Startseite Anti-inflammatory dihydroxanthones from a Diaporthe species
Artikel
Lizenziert
Nicht lizenziert Erfordert eine Authentifizierung

Anti-inflammatory dihydroxanthones from a Diaporthe species

  • Markus Rohr , Anna Maria Kiefer , Ulrich Kauhl , Jonathan Groß , Till Opatz EMAIL logo und Gerhard Erkel EMAIL logo
Veröffentlicht/Copyright: 2. August 2021
Biological Chemistry
Aus der Zeitschrift Biological Chemistry Band 403 Heft 1

Abstract

In a search for anti-inflammatory compounds from fungi inhibiting the promoter activity of the small chemokine CXCL10 (Interferon-inducible protein 10, IP-10) as a pro-inflammatory marker gene, the new dihydroxanthone methyl (1R, 2R)-1,2,8-trihydroxy-6-(hydroxymethyl)-9-oxo-2,9-dihydro-1H-xanthene-1-carboxylate (2) and the previously described dihydroxanthone AGI-B4 (1) were isolated from fermentations of a Diaporthe species. The structures of the compounds were elucidated by a combination of one- and two-dimensional NMR spectroscopy, mass spectrometry, and calculations using density functional theory (DFT). Compounds 1 and 2 inhibited the LPS/IFNγ induced CXCL10 promoter activity in transiently transfected human MonoMac6 cells in a dose-dependent manner with IC50 values of 4.1 µM (±0.2 µM) and 1.0 µM (±0.06 µM) respectively. Moreover, compounds 1 and 2 reduced mRNA levels and synthesis of pro-inflammatory mediators such as cytokines and chemokines in LPS/IFNγ stimulated MonoMac6 cells by interfering with the Stat1 and NFκB pathway.

Keywords: CXCL10; dihydroxanthones; inflammation; inhibitor
Corresponding authors: Till Opatz, Department of Chemistry, University of Mainz, Duesbergweg 10-14, D-55128 Mainz, Germany, E-mail: ; and Gerhard Erkel, Department of Molecular Biotechnology and Systems Biology, University of Kaiserslautern, Paul-Ehrlich-Strasse 23, D-67663 Kaiserslautern, Germany, E-mail:

Funding source: Stiftung Rheinland-Pfalz für Innovation

Funding source: Rhineland Palatinate Natural Products Research Center

Acknowledgments

We thank L. Geske (Mainz) for assistance with chiral HPLC analysis, Dr. J. C. Liermann (Mainz) for NMR spectroscopy, Dr. N. Hanold (Mainz), Dr. C. Kampf (Mainz) for high resolution mass spectrometry as well as Prof. Z. Storchova (Kaiserslautern) for FACS analyses. Parts of this research were conducted using the supercomputer Mogon and/or advisory services offered by Johannes Gutenberg University Mainz (hpc.uni-mainz.de), which is a member of the AHRP (Alliance for High Performance Computing in Rhineland Palatinate, www.ahrp.info) and the Gauss Alliance e.V. The authors gratefully acknowledge the computing time granted on the supercomputer Mogon at Johannes Gutenberg University Mainz (hpc.uni-mainz.de).

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This work was supported by a grant from the Stiftung Rheinland-Pfalz für Innovation and by the Rhineland Palatinate Natural Products Research Center.

  3. Conflict of interest statement: The authors declare no conflict of interest.

Supplementary Information

Computational details and FACS analyses associated with this paper can be found in the online version of the article.

References

Adamo, C. and Barone, V. (1998). Exchange functionals with improved long-range behavior and adiabatic connection methods without adjustable parameters: the mPW and mPW1PW models. J. Chem. Phys. 108: 664–675, https://doi.org/10.1063/1.475428.Suche in Google Scholar

Bartoli, M., Gu, X., Tsai, N.T., Venema, R.C., Brooks, S.E., Marrero, M.B., and Caldwell, R.B. (2000). Vascular endothelial growth factor activates stat proteins in aortic endothelial cells. J. Biol. Chem. 275: 33189–33192, https://doi.org/10.1074/jbc.c000318200.Suche in Google Scholar PubMed

Becke, A.D. (1988). Density-functional exchange-energy approximation with correct asymptotic behavior. Phys. Rev. A 38: 3098–3100, https://doi.org/10.1103/physreva.38.3098.Suche in Google Scholar PubMed

Becke, A.D. (1993). Density‐functional thermochemistry. III. The role of exact exchange. J. Chem. Phys. 98: 5648–5652, https://doi.org/10.1063/1.464913.Suche in Google Scholar

Budavari, S., O'Neil, M.J., Smith, A., and Heckelman, P.E. (1989). The Merck index, an encyclopedia of chemicals, drugs, and biologicals, 11th ed. Rahway: Merck Co., Inc.Suche in Google Scholar

Chepkirui, C. and Stadler, M. (2017). The genus Diaporthe: a rich source of diverse bioactive metabolites. Mycol. Prog. 16: 477–494, https://doi.org/10.1007/s11557-017-1288-y.Suche in Google Scholar

Chung, Y.M., Wei, C.K., Chuang, D.W., El-Shazly, M., Hsieh, C.T., Asai, T., Oshima, Y., Hsieh, T.J., Hwang, T.L., Wu, Y.C., et al.. (2013). An epigenetic modifier enhances the production of anti-diabetic and anti-inflammatory sesquiterpenoids from Aspergillus sydowii. Bioorg. Med. Chem. 21: 3866–3872, https://doi.org/10.1016/j.bmc.2013.04.004.Suche in Google Scholar PubMed

Clària, J. and Romano, M. (2005). Pharmacological intervention of cyclooxygenase-2 and 5-lipoxygenase pathways. Impact on inflammation and cancer. Curr. Pharmaceut. Des. 11: 3431–3447, https://doi.org/10.2174/138161205774370753.Suche in Google Scholar PubMed

Clark, T., Chandrasekhar, J., Spitznagel, G.W., and Schleyer, P.V.R. (1983). Efficient diffuse function‐augmented basis sets for anion calculations. III. The 3‐21+G basis set for first‐row elements, Li-F. J. Comput. Chem. 4: 294–301, https://doi.org/10.1002/jcc.540040303.Suche in Google Scholar

De Nardo, D. (2015). Toll-like receptors: activation, signaling and transcriptional modulation. Cytokine 74: 181–189, https://doi.org/10.1016/j.cyto.2015.02.025.Suche in Google Scholar PubMed

Decker, T. and Kovarik, P. (2000). Serine phosphorylation of STATs. Oncogene 19: 2628–2637, https://doi.org/10.1038/sj.onc.1203481.Suche in Google Scholar PubMed

Ditchfield, R. (1974). Self-consistent perturbation theory of diamagnetism. Mol. Phys. 27: 789–807, https://doi.org/10.1080/00268977400100711.Suche in Google Scholar

El-Seedi, H.R., El-Ghorab, D.M.H., El-Barbary, M.A., Zayed, M.F., Göransson, U., Larsson, S., and Verpoorte, R. (2009). Naturally occurring xanthones; latest investigations: isolation, structure elucidation and chemosystematic significance. Curr. Med. Chem. 16: 2581–2626, https://doi.org/10.2174/092986709788682056.Suche in Google Scholar PubMed

Ermanis, K., Parkes, K.E.B., Agback, T., and Goodman, J.M. (2019). The optimal DFT approach in DP4 NMR structure analysis – pushing the limits of relative configuration elucidation. Org. Biomol. Chem. 17: 5886–5890, https://doi.org/10.1039/c9ob00840c.Suche in Google Scholar PubMed

Feng, Z., Lu, X., Gan, L., Zhang, Q., and Lin, L. (2020). Xanthones, a promising anti-inflammatory scaffold: structure, activity, and drug likeness analysis. Molecules 25: 598, https://doi.org/10.3390/molecules25030598.Suche in Google Scholar PubMed PubMed Central

Fenwick, P.S., Macedo, P., Kilty, I.C., Barnes, P.J., and Donnelly, L.E. (2015). Effect of JAK inhibitors on release of CXCL9, CXCL10 and CXCL11 from human airway epithelial cells. PloS One 10: e0128757, https://doi.org/10.1371/journal.pone.0128757.Suche in Google Scholar PubMed PubMed Central

Fotie, J. and Bohle, D.S. (2006). Pharmacological and biological activities of xanthones. Anti-Infect. Agents Med. Chem. 5: 15–31, https://doi.org/10.2174/187152106774755563.Suche in Google Scholar

Frisch, M.J., Pople, J.A., and Binkley, J.S. (1984). Self‐consistent molecular orbital methods 25. Supplementary functions for Gaussian basis sets. J. Chem. Phys. 80: 3265–3269, https://doi.org/10.1063/1.447079.Suche in Google Scholar

Gottlieb, H.E., Kotlyar, V., and Nudelman, A. (1997). NMR chemical shifts of common laboratory solvents as trace impurities. J. Org. Chem. 62: 7512–7515, https://doi.org/10.1021/jo971176v.Suche in Google Scholar PubMed

Griffith, J.W., Sokol, C.L., and Luster, A.D. (2014). Chemokines and chemokine receptors: positioning cells for host defense and immunity. Annu. Rev. Immunol. 32: 659–702, https://doi.org/10.1146/annurev-immunol-032713-120145.Suche in Google Scholar PubMed

Grimblat, N., Gavín, J.A., Hernández Daranas, A., and Sarotti, A.M. (2019). Combining the power of J coupling and DP4 analysis on stereochemical assignments: The J-DP4 methods. Org. Lett. 21: 4003–4007, https://doi.org/10.1021/acs.orglett.9b01193.Suche in Google Scholar PubMed

Grimblat, N., Zanardi, M.M., and Sarotti, A.M. (2015). Beyond DP4: an improved probability for the stereochemical assignment of isomeric compounds using quantum chemical calculations of NMR shifts. J. Org. Chem. 80: 12526–12534, https://doi.org/10.1021/acs.joc.5b02396.Suche in Google Scholar

Gupta, S.C., Sundaram, C., Reuter, S., and Aggarwal, B.B. (2010). Inhibiting NF-kappaB activation by small molecules as a therapeutic strategy. Biochim. Biophys. Acta 1799: 775–787, https://doi.org/10.1016/j.bbagrm.2010.05.004.Suche in Google Scholar

Halgren, T.A. (1996). Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94. J. Comput. Chem. 17: 490–519, https://doi.org/10.1002/(sici)1096-987x(199604)17:5/6<490::aid-jcc1>3.0.co;2-p.10.1002/(SICI)1096-987X(199604)17:5/6<490::AID-JCC1>3.0.CO;2-PSuche in Google Scholar

Hariharan, P.C. and Pople, J.A. (1973). The influence of polarization functions on molecular orbital hydrogenation energies. Theor. Chim. Acta 28: 213–222, https://doi.org/10.1007/bf00533485.Suche in Google Scholar

Hehre, W.J., Ditchfield, R., and Pople, J.A. (1972). Self-consistent molecular orbital methods. XII. Further extensions of Gaussian-type basis sets for use in molecular orbital studies of organic molecules. J. Chem. Phys. 56: 2257–2261, https://doi.org/10.1063/1.1677527.Suche in Google Scholar

Jamilloux, Y., El Jammal, T., Vuitton, L., Gerfaud-Valentin, M., Kerever, S., and Sève, P. (2019). JAK inhibitors for the treatment of autoimmune and inflammatory diseases. Autoimmun. Rev. 18: 102390, https://doi.org/10.1016/j.autrev.2019.102390.Suche in Google Scholar

Kauhl, U. (2017). Dissertation. Johannes Gutenberg-Universität, Mainz.Suche in Google Scholar

Kim, C.S., Oh, J., and Lee, T.H. (2020). Structure elucidation of small organic molecules by contemporary computational chemistry methods. Arch. Pharm. Res. 43: 1114–1127, https://doi.org/10.1007/s12272-020-01277-4.Suche in Google Scholar

Kim, H.S., Park, I.Y., Park, Y.J., Lee, J.H., Hong, Y.S., and Lee, J.J. (2002). A novel dihydroxanthenone, AGI-B4 with inhibition of VEGF-induced endothelial cell Growth. J. Antibiot. 55: 669–672, https://doi.org/10.7164/antibiotics.55.669.Suche in Google Scholar

Kopitar-Jerala, N. (2017). The role of interferons in inflammation and inflammasome activation. Front. Immunol. 8: 873, https://doi.org/10.3389/fimmu.2017.00873.Suche in Google Scholar

Krishnan, R., Binkley, J.S., Seeger, R., and Pople, J.A. (1980). Self‐consistent molecular orbital methods. XX. A basis set for correlated wave functions. J. Chem. Phys. 72: 650–654, https://doi.org/10.1063/1.438955.Suche in Google Scholar

Lee, C., Yang, W., and Parr, R.G. (1988). Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. Phys. Rev. B 37: 785–789, https://doi.org/10.1103/physrevb.37.785.Suche in Google Scholar PubMed

Lee, E.Y., Lee, Z.H., and Song, Y.W. (2009). CXCL10 and autoimmune diseases. Autoimmun. Rev. 8: 379–383, https://doi.org/10.1016/j.autrev.2008.12.002.Suche in Google Scholar PubMed

Lee, E.Y., Lee, Z.H., and Song, Y.W. (2013). The interaction between CXCL10 and cytokines in chronic inflammatory arthritis. Autoimmun. Rev. 12: 554–557, https://doi.org/10.1016/j.autrev.2012.10.001.Suche in Google Scholar PubMed

Lippke, G. and Thaler, H. (1970). The specific rotation of sorbitol and of the sorbitol molybdate complex. Starch 22: 344–351, https://doi.org/10.1002/star.19700221005.Suche in Google Scholar

Liu, Q.Y., Wang, Y.T., and Lin, L.G. (2015). New insights into the anti-obesity activity of xanthones from Garcinia mangostana. Food Funct. 6: 383–393, https://doi.org/10.1039/c4fo00758a.Suche in Google Scholar PubMed

Martínez-García, D., Manero-Rupérez, N., Quesada, R., Korrodi-Gregório, L., and Soto-Cerrato, V. (2019). Therapeutic strategies involving survivin inhibition in cancer. Med. Res. Rev. 39: 887–909, https://doi.org/10.1002/med.21547.Suche in Google Scholar PubMed

Masters, K.-S. and Bräse, S. (2012). Xanthones from fungi, lichens, and bacteria: the natural products and their synthesis. Chem. Rev. 112: 3717–3776, https://doi.org/10.1021/cr100446h.Suche in Google Scholar PubMed

Mohan, S., Syam, S., Abdelwahab, S.I., and Thangavel, N. (2018). An anti-inflammatory molecular mechanism of action of α-mangostin, the major xanthone from the pericarp of Garcinia mangostana: an in silico, in vitro and in vivo approach. Food Funct. 9: 3860–3871, https://doi.org/10.1039/c8fo00439k.Suche in Google Scholar PubMed

Nazarski, R.B., Pasternak, B., and Leśniak, S. (2011). Three-component conformational equilibria of some flexible pyrrolidin-2-(thi)ones in solution by NMR data (δC, δH, and nJHH) and their DFT predictions: a confrontation of different approaches. Tetrahedron 67: 6901–6916, https://doi.org/10.1016/j.tet.2011.06.095.Suche in Google Scholar

Oeckinghaus, A. and Ghosh, S. (2009). The NF-kappaB family of transcription factors and its regulation. Cold Spring Harb. Perspect. Biol. 1: a000034, https://doi.org/10.1101/cshperspect.a000034.Suche in Google Scholar PubMed PubMed Central

Ohmori, Y. and Hamilton, T.A. (2001). Requirement for STAT1 in LPS‐induced gene expression in macrophages. J. Leukoc. Biol. 69: 598–604.10.1189/jlb.69.4.598Suche in Google Scholar

Pérez, M., Soler-Torronteras, R., Collado, J.A., Limones, C.G., Hellsten, R., Johansson, M., Sterner, O., Bjartell, A., Calzado, M.A., and Muños, E. (2014). The fungal metabolite galiellalactone interferes with the nuclear import of NF-κB and inhibits HIV-1 replication. Chem. Biol. Interact. 214: 69–76, https://doi.org/10.1016/j.cbi.2014.02.012.Suche in Google Scholar

Pfaffl, M.W. (2001). A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 29: 45e, https://doi.org/10.1093/nar/29.9.e45.Suche in Google Scholar

Riley, K.F., Hobson, M.P., and Bence, S.J. (2006). Mathematical methods for physics and engineering, 3rd ed. Cambridge: Cambridge University Press.10.1017/CBO9780511810763Suche in Google Scholar

Roehm, N.W., Rodgers, H., Hatfield, S.M., and Glasebrook, A.L. (1991). An improved colorimetric assay for cell proliferation and viability utilizing the tetrazolium salt XTT. J. Immunol. Methods 142: 257–265, https://doi.org/10.1016/0022-1759(91)90114-u.Suche in Google Scholar

Rohr, M., Oleinikov, K., Jung, M., Sandjo, L.P., Opatz, T., and Erkel, G. (2017). Anti-inflammatory tetraquinane diterpenoids from a Crinipellis species. Bioorg. Med. Chem. 25: 514–522, https://doi.org/10.1016/j.bmc.2016.11.016.Suche in Google Scholar PubMed

Russo, R.C., Garcia, C.C., Teixeira, M.M., and Amaral, F.A. (2014). The CXCL8/IL-8 chemokine family and its receptors in inflammatory diseases. Expet Rev. Clin. Immunol. 10: 593–619, https://doi.org/10.1586/1744666x.2014.894886.Suche in Google Scholar

Shagufta, I.A. (2016). Recent insight into the biological activities of synthetic xanthone derivatives. Eur. J. Med. Chem. 116: 267–280, https://doi.org/10.1016/j.ejmech.2016.03.058.Suche in Google Scholar PubMed

Smith, S.G. and Goodman, J.M. (2010). Assigning stereochemistry to single diastereoisomers by GIAO NMR calculation: the DP4 probability. J. Am. Chem. Soc. 132: 12946–12959, https://doi.org/10.1021/ja105035r.Suche in Google Scholar PubMed

Spurrell, J.C., Wiehler, S., Zaheer, R.S., Sanders, S.P., and Proud, D. (2005). Human airway epithelial cells produce IP-10 (CXCL10) in vitro and in vivo upon rhinovirus infection. Am. J. Physiol. Lung Cell Mol. Physiol. 289: L85–L95, https://doi.org/10.1152/ajplung.00397.2004.Suche in Google Scholar PubMed

Stephens, P.J., McCann, D.M., Cheeseman, J.R., and Frisch, M.J. (2005). Determination of absolute configurations of chiral molecules using ab initio time‐dependent density functional theory calculations of optical rotation: how reliable are absolute configurations obtained for molecules with small rotations. Chirality 17: S52–S64, https://doi.org/10.1002/chir.20109.Suche in Google Scholar PubMed

Su, Q.G., Liu, Y., Cai, Y.C., Sun, Y.L., Wang, B., and Xian, L.J. (2011). Anti-tumour effects of xanthone derivatives and the possible mechanisms of action. Invest. N. Drugs 29: 1230–1240, https://doi.org/10.1007/s10637-010-9468-5.Suche in Google Scholar

Tamassia, N., Calzetti, F., Ear, T., Cloutier, A., Gasperini, S., Bazzoni, F., McDonald, P.P., and Cassatella, M.A. (2007). Molecular mechanisms underlying the synergistic induction of CXCL10 by LPS and IFN-γ in human neutrophils. Eur. J. Immunol. 37: 2627–2634, https://doi.org/10.1002/eji.200737340.Suche in Google Scholar

Tashiro, E., Tsuchiya, A., and Imoto, M. (2007). Functions of cyclin D1 as an oncogene and regulation of cyclin D1 expression. Canc. Sci. 98: 629–635, https://doi.org/10.1111/j.1349-7006.2007.00449.x.Suche in Google Scholar

Tomasi, J., Mennucci, B., and Cancès, E. (1999). The IEF version of the PCM solvation method: an overview of a new method addressed to study molecular solutes at the QM ab initio level. J. Mol. Struct. THEOCHEM 464: 211–226, https://doi.org/10.1016/s0166-1280(98)00553-3.Suche in Google Scholar

Turner, M.D., Nedjai, B., Hurst, T., and Pennington, D.J. (2014). Cytokines and chemokines: at the crossroads of cell signalling and inflammatory disease. Biochim. Biophys. Acta 1843: 2563–2582, https://doi.org/10.1016/j.bbamcr.2014.05.014.Suche in Google Scholar

Vosko, S.H., Wilk, L., and Nusair, M. (1980). Accurate spin-dependent electron liquid correlation energies for local spin density calculations: a critical analysis. Can. J. Phys. 58: 1200–1211, https://doi.org/10.1139/p80-159.Suche in Google Scholar

Wan, F. and Lenardo, M.J. (2009). Specification of DNA binding activity of NF-kB proteins. Cold Spring Harb. Perspect. Biol. 1: a000067, https://doi.org/10.1101/cshperspect.a000067.Suche in Google Scholar

Waugh, D.J.J. and Wilson, C. (2008). The interleukin-8 pathway in cancer. Clin. Canc. Res. 14: 6735–6741, https://doi.org/10.1158/1078-0432.ccr-07-4843.Suche in Google Scholar

Weidler, M., Rether, J., Anke, T., and Erkel, G. (2000). Inhibition of interleukin-6 signaling by galiellalactone. FEBS Lett. 484: 1–6, https://doi.org/10.1016/s0014-5793(00)02115-3.Suche in Google Scholar

Wen, Z., Zhong, Z., and Darnell, J.E. (1995). Maximal activation of transcription by Stat1 and Stat3 requires both tyrosine and serine phosphorylation. Cell 82: 241–250, https://doi.org/10.1016/0092-8674(95)90311-9.Suche in Google Scholar

White, T.J., Bruns, T., Lee, S., and Taylor, J. (1990). Amplification and direct sequencing of fungal ribosomal RNA genes for phylogenetics. In: Innis, M.A., Gelfand, D.H., Sninsky, J.J., and White, T.J. (Eds.), PCR protocols: a guide to methods and applications. Academic Press, San Diego, pp. 315–322.10.1016/B978-0-12-372180-8.50042-1Suche in Google Scholar

Willwacher, J., Heggen, B., Wirtz, C., Thiel, W., and Fürstner, A. (2015). Total synthesis, stereochemical revision, and biological reassessment of mandelalide A: chemical mimicry of intrafamily relationships. Chem. Eur J. 21: 10416–10430, https://doi.org/10.1002/chem.201501491.Suche in Google Scholar PubMed

Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/hsz-2021-0192).

Received: 2021-03-12
Accepted: 2021-07-09
Published Online: 2021-08-02
Published in Print: 2022-01-26

© 2021 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Highlight: Drug Development for Neurodegenerative Diseases
  3. Drug development for neurodegenerative diseases
  4. The role of mycotoxins in neurodegenerative diseases: current state of the art and future perspectives of research
  5. Emerging contributions of formyl peptide receptors to neurodegenerative diseases
  6. Brothers in arms: proBDNF/BDNF and sAPPα/Aβ-signaling and their common interplay with ADAM10, TrkB, p75NTR, sortilin, and sorLA in the progression of Alzheimer’s disease
  7. Artemisinin-treatment in pre-symptomatic APP-PS1 mice increases gephyrin phosphorylation at Ser270: a modification regulating postsynaptic GABAAR density
  8. Anti-inflammatory dihydroxanthones from a Diaporthe species
  9. The antioxidant Rutin counteracts the pathological impact of α-synuclein on the enteric nervous system in vitro
  10. A liquid-culture-based screening approach to study compounds affecting inflammatory processes in Caenorhabditis elegans
https://doi.org/10.1515/hsz-2021-0192
Schlagwörter für diesen Artikel
CXCL10; dihydroxanthones; inflammation; inhibitor

Artikel in diesem Heft

  1. Frontmatter
  2. Highlight: Drug Development for Neurodegenerative Diseases
  3. Drug development for neurodegenerative diseases
  4. The role of mycotoxins in neurodegenerative diseases: current state of the art and future perspectives of research
  5. Emerging contributions of formyl peptide receptors to neurodegenerative diseases
  6. Brothers in arms: proBDNF/BDNF and sAPPα/Aβ-signaling and their common interplay with ADAM10, TrkB, p75NTR, sortilin, and sorLA in the progression of Alzheimer’s disease
  7. Artemisinin-treatment in pre-symptomatic APP-PS1 mice increases gephyrin phosphorylation at Ser270: a modification regulating postsynaptic GABAAR density
  8. Anti-inflammatory dihydroxanthones from a Diaporthe species
  9. The antioxidant Rutin counteracts the pathological impact of α-synuclein on the enteric nervous system in vitro
  10. A liquid-culture-based screening approach to study compounds affecting inflammatory processes in Caenorhabditis elegans
Jetzt anmelden und 20% sparen
Institutioneller Zugang
Wie funktioniert Authentifizierung?
Haben Sie eine Idee, wie wir unsere Website verbessern können?
Bitte schreiben Sie uns.
© 2025 De Gruyter Brill
Heruntergeladen am 27.10.2025 von https://www.degruyterbrill.com/document/doi/10.1515/hsz-2021-0192/html
Button zum nach oben scrollen