Abstract
A new rearranged eudesmane sesquiterpene, named eudeglaucone (1), and five known sesquiterpenes including (+)-faurinone (2) and four eudesmane-type sesquiterpenes (3–6), were isolated from the twigs of Lindera glauca (Sieb. et Zucc.) Blume. The structure of 1 was elucidated by a combination of extensive spectroscopic analyses, including extensive 2D NMR (1H-1H COSY, HMQC, HMBC, and NOESY) and HR-MS. Compound 1 was a relatively rare rearranged eudesmane sesquiterpene in terpenoids. All isolates were evaluated for their antiproliferative activities against four human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and HCT-15). Compounds 3 and 6 showed significant cytotoxicity against SK-MEL-2 and HCT-15 cell lines with IC50 values ranging from 9.98 to 12.20 μM. We also investigated the anti-neuroinflammatory activities of the isolates (1–6) in the lipopolysaccharide (LPS)-stimulated murine microglia BV-2 cell line by measuring nitric oxide (NO) levels. All isolates significantly inhibited NO production with IC50 values of 3.67–26.48 μM without inducing cell toxicity.
Similar content being viewed by others
Avoid common mistakes on your manuscript.
Introduction
Lindera glauca (Sieb. et Zucc.) Blume (Lauraceae) is a deciduous shrub widely distributed in Korea, Japan, and China (Lee 1998). L. glauca has been used to treat various diseases in Korean traditional medicine (Park et al. 2014; Chung and Shin 1990). Traditionally, its fruit has been applied in the treatment of symptoms of paralysis, abdominal pain, and speech disorders. Its roots have also been used as a remedy for extravasation, contusion, and pain due to rheumatoid arthritis. Most importantly, the extract of this tree has long been used to cure cancers in Korean traditional medicine (Park et al. 2014; Chung and Shin 1990), and its effectiveness is supported by our preliminary study showing that the MeOH extract of L. glauca twigs had excellent cytotoxic activity against A549, SK-OV-3, SK-MEL-2, and HCT-15 cells in a sulforhodamine B (SRB) bioassay (Kim et al. 2014). Previous phytochemical investigations on L. glauca revealed a variety of bioactive compounds including sterols (Chang et al. 2000; Huh et al. 2011), alkaloids (Chang et al. 2000, 2001), butanolides (Chang et al. 2000; Seki et al. 1994, 1995), sesquiterpenoids (Nii et al. 1983), diarylpropanoids (Huh et al. 2012), flavonoids (Chang et al. 2000), and phenolic compounds (Chang et al. 2000). However, the constituents associated with the anti-tumor activity from L. glauca have not been investigated thoroughly. In the course of our search for the anti-tumor constituents from L. glauca, we recently reported the isolation and identification of several lignan derivatives with cytotoxic activity as well as anti-inflammatory activity from the MeOH extract of L. glauca (Kim et al. 2014; Suh et al. 2015).
In our ongoing search for bioactive constituents from the twigs of L. glauca, we further investigated the MeOH extract of L. glauca twigs to search for other types of compounds associated with anti-tumor activity. As a result, a new rearranged eudesmane sesquiterpene, named eudeglaucone (1), together with five known sesquiterpenes including faurinone (2) and four eudesmane-type sesquiterpenes (3–6), were isolated from the most active CHCl3-soluble fraction of the MeOH extract (Fig. 1). The structure of 1 was elucidated by a combination of extensive spectroscopic analyses, including 2D NMR (1H-1H COSY, HMQC, HMBC, and NOESY) and HR-MS. The current report describes the isolation and structure elucidation of the compounds 1–6, as well as their bioactive properties.
Materials and methods
General experimental procedures
Optical rotations were measured on a Jasco P-1020 polarimeter using methanol as a solvent. IR spectra were recorded on a Bruker IFS-66/S FT-IR spectrometer using methanol as a solvent. UV spectra were recorded using an Agilent 8453 UV–Vis spectrophotometer. HR-ESI MS and ESIMS spectra were recorded on a Micromass QTOF2-MS. LC/MS analysis was performed on an Agilent 1200 Series HPLC/6130 Series mass spectrometer. NMR spectra, including 1H-1H COSY, HMQC, HMBC, NOESY experiments, were recorded on a Varian UNITY INOVA 500 NMR spectrometer operating at 500 MHz (1H) and 125 MHz (13C), with chemical shifts given in ppm (δ). Semi-preparative HPLC was conducted with a Shimadzu Prominence HPLC System with SPD-20A/20AV Series Prominence HPLC UV–Vis Detectors (Shimadzu). Silica gel 60 (Merck, 230–400 mesh) and RP-C18 silica gel (Merck, 230–400 mesh) were used for column chromatography. The packing material for molecular sieve column chromatography was Sephadex LH-20 (Pharmacia Co. Ltd). Merck precoated silica gel F254 plates and RP-18 F254s plates were used for TLC. Spots were detected on TLC under UV light or by heating after spraying with anisaldehyde-sulfuric acid.
Plant materials
The twigs of L. glauca (Sieb. et Zucc.) Blume were collected from Hongcheon, Chungcheongbuk-do, Korea, in March 2010. Samples of plant material were identified by one of the authors (K. H. Kim). A voucher specimen (SKKU 2010-3B) has been deposited in the herbarium of the School of Pharmacy, Sungkyunkwan University, Suwon, Korea.
Extraction and isolation
The pulverized twigs of L. glauca (6 kg) were extracted twice with 80 % aqueous MeOH (2 × 4 h) under reflux, and then filtered. The filtrate was concentrated under vacuum to afford a crude MeOH extract (120 g), which was suspended in distilled water (2 L) and successively partitioned with hexane, CHCl3, EtOAc, and n-BuOH, yielding 2.5, 13.3, 7.6, and 17.5 g of residues, respectively. Each fraction was evaluated for its cytotoxicity against A549, SK-OV-3, SK-MEL-2, and HCT-15 cells using the SRB bioassay. The most active fraction was the CHCl3-soluble fraction, which we selected for phytochemical investigation. The CHCl3-soluble fraction (13.3 g) was separated over RP-C18 silica gel (230–400 mesh, 300 g) column chromatography using a gradient of increasing MeOH in H2O from 50 to 100 % to give four fractions (C1–C4). Fraction C3 (2.1 g) was applied to a Sephadex LH-20 column using a solvent system of CH2Cl2–MeOH (1:1) to yield eight subfractions (C31–C38). Subfraction C36 (135 mg) was further purified by semi-preparative HPLC using a 250 × 10 mm i.d., 10 μm, Econosil RP-18 column (Alltech, Nicholasville, KY, USA) using isocratic elution with 75 % MeOH/H2O (flow rate; 2 mL/min) to yield compound 2 (4 mg). Subfraction C37 (120 mg) was purified by semi-preparative HPLC using the same column with an isocratic solvent system of 75 % MeOH/H2O (flow rate; 2 mL/min) to obtain compounds 3 (3 mg) and 4 (3 mg). Compound 5 (3 mg) was isolated from subfraction C38 (275 mg) by the purification of semi-preparative HPLC using the same column with 90 % MeOH/H2O. Fraction C4 (1.5 g) was separated over RP-C18 silica gel (230–400 mesh, 50 g) column chromatography using a solvent system of 80 % MeOH/H2O to give 12 subfractions (C4A–C4L). Subfraction C4A (180 mg) was separated over a pre-packed C18 Sep-Pak cartridge (10 g, Waters) using 90 % MeOH/H2O, and further purified by semi-preparative HPLC using a 250 × 10 mm i.d., 10 μm, Econosil RP-18 column (Alltech) using isocratic elution with 70 % MeOH/H2O (flow rate; 2 mL/min) to furnish compound 1 (7 mg). Subfraction C4B (85 mg) was purified by semi-preparative HPLC using the same column with an isocratic solvent system of 95 % MeCN/H2O (flow rate; 2 mL/min) to give compound 6 (9 mg).
Eudeglaucone (1): colorless gum; \([\alpha ]_{\text{D}}^{25}\) −20.5 (c 0.30, MeOH); UV (MeOH) λmax (log ε) nm 208 (3.8); IR (neat) ν max cm−1: 3421, 2938, 2831, 1685, 1455, 1256, 1032; 1H (CD3OD, 500 MHz) and 13C (CD3OD, 125 MHz) NMR data, see Table 1; HR-ESIMS (positive-ion mode) m/z: 289.1421 [M+Na]+ (calcd for C15H22O4Na, 289.1416).
In vitro cytotoxicity test
A sulforhodamine B (SRB) bioassay was used to determine the cytotoxicity of each isolated compound against four cultured human tumor cell lines (Song et al. 2014). The assays were performed at the Korea Research Institute of Chemical Technology. The cell lines used were A549 (non-small cell lung carcinoma), SK-OV-3 (ovary malignant ascites), SK-MEL-2 (skin melanoma), and HCT-15 (colon adenocarcinoma). Each tumor cell line was inoculated over standard 96-well flat-bottom microplates and then incubated for 24 h at 37 °C in a humidified atmosphere of 5 % CO2. The attached cells were then incubated with the serially diluted isolates. After continuous exposure to the compounds for 48 h, the culture medium was removed from each well and the cells were fixed with 10 % cold trichloroacetic acid at 4 °C for 1 h. After washing with tap water, the cells were stained with 0.4 % SRB dye and incubated for 30 min at room temperature. The cells were washed again and then solubilized with 10 mM unbuffered Tris base solution (pH 10.5). The absorbance was measured spectrophotometrically at 520 nm with a microtiter plate reader. Doxorubicin (purity ≥98 %, Sigma) was used as a positive control. The cytotoxicities of doxorubicin against the A549, SK-OV-3, SK-MEL-2, and HCT-15 cell lines were IC50 0.002, 0.012, 0.001, and 0.109 μM, respectively. Tested compounds were demonstrated to be pure as evidenced by NMR and HPLC analyses (purity ≥95 %).
Determination of NO content
BV-2 microglia cells (4 × 104 cells/well in 96 well plates) were treated with the samples to be tested for 30 min before exposure to 100 ng/mL of LPS. After 24 h incubation, nitrite in culture medium was measured to assess NO production in BV-2 microglia cells using Griess reaction. The supernatant (50 μL) was harvested and mixed with an equal volume of Griess reagent (1 % sulfanilamide, 0.1 % N-1-napthylethylenediamine dihydrochloride in 5 % phosphoric acid). After 10 min, the absorbance at 540 nm was measured using a microplate reader. Sodium nitrite was used as a standard to calculate the \({\text{NO}}_{2}^{\text{ - }}\) concentration. N G-Monomethyl-l-arginine (l-NMMA, purity ≥98 %, Sigma, USA), a well-known NOS inhibitor, was tested as a positive control. Cell viability was assessed by a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay.
Results
Structural elucidation of isolated compounds
Compound 1 was isolated as an optically active colorless gum. The molecular formula of 1 was determined as C15H22O4 from its positive mode HR-ESIMS data at m/z 289.1421 [M+Na]+ (calcd for C15H22O4Na, 289.1416), which was compatible with the 1H and 13C NMR data. Its IR spectrum exhibited characteristic absorptions of hydroxy (3421 cm−1) and conjugated carboxylic (1685 cm−1) groups. The 1H and 13C NMR spectral data (Table 1) of 1, in combination with HMQC, indicated a total of 15 carbon signals, including one tertiary methyl group [δH 0.96 (3H, s); δC 21.8], one characteristic acetyl moiety composed of one methyl signal [δH 2.15 (3H, s); δC 28.9] and a carbonyl carbon signal [δC 215.4], and one oxygenated methine signal [δH 4.36 (1H, dd, J = 8.5, 4.5 Hz); δC 78.6]. The NMR data also showed an olefinic methylene signal [δH 6.13 (1H, s) and 5.62 (1H, s); δC 21.8], one quaternary carbon [δC 147.4], and a carboxyl signal [δC 172.5], whose characteristic resonances indicated the presence of an allylic acid moiety in the molecule (Ceccherelli et al. 1985; Oksuz and Topcu 1991; Leon et al. 2009). The 1H and 13C NMR spectra of 1 were shown to have a rearranged-type sesquiterpene skeleton. The correlations in the 1H-1H-COSY and HMQC spectra revealed the presence of two proton-bearing structural fragments, –CH2CH2CH–OH (a) and –CH2CHCH2CH2– (b) (Fig. 2). Detailed HMBC analysis showed the correlation of H-14 (δH 0.96)/C-1 (δC 37.2), C-5 (δC 64.5), C-9 (δC 37.1), and C-10 (δC 43.3), H-15 (δH 2.15)/C-4 (δC 215.4) and C-5 (δC 64.6), H-6 (δH 2.06 and 1.99)/C-3 (δC 78.6) and C-11 (δC 147.4), H-7 (δH 3.22)/C-12 (δC 172.5), and H-13 (δH 6.13)/C-7 (δC 35.9) and C-12 (δC 172.5) (Fig. 2), which suggested that the planar structure of 1 was identical to that of 3α-hydroxyisoiphion-11(13)-en-12-oic acid, a known isoiphionane-type sesquiterpene (Garcez et al. 2010). However, there was a major difference between the two compounds in the 13C chemical shifts of the allylic acid moiety [δC 175.1 (C-12), 153.1 (C-11), 117.6 (C-13) in 3α-hydroxyisoiphion-11(13)-en-12-oic acid] (Garcez et al. 2010), which suggested that compound 1 is a stereoisomer of 3α-hydroxyisoiphion-11(13)-en-12-oic acid.
The relative stereochemistry of 1 was established from the observed data of the NOESY experiment. The cis-fused hydrindane system of 1 was assigned by the chemical shift of the methyl of C-14 (δC 21.8) (Todorova and Tsankova 1999), which was supported by NOESY correlation between H-14 and H-15 (Fig. 2). The OH group of C-3 was established as being in the α-position by the observed coupling constants of H-3 (J = 8.5, 4.5 Hz) and its downfield shift (δH 4.36) caused by the neighboring acetyl group (Todorova and Tsankova 1999). The β-orientated H-3 was further confirmed by the NOESY correlation of H-3/H-15 (Fig. 2). Finally, the NOESY correlation of H-7/H-15 indicated a β-orientated H-7 (Fig. 2), which confirmed that compound 1 is an epimer of 3α-hydroxyisoiphion-11(13)-en-12-oic acid. Determination of the absolute configuration in natural products is crucial because it provides essential information for both molecular mode of action and total synthesis of bioactive compounds. The determination of the absolute configuration of 1 was attempted by using the modified Mosher’s method (Kim et al. 2011, 2015a, b). However, the reaction failed to yield the corresponding acylation product, possibly due to steric hindrance at C-3/C-5. So the absolute configuration of 1 remains unknown. On the basis of the above data, the structure of 1 was elucidated as shown in Fig. 1 and named eudeglaucone.
The known compounds were identified as (+)-faurinone (2) (Bos et al. 1983), 3α-hydroxycostic acid (3) (Ceccherelli et al. 1985), ilicic acid (4) (Oksuz and Topcu 1991), γ-costic acid (5) (Leon et al. 2009), and costic acid (6) (Watanabe et al. 2005) by comparing the physicochemical and spectroscopic data with previously reported data. Besides the known sesquiterpenes, other known lignan derivatives such as lyoniresinol, linderuca A, linderuca C, (+)-9′-O-(E)-feruloyl-5,5′-dimethoxylariciresinol, and (+)-5,5′-dimethoxylariciresinol were also isolated and identified, however, they were all compounds previously reported from this plant by our group (Kim et al. 2014; Suh et al. 2015).
Biological activities
The cytotoxic activities of all the isolates 1–6 were evaluated by determining their inhibitory effects on human tumor cell lines, including A549 (non-small cell lung carcinoma), SK-OV-3 (ovary malignant ascites), SK-MEL-2 (skin melanoma), and HCT-15 (colon adenocarcinoma) using the SRB bioassay (Song et al. 2014), since all of the compounds 1–6 were isolated from the CHCl3-soluble fraction of the MeOH extract, which showed potent cytotoxicity against the tumor cell lines. Some eudesmane-type sesquiterpenes have been reported to possess cytotoxic activity against cancer cell lines in recent studies (Zhang et al. 2015; Zhao et al. 2014; Nie et al. 2014; Cheng et al. 2013). However, no reports are available regarding the evaluation of cytotoxic activities of the rearranged eudesmane sesquiterpenes. The results (Table 2) demonstrated that compounds 3 and 6 showed significant cytotoxicity against SK-MEL-2 and HCT-15 cell lines with IC50 values ranging from 9.98 to 12.20 μM. However, other compounds including the new compound, rearranged eudesmane sesquiterpene (1) were inactive (IC50 > 30.0 μM). These results suggested that the exomethylene unit at C-4 in eudesmane-type sesquiterpenes may play a positive role in mediating the cytotoxicity against SK-MEL-2 and HCT-15 cell lines.
The anti-neuroinflammatory activities of the isolates 1–6 were also evaluated by measuring the levels of nitric oxide (NO) produced in lipopolysaccharide (LPS)-activated microglia BV-2 cells (Ko et al. 2015). Recently, several eudesmane sesquiterpenes were reported to inhibit LPS-induced NO production in BV-2 microglial cells (Tian et al. 2013; Wang et al. 2014; Jiang et al. 2013). However, research on the NO inhibitory effect of rearranged eudesmane sesquiterpenes in LPS-stimulated murine microglia BV-2 cells has not been reported until now. Microglia, the immune resident cells of the brain, have been implicated in the pathogenesis of a variety of neurodegenerative diseases including Parkinson’s disease and Alzheimer’s disease (Wilms et al. 2007; McGeer and McGeer 1995). Under pathological conditions, microglia cells are over-activated and produce a variety of pro-inflammatory mediators including NO (Yang et al. 2015; Kim et al. 2015a, b), which consequently leads to various neurodegenerative conditions of the CNS. In this study, the isolated compounds 1–6 significantly inhibited NO levels in LPS-stimulated BV-2 cells with IC50 values in the range of 3.67–26.48 μM (Table 3). None of the compounds showed any significant cellular toxicity up to 20 μM (Table 3). In particular, compound 2 potently inhibited LPS-stimulated NO production with an IC50 value of 3.67 μM, and the new compound, rearranged eudesmane sesquiterpene (1) (IC50 = 15.90 μM) along with compounds 2 (IC50 = 3.67 μM), 4 (IC50 = 14.92 μM), and 6 (IC50 = 12.13 μM) displayed better inhibitory activity on NO production than the positive control, N G-nonomethyl-l-arginine (NMMA), a well-known NOS inhibitor (IC50 = 18.35 μM). Regarding to the other known lignan derivatives, they were not evaluated for the cytotoxic and anti-inflammatory activities in this study since we already reported the biological data of them (Kim et al. 2014; Suh et al. 2015).
Discussion
We isolated and identified a new rearranged eudesmane sesquiterpene, eudeglaucone (1), together with five known sesquiterpenes including faurinone (2) and four eudesmane-type sesquiterpenes (3–6) from the twigs of L. glauca and evaluated their cytotoxic and anti-neuroinflammatory activities. The new compound 1 was a relatively rare rearranged eudesmane sesquiterpene in terpenoids, and to the best of our knowledge, this is the first report of the presence of the rearranged eudesmane sesquiterpene in this plant. In addition, this is the first report of the occurrence of the eudesmane sesquiterpenes in this plant, and compounds 2 and 3 were isolated from the family of Lauraceae for the first time. The co-occurrence of the rearranged eudesmane sesquiterpene 1 and eudesmane sesquiterpenes 3–6 in the same plant reinforces the biogenetic inter-relationship between the rearranged sesquiterpene and eudesmanes, and suggested the rearrangement of 4,5-epoxy-eudesmanes into the rearranged eudesmane sesquiterpenes (Garcez et al. 2010; Todorova and Tsankova 1999). Compounds 3 and 6 showed significant cytotoxicity against SK-MEL-2 and HCT-15 cell lines and all the isolated compounds 1–6 had anti-neuroinflammatory properties in murine BV-2 microglia cells. Therefore, it is possible that these compounds could be applicable in the development of treatments for activated microglia-mediated brain diseases and/or tumors.
References
Bos R, Hendriks H, Kloosterman J, Sipma G (1983) A structure of faurinone, a sesquiterpene ketone isolated from Valeriana officinalis. Phytochemistry 22:1505–1506
Ceccherelli P, Curini M, Marcotullio MC, Menghini A (1985) Sesquiterpene acids from Dittrichia viscosa. Phytochemistry 24:2987–2989
Chang YC, Chang FR, Wu YC (2000) The constituents of Lindera glauca. J Chin Chem Soc 47:373–380
Chang YC, Chen CY, Chang FR, Wu YC (2001) Alkaloids from Lindera glauca. J Chin Chem Soc 48:811–815
Cheng XR, Zhang SD, Wang CH, Ren J, Qin JJ, Tang X, Shen YH, Yan SK, Jin HZ, Zhang WD (2013) Bioactive eudesmane and germacrane derivatives from Inula wissmanniana Hand.-Mazz. Phytochemistry 96:214–222
Chung BS, Shin MK (1990) Dictionary of Korean folk medicine. Young Lim, Seoul
Garcez FR, Garcez WS, Hamerski L, Miranda ACDM (2010) Eudesmane and rearranged eudesmane sesquiterpenes from Nectandra cissiflora. Quim Nova 33:1739–1742
Huh GW, Park JH, Shrestha S, Lee YH, Ahn EM, Kang HC, Baek NI (2011) Sterols from Lindera glauca Blume stem wood. J Appl Biol Chem 54:309–312
Huh GW, Park JH, Shrestha S, Lee YH, Ahn EM, Kang HC, Kim YB, Baek NI (2012) New diarylpropanoids from Lindera glauca Bl Heartwood. Holzforschung 66:585–590
Jiang B, Wang WJ, Li MP, Huang XJ, Huang F, Gao H, Sun PH, He MF, Jiang ZJ, Zhang XQ, Ye WC (2013) New eudesmane sesquiterpenes from Alpinia oxyphylla and determination of their inhibitory effects on microglia. Bioorg Med Chem Lett 23:3879–3883
Kim KH, Choi SU, Kim YC, Lee KR (2011) Tirucallane triterpenoids from Cornus walteri. J Nat Prod 74:54–59
Kim KH, Moon E, Ha SK, Suh WS, Kim HK, Kim SY, Choi SU, Lee KR (2014) Bioactive lignan constituents from the twigs of Lindera glauca. Chem Pharm Bull 62:1136–1140
Kim KH, Clardy J, Senger D, Cao S (2015a) Chakyunglupulins A and B, two novel 4,8,8-trimethylcyclooct-2-enone derivatives from Barleria lupulina. Tetrahedron Lett 56:2732–2734
Kim S, Oh MH, Kim BS, Kim WI, Cho HS, Park BY, Park C, Shin GW, Kwon J (2015b) Upregulation of heme oxygenase-1 by ginsenoside Ro attenuates lipopolysaccharide-induced inflammation in macrophage cells. J Ginseng Res 39:365–370
Ko W, Sohn JH, Kim YC, Oh H (2015) Viridicatol from marine-derived fungal strain Penicillium sp. SF-5295 exerts anti-inflammatory effects through inhibiting NF-κB signaling pathway on lipopolysaccharide-induced RAW264.7 and BV2 cells. Nat Prod Sci 21:240–247
Lee TB (1998) Coloured flora of Korea. Hyangmunsa, Seoul
Leon LG, Donadel OJ, Tonn CE, Padron JM (2009) Tessaric acid derivatives induce G2/M cell cycle arrest in human solid tumor cell lines. Bioorg Med Chem 17:6251–6256
McGeer PL, McGeer EG (1995) The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative diseases. Brain Res Rev 21:195–218
Nie XP, Yao F, Yue XD, Li GS, Dai SJ (2014) New eudesmane-type sesquiterpenoid from Solanum lyratum with cytotoxic activity. Nat Prod Res 28:641–645
Nii H, Furukawa K, Iwakiri M, Kubota T (1983) A new sesquiterpene carboxylic acid from Lindera glauca (Sieb. et Zucc.) Blume. Nippon Nogei Kagaku Kaishi 57:725–732
Oksuz S, Topcu G (1991) A eudesmanolide and other constituents from Inula graveolens. Phytochemistry 31:195–197
Park SY, Neupane GP, Lee SO, Lee JS, Kim MY, Kim SY, Park BC, Park YJ, Kim JA (2014) Protective effects of Pogostemon cablin Bentham water extract on inflammatory cytokine expression in TNBS-induced colitis in rats. Arch Pharm Res 37:253–262
Seki K, Sasaki T, Haga K, Kaneko R (1994) Two methoxybutanolides from Lindera glauca. Phytochemistry 36:949–951
Seki K, Sasaki T, Wano S, Haga K, Kaneko R (1995) Linderanolides and isolinderanolides, ten butanolides from Lindera glauca. Phytochemistry 40:1175–1181
Song JH, Choi HJ, Song HH, Hong EH, Lee BR, Oh SR, Choi K, Yeo SG, Lee YP, Cho S, Ko HJ (2014) Antiviral activity of ginsenosides against coxsackievirus B3, enterovirus 71, and human rhinovirus 3. J Ginseng Res 38:173–179
Suh WS, Kim KH, Kim HK, Choi SU, Lee KR (2015) Three new lignan derivatives from Lindera glauca (Siebold et Zucc.) Blume. Helv Chim Acta 98:1087–1094
Tian SH, Chai XY, Zan K, Zeng KW, Tu PF (2013) Three new eudesmane sesquiterpenes from Artemisia vestita. Chin Chem Lett 24:797–800
Todorova MN, Tsankova ET (1999) New sesquiterpenoids from Achillea clypeolata. Phytochemistry 52:1515–1518
Wang S, Sun J, Zeng K, Chen X, Zhou W, Zhang C, Jin H, Jiang Y, Tu P (2014) Sesquiterpenes from Artemisia argyi: absolute configurations and biological activities. Eur J Org Chem 2014:973–983
Watanabe Y, Mihara R, Mitsunaga T, Yoshimura T (2005) Termite repellent sesquiterpenoids from Callitris glaucophylla heartwood. J Wood Sci 51:514–519
Wilms H, Zecca L, Rosenstiel P, Sievers J, Deuschl G, Lucius R (2007) Inflammation in Parkinson’s diseases and other neurodegenerative diseases: cause and therapeutic implications. Curr Pharm Des 13:1925–1928
Yang Y, Lee J, Rhee MH, Yu T, Baek KS, Sung NY, Kim Y, Yoon KY, Kim JH, Kwak YS, Hong S, Kim JH, Cho JY (2015) Molecular mechanism of protopanaxadiol saponin fraction-mediated anti-inflammatory actions. J Ginseng Res 39:61–68
Zhang L, Lin HQ, Li GS, Yue XD, Dai SJ (2015) New sesquiterpenoid derivatives from Solanum septemlobum with cytotoxicities. Nat Prod Res 29:1889–1893
Zhao J, Wu J, Yan F (2014) A new sesquiterpenoid from the rhizomes of Homalomena occulta. Nat Prod Res 28:1669–1673
Acknowledgments
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2015R1C1A1A02037383) and by the Ministry of Education (NRF-2012R1A5A2A28671860).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Yu, J.S., Baek, J., Park, H.B. et al. A new rearranged eudesmane sesquiterpene and bioactive sesquiterpenes from the twigs of Lindera glauca (Sieb. et Zucc.) Blume. Arch. Pharm. Res. 39, 1628–1634 (2016). https://doi.org/10.1007/s12272-016-0838-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12272-016-0838-1