Nuciferine

Nuciferine is an alkaloid that has been found in N. nucifera and has diverse biological activities.^1,2,3,4,5 It acts as a partial agonist at dopamine D₂ receptors, as well as an inverse agonist at the serotonin receptor subtype 5-HT₇, and an antagonist at the 5-HT_2B and 5-HT_2C receptors (EC₅₀s = 65.07, 150, 478, and 131 nM, respectively).¹ Nuciferine is also an antagonist at schistosome Sm.5-HTR_L receptors (IC₅₀ = 240 nM) and inhibits 5-HT-induced motility of larval and adult S. mansoni when used at a concentration of 10 µM.² It activates PPARα, PPARβ/δ, and PPARγ transcriptional activity in reporter assays and inhibits IL-6 and TNF-α production induced by LPS in RAW 264.7 cells.³ It prevents ferroptotic cell death induced by the GPX4 inhibitor RSL3 in HK-2 and HEK293T cells when used at concentrations of 10, 20, and 40 µM and prevents lipid peroxidation in a mouse model of acute kidney injury.⁴ Dietary administration of nuciferine (15 mg/kg) reduces increases in serum triglyceride, total cholesterol, LDL, and free fatty acid levels, as well as markers of hepatic steatosis, in a mouse model of high-fat diet-induced hyperlipidemia.⁵

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1. Farrell, M.S., McCorvy, J.D., Huang, X.-P., et al. In vitro and in vivo characterization of the alkaloid nuciferine. PLoS One 11(3), e0150602 (2016).

2. Chan, J.D., Acharya, S., Day, T.A., et al. Pharmacological profiling an abundantly expressed schistosome serotonergic GPCR identifies nuciferine as a potent antagonist. Int. J. Parasitol. Drugs Drug Resist. 6(3), 364-370 (2016).

3. Zhang, C., Deng, J., Liu, D., et al. Nuciferine Inhibits Proinflammatory Cytokines via the PPARs in LPS-Induced RAW264.7 Cells. Molecules 23(10), 2723 (2018).

4. Li, D., Liu, B., Fan, Y., et al. Nuciferine protects against folic acid-induced acute kidney injury by inhibiting ferroptosis. Br. J. Pharmacol. 178(5), 1182-1199 (2021).

5. Guo, F., Yang, X., Li, X., et al. Nuciferine prevents hepatic steatosis and injury induced by a high-fat diet in hamsters. PLoS One 8(5), e63770 (2013).