Abstract
Alzheimer's disease (AD), characterized by progressive dementia and deterioration of cognitive function, is an unsolved social and medical problem. Age, nutrition, and toxins are the most common causes of AD. However, currently no credible treatment is available for AD. Traditional herbs and phytochemicals may delay its onset and slow its progression and also allow recovery by targeting multiple pathological causes by antioxidative, anti-inflammatory, and antiamyloidogenic properties. They also regulate mitochondrial stress, apoptotic factors, free radical scavenging system, and neurotrophic factors. Neurotrophins such as BDNF, NGF, NT3, and NT4/5 play a vital role in neuronal and nonneuronal responses to AD. Neurotrophins depletion accelerates the progression of AD and therefore, replacing such neurotrophins may be a potential treatment for neurodegenerative disease. Here, we review the phytochemicals that mediate the signaling pathways involved in neuroprotection specifically neurotrophin-mediated activation of Trk receptors and members of p75NTR superfamily. We focus on representative phenolic derivatives, iridoid glycosides, terpenoids, alkaloids, and steroidal saponins as regulators of neurotrophin-mediated neuroprotection. Although these phytochemicals have attracted attention owing to their in vitro neurotrophin potentiating activity, their in vivo and clinical efficacy trials has yet to be established. Therefore, further research is necessary to prove the neuroprotective effects in preclinical models and in humans.
Highlights
We revealed that the L. platyphylla extract contains spicatoside A (Figure 4), a steroidal saponin that exerts a neurotrophic effect by inducing neurite outgrowth in PC12 cells and by inducing nerve growth factor (NGF) synthesis in astrocytes through TrkA receptor-mediated PI3-kinase and ERK1/2 activation of CREB, which regulates neuronal function and long-term potentiation (LTP) [35]
Based on the above review, several pieces of evidence suggest that naturally occurring phytochemicals that affect neurotrophins and downstream signaling targets should be a first-line treatment of several types of neurodegenerative disease
The review provides a comprehensive discussion of the literature regarding phytochemicals and demonstrates that these compounds offer a safe approach to protect against the neuronal damage caused by neurotrophin deficits and toxin-induced degenerative diseases
Summary
Phytochemicals provide an effective way of halting neurodegenerative disease Phytochemicals and derivatives such as 3,7-dihydroxy-2,4,6-trimethoxy-phenanthrene, diosniposide B, lignan derivatives, ginkgolide B, 4,6-dimethoxyphenanthrene-2,3,7-triol, spicatoside A, ginsenoside Rg3, limonoid derivatives, quercetin, cyanidin-3-O-βglucopyranoside, clerodane diterpenoids, apigenin derivatives, and quinic acid derivatives induce neuronal cell differentiation and upregulate neurotrophic factors such as NGF and BDNF [18, 35, 44, 45]. NGF triggers the TrkA signaling pathway [18, 35, 44, 45] by inhibiting caspase protein expression [46] and via degradation of beta amyloid oligomers in the brain [47] Phytochemicals such as ladostigil have multiple targets on neurons and appear to be effective in treating neurodegenerative diseases. Our review focuses on phytochemicals that have the potential to treat neurodegenerative diseases by targeting neurotrophins
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