Therapeutic approaches using natural substances on the streptozotocin-induced animal model of sporadic Alzheimer’s disease: a systematic review

With the worldwide increase in life expectancy, cases of Alzheimer’s disease (AD) have also risen. Although new disease-modifying treatments are now available, novel drugs for the pharmacological modulation of AD are still needed. To that end, animal models are widely employed, and one of the used models of AD is the intracerebroventricular Streptozotocin-induced (STZ) animal model of sporadic Alzheimer’s disease. STZ triggers neuroinflammatory and oxidative stress pathways, besides increasing Aβ and hyperphosphorylated tau protein expression, ultimately leading to neurodegeneration and impairments in cognitive function. Regarding drug development, natural substances, such as plant extracts and their isolated bioactive compounds, have shown a myriad of relevant pharmacological properties for AD, such as neuroprotective, anti-inflammatory, and antioxidative activities. Considering that, previous studies have investigated the effects of compounds obtained from plants on the STZ model, and the aim of this systematic review was to collect and discuss the published results. Searching in four different databases, we selected and included seventy studies in this review, and their characteristics, methods, and results were extracted and discussed. The main results showed that natural substances obtained from plants can reverse STZ damage through the modulation of antioxidative, antiapoptotic, and anti-inflammatory pathways, improving cognitive function, especially memory. In conclusion, natural substances are potential candidates for novel drug development for the treatment of AD-related symptoms.