ne sulforaphane can be a all-natural dietary compound, derived from numerous cruciferous plants, which include broccoli, cabbage, and cauliflower, with potent anticancer activity [136,137]. Previous placebo-controlled, double-blinded, randomized clinical trial, studies showed thatInt. J. Mol. Sci. 2021, 22,13 ofsulforaphane treatment significantly lowered the symptoms of and enhanced the behavioral abnormalities in male ASD [136,138]. The cytoprotective impact of sulforaphane is primarily mediated by the activation of nuclear element erythroid two elated factor 2 (NRF2)dependent antioxidant genes, such as NAD(P)H: quinone oxidoreductase-1 (NQO1), and heme oxygenase-1 (HO-1) [139,140]. As well as its effect around the NRF2 pathway, it was shown that sulforaphane can be a potent antagonist for AhR activation and CYP1A1 and CYP1A2 induction in human hepatoma HepG2 and breast cancer MCF-7 cells [141], and in rat precision-cut liver slices [142], suggesting that the AhR/CYP pathway could mediate sulforaphane’s protective effect on autism. Mechanistically, it may very well be postulated that sulforaphane inhibits AhR/CYP1 activation, causing DNA adduct in addition to a DNA strand break [143]. This really is supported by the observations that higher levels of oxidative stress and oxidative DNA damage, including 8-oxo-7-hydrodeoxyguanosine, 5-methylcytosine, and 5-hydroxymethylcytosinehave, have already been reported in subjects with ASD [144], and in the cerebellum of a BTBR T+tf/J autistic mouse model [100]. A current systematic overview aimed to evaluate the therapeutic use of sulforaphane on patients with autism showed proof that sulforaphane is definitely an effective remedy option for treating ASD [145]. five.two. Valproic Acid Valproic acid, or sodium valproate, is an archaic drug made use of to treat bipolar disorder and epilepsy with low safety margins [146]. Maternal exposure to valproic acid during pregnancy leads to development of autism-like behavior and inside the offspring and childhood [147,148]. This effect appears to be only a home of valproic acid and no other antiepileptic agents as exposures to carbamazepine, oxcarbazepine, lamotrigine, and clonazepam monotherapy didn’t raise risks of childhood autism, which may be attributed towards the distinction in their structures [149]. Thus, valproic acid is usually a preferred model of studying autism in rodents [115,149,150]. An ASD gene-environment interaction study showed that around 130 ASGs are targeted by valproic acid [34]. Even so, some studies have linked valproic acid-Caspase 3 Inducer review induced autism and AhR as a postulated mechanism. Being aware of that valproic acid is often a HDA enzyme inhibitor that could alter histone structure and bring about adjustments in the binding of transcription aspects to DNA, valproic acid induces the expression of both AhR and CYP1A1 [151] via DNA methylation [152]. Nonetheless, additional studies are needed to investigate the part of the AhR pathway in valproate-induced autism. 5.3. Resveratrol Resveratrol is actually a dietary Caspase Inhibitor supplier compound with neuroprotective, anti-inflammatory and antioxidant properties. It really is a known repressor with the AhR pathway [153]. Resveratrol and its methoxy derivatives are capable of downregulating AhR-related genes [154]. Interestingly, resveratrol, when administered prenatally, prevents social impairments in mice models induced with autism-like behavior using valproic acid [155]. It was also located to reverse cellular and behavioral sensory alteration in valproic acid-induced rat models of ASD [156]. In addition, treatment with resveratrol of rats expose