• Journal of Plant Biology
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• 제17권1호
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• pp.9-14
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• 1974

Inhibitory effect of alantolactone and isoalantolactone was shwon in Avena straight growth test and in the formation of adventitious root in Phaseolus seedling. However, di-, and tetrahydroalantolactones given no effect on the elongation and the rooting. Inhibitory effect of alantolactone could partly be removed by cysteine, cystine, and reduced glutthione. The plant materials were made less sensitive to alantolactone by the pretreatment of cysteine, but cysteine supplied after the treatment of alantolactone brought about no effect on the action of alantolactone. A new spot was shown on TLC plate from the mixture of alantolactone and cysteine, indicating that alantolactone can be inactivated by cysteine, not cystine, without any biological processes.

• Journal of Plant Biology
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• 제17권2호
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• pp.69-83
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• 1974

To elucidate the relationship between chemical structure and biological activity of alantolactone, and also to investigate the relationship between the growth of cells and the respiration of Chlorella pyrenoidosa affected by alantolactone, alantolactone and isoalantolactone were isolated from Inula helenium L., and di-, and tetrahydroalantolactones were prepared by the hydrogenation. At a concentration of 5$\times$10-5M alantolactone, the growth rate of Chlorella was greatly reduced. The viability of cells was also reduced over 50% within 2 hr at a concentration of 2.5$\times$10-4M alantolactone. However, oxygen uptake was increased by 20% over 3 hr. And 14CO2 production from glucose-1-14C, glucose-6-14C and 14C-acetate-U.L. was also increased by alantolactone. Biological activityof alantolactone was significantly reduced by cysteine, reduced glutathione or cystine but not by tryptophan or histidine. It was detected by spectrophotometrically and by TLC that alantolactone was also reacted with thiols except cystine. The solution of alantolactone reached with thiol gave the UV absorption spectrum of $\alpha$-saturated ${\gamma}$-lactone, and most of SH groups were disappeared by the addition reaction. From the reaction mixture of alantolactone and cysteine, a lactone adduct was isolated and purified. Isoalantolactone had shown similar activity as alantolactone, however, it was appeared that di-, and tetrahydroalantolactones were not only inactive biologically but also in vitro. It was concluded that there was no correlationship between increased respiration rate and mortality of Chlorella. During the respiration TCA cycle was activated, however it was uncertain that the activation of EMP or HMP was also appeared. Alantolactone and isoalantolactone were biologically active compounds but others were inactive. The reactivity of $\alpha$-methylene ${\gamma}$-lactone moiety toward SH group was principally responsible for its biological activity in sesquiterpene lactones.

• Journal of Plant Biology
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• 제25권2호
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• pp.65-72
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• 1982

The oxygen consumption of fresh and aged slices of potato tuber was 40.6 and 168.0 ,$0_2$ $\mu$l/g fr $wt{\cdot}h$, respectively. After initial burst of oxygen consumption within 2 minutes(i.e., 40% for fresh and 12% for aged slices) in the treatmentof $50{\mu}M$ alantolactone, gradual decrease of respiration rate was observed during 3 hours of incubation. In case of the aged slices the initial burst of oxygen consumption was not observed by salicylhydroxamic acid (SHAM) or KCN. The combined effect of SHAM and alantolactone showed increase of 12%, while SHAM and KCN combination showed 60% decrease. In addition, the lipophilicity of cell membrane of onion inner epidermis was increased by lantolactone treatment. The results suggest that the primary effect of alantolactone on the cellular respiration may be associated with an alteration of lipophilic phase of cell membrane and a consequent increase of electron flow throuh the cytochrome system.

• 생약학회지
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• 제5권1호
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• pp.9-16
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• 1974

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2003년도 Annual Meeting of KSAP : International Symposium on Pharmaceutical and Biomedical Sciences on Obesity
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• pp.101-101
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• 2003

Prostaglandins (PGs) and nitric oxide (NO) produced by inducible cyclooygenase (COX-2) and nitric oxide synthase (iNOS), respectively, have been implicated as important mediators in the process of inflammation and carcinogenesis. On this line, the potential COX-2 or iNOS inhibitors have been considered as anti-inflammatory and cancer chemopreventive agents. In our continuing efforts of searching for novel cancer chemopreventive agents from natural products, we isolated natural sesquiterpenoids as potential COX-2 and iNOS inhibitors in cultured lipopolysaccharide (LPS)-activated mouse macrophage RAW 264.7 cells. Alantolactone, a natural eudesmane-type sesquiterpenoid, exhibited a potent inhibition of COX-2 (IC50 = 0.4 $\mu\textrm{g}$/$m\ell$) and iNOS activity (IC50 = 0.08 $\mu\textrm{g}$/$m\ell$) in the assay system determined by PGE2 and NO accumulation, respectively. The inhibitory potential of alantolactone on the PGE2 and NO production was well coincided with the suppression of COX-2 and iNOS protein and mRNA expression in LPS-induced macrophages. Furthermore, alantolactone inhibited NF-kB but not AP-l binding activity on nuclear extracts evoked by LPS-stimulated macrophage cells, suggesting the possible involvement of NF-kB in the regulation of COX-2 and iNOS expression. In further study with COX-2-expressing human colon HT-29 cells, alantolactone inhibited the cell proliferation, down-regulated COX-2, and inhibited the ERK phosphorylation in the early time. These results suggest that a natural sesquiterpenoid alantolactone might be a potential lead candidate for further developing COX-2 or iNOS inhibitor possessing cancer chemopreventive or anti-inflammatory activity

• Natural Product Sciences
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• 제25권1호
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• pp.16-22
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• 2019

Inula helenium L. is rich source of eudesmane-type sesquiterpene lactones, mainly alantolactone and isoalantolactone, which have the various pharmacological functions. In this study, we examined the inhibitory effects of nitric oxide (NO) production of hexane, methylene chloride, ethyl acetate, butanol, and water fractions from I. helenium and investigated the anti-inflammatory effect of hexane fraction of I. helenium (HFIH) in LPS-induced RAW 264.7 cells. Quantification of alantolactone and isoalantolactone from HFIH was carried out for the standardization by multiple reaction monitoring using triple quadrupole mass spectrometer. HFIH significantly inhibited inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) protein as well as their downstream products NO and prostaglandin $E_2$ ($PGE_2$) in LPS-stimulated RAW 264.7 cells. Moreover, HFIH suppressed $NF-{\kappa}B$ transcriptional activity by decreasing the translocation of p65 to the nucleus. The in vivo study further confirmed that HFIH attenuated the paw edema induced by carrageenan in an acute inflammation model. These findings suggest that HFIH may be useful as a promising phytomedicine for inflammatory-associated diseases.

• Biomolecules & Therapeutics
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• 제32권5호
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• pp.627-634
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• 2024

Sesquiterpene lactones, a class of natural compounds abundant in the Asteraceae family, have gained attention owing to their diverse biological activities, and particularly their anti-proliferative effects on human cancer cells. In this study, we systematically investigated the structure-activity relationship of ten sesquiterpene lactones with the aim of elucidating the structural determinants for the STAT3 inhibition governing their anti-proliferative effects. Our findings revealed a significant correlation between the STAT3 inhibitory activity and the anti-proliferative effects of sesquiterpene lactones in MDA-MB-231 breast cancer cell lines. Among the compounds tested, alantolactone and isoalantolactone emerged as the most potent STAT3 inhibitors, highlighting their potential as candidates for anticancer drug development. Through protein-ligand docking studies, we revealed the structural basis of STAT3 inhibition by sesquiterpene lactones, emphasizing the critical role of hydrogen-bonding interactions with key residues, including Arg609, Ser611, Glu612, and Ser613, in the SH2 domain of STAT3. Furthermore, our conformational analysis revealed the decisive role of the torsion angle within the geometry-optimized structures of sesquiterpene lactones in their STAT3 inhibitory activity (R=0.80, p<0.01). These findings not only provide preclinical evidence for sesquiterpene lactones as promising phytomedicines against diseases associated with abnormal STAT3 activation, but also highlight the importance of stereochemical aspects in their activity.

• 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.

• 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.

• 약학회지
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• 제30권5호
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• pp.253-265
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• 1986

Among 230 species of herbal drugs screened, thirty one show the anthelmintic activities in vitro against Clonorchis sinensis, the chinese liver fluke. The active substances have been isolated and their structures identified. Some of the active substances and their derivatives have been synthesized, followed by anthelmintic activity tests. The extracts from the active drugs cause damages in organs of the adult worm in the hepatic duct of rabbit. Some fresh water fish, which function as bad hosts for the fluke, excrete defense substances against the cercaria of the fluke. The defense substances have been isolated from Cyprinus carpio and Cyprinus carpio nudus, followed by structural identification. The results are summarized as follows: l) The bark of Machilus thunbergii as well as the seed of Schizandra chinensis contain meso-dihydro-guaiaretic acid as the anthelmintic component. Among derivatives synthesized, 4-phenyl-1-((3, 4-dihydroxyphenyl)-, 4-phenyl-1-(3-hydroxy-4-methoxy phenyl)-and 4-phenyl-1-(4-hydroxy-3-methoxy phenyl)-2, 3-dimethyl butanes show considerable activities. Administration of the bark extract mainly damages the bladder of the adult worm. 2) The active substance from the roasted fruit of Prunus mume is 2-hydroxymethylfurfural. This substance is produced during the roasting process. Administration of the fruitextract causes a damage of the bladder of the adult worm. 3) The active substance from the root of Scutellaria baicalensis is 5.2'-dihydroxy-6, 7, 8, 6'-tetramethoxyflavone. 4) Beside alantolactone, a very strong anthelmintic component is contained in the root of Inula helenium. Administration of the root extract causes irreversible damage on the worm, affecting mainly the reproductive organs. 5) The cercaricidal substances from the epidermis of C. carpio and C. carpio nudus are ethyl linoleate and linoleic acid, respertively. 6) The cercaricidal substances from various kinds of fresh water fish have different $R_f$ values, implying that the defense substances are species-specific. Unexpectedly, the fish with good host function, for example Pseudorasbora parva, excrete the defense substances, too. The defense substances are possibly organ-specific in individual species; the organs essenstial for the existence of the species excrete the defense substances, allowing other parts to be invaded by the cercaria. 7) The cercaricidal fraction of Carassius carassius is detected only in the fish which have been collected during the summer time from May to September, Its secretion is not dependent on water temperature. Thus, it seems to be possible that the secretion of the defense substance would be stimulated through a contact between the fish and cercaria.