• Biomedical Science Letters
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• v.25 no.3
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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.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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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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• v.23 no.1
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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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• v.8 no.1
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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.

• Korean Journal of Weed Science
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• v.30 no.4
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• pp.421-428
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• 2010

A foliage contact herbicidal substance was separated from ethyl ether fraction in n-hexane extract of Saussurea lappa roots and identified as 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). When DHCL at 4,000 ppm was foliage-applied to two grasses and two broadleaf plants, greater than 85% necrotic injury was obtained from large crabgrass, maize and soybean, whereas only about 40% necrotic injury appeared in black nightshade, indicating that DHCL has no gross morphological selectivity, but shows difference in contact response among the plant species tested. Conductivity in incubation medium of the leaf disks treated with DHCL increased as the incubation time continued. Relatively low contact injury in black nightshade as compared with the other three plant species tested was attributed to decrease in absorption of DHCL due to relatively high amount of cuticle. DHCL did not require light in the herbicidal action and there were no inhibitory effects on seed germination and cell elongation. Acetyl-CoA carboxylase activity was inhibited by 30% and 58% at $100\;{\mu}M$ and $1000\;{\mu}M$ DHCL, respectively. These results suggested that the herbicidal action of DHCL was related with inhibition of fatty acid synthesis which in turn caused to weaken cell membrane integrity.

• Herbal Formula Science
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• v.16 no.2
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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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• v.27 no.6
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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.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2004.04a
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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.

• Korean Journal of Oriental Medicine
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• v.12 no.3 s.18
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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.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.38 no.2
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• pp.171-179
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• 2012

This study is focused on finding new natural materials that have antimicrobial activity. We found that 3 plants extracts, Magnolia sieboldii K. Koch (M. sieboldii K. Koch), Rhus chinensis (R. chinensis) and Metasequioa glyptostroboides (M. glyptostroboides), have antimicrobial activities by disk diffusion method. We determined the Minimum Inhibitory Concentation (MIC) of each and found that 0.3 ~ 0.35 % of M. glyptostroboides essential oil and 0.35 ~ 0.4 % of M. sieboldii K. Koch extracts inhibited fungal growth and 0.45 ~ 0.5 % of R. chinensis extracts inhibited bacterial growth. We isolated compounds from extracts and verified what have antimicrobial activity. As a result we found that caryophyllene oxide and caryophyllene isolated from M. glyptostroboides, costunolide and dehydrocostus lactone from M. sieboldii K. Koch and ethyl gallate, ethyl-3-gallate from R. chinensis have antimicrobial activities. In accordance with antimicrobial activity, O/W cosmetic emulsion containing mixture of 3 plants extracts showed preservative efficacy against both bacteria and fungi. Based on the above data we suggest that extracts from M. siebodii K. Koch, R. chinensis, and M. glyptostroboides, replace chemical synthetic preservatives and be applied as a natural preservative.