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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2001-8-23
pubmed:abstractText
We have investigated biochemical mechanisms that may underlie the antidepressant effects of Hypericum LI 160. We found that LI 160 inhibits uptake of serotonin and norepinephrine in cultures of rat cortical astrocytes. Observed differences in the kinetic parameters Km and Vmax as well as in the recovery of uptake after removal of Hypericum indicates that LI 160 does not affect serotonin and norepinephrine transport in the same manner. This suggests that multiple components of the extract can mediate inhibition of these neurotransmitter transporters. Hypericum LI 160 also inhibits serotonin uptake in neuronal cultures from serotonergic-rich raphe nuclei; concentration-response studies indicate LI 160 is 25 times more potent in terms of inhibition of serotonin uptake in neurons than in astrocytes. In addition, Hypericum LI 160 inhibits norepinephrine uptake in SK-N-SH cells, a human neuroblastoma cell line enriched in norepinephrine transporters. A chemical constituent of LI 160, hyperforin, is about 10 to 20 times more potent than LI 160 in inhibiting neurotransmitter uptake in astrocytes and neuronal cells; this finding is consistent with the observation that hyperforin comprises 5% of LI 160 extracts. As several weeks are needed to achieve a clinical response with antidepressants, we have also investigated whether Hypericum LI 160 affects biochemical mechanisms that underlie long-term changes such as gene expression. We found that LI 160 stimulates a sustained activation of extracellular signal regulated protein kinase (ERK), a key component of a signal transduction pathway involved in gene expression. Taken together, our findings suggest that Hypericum LI 160 can affect rapidly-acting as well as slower-developing, long-term biochemical mechanisms related to depressive disorders.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0176-3679
pubmed:author
pubmed:issnType
Print
pubmed:volume
34 Suppl 1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
S103-7
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Biochemical mechanisms of action of Hypericum LI 160 in glial and neuronal cells: inhibition of neurotransmitter uptake and stimulation of extracellular signal regulated protein kinase.
pubmed:affiliation
Miami VA Medical Center, and Department of Pathology, University of Miami School of Medicine, Florida, USA. jneary@med.miami.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Review, Research Support, Non-U.S. Gov't