• 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 PSK Conference
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• 2001.04a
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• pp.172.1-172.1
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• 2001

• Korean Journal of Pharmacognosy
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• v.30 no.1
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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 $100\; {\mu}g/ml.$.

• Applied Biological Chemistry
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• v.42 no.2
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• pp.176-179
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• 1999

In the bioactivity test of nine sesquiterpene lactons isolated from Hemisteptia lyrata, Chrysanthemum zawadskii and Chrysanthemum boreale, we investigated their antimicrobial activities against ten bacteria and six phytopathogenic fungi. Hemistepsin A and hemistepsin B isolated from H. lyrata and tulipinolide isolated from C. boreale exhibited strong antibacterial activity. In the antifungal test, hemistepsin B, angeloylcumambrin B, tigloylcumambrin B and costunolide showed broad activity. Both antibacterial and antifungal experiments exhibited quite clear specificity against microbial strains.

• YAKHAK HOEJI
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• v.51 no.2
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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.

• 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.

• Journal of Life Science
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• v.31 no.4
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• pp.430-441
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• 2021

Sesquiterpene lactones (STLs) are terpenoids found mostly in the Asteraceae family and are known for their strong cytotoxic properties, among other notable bioactivities. Some STLs, such as artemisinin and mipsagargin, are already commercially available and are used to fight malaria and tumor growth, respectively. Although the interest in STLs was low for a time after their discovery due to their toxic nature, past decades have witnessed a soar in STL-based studies focused on developing novel pharmaceuticals via chemical diversification. These studies have reported several promising physiological effects for STLs, including lower toxicity and diverse modes of action, and have demonstrated the antimicrobial, antioxidant, hepatoprotective, antiviral, antiprotozoal, phytotoxic, antitumor, and antiaging properties of STLs. STLs are mainly considered as valuable natural molecules for the fight against cancer since most STLs induce death of different types of cancer cells, as shown by in vitro and in vivo studies. Some STLs can also enhance the effects of drugs that are already in clinical use. Medicinal chemists use various STLs as starting molecules for the synthesis of new STLs or different bioactive compounds. All these developments warrant future research to provide more information on STLs, their bioactivities, and their mode of action. In this context, this review has summarized the bioactivities of some of the widely studied STLs, namely artemisinin, costunolide, thapsigargin, arglabin, parthenolide, alantolactone, cynaropicrin, helenalin, and santonin.

• Korean Journal of Pharmacognosy
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• v.46 no.4
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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.

• Molecules and Cells
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• v.38 no.9
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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 Journal of Korean Medicine
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• v.35 no.4
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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'.