| Description: |
Nuciferine possesses anti-diabetic, anti-obesity, anti-hyperlipidemia, anti-hypotensive, anti-arrhythmic, vasorelaxant, and insulin secretagogue activities. Nuciferine may be potential for the prevention and treatment of hyperuricemia with kidney inflammation. It inhibited tumor-promoting effect of nicotine involving Wnt/β-catenin signaling in non-small cell lung cancer. |
| In vitro: |
| Br J Pharmacol. 2014 Nov 19. | | Nuciferine relaxes rat mesenteric arteries through endothelium-dependent and -independent mechanisms.[Pubmed: 25409881] | Nuciferine, a constituent of lotus leaf, is an aromatic ring-containing alkaloid, with antioxidative properties. We hypothesize Nuciferine might affect vascular reactivity. This study aimed at determining the effects of Nuciferine on vasomotor tone and the underlying mechanism.
METHODS AND RESULTS:
Nuciferine-induced relaxations in rings of rat main mesenteric arteries were measured by wire myographs. Endothelial NOS (eNOS) was determined by immunoblotting. Intracellular NO production in HUVECs and Ca2+ level in both HUVECs and vascular smooth muscle cells (VSMCs) from rat mesenteric arteries were assessed by fluorescence imaging. Nuciferine induced relaxations in arterial segments pre-contracted by KCl or phenylephrine. Nuciferine-elicited arterial relaxations were reduced by removal of endothelium or by pretreatment with the eNOS inhibitor L-NAME or the NO-sensitive guanylyl cyclase inhibitor ODQ. In HUVECs, the phosphorylation of eNOS at Ser1177 and increase in cytosolic NO level induced by Nuciferine were mediated by extracellular Ca2+ influx. Under endothelium-free conditions, Nuciferine attenuated CaCl2 -induced contraction in Ca2+ -free depolarizing medium. In the absence of extracellular calcium, Nuciferine relieved the vasoconstriction induced by phenylephrine and the addition of CaCl2 . Nuciferine also suppressed Ca2+ influx in Ca2+ -free K+ -containing solution in VSMCs.
CONCLUSIONS:
Nuciferine has a vasorelaxant effect via both endothelium-dependent and -independent mechanisms.
These results suggest that Nuciferine may have a therapeutic effect on vascular diseases associated with aberrant vasoconstriction. | | PLoS One . 2016 Mar 10;11(3):e0150602. | | In Vitro and In Vivo Characterization of the Alkaloid Nuciferine[Pubmed: 26963248] | | Abstract
Rationale: The sacred lotus (Nelumbo nucifera) contains many phytochemicals and has a history of human use. To determine which compounds may be responsible for reported psychotropic effects, we used in silico predictions of the identified phytochemicals. Nuciferine, an alkaloid component of Nelumbo nucifera and Nymphaea caerulea, had a predicted molecular profile similar to antipsychotic compounds. Our study characterizes nuciferine using in vitro and in vivo pharmacological assays.
Methods: Nuciferine was first characterized in silico using the similarity ensemble approach, and was followed by further characterization and validation using the Psychoactive Drug Screening Program of the National Institute of Mental Health. Nuciferine was then tested in vivo in the head-twitch response, pre-pulse inhibition, hyperlocomotor activity, and drug discrimination paradigms.
Results: Nuciferine shares a receptor profile similar to aripiprazole-like antipsychotic drugs. Nuciferine was an antagonist at 5-HT2A, 5-HT2C, and 5-HT2B, an inverse agonist at 5-HT7, a partial agonist at D2, D5 and 5-HT6, an agonist at 5-HT1A and D4 receptors, and inhibited the dopamine transporter. In rodent models relevant to antipsychotic drug action, nuciferine blocked head-twitch responses and discriminative stimulus effects of a 5-HT2A agonist, substituted for clozapine discriminative stimulus, enhanced amphetamine induced locomotor activity, inhibited phencyclidine (PCP)-induced locomotor activity, and rescued PCP-induced disruption of prepulse inhibition without induction of catalepsy.
Conclusions: The molecular profile of nuciferine was similar but not identical to that shared with several approved antipsychotic drugs suggesting that nuciferine has atypical antipsychotic-like actions. | | Int J Parasitol Drugs Drug Resist . 2016 Dec;6(3):364-370. | | Pharmacological profiling an abundantly expressed schistosome serotonergic GPCR identifies nuciferine as a potent antagonist[Pubmed: 27397763] | | Abstract
5-hydroxytryptamine (5-HT) is a key regulator of muscle contraction in parasitic flatworms. In Schistosoma mansoni, the myoexcitatory action of 5-HT is effected through activation of a serotonergic GPCR (Sm.5HTRL), prioritizing pharmacological characterization of this target for anthelmintic drug discovery. Here, we have examined the effects of several aporphine alkaloids on the signaling activity of a heterologously expressed Sm.5HTRL construct using a cAMP biosensor assay. Four structurally related natural products - nuciferine, D-glaucine, boldine and bulbocapnine - were demonstrated to block Sm.5HTRL evoked cAMP generation with the potency of GPCR blockade correlating well with the ability of each drug to inhibit contractility of schistosomule larvae. Nuciferine was also effective at inhibiting both basal and 5-HT evoked motility of adult schistosomes. These data advance our understanding of structure-affinity relationships at Sm.5HTRL, and demonstrate the effectiveness of Sm.5HTRL antagonists as hypomotility-evoking drugs across different parasite life cycle stages.
Keywords: 5-HT; Methoxyisoquinoline; Natural products; Schistosomiasis. |
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| In vivo: |
| PLoS One. 2013 May 15;8(5):e63770. | | Nuciferine prevents hepatic steatosis and injury induced by a high-fat diet in hamsters.[Pubmed: 23691094] | Nuciferine is a major active aporphine alkaloid from the leaves of N. nucifera Gaertn that possesses anti-hyperlipidemia, anti-hypotensive, anti-arrhythmic, and insulin secretagogue activities. However, it is currently unknown whether Nuciferine can benefit hepatic lipid metabolism.
METHODS AND RESULTS:
In the current study, male golden hamsters were randomly divided into four groups fed a normal diet, a high-fat diet (HFD), or a HFD supplemented with Nuciferine (10 and 15 mg/kg·BW/day). After 8 weeks of intervention, HFD-induced increases in liver and visceral adipose tissue weight, dyslipidemia, liver steatosis, and mild necroinflammation in hamsters were analyzed. Nuciferine supplementation protected against HFD-induced changes, alleviated necroinflammation, and reversed serum markers of metabolic syndrome in hamsters fed a HFD. RT-PCR and western blot analyses revealed that hamsters fed a HFD had up-regulated levels of genes related to lipogenesis, increased free fatty acid infiltration, and down-regulated genes involved in lipolysis and very low density lipoprotein secretion. In addition, gene expression of cytochrome P4502E1 and tumor necrosis factor-α were also increased in the HFD group. Nuciferine supplementation clearly suppressed HFD-induced alterations in the expression of genes involved in lipid metabolism.
CONCLUSIONS:
Nuciferine supplementation ameliorated HFD-induced dyslipidemia as well as liver steatosis and injury. The beneficial effects of Nuciferine were associated with altered expression of hepatic genes involved in lipid metabolism. |
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