7,8-Dihydroxyflavone is a naturally-occurring plant-based flavone and high-affinity tyrosine kinase receptor B (TrkB) agonist with an IC50 value of 0.26μM[1,2]. TrkB is a protein tyrosine kinase receptor, and its primary ligand Brain-derived neurotrophic factor (BDNF) is expressed in neurons and skeletal muscles during the differentiation period and in the adult, promoting neuronal survival and differentiation, synaptic plasticity, and development of myoblasts and muscle fibers, as well as regulating energy metabolism and regeneration of the muscles[3]. 7,8-Dihydroxyflavone can be used as an adjunctive treatment in schizophrenia[4].
In vitro, treatment of MC3T3-E1 cells with 7,8-Dihydroxyflavone (0.5-5μM) for 24-48h resulted in a significant increase in cyclin mRNA levels in the cells, promoting cell proliferation and differentiation[5]. After 48h treatment with 7,8-Dihydroxyflavone (10-300μM) in cardiac fibroblasts (CFs) stimulated by TGF-β1, 7,8-Dihydroxyflavone significantly reduced the viability of CFs and inhibited TGF-β1-induced CFs activity in a dose-dependent manner[6].
In vivo, administration of 7,8-Dihydroxyflavone (5mg/kg/day) via intraperitoneal injection for 28days in mice fed a high-energy diet (cafeteria diet, CAF). 7,8-Dihydroxyflavone reduced body weight and downregulated the percentage indices of epididymal adipose tissue and adipocytes. The treatment also significantly decreased triglyceride, cholesterol, amylase, alanine aminotransferase (ALT), and glucose levels[7]. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mice, 5-day intraperitoneal treatment with 7,8-Dihydroxyflavone (5mg/kg/day) effectively blocked the loss of tyrosine hydroxylase (TH)-positive neurons, exerted beneficial effects on motor function and neuropathology through autophagy mechanisms[8].
References:
[1] Paul R, Nath J, Paul S, et al. Suggesting 7,8-dihydroxyflavone as a promising nutraceutical against CNS disorders[J]. Neurochem Int, 2021, 148: 105068.
[2] Tasdemir D, Kaiser M, Brun R, et al. Antitrypanosomal and antileishmanial activities of flavonoids and their analogues: in vitro, in vivo, structure-activity relationship, and quantitative structure-activity relationship studies[J]. Antimicrob Agents Chemother, 2006, 50(4): 1352-64.
[3] Deng C, Chen H. Brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling in spinal muscular atrophy and amyotrophic lateral sclerosis[J]. Neurobiol Dis, 2024, 190: 106377.
[4] Du X, Hill R A. 7,8-Dihydroxyflavone as a pro-neurotrophic treatment for neurodevelopmental disorders[J]. Neurochem Int, 2015, 89: 170-80.
[5] Xue F, Zhao Z, Gu Y, et al. 7,8-Dihydroxyflavone modulates bone formation and resorption and ameliorates ovariectomy-induced osteoporosis[J]. Elife, 2021, 10.
[6] Hang P Z, Liu J, Wang J P, et al. 7,8-Dihydroxyflavone alleviates cardiac fibrosis by restoring circadian signals via downregulating Bmal1/Akt pathway[J]. Eur J Pharmacol, 2023, 938: 175420.
[7] Sahin E, Saglam N, Erdem S, et al. 7,8-Dihydroxyflavone alleviates Endoplasmic Reticulum Stress in cafeteria diet-induced metabolic syndrome[J]. Life Sci, 2022, 306: 120781.
[8] Zuo L, Dai C, Yi L, et al. 7,8-dihydroxyflavone ameliorates motor deficits via regulating autophagy in MPTP-induced mouse model of Parkinson's disease[J]. Cell Death Discov, 2021, 7(1): 254.
7,8-Dihydroxyflavone（7,8-二羟基黄酮）是一种高亲和力酪氨酸激酶受体B（TrkB）激动剂，IC50值为0.26μM [1,2]。TrkB是一种蛋白酪氨酸激酶受体，和其主要配体脑源性神经营养因子（BDNF）在分化期和成人的神经元和骨骼肌中表达，促进神经元的存活和分化、突触可塑性、成肌细胞和肌纤维的发育，以及调节肌肉的能量代谢和再生[3]。7,8-二羟基黄酮可作为精神分裂症的辅助治疗药物[4]。
在体外，7,8-二羟基黄酮（0.5-5μM）处理MC3T3-E1细胞24-48h，引起细胞中细胞周期蛋白mRNA水平的显著增加，促进了细胞的增殖和分化[5]。在TGF-β1 刺激下的心肌成纤维细胞（CFs）用7,8-二羟基黄酮（10-300μM）处理48h后，7,8-二羟基黄酮显著降低了CFs的存活力，同时以剂量依赖的方式抑制TGF-β1诱导的CFs的活性[6]。
在体内，7,8-二羟基黄酮（5mg/kg/day）通过腹腔注射治疗高能量饮食（自助餐饮食 (CAF)）小鼠28天，降低了小鼠体重，同时下调了附睾脂肪组织和脂肪细胞指数百分比。7,8-二羟基黄酮治疗后甘油三酯、胆固醇、淀粉酶、丙氨酸氨基转移酶（ALT）和葡萄糖值显著降低[7]。7,8-二羟基黄酮（5mg/kg/day）通过腹腔注射治疗1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）诱导的帕金森病小鼠5天，显著阻断酪氨酸羟化酶（TH）阳性神经元的丢失，通过自噬对运动功能和神经病理学发挥有益作用[8]。