Therapeutic Potential of Plant-Derived Isothiocyanates in Mental Health Plant-derived isothiocyanates (ITCs) are generated from the glucosinolates, generally through enzymatic action of myrosinase see Fig. 1. They are widly found in the Cruciferous vegetables, some notable ones, and their corrosponding glucosinolates are sulforaphane (from glucoraphinin) from Brassica oleracea , 2-phenethylisothiocyate (from gluconasturtiin) from watercress ( Nasturtium officinale ), benzyl isothiocyanate (from glucotropaeolin) from Tropaeolum majus (common nasturtium), 4-(methylthio)-butyl-isothiocyanate (from erucin) from rocket. Other sources include Moringa (moringin) and Papaya seed (benzyl isothiocyanate). Figure 1. Generally all the isothiocyanates are potent Nrf2 activators, targeting the inflammasome, and act via several mechanisms which exert anti-oxidant, anti-inflammatory and chemo- protective effects and upregulate antioxidant defences eg glutathione. Chronic oxidative stress and inflammation are central to the pathogenesis of many chronic diseases, including psychiatric and neurologic disorders. The evidence supporting a protective effect of ITCs in neurodevelopmental, neurodegenerative, and other neurologic disorders is rapidly accumulating. A description of some of the beneficial activities of ITCs is pictured in the below figure. 1 Modified from: https://www.frontiersin.org/articles/10.3389/fphar.2021.767975/full ITCs have: - improved neuroinflammation - ameliorated anxiety and depressive-like behaviours in animal models - some beneficial effects on behavior and social interaction and communication in ASD [significant improvement in behavioral phenotypes such as irritability and motivation, alongside social and cognitive scores] - consumption of isothiocyanates was expected to promote clinical improvements in cognitive impairment caused by schizophrenia - facilitates the restoration of memory and learning deficits in patients with frontal brain damage - Sulforaphane can ameliorate neurobehavioral deficits and reduce the Aβ burden in Alzheimer's disease model mice, and the mechanism underlying these effects may be associated with up-regulation of neurotrophin receptor mediated processed, apparently at least in part, via reducing the expression of histone deacetylases Perhaps the most well studied and utilised isothiocyanate for mental health is brocoli sprout 2 derived sulforaphane. It is of interest clinically in ASD, cognitive disorders and some preclinical evidence suggest it may have merits in neurodegenerative, psychotic and mood disorders. It has a broad spectrum of pharmacological activities, most notably anti- inflammatory, anti-oxidant, neuroprotective effects, primarily from Nrf2 activation. It also has epigenetic modulatory effects through HDAC inhibition. There are also effects on mitochondrial and synaptic function, neuroinflammation etc. Early placebo-controlled trials in ASD showed some improvements in various symptom domains in young men (Kanwaljit et al. 2014, Lynch et al. 2017) which was not replicated in younger children by Magner et al 2023. It seems to stimulate neurogenesis and increases the expression of BDNF and reduces microglial activation and proinflammatory cytokine production. Tropaeolum majus The Brassicales species Nasturtium (Tropaeolum majus) pictured above is characterised especially by high concentrations of the predominant aromatic benzyl glucosinolate (1000 mg/100 g fresh matter) which yields benzyl isothiocyanate which is a potent inducer of phase II detoxifying enzymes and subsequently confers protection against oxidative stress and chronic inflammation Brassica juncea Red Giant The leaf mustards ( Brassica juncea ) accumulate glucosinolates in the leaves, leaving a pungent when fresh dietary option. Generally cooking decreases the pungency, likely volatilising the ITCs.It is a rich source of carotenoids, glucosinolates/ITCs, flavonoids/phenolics and possess potential anxiolytic and other therapeutically interesting CNS function modulating activities. It is proposed to be a therapeutic option for treatment of cognitive disorders and mood disorders and "glucosinolates accumulate in the mustard 3 leaves from young, immature stage to mature stage, and therefore mature mustard leaves may provide greater glucosinolate-derived health benefits" Erucin from rocket showed an interesting profile of antioxidant, anti-inflammatory and neuroprotective effects similar to those observed with sulforaphane. In general, isothiocyanates are a promising dietary and therapeutic intervention for CNS disorders. Initial research is promising in a variety of disorders and their potential for optimising mental health has yet to be fully studied but holds significant promise. References: Alena Vanduchova, Pavel Anzenbacher, and Eva Anzenbacherova. Isothiocyanate from Broccoli, Sulforaphane, and Its Properties. Journal of Medicinal Food.Feb 2019.121-126. https://doi.org/10.1089/jmf.2018.0024 Albena Dinkova-Kostova, Rumen V. Kostov. Glucosinolates and isothiocyanates in health and disease Trends in Molecular Medicine, Vol. 18, IS 6, P337-347, JUNE 2012 https://doi.org/10.1016/j.molmed.2012.04.003 Chao Huang, Jingjing Wu et al. Effects of sulforaphane in the central nervous system, European Journal of Pharmacology, Volume 853, 2019, Pages 153-168, https://doi.org/10.1016/j.ejphar.2019.03.010 Sabrina Giacoppo, Maria Galuppo et al. An overview on neuroprotective effects of isothiocyanates for the treatment of neurodegenerative diseases, Fitoterapia, Volume 106, 2015, Pages 12-21, ISSN 0367-326X, https://doi.org/10.1016/j.fitote.2015.08.001 Kanwaljit Singh, Susan L. Connors et al. Sulforaphane treatment of autism spectrum disorder (ASD)] PNAS 2014, 111 (43) 15550-15555 https://doi.org/10.1073/pnas.1416940111 Lynch R, Diggins EL, Connors SL, et al. Sulforaphane from Broccoli Reduces Symptoms of Autism: A Follow-up Case Series from a Randomized Double-blind Study. Global Advances in Health and Medicine. 2017;6 https://doi.org/10.1177/2164957x17735826 Magner, M.; Thorová, K et al. Sulforaphane Treatment in Children with Autism: A Prospective Randomized Double-Blind Study. Nutrients 2023, 15, 718. https://doi.org/10.3390/nu15030718 Panjwani AA, Liu H, Fahey JW. Crucifers and related vegetables and supplements for neurologic disorders: what is the evidence? Curr Opin Clin Nutr Metab Care. 2018 Nov;21(6):451-457 https://doi.org/10.1097/mco.0000000000000511 Connolly EL, Sim M, et al. Glucosinolates From Cruciferous Vegetables and Their Potential Role in Chronic Disease: Investigating the Preclinical and Clinical Evidence. Front Pharmacol. 2021 Oct 26;12:767975. https://doi.org/10.3389/fphar.2021.767975 4 5