Background
Peroxisome proliferator-activated receptor γ (PPARγ) is a central regulator of adipocyte differentiation and is the principle target of the thiazolidinedione (TZD) class of antidiabetic drugs.1 Harmine is a β-carboline alkaloid that was first isolated from seeds of Peganum harmala (Syrian rue) and Banisteriopsis caapi. Recent work indicates that harmine is a unique regulator of PPARγ expression that acts by inhibiting the Wnt signalling pathway in a cell-specific manner.2 Administration of harmine (30 mg/kg) to obese db/db mice resulted in reduced blood glucose, free fatty acids, and triglyceride levels, delayed hyperglycemia, and improved insulin sensitivity. Harmine also attenuates inflammatory gene expression (TNF-α, IL-1β, iNOS) and macrophage accumulation in adipose tissue.2
1.Hauner, H.The mode of action of thiazolidinedionesDiabetes Metab. Res. Rev.18(Suppl. 2)S10-S15(2002)
2.Waki, H., Park, K.W., Mitro, N., et al.The small molecule harmine is an antidiabetic cell-type-specific regulator of PPARγ expressionCell Metab.5(5)357-370(2007)
Protocol
Animal experiment: | Rats[4]A total of 150 male Sprague-Dawley rats (age, 10-12 weeks; weighing, 280-320 g; are used in the present study. The rats are randomly divided into three groups: Sham-operated group (sham; n=15); the TBI group (TBI; n=35) and the TBI + Harmine-treated group (Harmine; n=35). Harmine is administered immediately following TBI (i.p, 30 mg/kg per day) for up to 5 days. The sham and TBI groups receive equal volumes of 0.9% saline solution (i.p.). The rats are grouped as follows for examination of behavioral recovery: Sham, n=3; TBI, n=7; and Harmine, n=7. Following TBI, the NSS is evaluated at 1, 3 and 5 days. Each rat is assessed by an observer who is blinded to the animal treatment[4]. |
参考文献: [1]. Glennon RA, et al. Binding of beta-carbolines and related agents at serotonin (5-HT(2) and 5-HT(1A)), dopamine (D(2)) and benzodiazepine receptors. Drug Alcohol Depend. 2000 Aug 1;60(2):121-32.
[2]. Neumann F, et al. DYRK1A inhibition and cognitive rescue in a Down syndrome mouse model are induced by new fluoro-DANDY derivatives. Sci Rep. 2018 Feb 12;8(1):2859.
[3]. Zhang L, et al. Harmine suppresses homologous recombination repair and inhibits proliferation of hepatoma cells. Cancer Biol Ther. 2015;16(11):1585-92.
[4]. Zhong Z, et al. Treatment with harmine ameliorates functional impairment and neuronal death following traumatic brain injury. Mol Med Rep. 2015 Dec;12(6):7985-91. |
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