23 results on '"Li, Tian-Ze"'
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2. Artemeriosides A–F, the first examples of natural sesquiterpenoids substituted by a 6′-O-crontonyl β-glucopyranoside from Artemisia annua
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He, Xiao-Feng, Wang, Meng-Fei, Ma, Yun-Bao, Li, Tian-Ze, and Chen, Ji-Jun
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- 2023
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3. Tsaokols A and B, unusual flavanol-monoterpenoid hybrids as α-glucosidase inhibitors from Amomum tsao-ko
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He, Xiao-Feng, Chen, Ji-Jun, Li, Tian-Ze, Hu, Jing, Zhang, Xu-Ke, Guo, Yuan-Qiang, Zhang, Xue-Mei, and Geng, Chang-An
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- 2021
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4. Unusual cadinane-involved sesquiterpenoid dimers from Artemisia annua and their antihepatoma effect.
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He, Xiao-Feng, Li, Tian-Ze, Ma, Yun-Bao, Wang, Meng-Fei, and Chen, Ji-Jun
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ARTEMISIA annua , *DIMERS , *HERBAL medicine , *SESQUITERPENES , *CELL lines - Abstract
Artemisia annua L. ("Qinghao" in Chinese) is a famous traditional Chinese medicinal herb and has been used to treat malaria and various tumors. Our preliminary screening indicated that the EtOAc extract of A. annua manifested activity against HepG2, Huh7, and SK-Hep-1 cell lines with inhibitory ratios of 53.2%, 52.1%, and 59.6% at 200 μg/mL, respectively. Bioassay-guided isolation of A. annua afforded 14 unusual cadinane-involved sesquiterpenoid dimers, artemannuins A‒N (1 – 14), of which the structures were elucidated by extensive spectral analyses, ECD calculations, and single-crystal X-ray diffraction. Structurally, these compounds were classified into five different types based on the coupled modes of two monomeric sesquiterpenoids. Among them, compounds 1 – 9 represented the first examples of sesquiterpenoid dimers formed via the C-3‒C-3′ single bond of two 5(4 → 3)- abeo -cadinane sesquiterpenoid monomers, while compounds 13 and 14 were dimers fused by cadinane and humulane sesquiterpenoids via an ester bond. Methylated derivatives of 1 , 4 , 6 , and 8 showed antihepatoma activity against HepG2, Huh7, and SK-Hep-1 cell lines with IC 50 values ranging from 30.5 to 57.2 μM. Fourteen cadinane-involved sesquiterpenoid dimers with unprecedented connecting model via the C-3‒C-3′ single bond of two 5(4 → 3)- abeo -cadinane sesquiterpenoid were isolated from Artemisia annua. Antihepatoma activity of the isolates and their derivatives were investigated. [Display omitted] • Fourteen undescribed sesquiterpenoid dimers were isolated from Artemisia annua. • Five different connecting modes of two monomeric sesquiterpenoids were involved. • Compounds 1–9 were the first dimers via C-3‒C-3′ bond of two 5(4. → 3)- abeo -cadinane. • Moderate antihepatoma activity was observed for these sesquiterpenoid dimers. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Artemyriantholides A–K, guaiane-type sesquiterpenoid dimers from Artemisia myriantha var. pleiocephala and their antihepatoma activity.
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Wang, Meng-Fei, Li, Tian-Ze, Ma, Yun-Bao, Ma, Wen-Jing, Wang, Yong-Cui, Li, Feng-Jiao, and Chen, Ji-Jun
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DIMERS , *SURFACE plasmon resonance , *ARTEMISIA , *CELL lines , *CIRCULAR dichroism , *GAS chromatography/Mass spectrometry (GC-MS) - Abstract
Artemyriantholides A−K (1 − 11) as well as 14 known compounds (12 − 25) were isolated from Artemisia myriantha var. pleiocephala (Asteraceae). The structures and absolute configuration of compounds 2 and 8 − 9 were confirmed by the single crystal X - ray diffraction analyses, and the others were elucidated by MS, NMR spectral data and electronic circular dichroism calculations. All compounds were chemically characterized as guaiane-type sesquiterpenoid dimers (GSDs). Compound 1 was the first example of the GSD fused via C-3/C-11′ and C-5/C-13′ linkages, and compounds 2 and 5 were rare GSDs containing chlorine atoms. Eleven compounds showed obvious inhibitory activity in HepG2, Huh7 and SK-Hep-1 cell lines by antihepatoma assay to provide the IC 50 values ranging from 7.9 to 67.1 μM. Importantly, compounds 5 and 8 exhibited the best inhibitory activity with IC 50 values of 14.2 and 18.8 (HepG2), 9.0 and 11.5 (Huh7), and 8.8 and 11.3 μM (SK-Hep-1), respectively. The target of compound 5 was predicted to be MAP2K2 by a computational prediction model. The interaction between compound 5 and MAP2K2 was conducted to give docking score of −9.0 kcal/mol by molecular docking and provide K D value of 43.7 μM by Surface Plasmon Resonance assay. Eleven previously undescribed guaiane-type sesquiterpenoid dimers together with 14 known ones were isolated and identified from A. myriantha var. pleiocephala , and compound 5 showed obvious activity against hepatoma cell lines possibly via targeting MAP2K2. [Display omitted] • Eleven undescribed guaiane-type sesquiterpenoid dimers (GSDs) were isolated from A. myriantha var. pleiocephala. • Artemyriantholide A (1) was the first example of the GSD fused via C-3/C-11′ and C-5/C-13′ linkages. • Eleven compounds displayed inhibitory activity in three hepatoma cell lines (HepG2, Huh7, and SK-Hep-1). • Artemyriantholide E (5) showed obvious inhibitory activity in hepatoma cell lines possibly via targeting MAP2K2. [ABSTRACT FROM AUTHOR]
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- 2024
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6. Synthesis and antihepatoma activity of guaianolide dimers derived from lavandiolide I.
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Wang, Xing, Li, Tian-Ze, Ma, Yun‐Bao, Ma, Wen‐Jing, Xue, Dong, and Chen, Ji-Jun
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DIMERS , *STRUCTURE-activity relationships , *LIVER cells , *CELL lines , *NATURAL products - Abstract
[Display omitted] Guaianolide dimers represent a unique class of natural products with anticancer activities, but their low content in plants has limited in-depth pharmacological studies. Lavandiolide I is a guaianolide dimer isolated from Artemisia species, and had been synthesized on a ten-gram scale in four steps with 60 % overall yield, which showed potent antihepatoma activity on the HepG2, Huh7, and SK-Hep-1 cell lines with IC 50 values of 12.1, 18.4, and 17.6 µM, respectively. To explore more active dimers, 33 lavandiolide I derivatives were designed, synthesized, and evaluated for their inhibitory activity on human hepatoma cell lines. Among them, 10 derivatives were more active than lavandiolide I and sorafenib on the three cell lines. The primary structure–activity relationship concluded that the introduction of aldehyde, ester, azide, amide, carbamate and urea functional groups at C-14′ of the guaianolide dimer significantly enhanced the antihepatoma activity. Among these compounds, derivatives 25 , 27 , and 33 enhanced antihepatoma activity more than 1.2–5.8 folds than that of lavandiolide I, and demonstrated low toxicity to the human liver cell lines (THLE-2) and good safety profiles with selective index ranging from 1.3 to 3.4, while lavandiolide I was more toxic to THLE-2 cells. This work provides new insights into enhancing the antihepatoma efficacy and reducing the toxicity of sesquiterpenoid dimers. [ABSTRACT FROM AUTHOR]
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- 2024
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7. Rubiginosin B selectively inhibits Treg cell differentiation and enhances anti-tumor immune responses by targeting calcineurin-NFAT signaling pathway.
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Geng, Chang-An, Chen, Feng-Yang, Zheng, Jing-Bin, Liao, Ping, Li, Tian-Ze, Zhang, Xue-Mei, Chen, Xin, and Chen, Ji-Jun
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• Rubiginosin B (RGB) and two new meroterpenoids were isolated from R. brachypodum. • Rhodobrachypodic acid was proposed as the precursor of RGB. • RGB selectively inhibits the differentiation of Treg cells. • RGB enhances anti-tumor immune responses and inhibits the growth of tumor in mice. • RGB inhibits Foxp3 expression through calcineurin-NFAT signaling. The accumulation of CD4
+ Foxp3+ regulatory T cells (Tregs) in the tumor microenvironment (TME) dampens anti-tumor immune responses and promotes tumor progression. Therefore, the elimination of Tregs has become a strategy to enhance the efficacy of tumor immunotherapy, although it is still a daunting challenge. Rhododendron brachypodum (R. brachypodum) is a perennial shrub mainly distributed in Southwestern China, whereas the chemical constituents in this plant remain elusive. To identify small-molecule inhibitors of Tregs from R. brachypodum. Meroterpenoids in R. brachypodum were isolated by column chromatography under the guidance of LCMS analyses. The structures of isolates were identified by spectroscopic data and quantum calculations. The activities of compounds were first evaluated on CD4+ T cell differentiation by flow cytometry in Th1, Th2, Th17, and Treg polarizing conditions, and then on CT26 and MC38 murine colorectal carcinoma cells-allografted mice models. The mechanism of action was first investigated by determining Foxp3 degradation in Jurkat T cells transfected with pLVX-TetOne-Puro-Foxp3-tGFP, and then through analyses of Foxp3 expression on several pre-transcriptional signaling molecules. Two new prenylated phenolic acids (1 and 2) and a chromane meroterpenoid, rubiginosin B (RGB, 3) were obtained from R. brachypodum. The structure of S -anthopogochromene C (1) was rectified according to the electronic circular dichroism (ECD) experiment, and rhodobrachypodic acid (2) was proposed as the precursor of RGB by photochemical transformation. In this investigation, we first found that RGB (3) selectively suppressed the de novo differentiation of TGFβ-induced CD4+ Foxp3+ regulatory T cells (iTregs), overcome the immunosuppressive TME, and consequently inhibited the growth of tumor in mouse models. The mechanistic study revealed that RGB could target calcineurin, inhibited the nuclear factor of activated T cells (NFAT) dephosphorylation, and down-regulated Foxp3 expression. The hypothetical binding modes of RGB with calcineurin were predicted by molecular docking, and the interactions were mainly hydrophobic effects and hydrogen bonds. These results suggest that RGB enhances anti-tumor immune responses by inhibiting Treg cell differentiation through calcineurin-NFAT signaling pathway, and therefore RGB or its analogs may be used as adjuvant agents meriting further investigation. [Display omitted] [ABSTRACT FROM AUTHOR]- Published
- 2023
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8. Distepharinamide, a novel dimeric proaporphine alkaloid from Diploclisia glaucescens, inhibits the differentiation and proliferative expansion of CD4+Foxp3+ regulatory T cells.
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Chen, Feng-Yang, Geng, Chang-An, Chou, Chon-Kit, Zheng, Jing-Bin, Yang, Yang, Wang, Yi-Fei, Li, Tian-Ze, Li, Ping, Chen, Ji-Jun, and Chen, Xin
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Background: CD4+Foxp3+ regulatory T cells (Tregs) represent the primary cellular mechanism of tumor immune evasion. Elimination of Treg activity by the pharmacological agent may enhance anti-tumor immune responses. However, Treg-eliminating agents, especially those with small molecules, are rarely reported.Purpose: To identify small molecule inhibitors of Treg cells from natural products.Methods: Compounds from Diploclisia glaucescens were isolated by column chromatography, and structures were identified by spectroscopic evidence and quantum calculations. The tet-On system for Foxp3-GFP expression in Jurkat T cells was generated to screen Treg inhibitors based on Foxp3 expression. The effect of the compound on TNF-induced proliferative expansion of naturally occurring Tregs (nTregs) and TGF-β-induced generation of Tregs (iTregs) from naive CD4+ Tcells was further examined.Results: A novel dimeric proaporphine alkaloid, designated as distepharinamide (DSA) with a symmetric structure isolated from the stems of D. glaucescens, restrained the doxycycline (Doxy)-induced Foxp3-tGFP expression, decreased the half-life of Foxp3 mRNA as well as reduced the mRNA levels of chemokine receptors (CCR4, CCR8 and CCR10) in Jurkat T cells with inducible Foxp3-tGFP expression. In lymphocytes or purified Tregs from wild-type C57BL/6 mice or from C57BL/6-Tg(Foxp3-DTR/EGFP)23.2Spar/Mmjax mice, DSA markedly inhibited TNF-induced proliferative expansion of Tregs present in the unfractionated CD4+ T cells, accompanied by the down-regulation of TNFR2, CD25 and CTLA4 expression on Tregs. Furthermore, DSA potently inhibited TGF-β-induced differentiation of Foxp3-expressing iTregs. Importantly, the expression of Foxp3 mRNA by both nTregs and iTregs was decreased by DSA treatment. Nevertheless, DSA at the same concentrations did not inhibit the proliferation of conventional CD4+ and CD8+ T cells stimulated by anti-CD3/CD28 antibodies.Conclusion: DSA, a novel dimeric proaporphine alkaloid, potently inhibited the expansion of nTregs and generation of iTregs. Therefore, DSA or its analogs may merit further investigation as novel immunotherapeutic agents. [ABSTRACT FROM AUTHOR]- Published
- 2022
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9. Catalytic enantioselective addition of alcohols to isatin-derived N-Boc ketimines.
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Li, Tian-Ze, Wang, Xi-Bo, Sha, Feng, and Wu, Xin-Yan
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ENANTIOSELECTIVE catalysis , *ALCOHOLS (Chemical class) , *ADDITION reactions , *ISATIN , *IMINES , *NITROGEN - Abstract
Abstract: The enantioselective addition of alcohols to isatin-derived N-Boc ketimines was investigated for the first time. Isatin-derived N,O-aminals were obtained in excellent yields with moderate-to-good enantioselectivities (up to 78% ee) in the presence of a quinine-based bifunctional catalyst. [Copyright &y& Elsevier]
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- 2013
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10. Turbine cavitation detection software design.
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Li, Zeng-xiang, Hai, Yuan, Li, Tian-ze, Yang, Xia, and Li, Hui
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TURBINES ,CAVITATION ,SOUND cards (Computers) ,SERVICE life ,PARAMETER estimation - Abstract
Abstract: This is a portable cavitations monitoring system for hydro turbine developed via the sound card of the computer which is based on the LabVIEW,It establishes monitoring and warning systems, It collects all the characteristics signal which is considered to be the reflection of cavitations on the spot, and analyze the characteristic of the signal which changed with the changing on the level of the cavitation,It can provide all-time monitor on the level of cavitations by monitoring signal, It believes the cavitations comes out once the selected parameters reached to the criteria setted by system, It alarms to the stuff, so that they can revise turbine operating parameters, and work conditions, on the one hand, it improve the efficiency of hydro turbine, trying to minimize the loss caused by cavitation,on the other hand, it can lengthen the service life, this is the method of the design. [Copyright &y& Elsevier]
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- 2011
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11. Synthesis and anti-fibrotic effects of santamarin derivatives as cytotoxic agents against hepatic stellate cell line LX2.
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Wang, Jin-Ping, Li, Tian-Ze, Huang, Xiao-Yan, Geng, Chang-An, Shen, Cheng, Sun, Jin-Jin, Xue, Dong, and Chen, Ji-Jun
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LIVER cells , *CELL lines , *EXTRACELLULAR matrix , *HYALURONIC acid , *HYDROXYL group , *STRUCTURE-activity relationships - Abstract
[Display omitted] Liver fibrosis is a final result of extensive deposition of extracellular matrix (ECM) and starts with the activation and proliferation of hepatic stellate cells (HSCs). Our previous study showed that eudesmane sesquiterpenoid santamarin had cytotoxicity against hepatic stellate cell line LX2 (HSC-LX2) with IC 50 values of 16.5 ± 0.7 μM. To explore the structure–activity relationships, twenty-six derivatives were synthesized by modifying the hydroxyl group, double-bond and unsaturated lactone. Cytotoxicity evaluation suggested that eight derivatives (6, 9, 13, 17, 20 and 25 – 27) increased activity against HSC-LX2. Especially, derivatives 17 , 20 and 25 displayed obvious cytotoxicity with IC 50 values of 6.4 ± 0.4, 4.6 ± 0.1, and 3.5 ± 0.1 μM, which were 3 to 5-fold higher than santamarin. Preliminary mechanisms study revealed that the active compound 20 exhibited more than 8-fold and 6-fold enhancement of inhibitory effect on the deposition of human hyaluronic acid (HA) and human laminin (HL) with IC 50 values of 7.6 ± 0.6 and 3.3 ± 1.2 μM. [ABSTRACT FROM AUTHOR]
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- 2021
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12. First total synthesis of rhuscholide A, glabralide B and denudalide.
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Li, Tian-Ze, Geng, Chang-An, and Chen, Ji-Jun
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ALDOL condensation , *NATURAL products , *PHENOL , *BENZOFURANS - Abstract
• It describes the first total synthesis of rhuscholide A, a benzofuran lactone possessing anti-HIV-1 activity. • Glabralide B and denudalide were also synthesized in a convergent manner. • Base-mediated phenol ortho -alkylation and piperidine promoted aldol condensation were used as key steps. The first total synthesis of rhuscholide A, a benzofuran lactone possessing anti-HIV-1 activity, had been accomplished in 14 linear steps with 10.6% overall yield. In this synthesis, base-mediated phenol ortho -alkylation and piperidine promoted aldol condensation were exploited as key steps. The synthesis was flexible and allowed for the convenient preparation of two analogous natural products glabralide B and denudalide. [ABSTRACT FROM AUTHOR]
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- 2019
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13. Highly oxygenated guaiane-type sesquiterpene lactones from Artemisia sacrorum and their antihepatoma activity.
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He, Xiao-Feng, Ma, Yun-Bao, Li, Tian-Ze, and Chen, Ji-Jun
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SESQUITERPENE lactones , *ARTEMISIA , *CELL lines , *X-ray diffraction , *KILLER cell receptors , *HEPATOCELLULAR carcinoma - Abstract
The ethanol and EtOAc extracts of Artemisia sacrorum exhibited inhibitory effect against HepG2, Huh7, and SK-Hep-1 cell lines with inhibitory ratios of 65.5%, 28.1%, 84.6%, and 93.5%, 82.0%, 89.0% at 200 μg/mL. Twenty-three undescribed guaiane-type sesquiterpene lactones, artemisacrolides A‒W, were isolated from A. sacrorum under the guidance of antihepatoma activity. Their structures were elucidated by spectral data (HRESIMS, IR, UV, 1D and 2D NMR), ECD calculations, and a single-crystal X-ray diffraction. Artemisacrolides A‒U were guaiane-type sesquiterpene lactones possessing α -methylene- γ -lactone and containing acetoxyl groups at C-8, and artemisacrolides V and W represented the first report from the genus Artemisia with a 1,10-rearranged guaiane-type sesquiterpene lactone. Antihepatoma assay suggested that artemisacrolides A‒U demonstrated better inhibitory activity in Huh7 and SK-Hep-1 cells than those of HepG2 cells. Among them, nine compounds exhibited significant inhibitory activity against Huh7 cells with IC 50 values of 8.2–14.3 μM, superior or equal to that of sorafenib; seven compounds demonstrated obvious activity against SK-Hep-1 cells with IC 50 values of 13.5–19.2 μM, which were equivalent to that of sorafenib. Artemisacrolides B and E were the most active ones in three human hepatoma cell lines with IC 50 values of 21.9, 8.2, 16.9 and 22.6, 9.0, 17.3 μM. Twenty-three undescribed guaiane-type sesquiterpenoid lactones with antihepatoma activity were isolated from A. sacrorum. Compounds 1 – 21 demonstrated better inhibitory activity in Huh7 and SK-Hep-1 cells than those of HepG2 cells. Artemisacrolides B and E were the most active ones. [Display omitted] • Artemisacrolides A‒W were isolated from A. sacrorum. • Artemisacrolides V–W were the first example from the genus Artemisia. • Nine compounds exhibited significant inhibitory activity against Huh7 cells. • Seven compounds demonstrated obvious activity against SK-Hep-1 cells. • Artemisacrolides B and E were the most active in three human hepatoma cell lines. [ABSTRACT FROM AUTHOR]
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- 2024
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14. Artemidubolides A−T, cytotoxic unreported guaiane-type sesquiterpenoid dimers against three hepatoma cell lines from Artemisia dubia.
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Gao, Zhen, Ma, Wen-Jing, Li, Tian-Ze, Ma, Yun-Bao, Hu, Jing, Huang, Xiao-Yan, Geng, Chang-An, He, Xiao-Feng, Zhang, Xue-Mei, and Chen, Ji-Jun
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CELL lines , *DIMERS , *HEPATOCELLULAR carcinoma , *CELL cycle , *ARTEMISIA , *CELL migration , *POLY(ADP-ribose) polymerase , *ELECTRONIC spectra - Abstract
A random bioassay revealed that the EtOH extract and EtOAc fraction of Artemisia dubia Wall. (Asteraceae) exhibited cytotoxic activity against HepG2 cells with inhibitory ratios of 57.1% and 84.2% at a concentration of 100.0 μg/mL. Bio-guided isolation combined by LC-MS-IT-TOF analyses of the active fractions led to the isolation of 20 previously undescribed guaiane-type sesquiterpenoid dimers named artemidubolides A−T (1 – 20). Their structures and the absolute configurations were determined by comprehensive spectral analyses, comparison of the experimental and calculated ECD spectra, and seven compounds (artemidubolides A, B, D, F, K, O and R) were confirmed unequivocally by single crystal X-ray diffraction analysis. Structurally, artemidubolides A–Q were [4 + 2] Diels–Alder adducts of two monomeric guaianolides, and artemidubolides R–T were linked though an ester bond. All the isolated compounds were evaluated for their hepatomatic cytotoxicity against HepG2, Huh7, and SK-Hep-1 cell lines to demonstrate that 18 compounds exhibited obvious cytotoxicity against three tested hepatoma cell lines with IC 50 values in the range of 5.4–87.6 μM. Importantly, artemidubolides B, D, and M exhibited hepatoma cytotoxicity with IC 50 values of 5.4, 5.7, and 9.7 (HepG2), 8.2, 4.3, and 12.2 (Huh7), and 13.4, 8.4, and 12.9 μM (SK-Hep-1), respectively. Mechanism investigation in HepG2 cells suggested the most active artemidubolide D dose-dependently inhibited cell migration and invasion, induced G1/M cell cycle arrest by down-regulating proteins CDK4, CDK6 and CyclinD1 and up-regulating the level of protein P21; and induced apoptosis by down-regulated of PARP-1 and BCL-2 expression and up-regulating Bax and cleaved PARP-1 levels. [Display omitted] • Twenty unreported guaiane-type sesquiterpenoid dimers was obtained from Artemisia dubia. • Eighteen compounds exhibited significant cytotoxicity against three hepatoma cell lines. • Mechanism investigation suggested compound 4 inhibited cell migration and invasion. [ABSTRACT FROM AUTHOR]
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- 2022
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15. Synthesis and biological evaluation of chepraecoxin A derivatives as α-glucosidase inhibitors.
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Yang, Xiao-Tong, Geng, Chang-An, Li, Tian-Ze, Deng, Zhen-Tao, and Chen, Ji-Jun
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BIOSYNTHESIS , *GLUCOSIDASES , *ENZYME kinetics , *STRUCTURE-activity relationships , *DOUBLE bonds , *CARBOXYL group - Abstract
The ent -kaurane diterpenoid chepraecoxin A (CA) obtained in our previous study showed a potential inhibitory activity on α -glucosidase (IC 50 274.5 ± 12.5 μM). In order to figure out the structure-activity relationships (SARs), twenty-two derivatives of chepraecoxin A were synthesized by modifying the ester, allyl, double bond and carboxyl groups, and assayed for their α -glucosidase inhibitory activity. Of them, eight compounds (14 – 17 , 19 – 22) significantly increased activity with IC 50 values ranging from 16.1 to 71.4 μM, even higher than the positive control, acarbose (IC 50 130.3 μM). Especially, compounds 17 , 19 and 21 could inhibit α -glucosidase with IC 50 values of 16.9 ± 3.4, 16.1 ± 1.2, and 17.1 ± 0.6 μM, 17-fold higher than CA. The most active compound 19 was proven to be a non-competitive inhibitor with a K i value of 19.4 μM based on enzyme kinetics study. The primary SARs of CA derivatives were summarized for exploring antidiabetic candidates. [ABSTRACT FROM AUTHOR]
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- 2020
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16. Polybenzyls from Gastrodia elata, their agonistic effects on melatonin receptors and structure-activity relationships.
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Chen, Si-Yue, Geng, Chang-An, Ma, Yun-Bao, Huang, Xiao-Yan, Yang, Xiao-Tong, Su, Li-Hua, He, Xiao-Feng, Li, Tian-Ze, Deng, Zhen-Tao, Gao, Zhen, Zhang, Xue-Mei, and Chen, Ji-Jun
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STRUCTURE-activity relationships , *MELATONIN , *MOLECULAR docking , *HERBAL medicine - Abstract
• Polybenzyls were initially discovered to activate melatonin receptors. • Compound 1 showed agonistic activity on MT 1 and MT 2 receptors with EC 50 values of 237 and 244 μM. • Two para -hydroxy groups were the key pharmacophore for maintaining activity. Gastrodia elata is a famous traditional Chinese herb with medicinal and edible application. In this study, nine polybenzyls (1 − 9), including six new ones (2 − 5 , 7 and 9), were isolated from the EtOAc extract of G. elata. Five compounds 1 , 3 , 4 , 6 and 8 were found to activate melatonin receptors. Especially, compound 1 showed agonistic effects on MT 1 and MT 2 receptors with EC 50 values of 237 and 244 μM. For better understanding their structure-activity relationships (SARs), ten polybenzyl analogs were further synthesized and assayed for their activities on melatonin receptors. Preliminary SARs study suggested that two para -hydroxy groups were the key pharmacophore for maintaining activity. Molecular docking simulations verified that compound 1 could strongly interact with MT 2 receptor by bonding to Phe 118, Gly 121, His 208, Try 294 and Ala 297 residues. [ABSTRACT FROM AUTHOR]
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- 2019
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17. Anti-hepatitis B virus effects of the traditional Chinese herb Artemisia capillaris and its active enynes.
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Geng, Chang-An, Yang, Tong-Hua, Huang, Xiao-Yan, Yang, Jing, Ma, Yun-Bao, Li, Tian-Ze, Zhang, Xue-Mei, and Chen, Ji-Jun
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BIOLOGICAL assay , *CELL lines , *CHROMATOGRAPHIC analysis , *DNA , *EPITHELIAL cells , *GLYCOSYLATION , *HEPATITIS viruses , *HERBAL medicine , *HYDROXYLATION , *CHINESE medicine , *SPECTRUM analysis , *WORMWOOD , *IN vitro studies - Abstract
Ethnopharmacological relevance Artemisia capillaris (Yin-Chen) is a famous traditional Chinese medicine (TCM) for treating acute and chronic hepatitis in China. Enynes are one type of characteristic constituents in this herb, while their anti-hepatitis B virus (anti-HBV) properties have not been systemically investigated. Aim of the study This study is to reveal the active part of A. capillaris , and systemically investigate the enynes and their anti-HBV activity. Materials and methods The total extract and each fraction of A. capillaris were assayed for the anti-HBV activity to reveal the active part. Bioassay-guided fractionation using various chromatographic techniques yielded the enynes, whose structures were elucidated by spectroscopic analyses and ECD calculations. The anti-HBV properties inhibiting HBsAg and HBeAg secretions and HBV DNA replication were evaluated on HepG 2.2.15 cell line in vitro . Results ACT-2 and ACT-3 was revealed to be the respective active and toxic part of A. capillaris . Twelve enynes ( 1 – 12 ) involving four new ones ( 1 – 4 ) and two unusual enyne analogs ( 13 – 14 ) were isolated from the active part (ACT-2). All the isolates were assayed for their anti-HBV activity, and the preliminary structure-activity relationships were summarized based on the structural features. In particular, compound 4 could significantly inhibit the secretions of HBsAg and HBeAg, and HBV DNA replication with IC 50 values of 197.2 (SI > 5.1), 48.7 (SI > 20.5) and 9.8 (SI > 102) μM. Conclusions Enynes are responsible for the anti-HBV effects of A. capillaris . Hydroxyl and glycosyl groups are preferable for maintaining activity. This is the first time to systematically investigate the anti-HBV activity of enynes in A. capillaris , which provides valuable information for understanding the ethnopharmacological application of Yin-Chen. [ABSTRACT FROM AUTHOR]
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- 2018
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18. Artemiprinolides A−M, thirteen undescribed sesquiterpenoid dimers from Artemisia princeps and their antihepatoma activity.
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Su, Li-Hua, Ma, Wen-Jing, Ma, Yun-Bao, Li, Tian-Ze, Geng, Chang-An, Dong, Wei, He, Xiao-Feng, and Chen, Ji-Jun
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DIMERS , *ARTEMISIA , *CELL migration , *MOLECULAR docking , *SINGLE crystals , *LIGANDS (Chemistry) - Abstract
Bioassay-guided investigation of the active fraction of Artemisia princeps led to 13 undescribed sesquiterpenoid dimers, artemiprinolides A−M (1 – 13), together with 11 known ones (14 − 24). Their structures were elucidated by comprehensive spectroscopic data and absolute configurations were assigned based on single crystal X-ray diffraction data and ECD calculations. Structurally, all compounds were postulated to be derived from the Diels–Alder cycloaddition. The isolated dimers except 11 and 15 were assayed for their cytotoxicity against HepG2, Huh7, and SK-Hep-1 cell lines, of which four compounds (3 , 13 , 17 , 18) exhibited obvious cytotoxicity with IC 50 values ranging from 8.8 to 20.1 μM. Interestingly, the most active compounds 1 and 16 manifested significant cytotoxicity on the three tested hepatoma cell lines with IC 50 values of 5.4, 4.1 (HepG2), 7.7, 5.6 (Huh7), and 11.8, 15.7 μM (SK-Hep-1), respectively, which were better than sorafenib. Compound 1 dose-dependently inhibited cell migration and invasion, and significantly induced the HepG2 cell arrest in G2/M phase by downregulating cdc2 and pcdc2 and upregulating cyclinB1; and induced apoptosis by downregulating Bcl-2 expression and upregulating Bax level. The molecular docking study implied that the carbonyl at the C-12′ of 1 had a strong binding affinity with PRKACA. Thirteen undescribed sesquiterpenoid dimers and 11 known ones were isolated from Artemisia princeps. The preliminary mechanism of the most active compound 1 in HepG2 cells was studied. [Display omitted] • Thirteen undescribed guaiane sesquiterpenoid dimers were isolated from A. princeps. • The absolute configuration of 1 was assigned by single-crystal X-ray diffraction. • Twenty-two compounds demonstrated cytotoxicity. • The preliminary mechanism of 1 in HepG2 cells was investigated. [ABSTRACT FROM AUTHOR]
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- 2023
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19. Synthesis and biological evaluation of magnolol derivatives as melatonergic receptor agonists with potential use in depression.
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Yang, Tong-Hua, Ma, Yun-Bao, Geng, Chang-An, Yan, De-Xiu, Huang, Xiao-Yan, Li, Tian-Ze, Zhang, Xue-Mei, and Chen, Ji-Jun
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MENTAL depression , *NEURAL transmission , *METABOLITES , *NEUROSES , *NEUROPHYSIOLOGY - Abstract
Depression is associated with high mortality and morbidity rates worldwide. By our random screening, it was first revealed that 23 magnolol derivatives were synthesized followed by in vitro and in vivo evaluation of their antidepressive potential. Compound 7c was found to be the most promising compound, with EC 50 values of 396.5 and 383.0 μM agitating on MT 1 and MT 2 receptors, respectively. Additionally, we carried out in vivo experiments to confirm the efficacy and safety of compound 7c ; the compound was found to be orally bioavailable and highly effective, leading to a significant reduction of immobility time in a mouse model of depression (forced swimming test and tail suspension test); the acting mechanism was explored by determining its effect on the levels of monoamine neurotransmitters and their metabolites in different mice brain regions; the acute toxicity study showed that the 50% lethal dose (LD50) of 7c was higher than 2000 mg/kg, p. o. A total of 25 metabolites of 7c were identified, including 5 metabolites in phase I and 20 metabolites in phase II. Altogether, these results indicate that magnolol derivative 7c is a promising lead compound for the development of a new chemical class of antidepressant drugs. [ABSTRACT FROM AUTHOR]
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- 2018
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20. LC-MS guided isolation of diterpenoids from Sapium insigne with α-glucosidase inhibitory activities.
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Yan, De-Xiu, Geng, Chang-An, Yang, Tong-Hua, Huang, Xiao-Yan, Li, Tian-Ze, Gao, Zhen, Ma, Yun-Bao, Peng, Hua, Zhang, Xue-Mei, and Chen, Ji-Jun
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ANALYTICAL chemistry , *GLYCOSIDASES , *TERPENES , *PLANT extracts , *IN vitro studies , *CHEMICAL inhibitors - Abstract
Ten new ( 1−10 ) and ten known ( 11−20 ) diterpenoids involving ent -atisane, ent - seco -atisane, ent -kaurane and ent - seco -kaurane types were isolated from Sapium insigne under the guidance of LCMS-IT-TOF analyses. Their structures were characterized by extensive spectroscopic analyses (HRESIMS, UV, IR, 1D and 2D NMR). A putative biosynthetic pathway was proposed for ent - seco -atisane diterpenoids. Their inhibitory activities on α -glucosidase in vitro were tested for the first time. Compound 4 showed moderate inhibitory effect on α -glucosidase with an IC 50 value of 0.34 mM via a noncompetitive inhibition mechanism (K i = 0.27 mM). The preliminary structure-activity relationships of the ent -atisane diterpenoids inhibiting α -glucosidase were discussed. [ABSTRACT FROM AUTHOR]
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- 2018
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21. New eudesmanolides from Artemisia verlotorum and their potential targets of hepatocellular carcinoma by network pharmacology.
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Dong, Wei, Yang, Ke-Xin, He, Xiao-Feng, Li, Tian-Ze, and Chen, Ji-Jun
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THERAPEUTIC use of antineoplastic agents , *STATISTICS , *TERPENES , *WORMWOOD , *PLANT extracts , *PHARMACEUTICAL chemistry , *ANALYTICAL chemistry techniques , *MOLECULAR structure , *COMPUTER-assisted molecular modeling , *BIOLOGICAL assay , *DATA analysis , *ETHANOL , *HEPATOCELLULAR carcinoma , *SURFACE plasmon resonance - Abstract
Fractionation of the ethanol extract of Artemisia verlotorum led to the identification of eight undescribed eudesmane-type sesquiterpenoids, artemverlolides A-H (1 – 8). Their structures were determined by spectral analyses (HRESIMS, 1D and 2D NMR, IR, and ECD). Network pharmacology predicted that compounds 1 – 8 might be target on AURKA, CCNA2, CYP2C19, and EPHX2 with possibly antihepatoma effect from Swiss TargetPrediction and Gene Expression Omnibus database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the targets significantly enriched in FoxO signaling pathway. The molecular docking suggested that compound 8 had high binding affinity with AURKA. Furthermore, the interaction between compound 8 and AURKA was determined by Surface Plasmon Resonance (SPR) assay. The result suggested that compound 8 bound to AURKA with KD value of 68.0 μM and was consistent with the predicted data, demonstrating that AURKA might be one of acting targets of 8. [Display omitted] • Eight undescribed eudesmane-type sesquiterpenoids were isolated from Artemisia verlotorum. • Network pharmacology demonstrated AURKA, CCNA2, CYP2C19, and EPHX2 were potential targets. • GO and KEGG analysis showed these targets were enriched in FoxO signaling pathway. • Molecular docking suggested these targets and compounds had the potential binding affinity. • SPR assay demonstrated that compound 8 bound to AURKA with KD value of 68.0 μM. [ABSTRACT FROM AUTHOR]
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- 2023
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22. Artemleucolides A−L, eudesmane-type sesquiterpenoids from Artemisia leucophylla and their antihepatoma cytotoxicity.
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Wang, Yuan, Ma, Yun-Bao, Huang, Xiao-Yan, Li, Tian-Ze, He, Xiao-Feng, Zhang, Xue-Mei, and Chen, Ji-Jun
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TERPENES , *TREATMENT effectiveness , *CELL lines , *COMPUTED tomography , *HEPATOCELLULAR carcinoma , *EVALUATION ,THERAPEUTIC use of plant extracts - Abstract
Twelve undescribed and 13 known eudesmane-type sesquiterpenoids were obtained from Artemisia leucophylla , and structurally elucidated based on comprehensive analyses of spectral data, including HRESIMS, IR, 1D and 2D NMR, and ECD calculation. The absolute configuration of compound 1 was determined by a single X-ray single crystal diffraction. Chemically, compounds 1–5 featured unprecedented 1,2- seco -1- nor- eudesmane-type skeleton with a cis -fused 6/5 bicyclic system. Antihepatoma evaluation against three human hepatoma cell lines (HepG2, Huh7, and SK-Hep-1) for all compounds demonstrated that compound 7 displayed the most active cytotoxicity with IC 50 values of 35.1, 35.0, and 32.7 μΜ. [Display omitted] • Twelve undescribed sesquiterpenoids were isolated from Artemisia leucophylla. • Compounds 1–5 featured unprecedented 1,2- seco -1- nor- eudesmane-type skeleton. • Compound 7 displayed cytotoxicity with IC 50 values of 35.1, 35.0, and 32.7 μΜ. • All known compounds were isolated from Artemisia leucophylla for the first time. [ABSTRACT FROM AUTHOR]
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- 2023
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23. Norlignans as potent GLP-1 secretagogues from the fruits of Amomum villosum.
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Ding, Min, Wu, Sheng-Li, Hu, Jing, He, Xiao-Feng, Huang, Xiao-Yan, Li, Tian-Ze, Ma, Yun-Bao, Zhang, Xue-Mei, and Geng, Chang-An
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GHRELIN receptors , *RESOLUTION (Chemistry) , *CHINESE medicine , *DRIED fruit , *ENANTIOMERS - Abstract
The dried fruit of Amomum villosum (Amomi Fructus) is an important spices and traditional Chinese medicine. In this study, the EtOH extract of Amomi Fructus was revealed with hypoglycemic effects on db/db mice by increasing plasma insulin levels. After extracted with EtOAc, the EtOAc fraction showed increased activity in stimulating glucagon-like peptide-1 (GLP-1) secretion compared with the EtOH extract. In order to clarify the antidiabetic constituents, four undescribed norlignans, amovillosumins A‒D, were isolated from the EtOAc fraction, and the subsequent chiral resolution yielded three pairs of enantiomers. Their structures were determined by extensive spectroscopic data (1D and 2D NMR, HRESIMS, IR, UV and [ α ] D) and ECD calculations. Amovillosumins A and B significantly stimulated GLP-1 secretion by 375.1% and 222.7% at 25.0 μ M, and 166.9% and 62.7% at 12.5 μ M, representing a new type of GLP-1 secretagogues. Four undescribed norlignans, amovillosumins A‒D, were isolated from Amomum villosum and the subsequent chiral resolution yielded three pairs of enantiomers. Amovillosumins A and B significantly stimulated GLP-1 secretion. [Display omitted] • Amomum villosum extract showed hypoglycemic effects on db/db mice by stimulating insulin secretion. • Four undescribed norlignans, amovillosumins A‒D, were isolated from Amomum villosum. • Chiral resolution yielded six enantiomers which were deduced by ECD calculations. • Amovillosumins A and B stimulated GLP-1 secretion by 375.1% and 222.7% at 25.0 μ M. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
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