Dantron

Danthron is a natural product extracted from the traditional Chinese medicine rhubarb. Danthron functions in regulating glucose and lipid metabolism by activating AMPK.

Signaling Pathways >> Epigenetics >> AMPK

Signaling Pathways >> PI3K/Akt/mTOR >> AMPK

Research Areas >> Others

AMPK

Danthron (0.1, 1, and 10 μM) dose-dependently promotes the phosphorylation of AMPK and acetyl-CoA carboxylase (ACC) in both HepG2 and C2C12 cells. Meanwhile, Danthron treatment significantly reduces the lipid synthesis related sterol regulatory element-binding protein 1c (SREBP1c) and fatty acid synthetase (FAS) gene expressions, and the total cholesterol (TC) and triglyceride (TG) levels. In addition, Danthron treatment efficiently increases glucose consumption. Danthron effectively reduces intracellular lipid contents and enhances glucose consumption in vitro via activation of AMPK signaling pathway. 10 μM Danthron/24 h is safe for HepG2 cells. With 80% confluence, HepG2 cells are incubated with Danthron (0.1-10 μM) in FBS-Free media for 8 h. Subsequently, cells are harvested for Western blot assay. Danthron increases the p-AMPK protein in a dose-dependent manner, and no changes in t-AMPK protein are observed[1]. Danthron inhibits 9-cis retinoic acid (9cRA)-induced retinoic X receptor α (RXRα) transactivation by IC50 at 0.11 μM. To further clarify the stoichimetric ratio of Danthron binding to RXRα-ligand-binding domain (LBD), isothermal titration calorimetry (ITC) experiment is performed. The KD value of Danthron binds to RXRα-LBD by ITC experiment is determined at 7.5 μM[2].

Danthron functions as an insulin sensitizer in vivo. Danthron improves insulin sensitivity in diet-induced obese (DIO) mice. The insulin tolerance test result shows that Danthron (5 mg/kg) treated diet-induced obesity mice exhibit lower glucose levels after insulin challenge, compared with the control vehicle-treated group[2].

HepG2 cells are transfected with pGL3-ABCA1 promoter-luc or pGL3-ABCG1 promoter-luc and pRL-SV40 plasmids. At 6 h post-transfection, the cells are incubated with Danthron (0-20 μM), TO90 (2 μM) or DMSO for 24 h. Luciferase activity is measured using the Dual Luciferase Reporter Assay kit[1].

Mice[2] C57/BL6 male mice are fed with a high fat diet for 3 months and treated with Danthron (5 mg/kg) or vehicle orally for 8 weeks. The animals are then fasted for 6 h and then given intraperitoneal injection of insulin at 1.5 units/kg. Blood samples are analyzed at 15, 30, 45, 60, 90, and 120 min using Accu-Chek active blood sugar test meter.

[1]. Zhou R, et al. Danthron activates AMP-activated protein kinase and regulates lipid and glucose metabolism in vitro. Acta Pharmacol Sin. 2013 Aug;34(8):1061-9.

[2]. Zhang H, et al. Danthron functions as a retinoic X receptor antagonist by stabilizing tetramers of the receptor. J Biol Chem. 2011 Jan 21;286(3):1868-75.

Dorsomorphin dihydrochloride | Acadesine (AICAR) | A-769662 | Phenformin (hydrochloride) | Bempedoic Acid | Flufenamic Acid | WZ 4003 | PF 06409577 | O-304 | 6-Gingerol | 7-Methoxyisoflavone | HTH 01-015 | YLF-466D | Ampkinone

MOLECULAR FORMULA :

C14-H8-O4

MOLECULAR WEIGHT :

240.22

WISWESSER LINE NOTATION :

L C666 BV IVJ DQ NQ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

Standard Draize test

ROUTE OF EXPOSURE :

Administration into the eye

SPECIES OBSERVED :

Rodent - rabbit

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

1110 mg/kg

TOXIC EFFECTS :

Sense Organs and Special Senses (Olfaction) - effect, not otherwise specified Behavioral - muscle weakness Lungs, Thorax, or Respiration - other changes

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

>7 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

500 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

>10 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

292 gm/kg/70W-C

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Gastrointestinal - tumors Gastrointestinal - colon tumors

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

129 gm/kg/77W-C

TOXIC EFFECTS :

Tumorigenic - Carcinogenic by RTECS criteria Gastrointestinal - colon tumors Liver - tumors

TYPE OF TEST :

TD - Toxic dose (other than lowest)

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

130 gm/kg/77W-C

TOXIC EFFECTS :

Tumorigenic - neoplastic by RTECS criteria Gastrointestinal - colon tumors

MUTATION DATA

TYPE OF TEST :

Mutation in mammalian somatic cells

TEST SYSTEM :

Rodent - mouse Lymphocyte

DOSE/DURATION :

42 umol/L

REFERENCE :

MUREAV Mutation Research. (Elsevier Science Pub. B.V., POB 211, 1000 AE Amsterdam, Netherlands) V.1- 1964- Volume(issue)/page/year: 371,165,1996 *** REVIEWS *** IARC Cancer Review:Animal Sufficient Evidence IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 50,265,1990 IARC Cancer Review:Human No Adequate Data IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 50,265,1990 IARC Cancer Review:Group 2B IMEMDT IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Man. (WHO Publications Centre USA, 49 Sheridan Ave., Albany, NY 12210) V.1- 1972- Volume(issue)/page/year: 50,265,1990 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOHS - National Occupational Hazard Survey (1974) NOHS Hazard Code - 80355 No. of Facilities: 110 (estimated) No. of Industries: 2 No. of Occupations: 7 No. of Employees: 3120 (estimated) NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - 80355 No. of Facilities: 36 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 357 (estimated) No. of Female Employees: 187 (estimated)