Acetylcorynoline

Neuropharmacology. 2014 Jul;82:108-20.

Acetylcorynoline attenuates dopaminergic neuron degeneration and α-synuclein aggregation in animal models of Parkinson's disease.[Pubmed: 23973292]

Parkinson's disease (PD), the second most common neurodegenerative disease, impairs motor skills and cognitive function. To date, the drugs used for PD treatment provide only symptomatic relief. The identification of new drugs that show benefit in slowing the decline seen in PD patients is the focus of much current research. Acetylcorynoline is the major alkaloid component derived from Corydalis bungeana, a traditional Chinese medical herb. It has been shown to have anti-inflammatory properties, but no studies have yet described the effects of Acetylcorynoline on PD. The aim of this study was to evaluate the potential for Acetylcorynoline to improve PD in Caenorhabditis elegans models.
METHODS AND RESULTS:
In the present study, we used a pharmacological strain (BZ555) that expresses green fluorescent protein specifically in dopaminergic neurons, and a transgenic strain (OW13) that expresses human α-synuclein in muscle cells to study the antiparkinsonian effects of Acetylcorynoline. Our experimental data showed that treatment with up to 10 mM Acetylcorynoline does not cause toxicity in animals. Acetylcorynoline significantly decreases dopaminergic neuron degeneration induced by 6-hydroxydopamine in BZ555 strain; prevents α-synuclein aggregation; recovers lipid content in OW13 strain; restores food-sensing behavior, and dopamine levels; and prolongs life-span in 6-hydroxydopamine-treated N2 strain, thus showing its potential as a possible antiparkinsonian drug.
CONCLUSIONS:
Acetylcorynoline may exert its effects by decreasing egl-1 expression to suppress apoptosis pathways and by increasing rpn5 expression to enhance the activity of proteasomes.

Yao Xue Xue Bao. 1997 May;32(5):331-6.

[Protective action of corynoline, acetylcorynoline and protopine against experimental liver injury in mice].[Pubmed: 11498866]

METHODS AND RESULTS:
Oral administration of two doses of corynoline, Acetylcorynoline or protopine at 50 and 100 mg.kg-1 in an interval of 8 to 24 h before i.p. injection of CCl4, acetaminophen or thioacetamide significantly impeded the elevation of serum transaminase (SGPT) and liver damage in mice. The three compounds were found to inhibit CCl4-induced microsomal lipid peroxidation and CCl4 conversing to carbon monoxide in liver microsomes in vitro.
CONCLUSIONS:
Of these compounds, Acetylcorynoline was shown to be more potent than corynoline and protopine. In addition, all the three compounds exhibited biphasic effects on the hepatic cytochrome P450, i.e. inhibition followed by induction, in mice.

PLoS One. 2013;8(3):e58398.

Acetylcorynoline impairs the maturation of mouse bone marrow-derived dendritic cells via suppression of IκB kinase and mitogen-activated protein kinase activities.[Pubmed: 23472193]

Dendritic cells (DCs) are major modulators in the immune system. One active field of research is the manipulation of DCs as pharmacological targets to screen novel biological modifiers for the treatment of inflammatory and autoimmune disorders. Acetylcorynoline is the major alkaloid component derived from Corydalis bungeana herbs. We assessed the capability of Acetylcorynoline to regulate lipopolysaccharide (LPS)-stimulated activation of mouse bone marrow-derived DCs.
METHODS AND RESULTS:
Our experimental data showed that treatment with up to 20 µM Acetylcorynoline does not cause cytotoxicity in cells. Acetylcorynoline significantly inhibited the secretion of tumor necrosis factor-α, interleukin-6, and interleukin-12p70 by LPS-stimulated DCs. The expression of LPS-induced major histocompatibility complex class II, CD40, and CD86 on DCs was also decreased by Acetylcorynoline, and the endocytic capacity of LPS-stimulated DCs was restored by Acetylcorynoline. In addition, LPS-stimulated DC-elicited allogeneic T-cell proliferation was blocked by Acetylcorynoline, and the migratory ability of LPS-stimulated DCs was reduced by Acetylcorynoline. Moreover, Acetylcorynoline significantly inhibits LPS-induced activation of IκB kinase and mitogen-activated protein kinase. Importantly, administration of Acetylcorynoline significantly attenuates 2,4-dinitro-1-fluorobenzene-induced delayed-type hypersensitivity.
CONCLUSIONS:
Acetylcorynoline may be one of the potent immunosuppressive agents through the blockage of DC maturation and function.

Xenobiotica. 2014 Aug;44(8):743-8.

Gradient elution liquid chromatography mass spectrometry determination of acetylcorynoline in rat plasma and its application to a pharmacokinetic study.[Pubmed: 24512634]

1. Acetylcorynoline is the major alkaloid component derived from Corydalis bungeana herbs.
METHODS AND RESULTS:
A sensitive and selective liquid chromatography mass spectrometry method for determination of Acetylcorynoline in rat plasma was developed over the range of 5-1000 ng/mL to characterize the pharmacokinetic properties. 2. Chromatographic separation was achieved on a C18 (2.1 mm× 150 mm, 5 μm) column with acetonitrile 0.1% formic acid in water as mobile phase with gradient elution. The flow rate was set at 0.4 mL/min. After addition of carbamazepine as internal standard (IS), protein precipitation by acetonitrile-methanol (9:1, v/v) was used as sample preparation. An electrospray ionization source was applied and operated in positive ion mode; selective ion monitoring mode was used for quantification using target ions m/z 410 for Acetylcorynoline and m/z 237 for the IS. 3. Mean recoveries of Acetylcorynoline in rat plasma were in the range of 72.3-87.6%. Matrix effects for Acetylcorynoline were measured to be between 88.7% and 93.5%. Coefficient of variation of intra-day and inter-day precision were both <13%. The accuracy of the method ranged from 95.8% to 112.1%. The analyte was stable under auto-sampler, room temperature, freeze-thaw and long-term (20 days), the bias in concentration was within ±15% of their nominal values. 4. The LC-MS method for the determination of Acetylcorynoline in rat plasma utilizing 100 µL of plasma with an LLOQ of 5.0 ng/mL developed and validated, it was sensitive, selective and simple.
CONCLUSIONS:
This method was successfully applied in pharmacokinetic study of Acetylcorynoline after intravenous administration of single dosage 3 mg/kg in rats.