• 제목/요약/키워드: Costunolide

검색결과 44건 처리시간 0.024초

Three sesquiterpene lactones suppress lung adenocarcinoma by blocking TMEM16A-mediated Ca2+-activated Cl- channels

  • Ruilian Xiu;Jie Jia;Qing Zhang;Fengjiao Liu;Yaxin Jia;Yuanyuan Zhang;Beibei Song;Xiaodan Liu;Jingwei Chen;Dongyang Huang;Fan Zhang;Juanjuan Ma;Honglin Li;Xuan Zhang;Yunyun Geng
    • The Korean Journal of Physiology and Pharmacology
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    • 제27권6호
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    • pp.521-531
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    • 2023
  • Transmembrane protein TMEM16A, which encodes calcium-activated chloride channel has been implicated in tumorigenesis. Overexpression of TMEM16A is associated with poor prognosis and low overall survival in multiple cancers including lung adenocarcinoma, making it a promising biomarker and therapeutic target. In this study, three structure-related sesquiterpene lactones (mecheliolide, costunolide and dehydrocostus lactone) were extracted from the traditional Chinese medicine Aucklandiae Radix and identified as novel TMEM16A inhibitors with comparable inhibitory effects. Their effects on the proliferation and migration of lung adenocarcinoma cells were examined. Whole-cell patch clamp experiments showed that these sesquiterpene lactones potently inhibited recombinant TMEM16A currents in a concentration-dependent manner. The half-maximal concentration (IC50) values for three tested sesquiterpene lactones were 29.9 ± 1.1 µM, 19.7 ± 0.4 µM, and 24.5 ± 2.1 µM, while the maximal effect (Emax) values were 100.0% ± 2.8%, 85.8% ± 0.9%, and 88.3% ± 4.6%, respectively. These sesquiterpene lactones also significantly inhibited the endogenous TMEM16A currents and proliferation, and migration of LA795 lung cancer cells. These results demonstrate that mecheliolide, costunolide and dehydrocostus lactone are novel TMEM16A inhibitors and potential candidates for lung adenocarcinoma therapy.

수종의 국화과 식물에서 분리한 Sesquiterpene Lactone들의 생리활성(제3보) -Nitric oxide 방출 및 ACAT 저해활성- (Biological Activities of Sesquiterpene Lactones isolated from Several Compositae Plants Part 3 -Inhibitory Activity on Nitric Oxide Release and ACAT-)

  • 장대식;박기훈;고학룡;이현선;권병목;양민석
    • 생약학회지
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    • 제30권1호
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    • pp.74-78
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    • 1999
  • Nine sesquiterpene lactones, which were isolated from Hemisteptia lyrata Bunge, Chrysanthemum zawadskii Herbich var. latilobum Kitamura and Chrysanthemum boreale Makino were evaluated for the inhibition upon the nitric oxide release from the Raw cell and for the ACAT (acyl Co A: cholesterol acyltransferase) inhibitory assay. In the nitric oxide release inhibitory experiment, hemistepsin B $(IC_{50}\;=\;0.05\;{\mu}g/ml,\;0.15\;{\mu}M),$ cumambrin B, tulipinolide and costunolide exhibited strong inhibition with $IC_{50}$ values $0.05\;{\mu}g/ml\;(0.15\;{\mu}M),\;0.1\;{\mu}g/ml\;(0.38\;{\mu}M),\;0.2\;{\mu}g/ml\;(0.69\;{\mu}M)$ and $0.2\;{\mu}g/ml(0.86\;{\mu}M),$ respectively. In the ACAT inhibitory assay, angeloylcumambrin B, tigloylcumambrin B, tulipinolide and costunolide exhibited strong inhibition with $IC_{50}$ values $33\;{\mu}g/ml\;(95.4\;{\mu}M),\;22\;{\mu}g/ml\;(63.6\;{\mu}M),\;38\;{\mu}g/ml\;(151\;{\mu}M)$ and $17\;{\mu}g/ml(73.3\;{\mu}M),$ respectively, whereas other compounds did not exhibit significant activity against ACAT above $100\; {\mu}g/ml.$.

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지칭개, 구절초 및 산국에서 분리한 Sesquiterpene lactones의 항균활성 (Antimicrobial Activities of Sesquiterpene Lactones Isolated from Hemisteptia lyrata, Chrysanthemum zawadskii and Chrysanthemum boreale)

  • 장대식;박기훈;이종록;하태정;박윤배;남상해;양민석
    • Applied Biological Chemistry
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    • 제42권2호
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    • pp.176-179
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    • 1999
  • 지칭개, 구절초 및 산국에서 분리한 9종류의 sesquiterpene lactones에 대한 생리활성 실험의 일환으로, 10종의 세균에 대한 항세균활성과 6종의 식물병원균에 대한 항진균활성을 조사하였다. 항세균 활성실험에서는 지칭개에서 분리한 hemistepsin A와 B 그리고 산국에서 분리한 tulipinolide가 시험균주 전반에 대하여 강한 활성을 보였으며, 항진균 활성실험에서는 hemistepsin B, angeloylcumambrin B, tigloylcumambrin B, 그리고 costunolide가 광범위한 활성을 보였다. 또한, 항세균 활성실험과 항진균 활성실험 모두 비교적 뚜렷한 균주특이성을 나타내었다.

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목향(木香)으로부터 분리된 Sesquiterpene 화합물의 암세포 생육저해에 대한 활성 (Sesquiterpene Lactones from Saussurea lappa and Their Cell Proliferation Effects on Human Breast Cell Lines)

  • 박현선;최은정;이용수;김건희
    • 약학회지
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    • 제51권2호
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    • pp.145-149
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    • 2007
  • Saussurea Radix, the dried roots of Saussurea lappa Clark (Compositae), has been used in oriental traditional medicine for aromatic stomachic. Present study was carried out for the anticancer effect of Saussurea Radix. Bioassay-directed fractionation of Saussurea Radix led to the isolation of two sesquiterpenes, dehydrocostuslactone (1) and costunolide (2). The structures of 1 and 2 were elucidated by spectral methods (MS, IR, $^1$H and $^{13}$C NMR). These compounds showed a potent cell proliferation activity against human breast cancer cell MCF-7 and MDA-MB-453.

항균활성을 갖는 천연물 개발과 화장품 응용에 관한 연구 (Development of Antimicrobial Plant Extracts and its Application to Cosmetics)

  • 이지영;이정노;이강태;이건국
    • 대한화장품학회지
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    • 제38권2호
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    • pp.171-179
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    • 2012
  • 본 연구는 항균 활성을 지니는 식물추출물을 찾고 화장품에서 방부제로서 적용하기 위해 진행되었다. 디스크 확산법(disk diffusion method)을 통해 3가지 식물 추출물, 함박꽃나무(천녀목란, Magnolia sieboldii), 오배자(Rhus chinensis), 메타세콰이어(Metasequioa glyptostroboides)가 항균활성을 지니고 있음을 확인하였다. 세 물질의 최소저해농도(MIC)를 측정한 결과 메타세콰이어는 0.3 ~ 0.35 %, 함박꽃나무는 0.35 ~ 0.4 % 농도에서 곰팡이의 생장을 억제하고 오배자는 0.45 ~ 0.5 % 농도에서 세균의 생장을 억제함을 확인하였다. 또한 추출물 내의 항균 활성을 지니는 성분을 분리하여 분석한 결과 메타세콰이어에서 분리한 caryophyllene oxide와 caryophyllene, 함박꽃나무에서 분리한 costunolide와 dehydrocostus lactone, 오배자에서 분리한 ethyl gallate, ethyl-3-gallate 등이 항균활성을 지닌 물질임을 확인하였다. O/W 에멀션 제형에서 식물 추출물을 넣고 방부력을 확인한 결과 혼합사용 시 세균과 곰팡이 모두에 대한 방부효과 가 있음을 확인하였다. 따라서 함박꽃나무, 오배자, 메타세콰이어 추출물의 혼합물은 기존의 화학 방부제를 대체할 천연 방부제로서 화장품에서 응용할 수 있을 것으로 기대된다.

세스퀴테르펜 락톤류: 생리활성 재검토 (Sesquiterpene Lactones: A Review of Biological Activities)

  • 카라데니즈 파티;오정환;공창숙
    • 생명과학회지
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    • 제31권4호
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    • pp.430-441
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    • 2021
  • 세스퀴테르펜 락톤(Sesquiterpene lactones; STL) 화합물은 테르페노이드의 일종으로 주로 국화과에서 발견이 되고 강한 세포 독성을 나타내는 생리학적 특성을 지니고 있다. 이러한 세스퀴테르펜 락톤은 강한 세포 독성으로 인해 연구가 미미하였으나, 최근 화학적 변형을 통해 독성이 적은 형태로 합성하여 새로운 의약품 개발로서의 연구가 활발히 진행되고 있다. 세스퀴테르펜 락톤 화합물인 artemisinin 및 mipsagargin 화합물은 현재 말라리아 및 종양성장에 대한 약물로 사용되고 있다. 또한 항산화, 간보호, 항바이러스, 항균, 항종양 및 항노화 등의 생리활성 효능이 보고되어 있으며, 종양세포에서 자멸사를 유도하여 항암제로서의 연구가 진행되고 있다. 본 연구에서는 세스퀴테르펜 락톤 화합물인 artemisinin, costunolide, thapsigargin, arglabin, parthenolide, alantolactone, cynaropicrin, helenalin, 및 santonin의 생리활성 효능에 대한 연구 동향을 검토하고자 한다.

LC-MS/MS를 이용한 향사육군자탕의 주요성분의 함량분석 (Quantitative Analysis of Hyangsayukgunja-Tang Using an Ultra-Performance Liquid Chromatography Coupled to Electrospray Ionization Tandem Mass Spectrometry)

  • 서창섭;신현규
    • 생약학회지
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    • 제46권4호
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    • pp.352-364
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    • 2015
  • The aim of this study was to quantitatively analyze for quality assessment of eighteen marker compounds, including homogentisic acid, 3,4-dihydroxybenzaldehyde, spinosin, liquiritin, hesperidin, ginsenoside Rg1, liquiritigenin, ginsenoside Rb1, glycyrrhizin, 6-gingerol, atractylenolide III, honokiol, costunolide, dehydrocostuslactone, atractylenolide II, nootkatone, magnolol, and atractylenolide I, in Hyangsayukgunja-tang using an ultra-performance liquid chromatography-electrospray ionization-mass spectrometer. The column for separation of eighteen marker components were used a UPLC BEH $C_{18}$ analytical column ($2.1{\times}100mm$, $1.7{\mu}$) and kept at $45^{\circ}C$ by gradient elution with 0.1% (v/v) formic acid in water and acetonitrile as mobile phase. The flow rate and injection volume were 0.3 mL/min and $2.0{\mu}l$, respectively. The correlation coefficient of all marker compounds was ${\geq}0.9914$, which means good linearity, within the test ranges. The limits of detection and quantification values of the all analytes were in the ranges 0.04-1.11 and 0.13-3.33 ng/mL, respectively. As a result, five compounds, homogentisic acid, 3,4-dihydroxybenzaldehyde, spinosin, liquiritigenin, and atractylenolide I, in this sample were not detected and the amounts of the 13 compounds except for the 5 compounds were $8.10-6736.37{\mu}g/g$ in Hyangsayukgunja-tang extract.

The Genome-Wide Expression Profile of Saussurea lappa Extract on House Dust Mite-Induced Atopic Dermatitis in Nc/Nga Mice

  • Lim, Hye-Sun;Ha, Hyekyung;Shin, Hyeun-Kyoo;Jeong, Soo-Jin
    • Molecules and Cells
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    • 제38권9호
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    • pp.765-772
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    • 2015
  • Saussurea lappa has been reported to possess anti-atopic properties. In this study, we have confirmed the S. lappa's anti-atopic properties in Nc/Nga mice and investigated the candidate gene related with its properties using microarray. We determined the target gene using real time PCR in in vitro experiment. S. lappa showed the significant reduction in atoptic dermatitis (AD) score and immunoglobulin E compared with the AD induced Nc/Nga mice. In the results of microarray using back skin obtained from animals, we found that S. lappa's properties are closely associated with cytokine-cytokine receptor interaction and the JAK-STAT signaling pathway. Consistent with the microarray data, real-time RT-PCR confirmed these modulation at the mRNA level in skin tissues from S. lappa-treated mice. Among these genes, PI3Kca and $IL20R{\beta}$ were significantly downregulated by S. lappa treatment in Nc/Nga mouse model. In in vitro experiment using HaCaT cells, we found that the S. lappa components, including alantolactone, caryophyllene, costic acid, costunolide and dehydrocostus lactone significantly decreased the expression of PI3Kca but not $IL20R{\beta}$ in vitro. Therefore, our study suggests that PI3Kca-related signaling is closely related with the protective effects of S. lappa against the development of atopic-dermatitis.

The Identification of Aucklandiae Radix, Inulae Radix, Vladimiriae Radix and Aristolochiae Radix, Using Macroscopic, Microscopic and Physicochemical Methods

  • Yoon, Jee-Hyun;Park, Ha-Yeong;Kim, Tae-Ju;Lee, Seung-Ho;Kim, Jung-Hoon;Lee, Guem-San;Kim, Hong-Jun;Ju, Young-Sung
    • 대한한의학회지
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    • 제35권4호
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    • pp.83-97
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    • 2014
  • Objectives: This study aimed for establishing the discriminative criteria for Aucklandiae Radix, Inulae Radix, Vladimiriae Radix and Aristolochiae Radix, which can be confused as 'Mokhyang', because of similar appearances and synonyms. Methods: Morphological characteristics of dried herbal medicines were compared by macroscopic observation. To examine microscopic features of 'Mokhyang', paraffin embedding and the staining by using Ju's method were conducted. Physicochemical experiments were performed using HPLC analysis and antioxidant assay. Results: The types of stem, phyllotaxy and leaf shape were chosen as macroscopic criteria and the size, oil spots, color and root top as well as phloem and central cylinder were compared using microscopic features. The HPLC results showed different amounts of costunolide and dehydrocostuslactone among Aucklandiae Radix, Inulae Radix and Vladimiriae Radix. However, Aristolochiae Radix only contained aristolochic acid. The antioxidant assays also showed that Vladimiriae Radix exhibited strongest antioxidant activity followed by Aucklandiae Radix, Inulae Radix and Aristolochiae Radix. Conclusions: These results demonstrate that macroscopic, microscopic and physicochemical methods would be useful tools for the discrimination of 4 kinds of 'Mokhyang'.