INT159058

Context Info Confidence 0.37 First Reported 2008 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 3 Total Number 11 Disease Relevance 2.93 Pain Relevance 1.60

extracellular region (Omd) cell adhesion (Omd) proteinaceous extracellular matrix (Omd)

Anatomy Link Frequency plasma 2 striatum 2 central nervous system 1 Omd (Rattus norvegicus)

Pain Link Frequency Relevance Heat Catechol-O-methyltransferase 58 99.98 Chronic pancreatitis 5 99.84 Bioavailability 60 98.84 Central nervous system 27 98.40 Dopamine 145 94.96 Catecholamine 46 83.84 Potency 27 75.80 Glutamate 171 64.56 glial activation 9 14.08 Hippocampus 36 7.20

Disease Link Frequency Relevance Heat Pancreatitis 5 99.84 Osteoporosis 2 96.80 Toxicity 9 95.84 Disease 260 95.76 Stress 110 89.16 Dyskinesias 31 82.04 Death 81 80.40 Overactive Bladder 9 78.12 Heart Rate Under Development 9 76.56 Alzheimer's Dementia 9 72.80

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Influence of chronic pancreatitis to the reduce of OMD was proved, especially in the patients with prolonged desease, analysis of the osteoporosis and osteopenia localization was performed in the patients with chronic pancreatitis.

Negative_regulation (reduce) of OMD associated with osteoporosis and chronic pancreatitis

1) Confidence 0.37 Published 2008 Journal Eksp Klin Gastroenterol Section Abstract Doc Link 19334441 Disease Relevance 0.65 Pain Relevance 0.46

When normal rats (treated with L-DOPA + carbidopa) were given an oral administration of EGCG (at 400 mg/kg), their 3-OMD levels in circulation and striatum were reduced by approximately 30%, clearly reflecting an in vivo inhibition of L-DOPA methylation.

Negative_regulation (reduced) of 3-OMD in striatum

2) Confidence 0.03 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2916818 Disease Relevance 0 Pain Relevance 0.07

Under this experimental condition, the plasma L-DOPA level was not significantly affected by oral administration of 100 or 400 mg/kg EGCG (Figure 5A), whereas a modest decrease in plasma 3-OMD level was observed in animals treated with 400 mg/kg EGCG, but not in animals treated with 100 mg/kg EGCG (Figure 5B).

Negative_regulation (decrease) of 3-OMD in plasma

3) Confidence 0.03 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2916818 Disease Relevance 0 Pain Relevance 0.08

The significant reduction of 3-OMD by EGCG may increase L-DOPA bioavailability in the central nervous system and particularly, reduce potential cytotoxicity associated with elevated levels of 3-OMD.

Negative_regulation (reduction) of 3-OMD in central nervous system associated with central nervous system and bioavailability

4) Confidence 0.03 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2916818 Disease Relevance 0.38 Pain Relevance 0.25

Our observation of a significant reduction in the striatal 3-OMD level in EGCG-treated rats is thought to be due to EGCG's direct inhibition of the central COMT-mediated L-DOPA methylation.

Negative_regulation (reduction) of 3-OMD

5) Confidence 0.03 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2916818 Disease Relevance 0.35 Pain Relevance 0.16

Similarly, while the striatal 3-OMD level was significantly reduced in animals co-treated with 400 mg/kg EGCG at both 2 and 6 h after L-DOPA/carbidopa administration, its level was not changed in animals co-treated with 100 mg/kg EGCG (Figure 5D).

Negative_regulation (reduced) of 3-OMD

6) Confidence 0.03 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2916818 Disease Relevance 0.31 Pain Relevance 0.15

It is of interest to point out that the reduction in striatal 3-OMD level may aid in reducing the side effects associated with the long-term L-DOPA/carbidopa therapy.

Negative_regulation (reduction) of 3-OMD

7) Confidence 0.03 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2916818 Disease Relevance 0.36 Pain Relevance 0.07

Notably, our observation of a strong reduction of 3-OMD level but a lack of meaningful increase in L-DOPA plasma concentration in rats treated with L-DOPA + carbidopa + EGCG was similar to the earlier observations with tolcapone or entacapone in rats [28]–[31] or human subjects [32]–[34] that were also treated with L-DOPA + carbidopa.

Negative_regulation (reduction) of 3-OMD in plasma

8) Confidence 0.03 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2916818 Disease Relevance 0 Pain Relevance 0.06

For instance, it was observed that while tolcapone or entacapone at relatively lower doses (3 and 7.5 mg/kg) effectively reduced the circulating and striatal levels of 3-OMD in normal rats co-treated with L-DOPA + carbidopa, their effect on the circulating and striatal L-DOPA levels was much smaller [28], [31], as seen in the present study with EGCG.

Negative_regulation (reduced) of 3-OMD

9) Confidence 0.02 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2916818 Disease Relevance 0.07 Pain Relevance 0.10

Based on these considerations, it is suggested that the ability of EGCG to markedly reduce 3-OMD levels in the periphery and particularly in the striatum would be beneficial for reducing the neuronal toxicity associated with high levels of 3-OMD.

Negative_regulation (reduce) of 3-OMD in striatum associated with toxicity

10) Confidence 0.02 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2916818 Disease Relevance 0.71 Pain Relevance 0

COMT inhibition and 3-OMD metabolism

Negative_regulation (inhibition) of 3-OMD associated with catechol-o-methyltransferase

11) Confidence 0.01 Published 2009 Journal Patient Prefer Adherence Section Body Doc Link PMC2778405 Disease Relevance 0.09 Pain Relevance 0.19

General Comments

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