Anti-inflammatory sesquiterpene polyol esters from the stem and branch of Tripterygium wilfordii / 中国天然药物

The stem and branch extract of Tripterygium wilfordii (Celastraceae) afforded seven new dihydroagarofuran sesquiterpene polyesters [tripterysines A-G (1-7)] and eight known ones (8-15). The chemical structures of these new compounds were established based on combinational analysis of HR-ESI-MS and NMR techniques. The absolute configurations of tripterysines A-C (1-3) and E-G (5-7) were determined by X-ray crystallographic analysis and circular dichroism spectra. All the compounds were screened for their inhibitory effect on inflammation through determining their inhibitory effect on nitric oxide production in LPS-induced RAW 264.7 cells and the secretion of inflammatory cytokines TNF-α and IL-6 in LPS-induced BV2 macrophages. Compound 9 exhibited significant inhibitory activity on NO production with an IC50 value of 8.77 μmol·L-1. Moreover, compound 7 showed the strongest inhibitory effect with the secretion of IL-6 at 27.36%.

Cytotoxic sesquiterpene aryl esters from Armillaria gallica 012m / 中草药·英文版

OBJECTIVE@#To study the chemical constituents of the EtOAc extract of Armillaria gallica 012m.@*METHODS@#The chemical constituents of the EtOAc extract of A. gallica 012m were isolated and purified by various column chromatography and their structures were elucidated on the basis of the 1D and 2D NMR spectroscopic and HRESIMS data. Cytotoxicity of all isolates against A549, HCT-116, M231 and W256 human tumor cells was determined by the MTT method.@*RESULTS@#A new sesquiterpene aryl ester, armimelleolide C ( 1), and eight known ones including armillarivin ( 2), melleolide F ( 3), 6'-chloromelleolide F ( 4), melleolide ( 5), melleolide K ( 6), melledonol ( 7), 13-hydroxydihydromelleolide ( 8), and armillane ( 9), were isolated from the EtOAc extract of A. gallica 012m. All isolates showed potential cytotoxic activities against at least one of the human cancer cell lines with IC50 values ranging from (3.17 ± 0.54) to (17.57 ± 0.47) μmol/L. Compound 1 showed significant inhibitory activity against M231 with an IC50 value of (7.54 ± 0.24) μmol/L compared with paclitaxel as the positive control. Compounds 2, 3, and 7, 9 showed obvious inhibitory activity against HCT-116 and were better than that of the positive control.@*CONCLUSION@#The chemical constituents including a new sesquiterpene aryl ester armimelleolide C ( 1) from the EtOAc extract of A. gallica 012m have a variety of structures and potential antitumor activities.

Cloning and expression analysis of cytochrome P450 AsCYP71D1 from Aquilaria sinensis (Lour.) Gilg / 药学学报

Cytochrome P450 (CYP450) is a kind of superfamily oxidase containing heme, which is distributed in various aerobic organisms. They are widely involved in the biosynthesis of terpenoids, alkaloids, flavonoids, fatty acids, etc. In this study, the full-length cDNA sequence of a P450 was cloned by reverse transcription-PCR (RT-PCR) and rapid amplification of cDNA ends (RACE) technology, with the specific primers that designed according to the sequence of a transcript annotated as P450 from the Aquilaria sinensis (Lour.) Gilg transcriptome database. The tissue expression and subcellular localization were also studied. The full-length cDNA of the cloned P450 gene is 1 920 bp, with 88 bp 5′-untranslated region (UTR), 344 bp 3′-UTR and a 21 bp polyA tail, and 1 488 bp open reading frame (ORF), encoding 495 amino acids. Sequence alignment revealed that the protein belonged to CYP71D family of cytochrome P450 family, and named AsCYP71D1. Tissue expression analysis indicated that AsCYP71D1 was mainly expressed in stem. Further subcellular localization of onion epidermis showed that AsCYP71D1 was expressed in cytoplasm, nucleus and cell membrane. This study will provide a foundation for further research on its function in agarwood sesquiterpene biosynthesis.

Dysideanones F-G and dysiherbols D-E, unusual sesquiterpene quinones with rearranged skeletons from the marine sponge Dysidea avara / 中国天然药物

Four new sesquiterpene quinone meroterpenoids, dysideanones F-G (1-2) and dysiherbols D-E (3-4), were isolated from the marine sponge Dysidea avara collected from the South China Sea. The new structures were elucidated by extensive analysis of spectroscopic data including HR-MS and 1D and 2D NMR spectra, and their absolute configurations were assigned by single-crystal X-ray diffraction and ECD calculations. Anti-inflammatory evaluation showed that dysiherbols D-E (3-4) exhibited moderate inhibitory activity on TNF-α-induced NF-κB activation in human HEK-293T cells with IC50 values of 10.2 and 8.6 μmol·L-1, respectively.

A new anisotane-type sesquiterpene from Anisodus tanguticus / 药学学报

To investigate the chemical constituents of Anisodus tanguticus, silica gel column chromatography, Sephadex LH-20 column chromatography, preparative thin layer chromatography, and semi-preparative HPLC were used to separate and purify the chemical constituents from the extract of A. tanguticus. The planar structure of the isolated compound was identified by HRMS, IR, and 2D NMR experiments. The absolute configuration of the isolated compound was determined by a combination of NOESY, coupling constant, circular dichroism (CD), and transition metal chelate reagent dimolybdenum tetraacetate [Mo2(OAc)4]-induced circular dichroism (ICD) data analysis. A new compound of the anisotane-type sesquiterpene (1) was isolated, which was determined to be (1R,2S,3R,4R,6R,7R,9R)-anisotane-11(13)-ene-3,4,9-triol and named anisotanol F. This is the second report of anisotane-type sesquiterpene, which has previously been reported as a novel sesquiterpenoid skeleton by our research group. Furthermore, the cytotoxicity against HUVECs and inhibitory effect on NO release in LPS-induced RAW264.7 cells of compound 1 were investigated. However, the results showed that it was inactive. Compound 1 is a new compound isolated from A. tanguticus. It belongs to the unusual anisotane-type sesquiterpene. This result enriches the chemical composition of A. tanguticus.

Camganoids A and B, two new sesquiterpenes with different carbon skeletons isolated from fruits of Cinnamomum migao / 中草药·英文版

Objective: To isolate and identify the undescribed compounds from the fruits of Cinnamomum migao and evaluate its nitric oxide inhibition potential. Methods: The chromatographic techniques of silica gel, Sephadex, and HPLC were used for isolation and purification of the compounds, while HR-ESI-MS, 1D NMR, 2D NMR, ECD, and X-ray diffraction techniques were used to characterize and confirm the isolated compounds. Moreover, the anti-inflammatory activity of the isolated compounds was carried out to check inhibitory potential against the production of nitric oxide with RAW264.7 cells stimulated by LPS. Results: Camganoid A (1), a novel sesquiterpene possessing an unprecedented skeleton, and camganoid B (2), containing a unique eight-membered sesquiterpene moiety with a new carbon skeleton, were isolated and identified from the fruits of C. migao. The absolute configurations of 1 and 2 were confirmed by single crystal X-ray diffraction and electronic circular dichroism (ECD) calculations. Among these compounds, compound 1 exhibited potent inhibitory activity against the production of nitric oxide with IC

New bisabolane-type phenolic sesquiterpenoids from the marine sponge Plakortis simplex / 中国天然药物

Six new bisabolane-type phenolic sesquiterpenoids, including plakordiols A-D (1-4), (7R, 10R)-hydroxycurcudiol (5) and (7R, 10S)-hydroxycurcudiol (6) were isolated from the marine sponge Plakortis simplex collected from the South China Sea. Their structures were determined based on extensive analysis of spectroscopic data. Their configurations were assigned by coupling constant analysis, NOESY correlations, and the modified Mosher's method. Furthermore, their cytotoxic and antibacterial activities were evaluated.

Research advances in methods of cyclezation mechanism of sesquiterpenes / 中国中药杂志

Terpenes are the largest group of natural products and contain the widest assortment of structural types. Terpene cyclization is also the most complex reaction found in nature. For a long time, terpenoids with diverse structures have attracted natural product chemists to explore their biosynthesis mechanism. Such a large number of terpene skeletons are catalyzed by enzymes called terpene synthase. Sesquiterpene synthase is a kind of terpene synthase, which can catalyze the cyclization of linear precursor farnesyl pyrophosphate(FPP) to sesquiterpene skeletons. Sesquiterpene synthase cyclize a single precursor FPP into many sesquiterpene skeletons. With the continuous discovery of sesquiterpene synthase, the cyclization mechanism of sesquiterpene synthase has been studied deeply. In recent years, with the development and improvement of isotope labeling of substrate FPP and structural analysis of sesquiterpene synthase, the structure and cyclization mechanism of sesquiterpene synthase have been studied more systematically and accurately. In this review, we reviewed the progress of the research methods on the mechanism of sesquiterpene cyclization by substrate isotope labeling and protein structure, as well as the summary and prospect of sesquiterpene synthase research.

Advances in biosynthesis of cadinane sesquiterpenes / 生物工程学报

Cadinanes are a class of bicyclic sesquiterpenes with complex stereochemistry and broad pharmacological activities, such as antibacterial, anti-inflammatory, and hypoglycemic activities. To date, structurally diverse and bioactive cadinane sesquiterpenes have been isolated and identified from a variety of plants and microorganisms. Moreover, deeper understandings on cadinane sesquiterpene synthases have been made. This article categorized the 124 new cadinanes which were published in the literatures in the past four years (2017-2020) into five structural types, and presented their pharmacological activities. We also illustrated the elucidation of the biosynthetic pathways for typical cadinanes, summarized the research progress on cadinane sesquiterpene synthases. Finally, current challenges and future prospects were proposed and discussed.

Effect of hot or warm property on skin toxicity of essential oil as penetration enhancer and its mechanism / 中国中药杂志

To compare the effect of hot or warm property of Chinese medicine(CM) on the skin toxicity of essential oils(EOs) as penetration enhancer in vitro and in vivo, and explore the mechanism. EOs were extracted from WIM of Bichengqie(Litseae Fructus), Dingxiang(Flos Syzygii Aromatici), Huajiao(Pericarpium Zanthoxyli Bungeani), and Xiaohuixiang(Fructus Foeniculi) with warm property, and Ganjiang(Rhizoma Zingiberis), Gaoliangjiang(Rhizoma Alpiniae Officinari), Hujiao(Fructus Piperis), and Wuzhuyu(Fructus Evodiae Rutaecarpae) with hot property, respectively. Then the in vitro toxicity was evaluated by human keratinocyte cytotoxicity. In vivo skin irritation potency was also evaluated through pathological observation after topical administration. The components, especially those located in stratum corneum, were analyzed by GC-MS. The main components, namely monoterpenes and sesquiterpenes, of EOs extracted from CM with hot property,were detected for the interaction with keratino-lipid ceramide 3 by molecular simulation technology; and the interaction energy value was calculated based on the optimal conformation. It was found that the skin cell toxicity of EOs from CM with hot property was significantly higher than that of EOs from CM with warm property. However, there was no significant difference between them by in vivo skin irritation evaluation. Whether from CM with hot property or warm property, EOs showed a significant reduced toxicity compared with azone. Sesquiterpenes(33.56%±19.38%) were found to be one of the main components in EOs from CM with hot property, while almost no sesquiterpenes was found in EOs from CM with warm property. After topical administration of EOs from CM with hot property, sesquiterpenes were demonstrated to be prone to locate in stratum corneum. The results of molecular simulation also revealed that the interaction between sesquiterpenes and ceramide 3 was significantly stronger than that of monoterpenes(P<0.01). In conclusion, the location of sesquiterpenes in stratum corneum resulted in the significant difference between in vitro skin cell toxicity and in vivo skin irritation potency. The EOs from CM with hot property shall be taken into account for further development of potent penetration enhancer.

Discovery of Eucalyptin C, derived from the fruits of Eucalyptus globulus Labill., as a novel selective PI3Kγ inhibitor for immunosuppressive treatment / 中国天然药物

The fruits of Eucalyptus globulus Labill. are known to have a plenty of medicinal properties, such as anti-tumor, anti-inflammatory, and immunosuppressive activity. Our previous study found that the phloroglucinol-sesquiterpene adducts in the fruits of E. globulus were immunosuppressive active constituents, especially Eucalyptin C (EuC). Phosphoinositide 3-kinases-γ (PI3Kγ) plays a pivotal role in T cell mediated excessive immune responses. In this study, EuC was first discovered to be a novel selective PI3Kγ inhibitor with an IC

Sesquiterpene lactones of Aucklandia lappa: Pharmacology, pharmacokinetics, toxicity, and structure–activity relationship / 中草药·英文版

The medicinal part of Aucklandia lappa (Asteraceae) is its dried root, which is one of the commonly used Chinese medicinal materials. Here we reviewed sesquiterpene lactones isolated from A. lappa over the past ten years in the following aspects of pharmacological activities, pharmacokinetics, toxicology, structure–activity relationship. Pharmacological activities consist of anti-cancer, anti-inflammatory activity, anti-immunity activity, anti-oxidant activity, antimicrobial activity, spasmolytic activity and so on. The extractive, showing similar pharmacokinetics parameters, may exert their various biological activities by the interaction of their α-methylene-γ-butyrolactone moiety with the thiol groups of biomacromolecules through Michael-addition. However, the poor aqueous solubility, non-selective binding as a Michael acceptor at undesired targets limited clinical translation of this class. In order to evaluate the potential effect of the extractive applied in clinical trial, the present review outlines information on pharmacological activities, pharmacokinetics, toxicology, and structure–activity relationship, as well as the future research directions of the extractive for further development and utilization of A. lappa.

A new seco-prezizaane-type sesquiterpene lactone from stems and branches of Illicium ternstroemioides / 中国中药杂志

Three seco-prezizaane-type sesquiterpene lactones, one phenylpropanoid, and two lignans were isolated from the 95% ethanol extract of stems and branches of Illicium ternstroemioides with silica gel column chromatography, ODS column chromatography, and preparative HPLC. Based on the spectral data, they were identified as burmanicumolide D(1), veranisatin A(2), veranisatin B(3), dihydroconiferylalcohol(4), pinoresinol(5),(-)-matairesinol(6), respectively. Among them, compound 1 was a new seco-prezizaane-type sesquiterpene lactone, and 2-6 were obtained from this plant for the first time. None of these compounds display antiviral or cytotoxic activities.

Germacrene-derived sesquiterpene lactones:opportunities and challenges for biosynthesis / 中国中药杂志

Sesquiterpene lactones are a kind of widely distributed natural organic compounds with anti-tumor, anti-malarial and other significant biological activities. Based on their carbocylic skeletons, sesquiterpene lactones are classified into germacranolide, guaia-nolide, xanthanolide, pseudo-guaianolide, elemonolide and eudesmanolide, etc. In recent years, with the development of various omics and synthetic biology technologies, the biosynthetic pathways of sesquiterpene lactone compounds of different structural types have gradually been resolved. Among them, the researches on germacrene-derived sesquiterpene lactones are relatively more than others. Therefore, this article focused on the germacrene-derived sesquiterpene lactone biosynthesis pathways and their key enzyme genes, which can lay the foundation for in-depth analysis of sesquiterpene lactone biosynthetic pathways, functional gene mining and heterologous synthesis of active ingredients.

Three new polyoxygenated bergamotanes from the endophytic fungus Penicillium purpurogenum IMM 003 and their inhibitory activity against pancreatic lipase / 中国天然药物

Purpurolides D-F (1-3), three new polyoxygenated bergamotanes bearing a 6/4/5/5 tetracyclic ring system, were isolated from the endophytic fungus Penicillium purpurogenum IMM 003. Their structures were unambiguously elucidated based on extensive spectroscopic data analyses, C NMR chemical shifts calculations coupled with the DP4+ probability method, and the calculated and experimental electronic circular dichroism (ECD) spectra. Compounds 1-3 showed significant inhibitory activity against pancreatic lipase (PL). The result highlights that the presence of 3-hydroxylated decanoic acid moiety at C-14 is important for increasing the inhibition potency against PL.

A new guaiane sesquiterpene glycoside from Ainsliaeafragrans / 中草药

Objective: To investigate the chemical constituents in whole plant of Ainsliaeafragrans. Methods: Silica gel, Sephadex LH-20 gel column chromatography, and semi-preparative HPLC were used to separate and purify the chemical constituents of ethanol extract. And the structures were elucidated on the basis of NMR and MS spectroscopic data. Results: Nine compounds were isolated and identified as zaluzanin C-3-O-β-glucopyranosyl-(1→3)-β-glucopyranosyl-(1→3)-β-glucopyranosyl-(1→3)-β-glucopyranoside (1), macrocliniside B (2), macrocliniside I (3), isochlorogenic acid C (4), 4,5-O-di-caffeoylquinic acid methyl ester (5), isochlorogenic acid A (6), 3,5-O-di-caffeoylquinic acid methyl ester (7), 3,4-O-di-caffeoylquinic acid methyl ester (8), and astragalin (9). Conclusion Compound 1 is a new guaiane sesquiterpene glycoside named as ainslifragsideA.Compounds2, 3, 5, 7, and 8are isolated from this plant for the first time.

A pair of enantiomeric sesquiterpenoids with neuroprotective effects from Chloranthus henryi / 药学学报

An ethanol extract of Chloranthus henryi (Chloranthaceae) was subjected to various chromatographic procedures including silica gel column chromatography, MCI column chromatography, Sephadex LH-20 column chromatography, and preparative HPLC. Five purified sesquiterpenes analyzed by spectroscopic analyses (MS, IR, NMR) and single crystal X-ray diffraction were elucidated as (1S,6S,8R)-8-ethoxychlomultin C (1a), (1R,6R,8S)-8-ethoxychlomultin C (1b), (+)-phaeocaulin D (2), atractylenolide Ⅰ (3), and 8-β-ethoxyasterolid (4). Compounds 1a and 1b were a new pair of sesquiterpene enantiomers and compounds 2-4 were isolated from this plant for the first time. Compounds 1a, 1b, 2 and 3 increased cell viability in H2O2-treated PC12 cells from (43.41 ± 1.59) % to (61.71 ± 7.56) %, (66.05 ± 5.61) %, (74.34 ± 3.32) % and (69.58 ± 5.02) % at 10 μmol·L-1, respectively.

Chemical constituents from ethyl acetate soluble extraction of Litsea cubeba / 中国中药杂志

Chemical investigation on the constituents of the ethyl acetate soluble extraction of Litsea cubeba has resulted in the isolation and structure elucidation of thirty compounds, including one sesquiterpene(1), four monoterpenes(2-5), two γ-butyrolactone derivatives(6 and 7), seven tyramine derivatives(8-14), fifteen aromatic compounds(15-29), and one pyrone derivative(30) via various chromatographic techniques and spectroscopic data analysis(MS, IR, 1 D and 2 D NMR). Compounds 1-7, 13 and 14 were obtained from the genus Litsea for the first time.

Cloning and functional characterization of farnesyl diphosphate synthase in Senecio scandens / 中国中药杂志

As a secondary metabolite, sesquiterpenes are not only have important functions in plant defense and signaling, but also play potential roles in basic materials for pharmaceuticals, cosmetic and flavor. As a traditional Chinese herbal medicine, Senecio scandens exhibits effects of anti-inflammatory and immunosuppressive, as well as invigorating the blood and removing extravasated blood. Over 600 sesquiterpenes with diverse structures were isolated from S. scandens and related species in the same genus. To characterize sesquiterpenes synthesis, two FPS genes(SsFPS1 and SsFPS2) were identified in S. scandens through transcriptomic analysis. Bioinformatic analysis showed that both SsFPSs have conserved motifs for FPS function. Both SsFPSs exhibited constitutive gene expression in S. scandens tissues and SsFPS2 accumulated higher transcript in leaves and roots than SsFPS1. Meanwhile consistent with constitutive sesquiterpene accumulation in S.scandens tissues, most of these sesquiterpenes were detected in leaves and roots more than stems and flowers. Recombinant expression through Escherichia coli metabolic engineering, SsFPS1 or SsFPS2 was co-transformed with ZmTPS11(maize β-macrocarpene synthase) into BL21 competent cells. The results showed that the content of β-macrocarpene was increased by co-transformation with SsFPSs. It is demonstrated that SsFPS1 and SsFPS2 catalyzed E,E-FPP formation and provided FPP precursor for downstream sesquiterpene synthases. Characterization of SsFPSs provided the foundation for the exploration of biosynthesis of sesquiterpenoid with diverse structures and potential pharmaceutical values in S.scandens, and provide an important theoretical basis for the development of S. scandens abundant resources.

Antifungal and Antioxidant Activities of Vernonia Chalybaea Mart. ex DC. Essential Oil and their Major Constituent β -caryophyllene

Abstract: This article describes the chemical composition of Vernonia chalybaea essential oil, and investigates its antimicrobial, antioxidant and hemolytic activities. The evaluation of the antifungal activity was performed by the broth microdilution method using strains of yeasts and dermatophytic fungi. The checkerboard technique to find antimicrobial modulatory effects was performed using ketoconazole as standard drug. The antioxidant activity was evaluated by DPPH scavenging assay and β-carotene/linoleic-acid system. The toxicity was characterized by the brine shrimp lethality test and hemolysis bioassays. The essential oil was obtained by hydrodistillation and analyzed by GC-MS method, showing to be rich in the sesquiterpenes β-caryophyllene (39.06%) and bicyclogermacrene (19.69%), and also demonstrated a relevant antifungal activity against strains of Trichophyton rubrum. In the modulatory activity assay, the essential oil of V. chalybaea and β-caryophyllene demonstrated a synergistic interaction with ketoconazole, with increasing of its antifungal action. The antioxidant activity was evidenced mainly by β-carotene/linoleic acid system, with IC50 value of 35.87 ± 0.32 µg/mL. The results suggest that V. chalybaea essential oil and β-caryophyllene are valuable natural medicinal agents with antioxidant and antimicrobial activities.