multiple tissue regeneration, including neurogenesis [4]. This suggested that neurogenesis could be promoted by endogenous factors exist or have higher concentration in the young organisms, compared to aged ones. Adult hippocampal neurogenesis is highly regulated by diverse neurotrophic growth factors, among which brain-derived neurotrophic factor (BDNF) and insulin-like growth factor 1 (IGF-1) are investigated most within the past two years [2,5]. The factors upregulate adult neurogenesis, stimulate neuron stem cell differentiation, and subserve newborn neurons survival and maturation [5, 6]. Reductions in the expression levels of BDNF and IGF-1 have been observed during ageing and could account for the age-related hippocampal neurogenesis attenuation [5, 3]. Accordingly, BDNF and IGF-1 are potential targets in therapeutic applications to revitalise hippocampal neurogenesis in old age. Recent researches proposed multiple strategies to reverse age-associated cognition decline via increasing the effects of BDNF and IGF-1.
Improve neurogenesis via increasing BDNF
BDNF promotes hippocampal neurogenesis through specific binding and activation of its receptor, tropomyosin-related kinase receptor B (TrkB) [7]. It has been reported that increasing BDNF level improves dendritic complexity during hippocampal neurogenesis [8] and subserves neural circuit formation and brain computation [9]. However, the limited delivery, short half-life [10] and poor permeability trough brain-blood barrier (BBB) [11] of BDNF impede its therapeutic potential, resulting in disappointed performance of direct use of BDNF in clinical trails. Hence, people are looking for strategies to induce BDNF production in vivo and for the past few decades, antidepressant treatment has been studied widely [12]. In recent years, more researches focus on alternatives to accelerate BDNF-induced neurogenesis.
In 2010, 7, 8-dihydroxyflavone (DHF) was first identified as a TrkB agonist that has potent neurotropic activities [10,11]. DHF imitates the behaviour of BDNF and activates downstream signaling pathways upon DHF-TrkB binding, which improves neurogenesis and dendrite development in adult mice after brain injury [10, 11, 13]. Compared to administration of BDNF, DHF has higher affinity for TrkB and is more permeable through BBB, making it a widely used TrkB agonist since its discovery. Lately, Wang et al. demonstrated the beneficial effects of DHF on promoting