Abstract
Anti-inflammatory activities of thymoquinone (TQ) have been demonstrated in in vitro and in vivo studies. However, the precise mechanism(s) of TQ in these anti-inflammatory activities is not well understood. Using a newly developed assay to detect sialidase activity in live macrophage cells (Glycoconj J doi:10.1007/s10719-009-9239-8), here we show that TQ has no inhibitory effect on endotoxin lipopolysaccharide (LPS) induced sialidase activity in live BMC-2 macrophage cells. In contrast, the parent black seed oil (BSO) and another constituent of BSO para-cymene (p-CY) completely block LPS induced sialidase activity. All of these compounds had no effect on cell viability. On the other hand, TQ induces a vigorous sialidase activity in live BMC-2 macrophage cells in a dose dependent manner as well in live DC-2.4 dendritic cells, HEK-TLR4/MD2, HEK293, SP1 mammary adenocarcinoma cells, human WT and 1140F01 and WG0544 type I sialidosis fibroblast cells. Tamiflu (oseltamivir phosphate) inhibits TQ-induced sialidase activity in live BMC-2 cells with an IC50 of 0.0194 μM compared to an IC50 of 19.1 μM for neuraminidase inhibitor DANA (2-deoxy-2,3-dehydro-N-acetylneuraminic acid). Anti-Neu1, -2 and -3 antibodies have no inhibition of TQ-induced sialidase activity in live BMC-2 and human THP-1 macrophage cells but anti-Neu4 antibodies completely block this activity. There is a vigorous sialidase activity associated with TQ treated live primary bone marrow (BM) macrophage cells derived from WT and hypomorphic cathepsin A mice with a secondary Neu1 deficiency (NeuI KD), but not from Neu4 knockout (Neu4 KO) mice. Pertussis toxin (PTX), a specific inhibitor of Gαi proteins of G-protein coupled receptor (GPCR) and the broad range inhibitors of matrix metalloproteinase (MMP) galardin and piperazine applied to live BMC-2, THP-1 and primary BM macrophage cells completely block TQ-induced sialidase activity. These same inhibitory effects are not observed with the GM1 ganglioside specific cholera toxin subunit B (CTXB) as well as with CTX, tyrosine kinase inhibitor K252a, and the broad range GPCR inhibitor suramin. The specific inhibitor of MMP-9, anti-MMP-9 antibody and anti-Neu4 antibody, but not the specific inhibitor of MMP-3 completely block TQ-induced sialidase activity in live THP-1 cells, which express Neu4 and MMP-9 on the cell surface. Neu4 sialidase activity in cell lysates from TQ-treated live THP-1 cells desialylates natural gangliosides and mucin substrates. RT-PCR and western blot analyses reveal no correlation between mRNA and protein values for Neu3 and Neu4 in human monocytic THP-1 cells, suggesting for the first time a varied post-transcriptional mechanism for these two mammalian sialidases independent of TQ activation. Our findings establish an unprecedented activation of Neu4 sialidase on the cell surface by thymoquinone, which is derived from the nutraceutical black cumin oil. The potentiation of GPCR-signaling by TQ via membrane targeting of Gαi subunit proteins and matrix metalloproteinase-9 activation may be involved in the activation process of Neu4 sialidase on the cell surface.
Similar content being viewed by others
Abbreviations
- TQ:
-
thymoquinone
- p-Cy:
-
para-cymene
- Oseltamivir phosphate:
-
Tamiflu
- DANA:
-
2-deoxy-2,3-dehydro-N-acetylneuraminic acid
- LPS:
-
lipopolysaccride
- IC50 :
-
50% inhibition concentration
- BM:
-
bone marrow
- M-CSF:
-
monocyte colony-stimulating factor
- 4-MUNANA:
-
2′-(4-methylumbelliferyl)-α-N-acetylneuraminic acid
- PVDF:
-
polyvinylidene fluoride
- DMSO:
-
dimethyl sulfoxide
- HEK293:
-
human embryonic kidney 293 cells
- Neu1 KD:
-
hypomorphic cathepsin A mice with the secondary ∼90% reduction of the Neu1 activity
- Neu4 KO:
-
Neu4 knockout
- GPCR:
-
G-protein coupled receptor
- CTX:
-
cholera toxin
- CTXB:
-
cholera toxin subunit B
- MMP:
-
matrix metalloproteinase
- MMP-9i:
-
specifc inhibitor of MMP-9
- MMP-3i:
-
specifc inhibitor of MMP-3
- PMA:
-
4-beta-phorbol 12-myristate 13-acetate
References
Salem, M.L.: Immunomodulatory and therapeutic properties of the Nigella sativa L. seed. Int. Immunopharmacol. 5, 1749–1770 (2005)
El Gazzar, M., El Mezayen, R., Marecki, J.C., Nicolls, M.R., Canastar, A., Dreskin, S.C.: Anti-inflammatory effect of thymoquinone in a mouse model of allergic lung inflammation. Int. Immunopharmacol. 6, 1135–1142 (2006)
El Mezayen, R., El Gazzar, M., Nicolls, M.R., Marecki, J.C., Dreskin, S.C., Nomiyama, H.: Effect of thymoquinone on cyclooxygenase expression and prostaglandin production in a mouse model of allergic airway inflammation. Immunol. Lett. 106, 72–81 (2006)
El Gazzar, M., El Mezayen, R., Nicolls, M.R., Marecki, J.C., Dreskin, S.C.: Downregulation of leukotriene biosynthesis by thymoquinone attenuates airway inflammation in a mouse model of allergic asthma. Biochim. Biophys. Acta 1760, 1088–1095 (2006)
El Gazzar, M.A., El Mezayen, R., Nicolls, M.R., Dreskin, S.C.: Thymoquinone attenuates proinflammatory responses in lipopolysaccharide-activated mast cells by modulating NF-kappaB nuclear transactivation. Biochim. Biophys. Acta 1770, 556–564 (2007)
Tekeoglu, I., Dogan, A., Ediz, L., Budancamanak, M., Demirel, A.: Effects of thymoquinone (volatile oil of black cumin) on rheumatoid arthritis in rat models. Phytother. Res. 21, 895–897 (2007)
Halperin, E.C., Gaspar, L., Imperato, J., Salter, M., Herndon 2nd, J., Dowling, S.: An analysis of radiotherapy data from the CNS cancer consortium’s randomized prospective trial comparing AZQ to BCNU in the treatment of patients with primary malignant brain tumors. The CNS cancer consortium. Am. J. Clin. Oncol. 16, 277–283 (1993)
Amith, S.R., Jayanth, P., Franchuk, S., Siddiqui, S., Seyrantepe, V., Gee, K., Basta, S., Beyaert, R., Pshezhetsky, A., Szewczuk, M.: Dependence of pathogen molecule-induced Toll-like receptor activation and cell function on Neu1 sialidase. Glycoconj. J. 26, 1197–1212 (2009)
Amith, S.R., Jayanth, P., Franchuk, S., Finlay, T., Seyrantepe, V., Beyaert, R., Pshezhetsky, A.V., Szewczuk, M.R.: Neu1 desialylation of sialyl alpha-2, 3-linked beta-galactosyl residues of TOLL-like receptor 4 is essential for receptor activation and cellular signaling. Cell. Signal. 22, 314–324 (2010)
Kovacsovics-Bankowski, M., Rock, K.L.: Presentation of exogenous antigens by macrophages: analysis of major histocompatibility complex class I and II presentation and regulation by cytokines. Eur. J. Immunol. 24, 2421–2428 (1994)
Shen, Z., Reznikoff, G., Dranoff, G., Rock, K.L.: Cloned dendritic cells can present exogenous antigens on both MHC class I and class II molecules. J. Immunol. 158, 2723–2730 (1997)
Bifsha, P., Landry, K., Ashmarina, L., Durand, S., Seyrantepe, V., Trudel, S., Quiniou, C., Chemtob, S., Xu, Y., Gravel, R.A., Sladek, R., Pshezhetsky, A.V.: Altered gene expression in cells from patients with lysosomal storage disorders suggests impairment of the ubiquitin pathway. Cell Death Differ. 14, 511–523 (2007)
Carlow, D.A., Kerbel, R.S., Feltis, J.T., Elliott, B.E.: Enhanced expression of class I major histocompatibility complex gene (Dk) products on immunogenic variants of a spontaneous murine carcinoma. J. Natl. Cancer Inst. 75, 291–301 (1985)
Seyrantepe, V., Canuel, M., Carpentier, S., Landry, K., Durand, S., Liang, F., Zeng, J., Caqueret, A., Gravel, R.A., Marchesini, S., Zwingmann, C., Michaud, J., Morales, C.R., Levade, T., Pshezhetsky, A.V.: Mice deficient in Neu4 sialidase exhibit abnormal ganglioside catabolism and lysosomal storage. Hum. Mol. Genet. 17, 1556–1568 (2008)
Seyrantepe, V., Hinek, A., Peng, J., Fedjaev, M., Ernest, S., Kadota, Y., Canuel, M., Itoh, K., Morales, C.R., Lavoie, J., Tremblay, J., Pshezhetsky, A.V.: Enzymatic activity of lysosomal carboxypeptidase (cathepsin) A is required for proper elastic fiber formation and inactivation of endothelin-1. Circulation 117, 1973–1981 (2008)
Alatery, A., Basta, S.: An efficient culture method for generating large quantities of mature mouse splenic macrophages. J. Immunol. Methods 338, 47–57 (2008)
Woronowicz, A., Amith, S.R., De Vusser, K., Laroy, W., Contreras, R., Basta, S., Szewczuk, M.R.: Dependence of neurotrophic factor activation of trk tyrosine kinase receptors on cellular sialidase. Glycobiology 17, 10–24 (2007)
Bigi, A., Morosi, L., Pozzi, C., Forcella, M., Tettamanti, G., Venerando, B., Monti, E., Fusi, P.: Human sialidase NEU4 long and short are extrinsic proteins bound to outer mitochondrial membrane and the endoplasmic reticulum, respectively. Glycobiology 20, 148–157 (2010)
Seyrantepe, V., Landry, K., Trudel, S., Hassan, J.A., Morales, C.R., Pshezhetsky, A.V.: Neu4, a novel human lysosomal lumen sialidase, confers normal phenotype to sialidosis and galactosialidosis cells. J. Biol. Chem. 279, 37021–37029 (2004)
Hata, K., Koseki, K., Yamaguchi, K., Moriya, S., Suzuki, Y., Yingsakmongkon, S., Hirai, G., Sodeoka, M., von Itzstein, M., Miyagi, T.: Limited inhibitory effects of oseltamivir and zanamivir on human sialidases. Antimicrob. Agents Chemother. 52, 3484–3491 (2008)
Lukong, K.E., Elsliger, M.A., Chang, Y., Richard, C., Thomas, G., Carey, W., Tylki-Szymanska, A., Czartoryska, B., Buchholz, T., Criado, G.R., Palmeri, S., Pshezhetsky, A.V.: Characterization of the sialidase molecular defects in sialidosis patients suggests the structural organization of the lysosomal multienzyme complex. Hum. Mol. Genet. 9, 1075–1085 (2000)
Liang, F., Seyrantepe, V., Landry, K., Ahmad, R., Ahmad, A., Stamatos, N.M., Pshezhetsky, A.V.: Monocyte differentiation up-regulates the expression of the lysosomal sialidase, Neu1, and triggers its targeting to the plasma membrane via major histocompatibility complex class II-positive compartments. J. Biol. Chem. 281, 27526–27538 (2006)
Nan, X., Carubelli, I., Stamatos, N.M.: Sialidase expression in activated human T lymphocytes influences production of IFN-gamma. J. Leukoc. Biol. 81, 284–296 (2007)
Yogalingam, G., Bonten, E.J., van de Vlekkert, D., Hu, H., Moshiach, S., Connell, S.A., d’Azzo, A.: Neuraminidase 1 is a negative regulator of lysosomal exocytosis. Dev. Cell 15, 74–86 (2008)
Hinek, A., Pshezhetsky, A.V., Von, I.M., Starcher, B.: Lysosomal sialidase (neuraminidase-1) is targeted to the cell surface in a multiprotein complex that facilitates elastic fiber assembly. J. Biol. Chem. 281, 3698–3710 (2006)
Duca, L., Blanchevoye, C., Cantarelli, B., Ghoneim, C., Dedieu, S., Delacoux, F., Hornebeck, W., Hinek, A., Martiny, L., Debelle, L.: The elastin receptor complex transduces signals through the catalytic activity of its Neu-1 subunit. J. Biol. Chem. 282, 12484–12491 (2007)
Starcher, B., d’Azzo, A., Keller, P.W., Rao, G.K., Nadarajah, D., Hinek, A.: Neuraminidase-1 is required for the normal assembly of elastic fibers. Am. J. Physiol. Lung Cell. Mol. Physiol. (2008)
Rodriguez, J.A., Piddini, E., Hasegawa, T., Miyagi, T., Dotti, C.G.: Plasma membrane ganglioside sialidase regulates axonal growth and regeneration in hippocampal neurons in culture. J. Neurosci. 21, 8387–8395 (2001)
Sasaki, A., Hata, K., Suzuki, S., Sawada, M., Wada, T., Yamaguchi, K., Obinata, M., Tateno, H., Suzuki, H., Miyagi, T.: Overexpression of plasma membrane-associated sialidase attenuates insulin signaling in transgenic mice. J. Biol. Chem. 278, 27896–27902 (2003)
Papini, N., Anastasia, L., Tringali, C., Croci, G., Bresciani, R., Yamaguchi, K., Miyagi, T., Preti, A., Prinetti, A., Prioni, S., Sonnino, S., Tettamanti, G., Venerando, B., Monti, E.: The plasma membrane-associated sialidase MmNEU3 modifies the ganglioside pattern of adjacent cells supporting its involvement in cell-to-cell interactions. J. Biol. Chem. 279, 16989–16995 (2004)
Yamaguchi, K., Hata, K., Koseki, K., Shiozaki, K., Akita, H., Wada, T., Moriya, S., Miyagi, T.: Evidence for mitochondrial localization of a novel human sialidase (NEU4). Biochem. J. 390, 85–93 (2005)
Seyrantepe, V., Poupetova, H., Froissart, R., Zabot, M.T., Maire, I., Pshezhetsky, A.V.: Molecular pathology of NEU1 gene in sialidosis. Hum. Mutat. 22, 343–352 (2003)
da Silva, J.S., Hasegawa, T., Miyagi, T., Dotti, C.G., bad-Rodriguez, J.: Asymmetric membrane ganglioside sialidase activity specifies axonal fate. Nat. Neurosci. 8, 606–615 (2005)
Chavas, L.M., Tringali, C., Fusi, P., Venerando, B., Tettamanti, G., Kato, R., Monti, E., Wakatsuki, S.: Crystal structure of the human cytosolic sialidase Neu2. Evidence for the dynamic nature of substrate recognition. J. Biol. Chem. 280, 469–475 (2005)
Yamaguchi, K., Hata, K., Wada, T., Moriya, S., Miyagi, T.: Epidermal growth factor-induced mobilization of a ganglioside-specific sialidase (NEU3) to membrane ruffles. Biochem. Biophys. Res. Commun. 346, 484–490 (2006)
Zanchetti, G., Colombi, P., Manzoni, M., Anastasia, L., Caimi, L., Borsani, G., Venerando, B., Tettamanti, G., Preti, A., Monti, E., Bresciani, R.: Sialidase NEU3 is a peripheral membrane protein localized on the cell surface and in endosomal structures. Biochem. J. 408, 211–219 (2007)
Stamatos, N.M., Liang, F., Nan, X., Landry, K., Cross, A.S., Wang, L.X., Pshezhetsky, A.V.: Differential expression of endogenous sialidases of human monocytes during cellular differentiation into macrophages. FEBS J. 272, 2545–2556 (2005)
Shiozaki, K., Koseki, K., Yamaguchi, K., Shiozaki, M., Narimatsu, H., Miyagi, T.: Developmental change of sialidase neu4 expression in murine brain and its involvement in the regulation of neuronal cell differentiation. J. Biol. Chem. 284, 21157–21164 (2009)
Hasegawa, T., Yamaguchi, K., Wada, T., Takeda, A., Itoyama, Y., Miyagi, T.: Molecular cloning of mouse ganglioside sialidase and its increased expression in neuro2a cell differentiation. J. Biol. Chem. 275, 14778 (2000)
Fischer, O.M., Hart, S., Ullrich, A.: Dissecting the epidermal growth factor receptor signal transactivation pathway. Methods Mol. Biol. 327, 85–97 (2006)
Lee, M.-H., Murphy, G.: Matrix metalloproteinases at a glance. J Cell Sci 117, 4015–4016 (2004)
Le Gall, S.M., Auger, R., Dreux, C., Mauduit, P.: Regulated cell surface pro-egf ectodomain shedding is a zinc metalloprotease-dependent process. J. Biol. Chem. 278, 45255–45268 (2003)
Murasawa, S., Mori, Y., Nozawa, Y., Gotoh, N., Shibuya, M., Masaki, H., Maruyama, K., Tsutsumi, Y., Moriguchi, Y., Shibazaki, Y., Tanaka, Y., Iwasaka, T., Inada, M., Matsubara, H.: Angiotensin II type 1 receptor–induced extracellular signal–regulated protein kinase activation is mediated by Ca2+/Calmodulin-dependent transactivation of epidermal growth factor receptor. Circ. Res. 82, 1338–1348 (1998)
Gooz, M., Gooz, P., Luttrell, L.M., Raymond, J.R.: 5-HT2A Receptor induces ERK phosphorylation and proliferation through ADAM-17 tumor necrosis factor-{alpha}-converting Enzyme (TACE) activation and heparin-bound epidermal growth factor-like growth factor (HB-EGF) shedding in mesangial cells. J. Biol. Chem. 281, 21004–21012 (2006)
Prenzel, N., Zwick, E., Daub, H., Leserer, M., Abraham, R., Wallasch, C., Ullrich, A.: EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF. Nature 402, 884–888 (1999)
Hasegawa, T., Sugeno, N., Takeda, A., Matsuzaki-Kobayashi, M., Kikuchi, A., Furukawa, K., Miyagi, T., Itoyama, Y.: Role of Neu4L sialidase and its substrate ganglioside GD3 in neuronal apoptosis induced by catechol metabolites. FEBS Lett. 581, 406–412 (2007)
Miyagi, T., Wada, T., Yamaguchi, K., Hata, K., Shiozaki, K.: Plasma membrane-associated sialidase as a crucial regulator of transmembrane signalling. J. Biochem. 144, 279–285 (2008)
Papini, N., Anastasia, L., Tringali, C., Croci, G., Bresciani, R., Yamaguchi, K., Miyagi, T., Preti, A., Prinetti, A., Prioni, S., Sonnino, S., Tettamanti, G., Venerando, B., Monti, E.: The plasma membrane-associated sialidase MmNEU3 modifies the ganglioside pattern of adjacent cells supporting its involvement in cell-to-cell interactions. J. Biol. Chem. 279, 16989–16995 (2004)
Monti, E., Bassi, M.T., Papini, N., Riboni, M., Manzoni, M., Venerando, B., Croci, G., Preti, A., Ballabio, A., Tettamanti, G., Borsani, G.: Identification and expression of NEU3, a novel human sialidase associated to the plasma membrane. Biochem. J. 349, 343–351 (2000)
Wang, P., Zhang, J., Bian, H., Wu, P., Kuvelkar, R., Kung, T.T., Crawley, Y., Egan, R.W., Billah, M.M.: Induction of lysosomal and plasma membrane-bound sialidases in human T-cells via T-cell receptor. Biochem. J. 380, 425–433 (2004)
Ha, K.T., Lee, Y.C., Cho, S.H., Kim, J.K., Kim, C.H.: Molecular characterization of membrane type and ganglioside-specific sialidase (Neu3) expressed in E. coli. Mol. Cells 17, 267–273 (2004)
Greenbaum, D., Colangelo, C., Williams, K., Gerstein, M.: Comparing protein abundance and mRNA expression levels on a genomic scale. Genome Biol. 4, 117 (2003)
Wang, D., Zaitsev, S., Taylor, G., d’Azzo, A., Bonten, E.: Protective protein/cathepsin A rescues N-glycosylation defects in neuraminidase-1. Biochim. Biophys. Acta 1790, 275–282 (2009)
Bonten, E.J., Campos, Y., Zaitsev, V., Nourse, A., Waddell, B., Lewis, W., Taylor, G., d’Azzo, A.: Heterodimerization of the sialidase NEU1 with the chaperone PPCA prevents its premature oligomerization. J. Biol. Chem. 284(41), 28430–41 (2009)
Wang, D., Zaitsev, S., Taylor, G., d’Azzo, A., Bonten, E.: Protective protein/cathepsin a rescues N-glycosylation defects in Neuraminidase-1. Biochim. Biophys. Acta. (2009)
Hinek, A., Pshezhetsky, A.V., von Itzstein, M., Starcher, B.: Lysosomal sialidase (neuraminidase-1) is targeted to the cell surface in a multiprotein complex that facilitates elastic fiber assembly. J. Biol. Chem. 281, 3698–3710 (2006)
Chen, X.P., Enioutina, E.Y., Daynes, R.A.: The control of IL-4 gene expression in activated murine T lymphocytes: a novel role for neu-1 sialidase. J. Immunol. 158, 3070–3080 (1997)
Seyrantepe, V., Iannello, A., Liang, F., Kanshin, E., Jayanth, P., Samarani, S., Szewczuk, M.R., Ahmad, A., Pshezhetsky, A.V.: Regulation of phagocytosis in macrophages by the neuraminidase 1. J. Biol. Chem. 285(1), 206–15 (2010)
Shi, D., Yang, J., Yang, D., LeCluyse, E.L., Black, C., You, L., Akhlaghi, F., Yan, B.: Anti-influenza prodrug oseltamivir is activated by carboxylesterase human carboxylesterase 1, and the activation is inhibited by antiplatelet agent clopidogrel. J. Pharmacol. Exp. Ther. 319, 1477–1484 (2006)
Lukong, K.E., Elsliger, M.A., Chang, Y., Richard, C., Thomas, G., Carey, W., Tylki-Szymanska, A., Czartoryska, B., Buchholz, T., Criado, G.R., Palmeri, S., Pshezhetsky, A.V.: Characterization of the sialidase molecular defects in sialidosis patients suggests the structural organization of the lysosomal multienzyme complex. Hum. Mol. Genet. 9, 1075–1085 (2000)
Ghosheh, O.A., Houdi, A.A., Crooks, P.A.: High performance liquid chromatographic analysis of the pharmacologically active quinones and related compounds in the oil of the black seed (Nigella sativa L.). J. Pharm. Biomed. Anal. 19, 757–762 (1999)
Hajhashemi, V., Ghannadi, A., Jafarabadi, H.: Black cumin seed essential oil, as a potent analgesic and antiinflammatory drug. Phytother. Res. 18, 195–199 (2004)
D’Antuono, L.F., Moretti, A., Lovato, A.F.S.: Seed yield, yield components, oil content and essential oil content and composition of Nigella sativa L. and Nigella damascena L. Ind. Crops Prod. 15, 59–69 (2002)
Acknowledgements
These studies are partially supported by grants to MRS from Natural Sciences and Engineering Research Council of Canada (NSERC). T.M.F. was a recipient of the Queen’s University Research Award. P.J. is a recipient of the Queen’s Graduate Award and the Robert J. Wilson Fellowship. S.R.A. was a recipient of the Queen’s University Research Award, the Robert J. Wilson Fellowship and the Ontario Graduate Scholarship. C.G. is a recipient of a Studentship Award from the Ontario HIV Treatment Network (OHTN). Research work on the TLR transfected cell lines is supported by grants to R.B. from the ‘Interuniversitaire Attractiepolen’ (IAP6/18), the ‘Fonds voor Wetenschappelijk Onderzoek-Vlaanderen’ (FWO; grant 3G010505), and the ‘Geconcerteerde Onderzoeksacties’ of the Ghent University (GOA; grant 01G06B6).
We acknowledge Prof. Alexey V. Pshezhetsky and Dr. Volkan Seyrantepe from the Departments of Pediatrics and Biochemistry, Montreal University, Service de Genetique, Ste-Justine Hospital, 3175 Cote-Ste-Catherine, H3T1C5, Montreal, QC, Canada for provided us the Neu1-deficient and Neu4 knockout mice as well as the sialidosis fibroblast cells.
Author information
Authors and Affiliations
Corresponding author
Additional information
Authors Contributions
M.R.S. and T.M.F. wrote the paper, designed and performed experiments; P.J. performed the free sialic acid assay and together with K.G. performed the flow cytometry; C.G. did the RT-PCR; A.G. did the Neu3 and Neu4 WB; R.B. generated HEK-TLR cells; S.R.A. helped with experiments and writing the paper; M.R.S. supervised the research design and the writing of the paper. All authors read and commented on the manuscript, and declare no competing financial interests.
Rights and permissions
About this article
Cite this article
Finlay, T.M., Jayanth, P., Amith, S.R. et al. Thymoquinone from nutraceutical black cumin oil activates Neu4 sialidase in live macrophage, dendritic, and normal and type I sialidosis human fibroblast cells via GPCR Gαi proteins and matrix metalloproteinase-9. Glycoconj J 27, 329–348 (2010). https://doi.org/10.1007/s10719-010-9281-6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10719-010-9281-6