| Description: |
Harmine is a natural dual-specificity tyrosine phosphorylation-regulated kinase ((DYRK)) inhibitor with neuroprotective, anticancer and anti-inflammatory activities. It regulates PPARγ expression through inhibition of the Wnt signaling pathway, it also selectively binds to MAO-A and reversibly inhibits monoamine oxidase A (MAO-A) but not the variant MAO-B. Harmine is able to induce beta cell proliferation, increase islet mass and improve glycemic control. Harmine induces apoptosis and inhibits proliferation, migration and invasion of human gastric cancer cells, which may be mediated by down-regulation of COX-2 expression.
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| Targets: |
DYRK | COX | Bcl-2/Bax | MMP(e.g.TIMP) | Wnt | PPARγ | MAO-A | MAO-B |
| In vitro: |
| Expert Opin Drug Deliv. 2014 Jun;11(6):843-54. | | Novel self-assembled micelles based on palmitoyl-trimethyl-chitosan for efficient delivery of harmine to liver cancer.[Pubmed: 24655139] | Polymeric micelles is a safe and effective delivery system, which belong to the targeted delivery system (TDS). An anticancer drug, harmine(HM) is a hydrophobic drug with much adverse effects when used for treatment of liver cancer. Chitosan (CS) is a polysaccharide and can be modified to be an amphiphilic polmer which could self-assemble into micelles and be applied for delivery of hydrophobic drugs.
To synthesize three kinds of novel biodegradable polymers, designated as palmitoyl-trimethyl-CS (TPCS)1, TPCS2 and Lac-TPCS2, and investigate their efficiency and mechanism of delivery HM to liver tumors in vitro and in viro.
METHODS AND RESULTS:
The self-assembled micelles presented satisfactory particle size (～ 200 nm) and drug release characteristics in vitro. It's proved that Lac-TPCS2/HM may enter HepG2 cell through endocytosis. Antitumor experiments in vivo revealed that Lac-TPCS2/HM could significantly inhibit tumor growth and extend the lifetime of mice bearing H22 tumors after intravenous administration. Subsequently in vivo near-infrared fluorescence imaging results demonstrated a satisfactory liver tumor-targeting effect of Lac-TPCS2/HM.
CONCLUSIONS:
Three novel polymers hold great potential in the development of nanomedicine for treatment of liver tumors, in particular Lac-TPCS2 exhibits the greatest antitumor potential through active target effect. |
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| In vivo: |
| Neurosci Lett. 2014 Nov 7;583:32-6. | | Harmine mediated neuroprotection via evaluation of glutamate transporter 1 in a rat model of global cerebral ischemia.[Pubmed: 25238961] | Global cerebral ischemia (GCI) causes energy deficiency results in excessive release of glutamate from neurons. Astrocytic glutamate transporters play a predominant role in keeping extracellular glutamate concentrations below excitotoxic levels.
Glutamate transporter 1 (GLT-1) may account for more than 90% of glutamate uptake in adult forebrain.
METHODS AND RESULTS:
Preclinical findings implicate that Harmine present neuroprotection effects in a rat model of amyotrophic lateral sclerosis disease, and the beneficial effects were specifically due to up-regulation of GLT-1. However, no experiments have explored the potential of Harmine to provide neuroprotection in the setting of GCI. The current study was designed to determine whether Harmine could attenuate cerebral infarction as well as improve neuronal survival after GCI. Furthermore, to test whether the mechanisms were associated with up-regulating of GLT-1, we used a GLT-1 specific inhibitor dihydrokainate (DHK) and analysis the expression of GLT-1 mRNA and protein in cortex of brain. We also examined whether Harmine treatment affected astrocytes activation via immunofluorescence.
CONCLUSIONS:
Our results showed that post-GCI administration of Harmine could attenuate cerebral infarct volume and decrease neurons death. It also caused significantly elevation of GLT-1 mRNA and protein and remarkably attenuation of astrocyte activation. We provide novel clues in understanding the mechanisms of which Harmine exerts its neuroprotective activity in neurological disorders. |
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