Neferine

Names

[ Name ]:
Neferine

[Synonym ]:
Neferine
4-{[(1R)-6,7-Dimethoxy-2-methyl-1,2,3,4-tetrahydro-1-isoquinolinyl]methyl}-2-{[(1R)-6-methoxy-1-(4-methoxybenzyl)-2-methyl-1,2,3,4-tetrahydro-7-isoquinolinyl]oxy}phenol
4-{[(1r)-6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinolin-1-yl]methyl}-2-{[(1r)-6-methoxy-1-(4-methoxybenzyl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl]oxy}phenol
Phenol, 4-[[(1R)-1,2,3,4-tetrahydro-6,7-dimethoxy-2-methyl-1-isoquinolinyl]methyl]-2-[[(1R)-1,2,3,4-tetrahydro-6-methoxy-1-[(4-methoxyphenyl)methyl]-2-methyl-7-isoquinolinyl]oxy]-
Neferin
Phenol,4-((1,2,3,4-tetrahydro-6,7-dimethoxy-2-methyl-1-isoquinolinyl)methyl)-2-((1,2,3,4-tetrahydro-6-methoxy-1-((4-methoxyphenyl)methyl)-2-methyl-7-isoquinolinyl)oxy)

Biological Activity

[Description]:

Neferine is a major bisbenzylisoquinline alkaloid. Neferine strongly inhibits NF-κB activation.

[Related Catalog]:

Signaling Pathways >> Autophagy >> Autophagy

Natural Products >> Alkaloid

Research Areas >> Metabolic Disease

[Target]

p65

Autophagy

[In Vitro]

Neferine down regulates hypoxia induced NF-κB p65 nuclear translocation and COX-2 expressions[1]. Neferine reduces high-glucose-induced collagen production and inhibits TGF-β1-Smad, ERK and p38 MAPK signaling activation in cardiac fibroblasts. Cardiac fibroblasts (CFs) are cultured in HG medium with varying concentrations of Neferine (1, 2, or 5 μM). CCK-8 assays are carried out at different time points (24, 48, and 72 h). Compared with normal glucose (NG) and osmotic control (OC) treatments, High glucose (30 mM) treatment significantly increases the proliferation of CFs in a time-dependent manner (P<0.05). High glucose (HG)-induced CF proliferation is markedly attenuated by Neferine treatment at either 2 or 5 μM compared with vehicle treatment. However, 1 μM Neferine does not inhibit HG-induced proliferation of CFs. Therefore, 2 and 5 μM Neferine are used in the remaining experiments[2].

[In Vivo]

Neferine treatment at both low-dose (60 mg/kg/day by gavage) and high-dose (120 mg/kg/day by gavage) reduces the increment of collagen I, III and TGF-β1 protein expression induced by hyperglycemia[2].

[Cell Assay]

Cardiac fibroblasts (CFs) are isolated from neonatal mouse ventricular tissues. After starvation in serum-free medium for 24 h, CFs are incubated in DMEM containing 5.6 mM glucose (normal glucose; NG), 30 mM D-glucose (HG), 30 mM D-glucose plus 1 μM Neferine, 30 mM D-glucose plus 2 μM Neferine, 30 mM D-glucose plus 5 μM Neferine, and 5.6 mM glucose plus 27.5 mM mannose. Cells are harvested at 24 h, 48 h, and 72h. Cell proliferation is measured with the Cell Counting Kit-8 (CCK-8) and the Cell-LightTM EdU assay[2].

[Animal admin]

Mice[2] Eight-week-old C57BL/6J male mice are used. Diabetes is induced by intraperitoneal injection of Streptozotocin dissolved in citrate buffer (pH 4.5) at 60 mg/kg body weight for five consecutive days. Control mice are injected with citrate buffer only. Whole blood glucose in mouse tail blood is detected with an Accu-Check Active glucometer. Mice with blood glucose concentrations higher than 18 mM are considered as diabetic animals and used in this study. The animals are randomly divided into four groups of eight animals each. Diabetic mice are divided into three groups: group 1, the diabetic control group (DM); group 2, which receive Neferine at a dose of 60 mg/kg/day (DM-NL); and group 3, which receive Neferine at a dose of 120 mg/kg/day (DM-NH). Neferine is administered twice per day by intragastric gavage for 12 weeks. Equivalent volumes of normal sodium are administered to the normal and DM control groups by gavage. Mice are anaesthetized and sacrificed at the end of the 12-week treatment[2].

[References]

[1]. Baskaran R, et al. Neferine prevents NF-κB translocation and protects muscle cells from oxidative stress and apoptosis induced by hypoxia. Biofactors. 2016 Jul 8;42(4):407-17.

[2]. Liu X, et al. Neferine inhibits proliferation and collagen synthesis induced by high glucose in cardiac fibroblasts and reduces cardiac fibrosis in diabetic mice. Oncotarget. 2016 Sep 20;7(38):61703-61715.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
710.9±60.0 °C at 760 mmHg

[ Molecular Formula ]:
C₃₈H₄₄N₂O₆

[ Molecular Weight ]:
624.766

[ Flash Point ]:
383.8±32.9 °C

[ Exact Mass ]:
624.319946

[ PSA ]:
72.86000

[ LogP ]:
5.49

[ Appearance of Characters ]:
white to beige

[ Vapour Pressure ]:
0.0±2.4 mmHg at 25°C

[ Index of Refraction ]:
1.601

[ Storage condition ]:
2-8°C

[ Water Solubility ]:
DMSO: >15mg/mL

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: SM9495000

CHEMICAL NAME :: Phenol, 4-((1,2,3,4-tetrahydro-6,7-dimethoxy-2-methyl-1-isoqu inolinyl)methyl)-2- ((1,2,3,4-tetrahydro-6-methoxy-1-((4-methoxyphenyl)me thyl)-2-methyl-7-isoq uinolinyl)oxy)-

CAS REGISTRY NUMBER :: 2292-16-2

LAST UPDATED :: 199612

DATA ITEMS CITED :: 1

MOLECULAR FORMULA :: C38-H44-N2-O6

MOLECULAR WEIGHT :: 624.84

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 26 mg/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: CTYAD8 Zhongcaoyao. Chinese Traditional and Herbal Medicine. (China International Book Trading Corp., POB 2820, Beijing, Peop. Rep. China) V.11- 1980- Volume(issue)/page/year: 19,217,1988

Safety Information

[ Hazard Codes ]:
C

[ RIDADR ]:
NONH for all modes of transport

[ RTECS ]:
SM9495000

Articles

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

J. Ethnopharmacol. 174 , 57-65, (2015)

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 c...

Anti-amnesic activity of neferine with antioxidant and anti-inflammatory capacities, as well as inhibition of ChEs and BACE1.

Life Sci. 87(13-14) , 420-30, (2010)

the multifunctional potential of neferine derived from the embryo of Nelumbo nucifera seeds for the age-related neurodegenerative disorders, in vivo anti-amnesic activities and in vitro cholinesterase...

Blockade of HERG K+ channel by isoquinoline alkaloid neferine in the stable transfected HEK293 cells.

Naunyn Schmiedebergs Arch. Pharmacol. 380(2) , 143-51, (2009)

We studied the effects of isoquinoline alkaloid neferine (Nef) extracted from the seed embryo of Nelumbo nucifera Gaertn on Human ether-à-go-go-related gene (HERG) channels stably expressed in human e...

Related Compounds

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