Resveratrol regulates Thoc5 to improve maternal immune activation-induced autism-like behaviors in adult mouse offspring

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that primarily occurs in young children and has a strong genetic component. ASD is characterized by deficits in social communication and the presence of restricted, repetitive behaviors or interests [1]. Epidemiological investigation has shown that ASD affects approximately 78 million people worldwide, and the number of patients with ASD has rapidly increased in the past 20 years [2]. However, these drugs antagonize dopaminergic and serotonin with limited effect and are prone to cause adverse reactions such as hyperglycemia, dyslipidemia, and weight gain [3]. Therefore, an effective treatment for ASD is urgently needed.

Maternal immune activation (MIA) is an important environmental factor that causes ASD in offspring. MIA refers to the activation of the immune system during pregnancy and childbirth due to infection, allergies, malignant tumors, autoimmune diseases, and other reasons, and it is closely related to the occurrence and development of psychiatric disorders [4]. MIA can affect the growth and survival of neurons through inflammation, and it can increase the level of oxidative stress to promote inflammation. Simultaneously, its ability to damage mitochondrial function leads to increased oxidative stress, resulting in a vicious cycle of neurological damage.

Traditional Chinese Medicine (TCM) has a 2,000-year history and has formed a complete methodology of diagnosis, pathophysiology, and therapy. Outside China, TCM is usually regarded as a supplementary or alternative medical treatment, and the international prevalence of TCM has been steadily increasing. In recent years, novel drugs produced in the field of Chinese herbs have drawn increasing interest [5]; indeed, the 2015 Nobel Prize in Physiology or Medicine was awarded to Youyou Tu, a TCM scientist who discovered and developed artemisinin. Encouragingly, TCM has recently shown beneficial effects in animal experiments and clinical treatments of ASD [6]. However, the practice of TCM for treating ASD is still rare.

Medicine food homologous (MFH) is an important TCM concept that originates from the sentence ‘eating on an empty stomach as food and administering to patients as medication’ in the traditional Chinese book Huangdi's Classic on Medicine. In many countries, MFH herbs have become the main component of functional foods and have received widespread attention, with many studies, including animal studies, demonstrating their benefits at the molecular level [7,8]. MFH perfectly combines food safety and drug treatment, and caters to the currently advocated green and healthy principles. MFH herbs have both medicinal and nutritive value, with positive effects and less adverse reactions.

In this study, we used bioinformatics analysis and molecular docking technology to conduct large-scale screening and verification to complete an analysis and prediction of the active ingredients, targets, and pathways of MFH herbs against ASD and confirmed the therapeutic effect of resveratrol on MIA-induced ASD by using in vitro and in vivo experiments.

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