• 대한의생명과학회지
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• 제25권3호
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• pp.267-274
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• 2019

Toll-like receptors (TLRs) are one of the families of pattern recognition receptors (PRR) to recognize pathogen-associated molecular patterns (PAMPs). PAMPs stimulate TLRs to initiate specific immunoactivity. The activation of TLRs signaling leads to the expression of pro-inflammatory gene products such as cytokines and inducible nitric oxide synthase (iNOS). To evaluate the therapeutic potential of dehydrocostus lactone (DHL), which is a natural sesquiterpene lactone derived from various medicinal plants, iNOS expression induced by LPS (TLR4 agonist), MALP-2 (TLR2 and TLR6 agonist), or Poly[I:C] (TLR3 agonist) were examined. DHL suppressed the iNOS expression induced by LPS, MALP-2, or Poly[I:C]. DHL also inhibited nitrite production induced by LPS, MALP-2, or Poly[I:C]. These results suggest that DHL can modulate TLRs signaling pathways resulting in anti-inflammatory effect.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
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• pp.176-176
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• 1998

An enhanced formation of nitric oxide (NO) is an important mediator of hypotention, peripheral vasodilation and vascular hyporeactivity to vasoconstrictor agents in endotoxaemia. And tumor necrosis factor (TNF${\alpha}$), as a primary mediator of circulatory shock has been known to induce inducible nitric oxide synthase (i-NOS), leading to excessive production of NO. We isolated two sesquiterpene lactone compounds from Saussurea lappa and their structures were elucidated as dehydrocostus lactone and costunolide. These compounds inhibit the production of both NO and TNF${\alpha}$ by LPS (1 $\mu\textrm{g}$/$m\ell$)-activated Raw 264.7 cells. NO was measured spectropho-tometrically as nitrite by the Griess reagent and TNF${\alpha}$ by ELISA. Dehydrocostus lactone (IC$\sub$50/ : 3.0 ${\mu}$M) and costunolide (IC$\sub$50/ : 4.5 ${\mu}$M) inhibited the production of NO in LPS-activated Raw 264.7 cells by suppressing inducible nitric oxide synthase enzyme expression. These compounds also decreased the TNF${\alpha}$ levels in LPS-activated system in vitro and in vivo.

• Archives of Pharmacal Research
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• 제23권1호
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• pp.54-58
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• 2000

To elucidate the molecular mechanisms for the suppression of LPS-induced nitric oxide (NO) production by a dehydrocostus lactone (DL) from Saussurea lappa, we examined the preventive effect of this compound on $NF-{\kappa}B$ activation in LPS-treated RAW 264.7 macrophages and U937 human monocytic cells. The results suggest that the suppression of NO production is mediated by the inhibitory action on the i-NOS gene expression through the inactivation of $NF-{\kappa}B$ and this sesquiterpene lactone can act as a pharmacological inhibitor of the $NF-{\kappa}B$ activation.

• Biomolecules & Therapeutics
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• 제8권1호
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• pp.22-26
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• 2000

In order to study the cytotoxic properties of sesquitepenes, dehydrocostus lactone (DL) and costunolide from Saussurea lappa, cytotoxicity was measured by SRB method using various human cancer cell lines. Dehydrocostus lactone(DL) and costunolide exhibited significant cytotoxicity against A-549, SK-OV-3, SK-MEL-2, XF-498 and HCT 15 cells. The U937 human leukemia cells treated with DL showed several apoptotic evidences like chromosome condensation and formation of apoptotic bodies. From the results of FACS analysis, early apoptosis was observed by phosphatidylserine externalization detected by annexin V-FITC. Furethermore, these studies determined hypodiploid contents and effects on the cell phase distribution of DL-treated U937 cells. After exposure of U937 cells to $30\mu\textrm{M}$ DL effectively led to G2/M modified cell cycle distribution within 24hr. These observations suggest that DL can be used efficiently for the cancer treatment.

• 한국잡초학회지
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• 제30권4호
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• pp.421-428
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• 2010

목향(Saussurea lappa) 뿌리 n-hexane 추출물의 ethyl ether 분획물로부터 경엽 살초 활성을 나타내는 물질로 dehydrocostus lactone (3aS,6aR,9aR,9bS)-3,6,9-trimethylidene-3a,4,5,6a,7,8,9a,9b-octahydroazuleno[5,4-d]furan-2-one)(DHCL)을 분리 동정하였다. DHCL 4,000ppm의 경엽처리 결과, 바랭이, 옥수수 및 콩에 대하여 85% 이상의 엽신 고사율을 보인 반면에 까마중에서는 약 40%의 저해율을 나타내어, 화본과 및 광엽식물 간 선택성 차이는 나타나지 않았으나, 검정식물 초종 간 반응성 차이를 나타내었다. 까마중에서의 반응성 차이는 다른 검정식물과 비교하여 까마중 잎의 비교적 높은 cuticle 함량에 의한 흡수량 감소 때문이었다. 광은 DHCL의 살초활성 발현과 관련이 없었으며, 종자 발아 및 세포 생장 억제 효과는 나타내지 않았다. DHCL 처리에 의한 엽절편의 전도도 증가 및 acetyl-CoA carboxylase의 활성 저해효과로부터 DHCL의 살초 활성 발현은 일정 부분 지방산 생합성 저해에 따른 세포막 약화에 의해 나타날 가능성이 있는 것으로 나타났다.

• 대한한의학방제학회지
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• 제16권2호
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• pp.193-204
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• 2008

Dehydrocostus lactone (DHL) and Mokko lactone (ML) were isolated from Saussureae Radix, and their effects on heme oxygenase-1 (HO-1) expression and hepatoprotection in the liver cell line HepG2 were investigated. DHL induced HO-1 expression and HO activity in a dose-dependent manner, whereas ML lacking one double bond property at 11 and 13 carbons on its own chemical structure had no apparent effects. DHL also induced Nrf2 nuclear translocation and enhanced antioxidant response element (ARE) activation which mediated HO-1 gene transcription. Pretreatment with DHL protected HepG2 cells against oxidative damages caused by H2O2. Interestingly, the hepatoprotective effects of DHL appeared to be associated with HO enzymatic activation, HO-1 expression and Nrf2 activation, because blockage of HO activity by a HO inhibitor and inhibition of HO-1 and Nrf2 cellular synthesis by small interfering RNA abolished heptoprotection afforded by DHL. Taken together, this investigation provides evidence supporting that Saussureae Radix is hepatoprotective against oxidative stress that causes abnormal liver damages.

• 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 (E_max) 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.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2004년도 Annual Meeting of KSAP : New Drug Development from Natural Products
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• pp.21-35
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• 2004

Heme oxygenase (HO)-l catabolizes heme into three products: carbon monoxide, bilirubin, and free iron. HO-l serves as a protective gene by virtue of the anti-inflammatory, anti-apoptotic and anti-proliferative actions of one or more of these three products. HO-l can be regarded as a potential therapeutic target in a variety of oxidant-mediated and inflammatory diseases. In this respect, it would be valuable to develop potent and selective inducers of HO-1 for therapeutic use. Here, we have shown that 1,2,3,4,6-penta-O-galloyl-beta-D-glucose, catalposide and dehydrocostus lactone are potent inducers of HO-1 and exert cytoprotective and anti-inflammatory activities via HO-1-ependent machanism.

• 한국한의학연구원논문집
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• 제12권3호통권18호
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• pp.117-130
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• 2006

The purpose of this study was to introduce the differential standard of Mok-Hyaeng Radix species. We established the classificatory standard according to the external and internal morphology and the pattern in 4 kinds of Mok-Hyaeng Radix. The results follow: 1. On the external morphology, Radix of Vladimiria souliei had a sticky material in the head of roots and it was yellowish white in the cut surface. It attached to teeth during chewing. Radix of Aucklandia lappa (=Saussurea lappa) was dark grayish brown and was grayish brown in the cut surface. It had special odor and was not attache to teeth chewing it. On the other hand, Radix of Inula helenium was dark brown. In the cut surface, cortical layer was different from wood layer. Radix of Aristolochia contorta was yellowish brown. In the cut surface, it was not smooth and cortical layer was different from wood layer. 2. On the internal morphology, Radix of Vladimiria souliei had many fascicular fibers and scattered large oil chambers in the bast ray, xylem ray, and parenchyma. On Radix of Aucklandia lappa (=Saussurea lappa), it was difficult to find out the trace when the cork layer was exfoliated. The cambium formed circle and the large oil chambers were scattered in the phloem and xylem. On the other hand, external cortical layer of Radix of Inula helenium was detached and cambium was formed to indistinct circle and large oil chambers were scattered in the phloem and xylem. On Radix of Arustolochia contorta, the large oil chambers were scattered in the surface later, bast part was relatively broad and cambium formed circle. 3. On the TLC pattern, Radix of Aristolochia contorta, Inula helenium, Aucklandia lappa, and Vladimiria souliei were chromogenic to violet and purple according to sulfuric acid colour pattern, especially faint on Aristolochia contorta. 4. On the pattern analysis of HPLC, we compared the content and the pattern of constunolide and dehydrocostus lactone, Radix of Aucklandia lappa was similar to Radix of Vladimiria souliei and Radix of Aristolochia contorta was similar to Radix of Inula helenium. On the total HPLC component pattern, constunolide and dehydrocostus lactone were similar in all four types, but it showed the Rf 5-6 peak was only in Radix of Aristolochia contorta, not in Radix of Inula helenium, Aucklandia lappa, and Vladimiria souliei. It is considered the results of this study will be furnished the basis to succeeding studies and it is needed to extensive comparative study for the same genus-degree of relatedness.

• 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.