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Abstract
Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder with limited available treatments and diverse causes. In ASD patients, numerous researches demonstrated various alterations in inflammation/immune, oxidative stress, and mitochondrial dysfunction, and these alterations could be regulated by Nrf2. Hence, we aimed to systematically review the current evidence about the effects of Nrf2 activator supplementation on ASD objects from in vitro studies, animal studies, and clinical studies. Relevant articles were retrieved through searching for the Cochrane Library, PubMed, Web of Science, Scope, Embase, and CNKI databases (through September 23, 2020). Ultimately, we identified 22 preclinical studies, one cell culture study, and seven clinical studies, covering a total of five Nrf2 activators. For each Nrf2 activator, we focused on its definition, potential therapeutic mechanisms, latest research progress, research limitations, and future development directions. Our systematic review provided suggestive evidence that Nrf2 activators have a potentially beneficial role in improving autism-like behaviors and abnormal molecular alterations through oxidant stress, inflammation, and mitochondrial dysfunction. These dietary phytochemicals are considered to be relatively safer and effective for ASD treatment. However, there are few clinical studies to support the Nrf2 activators as dietary phytochemicals in ASD, even though several preclinical studies. Therefore, caution should be warranted in attempting to extrapolate their effects in human studies, and better design and more rigorous research are required before they can be determined as a therapeutic option.
Highlights
Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder characterized by impaired communication and social interaction, as well as repetitive/stereotyped behaviors (1, 2)
We systematically reviewed current evidence on the effects of Nrf[2] activators administration on ASD objects from in vitro studies, animal studies, and clinical studies, aiming to elucidate molecular mechanisms related to the etiology of ASD and to open up a new approach to prevent and/or treat ASD
We employed keywords combined with medical subject headings (MeSH) search, using the following terms: (Autism OR Autism Spectrum Disorder OR autistic OR autism disorder OR ASD OR Asperger Syndrome OR Pervasive Developmental Disorder) AND (Nuclear factor erythroid 2 related factors 2 activators OR NFE2 Related Factor 2 activator OR Nrf[2] activator OR sulforaphane OR SFN OR broccoli OR Brussel sprouts OR watercress OR resveratrol OR curcumin OR naringenin OR agmatine)
Summary
Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder characterized by impaired communication and social interaction, as well as repetitive/stereotyped behaviors (1, 2). The world health organization (WHO) reported in 2017 that one in 160 children worldwide has ASD (3), currently affected 1 in 54 children in the United States (4, 5), predominantly males (6). ASDs greatly limit the capacity of individuals to perform daily activities and participate in society, which imposes a significant emotional and economic burden on affected individuals and their families (3). Many factors may cause ASD, no definite pathogenesis have been established yet (5). There is currently no cure for ASD. Current drugs can only be used to control symptoms related to ASD, including anxiety, hyperactivity, epilepsy, obsessive behavior, and gastrointestinal problems (7)
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