Alkaloid constituents from flower buds and leaves of sacred lotus (Nelumbo nucifera, Nymphaeaceae) with melanogenesis inhibitory activity in B16 melanoma cells

Nakamura, Seikou; Nakashima, Souichi; Tanabe, Genzo; Oda, Yoshimi; Yokota, Nami; Fujimoto, Katsuyoshi; Μatsumoto, Takahiro; Sakuma, Rika; Ohta, Tomoe; Ogawa, Koichi; Nishida, Shino; Miki, Hisako; Matsuda, Hisashi; Muraoka, Osamu; Yoshikawa, Masayuki

doi:10.1016/j.bmc.2012.11.038

Cited by 91 publications

(76 citation statements)

References 49 publications

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“…Among them, NF, an alkaloid that was extracted from lotus leaf has shown potent inhibition of melanoma (Nakamura et al, 2013). Our present study identified a novel effect of NF, inhibition of β-catenin expression in NSCLC.…”

Section: Discussionmentioning

confidence: 81%

“…NF was also found to reduce the development of atherosclerosis via inhibition of vascular smooth muscle cell proliferation and migration (Ho et al, 2010). Moreover, many in vivo studies have demonstrated that NF displays beneficial effects on non-alcoholic fatty liver disease, HIV, and melanoma (Guo et al, 2013;Kashiwada et al, 2005;Nakamura et al, 2013). However, it is still not clear whether NF, as a potential anti-cancer agent, may suppress tumor progression by directly affecting tumor cells.…”

Section: Introductionmentioning

confidence: 96%

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Nuciferine, extracted from Nelumbo nucifera Gaertn, inhibits tumor-promoting effect of nicotine involving Wnt/β-catenin signaling in non-small cell lung cancer

Liu

Guo

et al. 2015

Journal of Ethnopharmacology

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Section: Discussionmentioning

confidence: 81%

Section: Introductionmentioning

confidence: 96%

Nuciferine, extracted from Nelumbo nucifera Gaertn, inhibits tumor-promoting effect of nicotine involving Wnt/β-catenin signaling in non-small cell lung cancer

Liu

Guo

et al. 2015

Journal of Ethnopharmacology

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“…As a pilot study, the anti-tumor activities and molecular mechanisms of nuciferine, an aporphine alkaloid extracted from lotus leaves, were selected for further study and validation in our investigation, on the basis of evidence from the literature and in vivo/in vitro experiments. For example, nuciferine has been reported in studies of melanoma [16] , non-small cell lung cancer [17] and the DU-145 cell line [18] . In addition, we predicted that nuciferine and melphalan would exhibit similar anti-tumor profiles against the tested tumor cell lines.…”

Section: Introductionmentioning

confidence: 99%

Identification of the anti-tumor activity and mechanisms of nuciferine through a network pharmacology approach

et al. 2016

Acta Pharmacol Sin

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Aim: Nuciferine is an aporphine alkaloid extracted from lotus leaves, which is a raw material in Chinese medicinal herb for weight loss. In this study we used a network pharmacology approach to identify the anti-tumor activity of nuciferine and the underlying mechanisms. Methods: The pharmacological activities and mechanisms of nuciferine were identified through target profile prediction, clustering analysis and functional enrichment analysis using our traditional Chinese medicine (TCM) network pharmacology platform. The antitumor activity of nuciferine was validated by in vitro and in vivo experiments. The anti-tumor mechanisms of nuciferine were predicted through network target analysis and verified by in vitro experiments. Results: The nuciferine target profile was enriched with signaling pathways and biological functions, including "regulation of lipase activity", "response to nicotine" and "regulation of cell proliferation". Target profile clustering results suggested that nuciferine to exert anti-tumor effect. In experimental validation, nuciferine (0.8 mg/mL) markedly inhibited the viability of human neuroblastoma SY5Y cells and mouse colorectal cancer CT26 cells in vitro, and nuciferine (0.05 mg/mL) significantly suppressed the invasion of 6 cancer cell lines in vitro. Intraperitoneal injection of nuciferine (9.5 mg/mL, ip, 3 times a week for 3 weeks) significantly decreased the weight of SY5Y and CT26 tumor xenografts in nude mice. Network target analysis and experimental validation in SY5Y and CT26 cells showed that the anti-tumor effect of nuciferine was mediated through inhibiting the PI3K-AKT signaling pathway and IL-1 levels in SY5Y and CT26 cells. Conclusion: By using a TCM network pharmacology method, nuciferine is identified as an anti-tumor agent against human neuroblastoma and mouse colorectal cancer in vitro and in vivo, through inhibiting the PI3K-AKT signaling pathways and IL-1 levels.

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“…(Nymphaeaceae), known as sacred lotus, Chinese water lily or water lotus, is widely distributed throughout South-East Asia. In many Asian countries the aquatic plant has been reported to have a wide array of traditional, medicinal and therapeutic uses (Duke et al, 2002; Mehta et al, 2013; Mitra and Kapoor, 1976; Nakamura et al, 2013). In traditional Chinese medicine, seed embryos (or plumule) of the flower are used to overcome nervous disorder, high-fever with restlessness, and insomnia (Mehta et al, 2013; Nguyen, 1999) and arrow-root prepared from the rhizome “OCE FUN“ for enhancing the mental health and quieting the spirits (Porterfield, 1951).…”

Section: Introductionmentioning

confidence: 99%

In vitro opioid receptor affinity and in vivo behavioral studies of Nelumbo nucifera flower

Kumarihamy

León

Pettaway

et al. 2015

Journal of Ethnopharmacology

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Ethnopharmacological relevance Nelumbo nucifera Geartn., known as sacred lotus, has been used traditionally in South East Asia as a traditional medicine for various CNS disorders including stress, fever, depression, insomnia, and cognitive conditions. Aim of the study To investigate the in vitro cannabinoid and opioid receptor binding affinities, and in vivo behavioral actions of Nelumbo flower extracts and to isolate the potential compounds to treat CNS associated disorders. Materials and methods The white and pink flowers of N. nucifera were extracted with 95% EtOH, followed by acid-base partitioning using CHCl3 to give acidic and basic partitions. These partitions were subjected to Centrifugal Preparative TLC (CPTLC) to yield benzyltetrahydroisoquinoline (BTIQ) alkaloids and long chain fatty acids, identified by physical and spectroscopic methods. In addition, EtOH extracts and partitions were analyzed for chemical markers by UHPLC/MS and GC/MS. In vitro neuropharmacological effects were evaluated by cannabinoid (CB1 and CB2) and opioid [delta (δ), kappa (κ), and mu (μ)] competitive radioligand binding and GTPγS functional assays. The in vivo behavioral effect was studied through the use of the mouse tetrad assay at 10, 30, 75 and 100 mg/kg/ip doses that revealed the effect on locomotion, catalepsy, body temperature, and nociception of acidic and basic CHCl3 partitions, fractions, and compounds. Results Three aporphines, nuciferine (1), N-nor-nuciferine (2), asimilobine (3), and five BTIQs, armepavine (4), O-methylcoclaurine (5), N-methylcoclaurine (6), coclaurine (7), neferine (10), and a mixture of linoleic and palmitic acids (LA and PA), were identified and evaluated for cannabinoid and opioid receptor displacement activities. Compounds 5–7 showed binding affinities for the κ opioid receptor with equilibrium dissociation constant (Ki) values of 3.5±0.3, 0.9±0.1, 2.2±0.2 µM, respectively. Compound 10 displayed affinities for δ-and μ- opioid receptors with Ki values of 0.7±0.1 and 1.8±0.2 µM, respectively, and was determined to be a weak δ agonist by GTPγS functional assay. The mixture of LA and PA (1:1) showed an affinity for δ opioid receptor with a Ki value of 9.2±1.1 µM. The acidic and basic CHCl3 partitions, compounds 1 and 7, and 5–7 mixture were subjected to the tetrad assay, of which the acidic partition displayed decreased locomotion and increased catalepsy, antinociception, and hypothermia in animal at doses of 75–100 mg/kg/ip, and also showed clonic-tonic seizures upon touch at 100 mg/kg. Conclusion Bioassay-guided isolation revealed compounds 5–7, 10, and the mixture of LA and PA displayed various degrees of opioid receptor radioligand displacement affinities. The in vivo tetrad assay of acidic CHCl3 partition, enriched with aporphines 1 and 2, displayed actions on all four points of behavioral parameters. It can be concluded that the in vivo mild canabimimetic-type effect observed for the CHCl3 partition is likely mediated through other CNS mechanisms since the extracts, partitions, and...

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Alkaloid constituents from flower buds and leaves of sacred lotus (Nelumbo nucifera, Nymphaeaceae) with melanogenesis inhibitory activity in B16 melanoma cells

Cited by 91 publications

References 49 publications

Nuciferine, extracted from Nelumbo nucifera Gaertn, inhibits tumor-promoting effect of nicotine involving Wnt/β-catenin signaling in non-small cell lung cancer

Nuciferine, extracted from Nelumbo nucifera Gaertn, inhibits tumor-promoting effect of nicotine involving Wnt/β-catenin signaling in non-small cell lung cancer

Identification of the anti-tumor activity and mechanisms of nuciferine through a network pharmacology approach

In vitro opioid receptor affinity and in vivo behavioral studies of Nelumbo nucifera flower

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