ACONINE

Aconine inhibits receptor activator of nuclear factor (NF)-κB ligand (RANKL)-induced NF-κB activation.

Research Areas >> Inflammation/Immunology

Natural Products >> Alkaloid

NF-κB

Treatment with Aconine significantly inhibits the RANKL-induced transcriptional activity of NF-κB in a dose-dependent manner. Aconine inhibits RANKL-induced osteoclast differentiation in RAW264.7 cells by suppressing the activation of NF-κB and NFATc1 and the expression of the cell-cell fusion molecule DC-STAMP. Aconine (0.125, 0.25 μM) does not affect the viability of RAW264.7 cells, but dose-dependently inhibits RANKL-induced osteoclast formation and bone resorptive activity. Aconine dose-dependently inhibits the RANKL-induced activation of NF-κB and NFATc1 in RAW264.7 cells, and subsequently reduces the expression of osteoclast-specific genes (c-Src, β3-Integrin, cathepsin K and MMP-9) and the expression of dendritic cell-specific transmembrane protein (DC-STAMP), which plays an important role in cell-cell fusion[1].

To evaluate the effect of Aconine on the viability of RAW264.7 cells, cytotoxicity assays are performed using the Cell Counting Kit-8. Briefly, the cells are seeded in 96-well plates at a density of 2×104, 3×103, 1.2×103, 1×103 or 1×103 cells/well in the presence or absence of Aconine (0.125-0.5 mM) for 8 h, 24 h, 48 h, 5 d or 7 d, respectively. After incubating the cells with CCK-8 solution for 2 h, optical density is measured at 450 nm using a GENios microplate reader. Cell viability is expressed as a percentage of the control[1].

[1]. Zeng XZ, et al. Aconine inhibits RANKL-induced osteoclast differentiation in RAW264.7 cells by suppressing NF-κB and NFATc1 activation and DC-STAMP expression. Acta Pharmacol Sin. 2016 Feb;37(2):255-63.

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DATA ITEMS CITED :

4

MOLECULAR FORMULA :

C25-H41-N-O9

MOLECULAR WEIGHT :

499.67

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

374 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

YHHPAL Yaoxue Xuebao. Acta Pharmaceutica Sinica. Pharmaceutical Journal. (China International Book Trading Corp., POB 2820, Beijing, Peop. Rep. China) V.1- 1953- Suspended 1966-78. Volume(issue)/page/year: 19,641,1984

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

117 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

YHHPAL Yaoxue Xuebao. Acta Pharmaceutica Sinica. Pharmaceutical Journal. (China International Book Trading Corp., POB 2820, Beijing, Peop. Rep. China) V.1- 1953- Suspended 1966-78. Volume(issue)/page/year: 19,641,1984

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Mammal - cat

DOSE/DURATION :

400 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 5,324,1955

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

275 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold

REFERENCE :

ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 5,324,1955