Mechanisms underlying biological effects of cruciferous glucosinolate-derived isothiocyanates/indoles: a focus on metabolic syndrome

Abstract

An inverse correlation between vegetable consumption and the incidence of cancerhas long been described. This protective effect is strongerwhen cruciferous vegetablesare specifically consumed. The beneficial properties of vegetables are attributed totheir bioactive components like fiber, antioxidants vitamins, antioxidants, minerals, andphenolic compounds. Cruciferous vegetables contain all these molecules; however, whatmakes them different are their sulfurous components, called glucosinolates, responsiblefor their special smell and taste. Glucosinolates are inactive biologically in the organismbut are hydrolyzed by the enzyme myrosinase released as a result of chewing, leading tothe formation of active derivatives such as isothiocyanates and indoles. A considerablenumber ofin vitroandin vivostudies have reported that isothiocyanates and indoleselicit chemopreventive potency through multiple mechanisms that include modulationof phases I and II detoxification pathway enzymes, regulation of cell cycle arrest,and control of cell growth, induction of apoptosis, antioxidant activity, anti-angiogeniceffects, and epigenetic regulation. Nuclear erythroid 2-related factor 2 (Nrf2) and Nuclearfactor-κB (NF-κB) are key and central regulators in all these processes witha main rolein oxidative stress and inflammation control. It has been described that isothiocyanatesand indoles regulate their activity directly and indirectly. Today, the metabolic syndrome(central obesity, insulin resistance, hyperlipidemia, and hypertension) is responsible for amajority of deaths worldwide. All components of metabolic syndrome are characterizedby chronic inflammation with deregulation of the PI3K/AKT/mTOR, MAPK/EKR/JNK,Nrf2, and NF-κB signaling pathways. The effects of GLSs derivatives controlling thesepathways have been widely described in relation to cancer. Changes in food consumptionpatterns observed in the last decades to higher consumptionof ultra-processed foods,with elevation in simple sugar and saturated fat contents and lower consumptionof vegetables and fruits have been directly correlated withmetabolic syndromeprevalence. In this review, it is summarized the knowledge regarding the mechanismsby which cruciferous glucosinolate derivatives (isothiocyanates and indoles) directly and indirectly regulate these pathways. However, the review places a special focus onthe knowledge of the effects of glucosinolates derivativesin metabolic syndrome, sincethis has not been reviewed before.