by steaming process of Panax ginseng C. A., white ginseng. Even if it is not sure whether the steaming process of white ginseng would be better pharmacologically, it is sure that steaming reduces the level of dencichine causing a lower toxicity to the nervous system.

AMP-activated protein kinase determines apoptotic sensitivity of cancer cells to ginsenoside-Rh2

  • Kim, Min-Jung;Yun, Hee;Kim, Dong-Hyun;Kang, Insug;Choe, Wonchae;Kim, Sung-Soo;Ha, Joohun
    • Journal of Ginseng Research
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    • 제38권1호
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    • pp.16-21
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    • 2014
  • Ginseng saponins exert various important pharmacological effects with regard to the control of many diseases, including cancer. In this study, the anticancer effect of ginsenosides on human cancer cells was investigated and compared. Among the tested compounds, ginsenoside-Rh2 displays the highest inhibitory effect on cell viability in HepG2 cells. Ginsenoside-Rh2, a ginseng saponin isolated from the root of Panax ginseng, has been suggested to have potential as an anticancer agent, but the underlying mechanisms remain elusive. In the present study, we have shown that cancer cells have differential sensitivity to ginsenoside-Rh2-induced apoptosis, raising questions regarding the specific mechanisms responsible for the discrepant sensitivity to ginsenoside-Rh2. In this study, we demonstrate that AMP-activated protein kinase (AMPK) is a survival factor under ginsenoside-Rh2 treatment in cancer cells. Cancer cells with acute responsiveness of AMPK display a relative resistance to ginsenoside-Rh2, but cotreatment with AMPK inhibitor resulted in a marked increase of ginsenoside-Rh2-induced apoptosis. We also observed that p38 MAPK (mitogen-activated protein kinase) acts as another survival factor under ginsenoside-Rh2 treatment, but there was no signaling crosstalk between AMPK and p38 MAPK, suggesting that combination with inhibitor of AMPK or p38 MAPK can augment the anticancer potential of ginsenoside Rh2.

펩티도글라이칸에 의한 인터루킨-1 베타 발현 기전 연구 (Molecular Mechanisms through Which Peptidoglycan Induces IL-1β Expression in Monocytic Cells)

  • 서현철;김선미;이새아;임병용;김관회
    • 생명과학회지
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    • 제22권12호
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    • pp.1637-1643
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    • 2012
  • 본 연구에서는 IL-$1{\beta}$ 발현에 PG의 영향을 조사하였고, 단핵세포에서 PG에 의한 IL-$1{\beta}$ 상향조절에 포함된 세포인자를 밝혔다. PG에 사람의 THP-1 세포를 노출시키면 IL-$1{\beta}$ 분비 증가뿐만 아니라 IL-$1{\beta}$ 유전자 전사를 유도하는 결과를 가져왔고, TLR-2/4의 억제제인 OxPAPC에 의해 저해되었다. U0126, SP6001250, Akti IV, rapamycin, DPI 같은 약리학적 저해제도 PG에 의한 IL-$1{\beta}$의 상향조절을 상당히 약화시켰다. 그러나 polymyxin B는 IL-$1{\beta}$ 발현에 영향을 미치지 않았다. 본 연구는 PG는 TLR-2, Akt, mTOR, MAPKs, ROS를 통하여 IL-$1{\beta}$의 발현을 상향시킴을 확인하였다.