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Appears in Networks 9

In-Edges 9

path(MESH:Encephalomyelitis) negativeCorrelation a(CHEBI:Anatabine) View Subject | View Object

Clinical signs of EAE became apparent by day 6 following the immunization in the placebo group but were delayed to day 11 in the anatabine treatment group (Fig. 1A) PubMed:23383175

a(GO:"myelin sheath") positiveCorrelation a(CHEBI:Anatabine) View Subject | View Object

Interestingly, anatabine significantly prevented demyelination associated with EAE in the spinal cord (Fig. 12) PubMed:23383175

p(HGNC:QPRT) increases a(CHEBI:Anatabine) View Subject | View Object

To shed further light on pathway regulation, the question was asked about whether alteration of nicotine and anatabine content would affect the expression of other key enzyme, namely QPRT, which is a key enzyme in the biosynthesis of another precursor of nicotine, and also the key enzyme of anatabine (Fig. 1). PubMed:19165623

a(UNIPROT:Q9SEH4) decreases a(CHEBI:Anatabine) View Subject | View Object

Down-regulation of PMT expression led to elevation of anatabine level in transgenic tobacco root lines and leaf tissues of regenerated tobacco plants PubMed:19165623

Out-Edges 120

a(CHEBI:Anatabine) causesNoChange p(HGNC:MAPT) View Subject | View Object

No effect of the anatabine treatment was observed on tau expression (T-test, P>0.05) in Tg Tau P301S mice (Figure 4). DOI:10.4172/2168-975X.1000126

a(CHEBI:Anatabine) decreases p(HGNC:STAT3, pmod(Ph)) View Subject | View Object

We observed that anatabine inhibits basal STAT3 phosphorylation levels (Mann– Whitney U=0, Z=-2.882, P=0.004) and reduces the induction of p65 NFkB phosphorylation by TNFa (Mann–Whitney U=0, Z=-2.882, P=0.004) within this 15 min time-frame (Fig. 1) PubMed:23178521

Annotations
Experimental Factor Ontology (EFO)
SH-SY5Y

a(CHEBI:Anatabine) decreases p(HGNC:STAT3, pmod(Ph)) View Subject | View Object

Under these culture conditions, anatabine also inhibited both STAT3 and p65 NFkB phosphorylation induced by TNFa (Fig. 2) PubMed:23178521

Annotations
Experimental Factor Ontology (EFO)
SH-SY5Y

a(CHEBI:Anatabine) decreases p(HGNC:STAT3, pmod(Ph)) View Subject | View Object

A significant inhibition of STAT3 phosphorylation was observed with 600 mg/ml of anatabine (Mann–Whitney U=0, Z=-2.309, P=0.021) and with 800 mg/ml of anatabine (Mann–Whitney U=0, Z=-2.309, P=0.021) and a significant inhibition of p65 NFkB phosphorylation was observed with 600 mg/ml of anatabine (Mann–Whitney U=1.0, Z=-2.021, P=0.043) and with 800 mg/ml of anatabine (Mann–Whitney U=0,Z=-2.309, P=0.021) PubMed:23178521

Annotations
Experimental Factor Ontology (EFO)
SH-SY5Y

a(CHEBI:Anatabine) decreases p(HGNC:STAT3, pmod(Ph)) View Subject | View Object

We observed that anatabine significantly suppressed the stimulation of p65 NFkB and STAT3 phosphorylation by LPS in microglia (Fig. 3) PubMed:23178521

a(CHEBI:Anatabine) decreases p(HGNC:STAT3, pmod(Ph)) View Subject | View Object

Kruskal–Wallis test revealed that doses of anatabine significantly suppressed both LPS induced STAT3 phosphorylation (H=15.658, df=4, P=0.005) and p65 NFkB phosphorylation (H=14.150, df=4, P=0.007) in human microglia PubMed:23178521

a(CHEBI:Anatabine) decreases p(HGNC:STAT3, pmod(Ph)) View Subject | View Object

A significant inhibition of STAT3 phosphorylation was observed with 10 mg/ml of anatabine (Mann–Whitney U=1, Z=-2.021, P=0.043), with 100 mg/ml of anatabine (Mann–Whitney U=0, Z=-2.309, P=0.021), with 300 mg/ml of anatabine (Mann–Whitney U=0, Z=-2.309, P=0.021) and with 600 mg/ml of anatabine (Mann–Whitney U=0, Z=-2.309, P=0.021) PubMed:23178521

a(CHEBI:Anatabine) decreases p(HGNC:STAT3, pmod(Ph)) View Subject | View Object

An inhibition of TNFa induced STAT3 (Mann–Whitney U=0, Z=-2.121, P=0.034), and p65 NFkB phosphorylation (Mann–Whitney U=0, Z=-2.121, P=0.034) was observed in these cells following the anatabine treatment (Fig. 4) suggesting that anatabine may also mediate its anti-inflammatory activity independently of nicotinic acetylcholine receptor expression PubMed:23178521

Annotations
Experimental Factor Ontology (EFO)
HEK293

a(CHEBI:Anatabine) decreases p(HGNC:STAT3, pmod(Ph)) View Subject | View Object

Anatabine appears to completely antagonize LPS induced STAT3 (Mann–Whitney U=0, Z=-3.077, P=0.002) and p65 NFkB phosphorylation (Mann–Whitney U=0, Z=-3.077, P=0.002) in human mononuclear cells PubMed:23178521

a(CHEBI:Anatabine) decreases p(HGNC:RELA, pmod(Ph)) View Subject | View Object

We observed that anatabine inhibits basal STAT3 phosphorylation levels (Mann– Whitney U=0, Z=-2.882, P=0.004) and reduces the induction of p65 NFkB phosphorylation by TNFa (Mann–Whitney U=0, Z=-2.882, P=0.004) within this 15 min time-frame (Fig. 1) PubMed:23178521

Annotations
Experimental Factor Ontology (EFO)
SH-SY5Y

a(CHEBI:Anatabine) decreases p(HGNC:RELA, pmod(Ph)) View Subject | View Object

Under these culture conditions, anatabine also inhibited both STAT3 and p65 NFkB phosphorylation induced by TNFa (Fig. 2) PubMed:23178521

Annotations
Experimental Factor Ontology (EFO)
SH-SY5Y

a(CHEBI:Anatabine) decreases p(HGNC:RELA, pmod(Ph)) View Subject | View Object

A significant inhibition of STAT3 phosphorylation was observed with 600 mg/ml of anatabine (Mann–Whitney U=0, Z=-2.309, P=0.021) and with 800 mg/ml of anatabine (Mann–Whitney U=0, Z=-2.309, P=0.021) and a significant inhibition of p65 NFkB phosphorylation was observed with 600 mg/ml of anatabine (Mann–Whitney U=1.0, Z=-2.021, P=0.043) and with 800 mg/ml of anatabine (Mann–Whitney U=0,Z=-2.309, P=0.021) PubMed:23178521

Annotations
Experimental Factor Ontology (EFO)
SH-SY5Y

a(CHEBI:Anatabine) decreases p(HGNC:RELA, pmod(Ph)) View Subject | View Object

We observed that anatabine significantly suppressed the stimulation of p65 NFkB and STAT3 phosphorylation by LPS in microglia (Fig. 3) PubMed:23178521

a(CHEBI:Anatabine) decreases p(HGNC:RELA, pmod(Ph)) View Subject | View Object

Kruskal–Wallis test revealed that doses of anatabine significantly suppressed both LPS induced STAT3 phosphorylation (H=15.658, df=4, P=0.005) and p65 NFkB phosphorylation (H=14.150, df=4, P=0.007) in human microglia PubMed:23178521

a(CHEBI:Anatabine) decreases p(HGNC:RELA, pmod(Ph)) View Subject | View Object

Similarly, LPS induced p65 NFkB phosphorylation in microglia was significantly inhibited with 10 mg/ml of anatabine (Mann–Whitney U=0, Z=-2.309, P=0.021), with 100 mg/ml of anatabine (Mann– Whitney U=0, Z=-2.309, P=0.021), with 300 mg/ml of anatabine (Mann–Whitney U=0, Z=-2.309, P=0.021) PubMed:23178521

a(CHEBI:Anatabine) decreases p(HGNC:RELA, pmod(Ph)) View Subject | View Object

An inhibition of TNFa induced STAT3 (Mann–Whitney U=0, Z=-2.121, P=0.034), and p65 NFkB phosphorylation (Mann–Whitney U=0, Z=-2.121, P=0.034) was observed in these cells following the anatabine treatment (Fig. 4) suggesting that anatabine may also mediate its anti-inflammatory activity independently of nicotinic acetylcholine receptor expression PubMed:23178521

Annotations
Experimental Factor Ontology (EFO)
HEK293

a(CHEBI:Anatabine) decreases p(HGNC:RELA, pmod(Ph)) View Subject | View Object

Anatabine appears to completely antagonize LPS induced STAT3 (Mann–Whitney U=0, Z=-3.077, P=0.002) and p65 NFkB phosphorylation (Mann–Whitney U=0, Z=-3.077, P=0.002) in human mononuclear cells PubMed:23178521

a(CHEBI:Anatabine) regulates bp(GO:"inflammatory response") View Subject | View Object

An inhibition of TNFa induced STAT3 (Mann–Whitney U=0, Z=-2.121, P=0.034), and p65 NFkB phosphorylation (Mann–Whitney U=0, Z=-2.121, P=0.034) was observed in these cells following the anatabine treatment (Fig. 4) suggesting that anatabine may also mediate its anti-inflammatory activity independently of nicotinic acetylcholine receptor expression PubMed:23178521

Annotations
Experimental Factor Ontology (EFO)
HEK293

a(CHEBI:Anatabine) decreases p(MGI:Stat3, pmod(Ph)) View Subject | View Object

Western-blot experiments revealed that LPS significantly stimulated of STAT3 phosphorylation in the spleen (Mann–Whitney U=0, Z=-2.309, P=0.021) (Fig. 8) and kidney (Mann–Whitney U=0, Z=-2.882, P=0.004) (data not shown) whereas anatabine significantly inhibited STAT3 phosphorylation in the spleen (Mann–Whitney U=1, Z=-2.021, P=0.043) and kidney (Mann– Whitney U=5, Z=-2.082, P=0.037) (data not shown) PubMed:23178521

a(CHEBI:Anatabine) decreases p(MGI:Stat3, pmod(Ph)) View Subject | View Object

A significant elevation of STAT3 phosphorylation was detected in the brain of Tg APPsw compared to their control littermates (Mann–Whitney U=1, Z=-3.767, p<0.001) and a significant reduction in STAT3 phosphorylation (Mann–Whitney U=8, Z=-2.066, p=0.039) was observed in the brain of Tg APPsw treated with anatabine compared to untreated Tg APPsw littermates (Fig. 10). PubMed:23178521

a(CHEBI:Anatabine) decreases p(MGI:Tnf) View Subject | View Object

Following 90 days of treatment with anatabine, a significant reduction in brain TNF-a (Mann–Whitney U=6, Z=-2.146, p=0.032) and in IL-6 (Mann–Whitney U=0, Z=-2.887, p=0.004) was observed in Tg APPsw mice compared to Tg APPsw that received regular drinking water (Fig. 9) PubMed:23178521

a(CHEBI:Anatabine) decreases p(MGI:Il6) View Subject | View Object

Following 90 days of treatment with anatabine, a significant reduction in brain TNF-a (Mann–Whitney U=6, Z=-2.146, p=0.032) and in IL-6 (Mann–Whitney U=0, Z=-2.887, p=0.004) was observed in Tg APPsw mice compared to Tg APPsw that received regular drinking water (Fig. 9) PubMed:23178521

a(CHEBI:Anatabine) decreases p(MGI:Tnf) View Subject | View Object

Anatabine appears to fully suppress IL-1b, INF-gamma and TNF-a elevation in the spleen of EAE mice (Fig. 2C). PubMed:23383175

a(CHEBI:Anatabine) decreases a(MESH:Cytokines) View Subject | View Object

This particular dosage was selected from a previous study showing that this dosage is efficient at lowering brain cytokine levels in a mouse model of Alzheimer’s disease displaying chronic neuroinflammation PubMed:23383175

a(CHEBI:Anatabine) negativeCorrelation path(MESH:Encephalomyelitis) View Subject | View Object

Clinical signs of EAE became apparent by day 6 following the immunization in the placebo group but were delayed to day 11 in the anatabine treatment group (Fig. 1A) PubMed:23383175

a(CHEBI:Anatabine) decreases path(MESH:Encephalomyelitis) View Subject | View Object

The average clinical severity of EAE was also significantly reduced by the anatabine treatment (Fig. 1B) PubMed:23383175

a(CHEBI:Anatabine) decreases path(MESH:Paralysis) View Subject | View Object

Importantly, approximately 70% of the mice in the placebo group developed hind-limb weakness or paralysis compared to only 20% in the anatabine treatment group (Fig. 1C) showing that the mice treated with anatabine displayed significantly milder disease symptoms than the placebo group PubMed:23383175

a(CHEBI:Anatabine) decreases path(HP:"Limb muscle weakness") View Subject | View Object

Importantly, approximately 70% of the mice in the placebo group developed hind-limb weakness or paralysis compared to only 20% in the anatabine treatment group (Fig. 1C) showing that the mice treated with anatabine displayed significantly milder disease symptoms than the placebo group PubMed:23383175

a(CHEBI:Anatabine) decreases p(MGI:Il1b) View Subject | View Object

However, anatabine significantly suppressed the production of IL-1b, IL-6 and IL-17A in the serum of EAE mice (Fig. 2B) but did not significantly impact IFN-gamma and TNF-alpha PubMed:23383175

a(CHEBI:Anatabine) decreases p(MGI:Il1b) View Subject | View Object

Anatabine appears to fully suppress IL-1b, INF-gamma and TNF-a elevation in the spleen of EAE mice (Fig. 2C). PubMed:23383175

a(CHEBI:Anatabine) decreases p(MGI:Il6) View Subject | View Object

However, anatabine significantly suppressed the production of IL-1b, IL-6 and IL-17A in the serum of EAE mice (Fig. 2B) but did not significantly impact IFN-gamma and TNF-alpha PubMed:23383175

a(CHEBI:Anatabine) decreases p(MGI:Il17a) View Subject | View Object

However, anatabine significantly suppressed the production of IL-1b, IL-6 and IL-17A in the serum of EAE mice (Fig. 2B) but did not significantly impact IFN-gamma and TNF-alpha PubMed:23383175

a(CHEBI:Anatabine) decreases p(MGI:Il17a) View Subject | View Object

However, a significant reduction in IL-17 was observed in the spleen of EAE anatabine treated mice compared to EAE placebo mice (Fig. 2C) PubMed:23383175

a(CHEBI:Anatabine) causesNoChange p(MGI:Ifng) View Subject | View Object

However, anatabine significantly suppressed the production of IL-1b, IL-6 and IL-17A in the serum of EAE mice (Fig. 2B) but did not significantly impact IFN-gamma and TNF-alpha PubMed:23383175

a(CHEBI:Anatabine) decreases p(MGI:Ifng) View Subject | View Object

Anatabine appears to fully suppress IL-1b, INF-gamma and TNF-a elevation in the spleen of EAE mice (Fig. 2C). PubMed:23383175

a(CHEBI:Anatabine) causesNoChange p(MGI:Tnf) View Subject | View Object

However, anatabine significantly suppressed the production of IL-1b, IL-6 and IL-17A in the serum of EAE mice (Fig. 2B) but did not significantly impact IFN-gamma and TNF-alpha PubMed:23383175

a(CHEBI:Anatabine) decreases p(MGI:Stat3, pmod(Ph)) View Subject | View Object

We have shown previously that anatabine prevents STAT3 and p65 NFkB phosphorylation in various cell types and suggested that anatabine impact cytokine production by this mechanism as both STAT3 and p65 NFkB are known to regulate cytokine production. PubMed:23383175

a(CHEBI:Anatabine) decreases p(MGI:Stat3, pmod(Ph)) View Subject | View Object

Interestingly, a significant increase in STAT3 phosphorylation was observed in the spleen of EAE mice compared to control non immunized mice and a significant decrease in STAT3 phosphorylation level was detected in EAE mice treated with anatabine (Fig. 3) PubMed:23383175

a(CHEBI:Anatabine) decreases p(MGI:Stat3, pmod(Ph)) View Subject | View Object

Additionally, we observed that anatabine significantly prevented STAT3 and p65 NFkB phosphorylation in brain homogenates of EAE mice (Fig. 4) PubMed:23383175

a(CHEBI:Anatabine) decreases p(MGI:Stat3, pmod(Ph)) View Subject | View Object

A reduction in the number of phosphorylated STAT3 immunoreactive cells was observed in the cerebral cortex of EAE mice treated with anatabine further confirming the data obtained by western-blotting using brain homogenates (Fig. 5) PubMed:23383175

a(CHEBI:Anatabine) decreases p(MGI:Stat3, pmod(Ph)) View Subject | View Object

Similarly, we observed an increased number of phosphorylated STAT3 immunopositive cells in the spinal cord of EAE mice compared to control non-immunized mice and a decreased number of phosphorylated STAT3 immunoreactive cells in EAE mice treated with anatabine (Fig. 6) showing overall that anatabine reduces STAT3 phosphorylation in the brain, spinal cord and spleen of EAE mice. PubMed:23383175

a(CHEBI:Anatabine) decreases p(MGI:Rela, pmod(Ph)) View Subject | View Object

We have shown previously that anatabine prevents STAT3 and p65 NFkB phosphorylation in various cell types and suggested that anatabine impact cytokine production by this mechanism as both STAT3 and p65 NFkB are known to regulate cytokine production. PubMed:23383175

a(CHEBI:Anatabine) decreases p(MGI:Rela, pmod(Ph)) View Subject | View Object

Additionally, we observed that anatabine significantly prevented STAT3 and p65 NFkB phosphorylation in brain homogenates of EAE mice (Fig. 4) PubMed:23383175

a(CHEBI:Anatabine) causesNoChange bp(HBP:Astrogliosis) View Subject | View Object

Overall, anatabine did not significantly impact EAE induced astrogliosis for the different areas of the brain examined (Fig. 7) PubMed:23383175

a(CHEBI:Anatabine) decreases bp(HBP:Astrogliosis) View Subject | View Object

A marked increase in GFAP immunostaining was also observed in the spinal cord of EAE mice and was significantly suppressed by the anatabine treatment showing that anatabine prevents astrogliosis in the spinal cord of EAE mice (Fig. 11) PubMed:23383175

a(CHEBI:Anatabine) decreases bp(HBP:Microgliosis) View Subject | View Object

Interestingly, a significant reduction in the number of IBa1 immunopositive microglial cells was found in the hippocampus and medulla of anatabine treated EAE mice (Fig. 8) PubMed:23383175

a(CHEBI:Anatabine) decreases tloc(a(MESH:Leukocytes), fromLoc(GO:"extracellular region"), toLoc(MESH:"Spinal Cord")) View Subject | View Object

Less cellular infiltration was observed in the spinal cord of anatabine treated mice compared to EAE placebo mice (Fig. 9) PubMed:23383175

a(CHEBI:Anatabine) decreases a(MESH:Microglia) View Subject | View Object

In addition, anatabine markedly decreased the Iba1 immunostaining in the spinal cord of EAE mice showing that anatabine reduces the infiltration of macrophage/ microglia in the spinal cord of EAE mice (Fig. 10) PubMed:23383175

a(CHEBI:Anatabine) decreases tloc(a(MESH:Microglia), fromLoc(GO:"extracellular region"), toLoc(MESH:"Spinal Cord")) View Subject | View Object

In addition, anatabine markedly decreased the Iba1 immunostaining in the spinal cord of EAE mice showing that anatabine reduces the infiltration of macrophage/ microglia in the spinal cord of EAE mice (Fig. 10) PubMed:23383175

a(CHEBI:Anatabine) decreases tloc(a(MESH:Macrophages), fromLoc(GO:"extracellular region"), toLoc(MESH:"Spinal Cord")) View Subject | View Object

In addition, anatabine markedly decreased the Iba1 immunostaining in the spinal cord of EAE mice showing that anatabine reduces the infiltration of macrophage/ microglia in the spinal cord of EAE mice (Fig. 10) PubMed:23383175

a(CHEBI:Anatabine) positiveCorrelation a(GO:"myelin sheath") View Subject | View Object

Interestingly, anatabine significantly prevented demyelination associated with EAE in the spinal cord (Fig. 12) PubMed:23383175

a(CHEBI:Anatabine) decreases p(HGNC:MAPT, pmod(Ph, Ser, 396), pmod(Ph, Ser, 404)) View Subject | View Object

In both the detergent soluble and insoluble fractions of the brain and spinal cord homogenates of Tg Tau P301S mice, we found that tau phosphorylation was significantly reduced (T-tests, P<0.05) by the anatabine treatment for all the AD phosphorylated epitopes tested (Figure 6) DOI:10.4172/2168-975X.1000126

a(CHEBI:Anatabine) decreases p(HGNC:MAPT, pmod(Ph, Ser, 202)) View Subject | View Object

In both the detergent soluble and insoluble fractions of the brain and spinal cord homogenates of Tg Tau P301S mice, we found that tau phosphorylation was significantly reduced (T-tests, P<0.05) by the anatabine treatment for all the AD phosphorylated epitopes tested (Figure 6) DOI:10.4172/2168-975X.1000126

a(CHEBI:Anatabine) decreases p(HGNC:MAPT, pmod(Ph, Thr, 231)) View Subject | View Object

In both the detergent soluble and insoluble fractions of the brain and spinal cord homogenates of Tg Tau P301S mice, we found that tau phosphorylation was significantly reduced (T-tests, P<0.05) by the anatabine treatment for all the AD phosphorylated epitopes tested (Figure 6) DOI:10.4172/2168-975X.1000126

a(CHEBI:Anatabine) decreases a(GO:"neurofibrillary tangle") View Subject | View Object

Moreover, a significant reduction in MC1-immunoreactivity (P<0.05) was observed in the detergent soluble and insoluble fractions of brain and spinal cord homogenates from Tg Tau P301S mice treated with anatabine showing that anatabine prevents the formation of pathological tau conformers (Figure 7). DOI:10.4172/2168-975X.1000126

a(CHEBI:Anatabine) decreases a(HBP:"Tau oligomers") View Subject | View Object

Additionally, a significant reduction (P<0.05) in tau oligomers levels (TOC1 immunopositive) was detected both in the brain and the spinal cord of Tg Tau P301S treated with anatabine using dot-blots (Figure 8). DOI:10.4172/2168-975X.1000126

a(CHEBI:Anatabine) decreases a(HBP:"Tau oligomers") View Subject | View Object

We observed that anatabine significantly prevented the formation of MC1-positive tau oligomers (Figure 9) by western-blots in both the brain and the spinal cord of Tg Tau P301S mice (T-tests, P<0.05) further confirming the data obtained with the dot-blots DOI:10.4172/2168-975X.1000126

a(CHEBI:Anatabine) decreases bp(HBP:Microgliosis) View Subject | View Object

A significant reduction in Iba1 immunoreactivity was observed both in the brain (T-test, P<0.01) and spinal cord (T-test, P<0.01) homogenates of Tg Tau P301S mice treated with anatabine. Figure 10. DOI:10.4172/2168-975X.1000126

a(CHEBI:Anatabine) increases p(HGNC:GSK3B, pmod(Ph, Ser, 9)) View Subject | View Object

We found a significant increase in brain AKT Ser473 phosphorylation (T-test, P<0.001) and GSK3β Ser9 phosphorylation (T-test, P<0.001) in Tg Tau P301S mice treated with anatabine. Figure 11. DOI:10.4172/2168-975X.1000126

a(CHEBI:Anatabine) increases p(FPLX:AKT, pmod(Ph, Ser, 473)) View Subject | View Object

We found a significant increase in brain AKT Ser473 phosphorylation (T-test, P<0.001) and GSK3β Ser9 phosphorylation (T-test, P<0.001) in Tg Tau P301S mice treated with anatabine. Figure 11. DOI:10.4172/2168-975X.1000126

a(CHEBI:Anatabine) decreases act(p(FPLX:NFkappaB)) View Subject | View Object

Furthermore, anatabine has been recently shown to inhibit nuclear factor-kB(NF-kB) activation and reduce neuroinflammation in a mouse model of Alzheimer disease (15). PubMed:22807490

a(CHEBI:Anatabine) decreases bp(GO:"inflammatory response") View Subject | View Object

Furthermore, anatabine has been recently shown to inhibit nuclear factor-kB(NF-kB) activation and reduce neuroinflammation in a mouse model of Alzheimer disease (15). PubMed:22807490

a(CHEBI:Anatabine) decreases path(MESH:"Thyroiditis, Autoimmune") View Subject | View Object

Anatabine significantly decreased the severity of EAT induced with our standard induction protocol. PubMed:22807490

a(CHEBI:Anatabine) decreases a(MESH:Thyroglobulin) View Subject | View Object

Anatabine treated mice developed lower levels of thyroglobulin antibodies than controls on d 14 (P  0.029) and d 21 (P  0.045) (Fig. 2A), suggesting that anatabine atten- uates the thyroid-specific autoimmune response in- duced by thyroglobulin immunization. PubMed:22807490

a(CHEBI:Anatabine) decreases p(HGNC:IL1R2) View Subject | View Object

Anatabine suppressed the EAT-mediated increase of IL-1 receptor type 2 (IL-1R2, Figure 3A) and IL-18 (Fig. 3B), restoring their expression to levels similar to those seen in normal unimmunized thyroids. PubMed:22807490

a(CHEBI:Anatabine) decreases p(HGNC:NOS2) View Subject | View Object

Anatabine suppressed in a dose- dependent manner the increase of iNOS and COX2 in- duced by interferon-g (Fig.4),confirming in vitro its antiinflammatory properties. The effect seen with inter- feron-g was also seen when macrophages were stimulated with lipopolysaccharide (Supplemental Fig. 1). PubMed:22807490

a(CHEBI:Anatabine) decreases p(HGNC:PTGS2) View Subject | View Object

Anatabine suppressed in a dose- dependent manner the increase of iNOS and COX2 in- duced by interferon-g (Fig.4),confirming in vitro its antiinflammatory properties. The effect seen with inter- feron-g was also seen when macrophages were stimulated with lipopolysaccharide (Supplemental Fig. 1). PubMed:22807490

a(CHEBI:Anatabine) decreases bp(GO:"macrophage activation") View Subject | View Object

Anatabine suppressed in a dose- dependent manner the increase of iNOS and COX2 in- duced by interferon-g (Fig.4),confirming in vitro its antiinflammatory properties. The effect seen with inter- feron-g was also seen when macrophages were stimulated with lipopolysaccharide (Supplemental Fig. 1). PubMed:22807490

a(CHEBI:Anatabine) increases bp(GO:"motor behavior") View Subject | View Object

In addition, Tg Tau P301S mice treated with anatabine showed an increased latency to fall (T-test, P<0.05) from an accelerating rotarod apparatus compared to Tg Tau P301S mice receiving regular drinking water (Figure 2) showing improved motor coordination. DOI:10.4172/2168-975X.1000126

a(CHEBI:Anatabine) decreases path(MESH:Anxiety) View Subject | View Object

Tg Tau P301S mice treated with anatabine spent significantly more time (T-test, P<0.05) in the open arms of the elevated plus maze than placebo Tg Tau P301S mice (Figure 3). DOI:10.4172/2168-975X.1000126

a(CHEBI:Anatabine) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

Anatabine dose dependently inhibited Aβ1–40 and Aβ1–42 with an approximate half maximal inhibitory concentration of 640 μg/ml for both Aβ1–40 and Aβ1–42 (Fig. 2). PubMed:21958873

Annotations
Experimental Factor Ontology (EFO)
CHO cell

a(CHEBI:Anatabine) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

We then tested the impact of anatabine on sAPPα and sAPPβ production using 7W CHO cells and observed that anatabine inhibits sAPPβ secretion without impacting sAPPα suggesting that anatabine is preventing the β-cleavage of APP (Fig. 4). PubMed:21958873

Annotations
Experimental Factor Ontology (EFO)
CHO cell

a(CHEBI:Anatabine) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

A significant reduction in the accumulation of brain soluble and insoluble Aβ1–40 and Aβ1–42 was observed following four days of treatment with 2 mg/kg of anatabine (Fig. 9). PubMed:21958873

a(CHEBI:Anatabine) decreases a(CHEBI:"amyloid-beta polypeptide 40") View Subject | View Object

Anatabine dose dependently inhibited Aβ1–40 and Aβ1–42 with an approximate half maximal inhibitory concentration of 640 μg/ml for both Aβ1–40 and Aβ1–42 (Fig. 2). PubMed:21958873

Annotations
Experimental Factor Ontology (EFO)
CHO cell

a(CHEBI:Anatabine) decreases a(CHEBI:"amyloid-beta polypeptide 40") View Subject | View Object

We then tested the impact of anatabine on sAPPα and sAPPβ production using 7W CHO cells and observed that anatabine inhibits sAPPβ secretion without impacting sAPPα suggesting that anatabine is preventing the β-cleavage of APP (Fig. 4). PubMed:21958873

Annotations
Experimental Factor Ontology (EFO)
CHO cell

a(CHEBI:Anatabine) decreases a(CHEBI:"amyloid-beta polypeptide 40") View Subject | View Object

A significant reduction in the accumulation of brain soluble and insoluble Aβ1–40 and Aβ1–42 was observed following four days of treatment with 2 mg/kg of anatabine (Fig. 9). PubMed:21958873

a(CHEBI:Anatabine) causesNoChange sec(p(HGNC:LDHA)) View Subject | View Object

No cytotoxicity was observed (as measured by the release of lactate dehydrogenase in the culture medium of 7W CHO cells) with the dose range of anatabine tested (data not shown). PubMed:21958873

Annotations
Experimental Factor Ontology (EFO)
CHO cell

a(CHEBI:Anatabine) decreases a(CHEBI:"amyloid-beta") View Subject | View Object

Contrary to anatabine, (−)-nicotine and other nicotinic acetylcholine receptors agonists and antagonists do not inhibit Aβ production by 7W CHO cells (Fig. 3). PubMed:21958873

Annotations
Experimental Factor Ontology (EFO)
CHO cell

a(CHEBI:Anatabine) decreases a(CHEBI:"amyloid-beta") View Subject | View Object

In addition, a significant decreased in plasma Aβ levels was observed in mice treated with anatabine consistent with an inhibition of Aβ production (Fig. 10). PubMed:21958873

a(CHEBI:Anatabine) decreases sec(p(HBP:"sAPP-beta")) View Subject | View Object

We then tested the impact of anatabine on sAPPα and sAPPβ production using 7W CHO cells and observed that anatabine inhibits sAPPβ secretion without impacting sAPPα suggesting that anatabine is preventing the β-cleavage of APP (Fig. 4). PubMed:21958873

Annotations
Experimental Factor Ontology (EFO)
CHO cell

a(CHEBI:Anatabine) causesNoChange sec(p(HBP:"sAPP-alpha")) View Subject | View Object

We then tested the impact of anatabine on sAPPα and sAPPβ production using 7W CHO cells and observed that anatabine inhibits sAPPβ secretion without impacting sAPPα suggesting that anatabine is preventing the β-cleavage of APP (Fig. 4). PubMed:21958873

Annotations
Experimental Factor Ontology (EFO)
CHO cell

a(CHEBI:Anatabine) decreases act(complex(GO:"NF-kappaB complex")) View Subject | View Object

We observed that anatabine dose dependently inhibited NFκB activation by TNFα in HEK293 NFκB luciferase reporter cells (Fig. 5) whereas nicotine was ineffective PubMed:21958873

Annotations
Experimental Factor Ontology (EFO)
CHO cell

a(CHEBI:Anatabine) decreases act(complex(GO:"NF-kappaB complex")) View Subject | View Object

In addition, an inhibition of p65 NFκB phosphorylation was observed following treatment with anatabine in 7W CHO overexpressing APP (Fig. 6A), in HEK293 (Fig. 6B) and in human neuronal like SH-SY5Y cells (Fig. 6C) showing that anatabine can prevent NFκB activation in various cell lines. PubMed:21958873

Annotations
Experimental Factor Ontology (EFO)
CHO cell
Experimental Factor Ontology (EFO)
SH-SY5Y

a(CHEBI:Anatabine) increases path(MESH:"Spatial Learning") View Subject | View Object

Compared to age matched wild-type mice, 32 week-old Tg Tau P301S mice did not show spatial learning impairment in the RAWM (data not shown) DOI:10.4172/2168-975X.1000126

a(CHEBI:Anatabine) decreases act(complex(GO:"NF-kappaB complex")) View Subject | View Object

Since BACE-1 transcription is regulated by NFκB (Buggia-Prevot et al., 2008) and since we have shown that anatabine inhibits NFκB activation, we investigated the effect of anatabine on BACE-1 transcription using human neuronal like SH-SY5Y cells PubMed:21958873

a(CHEBI:Anatabine) decreases act(complex(GO:"NF-kappaB complex")) View Subject | View Object

Since anatabine lowers NFκB activation in vitro, we explored the possibility that anatabine may affect the level of C-reactive protein (CRP) whose expression is NFκB dependent (Karlsen et al., 2010; Yang et al.,2010). PubMed:21958873

a(CHEBI:Anatabine) decreases p(HGNC:RELA, pmod(Ph)) View Subject | View Object

In addition, an inhibition of p65 NFκB phosphorylation was observed following treatment with anatabine in 7W CHO overexpressing APP (Fig. 6A), in HEK293 (Fig. 6B) and in human neuronal like SH-SY5Y cells (Fig. 6C) showing that anatabine can prevent NFκB activation in various cell lines. PubMed:21958873

Annotations
Experimental Factor Ontology (EFO)
CHO cell
Experimental Factor Ontology (EFO)
SH-SY5Y

a(CHEBI:Anatabine) decreases r(HGNC:BACE1) View Subject | View Object

As expected, TNFα greatly stimulated BACE-1 transcription whereas anatabine fully prevented the increase in BACE-1 mRNA levels induced by TNFα (Fig. 7A). PubMed:21958873

Annotations
Experimental Factor Ontology (EFO)
SH-SY5Y

a(CHEBI:Anatabine) decreases p(HGNC:BACE1) View Subject | View Object

Following 24 h of treatment, a dose dependent inhibition of BACE-1 protein levels was observed with anatabine (Fig. 7B) PubMed:21958873

Annotations
Experimental Factor Ontology (EFO)
SH-SY5Y

a(CHEBI:Anatabine) decreases p(HGNC:CRP) View Subject | View Object

A statistically significant reduction in plasma CRP levels was observed following the 2 mg/kg treatment with anatabine showing that at this dosage anatabine displays an anti-inflammatory activity in vivo (Fig. 11). PubMed:21958873

a(CHEBI:Anatabine) decreases path(MESH:Paralysis) View Subject | View Object

During the time course of the treatment (40 days), 25% of Tg Tau P301S placebo mice became paralyzed (3 out of 12) whereas none (0 out of 11) in the anatabine treatment group developed paralysis during the study duration (Figure 1) DOI:10.4172/2168-975X.1000126

a(CHEBI:Anatabine) increases bp(GO:"motor behavior") View Subject | View Object

Approximately 44 % (4 out of 9 non-paralyzed mice) of the placebo group (33 week-old mice) elicited an abnormal hind-limb extension reflex when suspended by the tail compared to 18% (2 out of 11) of Tg Tau P301S mice treated with anatabine (Figure 1). DOI:10.4172/2168-975X.1000126

a(CHEBI:Anatabine) decreases bp(GO:"inflammatory response") View Subject | View Object

We have shown previously that anatabine displays some anti-inflammatory properties and reduces microgliosis and tau phosphorylation in a pure mouse model of tauopathy. PubMed:26010758

a(CHEBI:Anatabine) decreases bp(GO:"inflammatory response") View Subject | View Object

We have shown previously that anatabine displays some anti-inflammatory properties by reducing the activation of NFκB and STAT3 [17,18]. PubMed:26010758

a(CHEBI:Anatabine) decreases bp(GO:"inflammatory response") View Subject | View Object

We have previously shown that anatabine inhibits STAT3 and NFκB activation [18] resulting in decreased neuroinflammation in a mouse model of multiple sclerosis. PubMed:26010758

a(CHEBI:Anatabine) decreases path(MESH:Gliosis) View Subject | View Object

We have shown previously that anatabine displays some anti-inflammatory properties and reduces microgliosis and tau phosphorylation in a pure mouse model of tauopathy. PubMed:26010758

a(CHEBI:Anatabine) decreases p(HGNC:MAPT, pmod(Ph)) View Subject | View Object

We have shown previously that anatabine displays some anti-inflammatory properties and reduces microgliosis and tau phosphorylation in a pure mouse model of tauopathy. PubMed:26010758

a(CHEBI:Anatabine) increases act(p(HGNC:CHRNA7)) View Subject | View Object

Anatabine has a chemical structure closely related to nicotine and is a full agonist of α7 and α4β2 nicotinic acetylcholine receptors (nAChR) but is a more potent α7 nAChR agonist than nicotine [15,16]. PubMed:26010758

a(CHEBI:Anatabine) decreases act(p(FPLX:NFkappaB)) View Subject | View Object

We have shown previously that anatabine displays some anti-inflammatory properties by reducing the activation of NFκB and STAT3 [17,18]. PubMed:26010758

a(CHEBI:Anatabine) decreases act(p(FPLX:NFkappaB)) View Subject | View Object

We have previously shown that anatabine inhibits STAT3 and NFκB activation [18] resulting in decreased neuroinflammation in a mouse model of multiple sclerosis. PubMed:26010758

a(CHEBI:Anatabine) decreases act(p(FPLX:NFkappaB)) View Subject | View Object

Interestingly, we found a significant reduction in the expression of amyloid plaque associated phospho-p65 NFκB immunopositive cells in Tg PS1/APPswe mice treated with anatabine at either 10 or 20 mg/Kg/Day (Fig 7B) showing that anatabine prevents NFκB activation in the brain of Tg PS1/APPswe mice. PubMed:26010758

a(CHEBI:Anatabine) decreases act(p(HGNC:STAT3)) View Subject | View Object

We have shown previously that anatabine displays some anti-inflammatory properties by reducing the activation of NFκB and STAT3 [17,18]. PubMed:26010758

a(CHEBI:Anatabine) decreases act(p(HGNC:STAT3)) View Subject | View Object

We have previously shown that anatabine inhibits STAT3 and NFκB activation [18] resulting in decreased neuroinflammation in a mouse model of multiple sclerosis. PubMed:26010758

a(CHEBI:Anatabine) decreases act(p(HGNC:STAT3)) View Subject | View Object

A significant reduction in STAT3 phosphorylation was observed in the hippocampus and cortex of Tg PS1/APPswe mice treated with 10 or 20 mg/Kg/Day of anatabine compared to Tg PS1/APPswe receiving regular drinking water (Fig 6B) showing that anatabine prevents STAT3 activation in the brain of Tg PS1/APPswe mice. PubMed:26010758

a(CHEBI:Anatabine) decreases bp(GO:locomotion) View Subject | View Object

Interestingly, the hyper- active behavior of Tg PS1/APPswe mice was suppressed with the anatabine treatment at a dos- age of 20 mg/Kg/Day (Fig 2B and 2C). PubMed:26010758

a(CHEBI:Anatabine) increases path(MESH:Anxiety) View Subject | View Object

The disinhibition affecting Tg PS1/APPswe mice was suppressed following treatment with anatabine at a dosage of either 10 or 20 mg/Kg/Day at both the time points (Figs 2D and 3D). PubMed:26010758

a(CHEBI:Anatabine) increases path(MESH:"Interpersonal Relations") View Subject | View Object

Unlike wild-type mice, Tg PS1/APPswe mice elicited social interaction deficits and spent an equal amount of time in the chamber containing the empty cage or the chamber containing the unfamiliar (Stranger 1) mouse (Fig 4A). Anatabine at a dosage of 20mg/Kg/Day restored sociability in Tg PS1/APPswe mice as Tg PS1/APPswe mice treated with anatabine spent significantly more time in the chamber containing the unfamiliar mouse (Stranger 1) and less time in the chamber containing the empty cage (Fig 4B). PubMed:26010758

a(CHEBI:Anatabine) decreases p(HGNC:AIF1) View Subject | View Object

Interestingly, Tg PS1/APPswe mice treated with anata- bine at a dosage of 20 mg/Kg/Day, but not 10mg/Kg/day showed a significant reduction in Iba- 1 burden in the hippocampus compared to untreated Tg PS1/APPswe mice (Fig 5A and 5B), suggesting that anatabine suppresses microgliosis in the brain of Tg PS1/APPswe mice. PubMed:26010758

a(CHEBI:Anatabine) decreases bp(GO:"microglial cell activation") View Subject | View Object

Interestingly, Tg PS1/APPswe mice treated with anata- bine at a dosage of 20 mg/Kg/Day, but not 10mg/Kg/day showed a significant reduction in Iba- 1 burden in the hippocampus compared to untreated Tg PS1/APPswe mice (Fig 5A and 5B), suggesting that anatabine suppresses microgliosis in the brain of Tg PS1/APPswe mice. PubMed:26010758

a(CHEBI:Anatabine) decreases p(HGNC:PTPRC) View Subject | View Object

However, we observed a significant reduction in CD45 immunopositive microglia/macrophage in Tg PS1/APPswe mice receiving anatabine at a dosage of 10 and 20 mg/Kg/Day compared to Tg PS1/APPswe mice receiving regular drink- ing water (Fig 5C and 5D). PubMed:26010758

a(CHEBI:Anatabine) decreases p(HGNC:STAT3, pmod(Ph)) View Subject | View Object

A significant reduction in STAT3 phosphorylation was observed in the hippocampus and cortex of Tg PS1/APPswe mice treated with 10 or 20 mg/Kg/Day of anatabine compared to Tg PS1/APPswe receiving regular drinking water (Fig 6B) showing that anatabine prevents STAT3 activation in the brain of Tg PS1/APPswe mice. PubMed:26010758

a(CHEBI:Anatabine) decreases p(FPLX:NFkappaB, pmod(Ph, Ser, 536)) View Subject | View Object

Interestingly, we found a significant reduction in the expression of amyloid plaque associated phospho-p65 NFκB immunopositive cells in Tg PS1/APPswe mice treated with anatabine at either 10 or 20 mg/Kg/Day (Fig 7B) showing that anatabine prevents NFκB activation in the brain of Tg PS1/APPswe mice. PubMed:26010758

a(CHEBI:Anatabine) decreases a(CHEBI:"amyloid-beta") View Subject | View Object

We observed that anatabine reduces brain Aβ burden both in the cortex and the hippocampus of Tg PS1/APPswe mice using immunostaining with the antibody 4G8 which recognizes Aβ (Fig 8A and 8B). PubMed:26010758

a(CHEBI:Anatabine) decreases r(HGNC:BACE1) View Subject | View Object

Additionally, we found that Bace1 mRNA expression is significantly increased in the brain of Tg PS1/APPswe mice compared to wild- type littermates, whereas a significant reduction in Bace1 mRNA levels is observed in Tg PS1/ APPswe receiving 20 mg/Kg/Day of anatabine in their drinking water showing that at this dosage anatabine can mitigate the upregulation of Bace1 expression in Tg PS1/APPswe mice (Fig 9). PubMed:26010758

a(CHEBI:Anatabine) decreases r(HGNC:PTGS2) View Subject | View Object

We found a significant reduction in Cox-2 mRNA expression in Tg PS1/ APPswe mice treated with anatabine at a dosage of 20 mg/Kg/Day (Fig 10). PubMed:26010758

a(CHEBI:Anatabine) decreases r(HGNC:NOS2) View Subject | View Object

A dose dependent suppression of iNOS transcription was observed in Tg PS1/APPswe mice treated with anata- bine at a dosage of 10 or 20 mg/Kg/Day compared to untreated Tg PS1/APPswe mice (Fig 10). PubMed:26010758

a(CHEBI:Anatabine) decreases act(p(FPLX:NFkappaB)) View Subject | View Object

Anatabine lowered NF-B activation by inhibiting A production in vitro [195]. PubMed:29179999

a(CHEBI:Anatabine) decreases a(CHEBI:"amyloid-beta") View Subject | View Object

Anatabine lowered NF-B activation by inhibiting A production in vitro [195]. PubMed:29179999

a(CHEBI:Anatabine) decreases a(CHEBI:"amyloid-beta polypeptide 40") View Subject | View Object

It con-siderably lowered the expression of A 1-40 and A 1-42 in an AD transgenic mouse [195]. PubMed:29179999

a(CHEBI:Anatabine) decreases a(CHEBI:"amyloid-beta polypeptide 42") View Subject | View Object

It con-siderably lowered the expression of A 1-40 and A 1-42 in an AD transgenic mouse [195]. PubMed:29179999

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BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.