| Description: |
Harmaline is a central nervous system stimulant and an acetylcholinesterase (AChR) inhibitor; also inhibits histamine N-methyltransferase. Harmaline has antileishmanial, bioinsecticidal, and vasorelaxant effects. It has antagonist effects on alpha1-adrenorecepteors in non-competitive manner, it also exerts an antioxidant activity by scavenging the free radical generated by DPPH.Harmaline may prevent dopamine-induced mitochondrial damage and PC12 cell death through a scavenging action on reactive oxygen species and inhibition of monoamine oxidase and thiol oxidation.
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| Targets: |
NOS | cAMP | Calcium Channel | PKC | Antifection | AChR | alpha1-adrenorecepteor |
| In vitro: |
| Exp Parasitol. 2004 Mar-Apr;106(3-4):67-74. | | In vitro activity of the beta-carboline alkaloids harmane, harmine, and harmaline toward parasites of the species Leishmania infantum.[Pubmed: 15172213 ] | Harmane, harmine, and Harmaline were investigated for their in vitro antileishmanial activity toward parasites of the species Leishmania infantum.
METHODS AND RESULTS:
Harmane and Harmine displayed a moderate antiproliferative activity toward human monocytes and exerted a weak antileishmanial activity toward both the promastigote and the amastigote forms of the parasite. Their mechanism of action on the promastigote form of the parasite involved interactions with DNA metabolism leading to an accumulation of parasites in the S-G(2)M phases of the cell-cycle. Harmaline, at the contrary, was deprived from toxicity toward human cells and Leishmania promastigotes, however it exerted a strong antileishmanial activity toward the intracellular amastigote form of the parasite.
CONCLUSIONS:
This property was shown to partly result from the capacity of the molecule to prevent parasite internalization within macrophages by inhibiting Leishmania PKC activity. |
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| In vivo: |
| Pesticide Biochemistry & Physiology, 2007, 89(2):137-145. | | Bioinsecticidal effect of harmaline on Plodia interpunctella development (Lepidoptera: Pyralidae).[Reference: WebLink] | We have investigated the effects of Harmaline, a plant secondary metabolic compound belonging to β-carboline alkaloids, on the 4th instar larvae of Plodia interpunctella (Lepidoptera).
METHODS AND RESULTS:
When incorporated into the diet, Harmaline caused weight loss of larvae with a reduction in protein and glycogen contents and an inhibition of α-amylase activity. Using electron microscopy, we showed that Harmaline provoked a severe cytotoxicity on the epithelial cells of the midgut resulting in marked vacuolization of the cytoplasm, appearance of numerous autophagic vesicles and lysosomic structures, fragmentation of rough endoplasmic reticulum cisternae, disruption of microvilli, rupture of the plasma membrane leading to shedding of the cytoplasm contents into the midgut lumen.
CONCLUSIONS:
The development of larvae to the pupal and adult stages was prevented and high mortality was recorded. | | J Neurochem. 2000 Aug;75(2):521-31. | | Protective effect of harmalol and harmaline on MPTP neurotoxicity in the mouse and dopamine-induced damage of brain mitochondria and PC12 cells.[Pubmed: 10899927] | The present study elucidated the protective effect of beta-carbolines (Harmaline, harmalol, and harmine) on oxidative neuronal damage.
METHODS AND RESULTS:
MPTP treatment increased activities of total superoxide dismutase, catalase, and glutathione peroxidase and levels of malondialdehyde and carbonyls in the basal ganglia, diencephalon plus midbrain of brain compared with control mouse brain. Coadministration of harmalol (48 mg/kg) attenuated the MPTP effect on the enzyme activities and formation of tissue peroxidation products. Harmaline, harmalol, and harmine attenuated both the 500 microM MPP(+)-induced inhibition of electron flow and membrane potential formation and the 100 microM dopamine-induced thiol oxidation and carbonyl formation in mitochondria. The scavenging action of beta-carbolines on hydroxyl radicals was represented by inhibition of 2-deoxy-D-ribose degradation. Harmaline and harmalol (100 microM) attenuated 200 microM dopamine-induced viability loss in PC12 cells. The beta-carbolines (50 microM) attenuated 50 microM dopamine-induced apoptosis in PC12 cells. The compounds alone did not exhibit significant cytotoxic effects. The results indicate that beta-carbolines attenuate brain damage in mice treated with MPTP and MPP(+)-induced mitochondrial damage.
CONCLUSIONS:
The compounds may prevent dopamine-induced mitochondrial damage and PC12 cell death through a scavenging action on reactive oxygen species and inhibition of monoamine oxidase and thiol oxidation. |
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