Neuroprotective mechanisms of S-allyl-L-cysteine in neurological disease (Review)

Abstract

S-allyl-L-cysteine (SAC) is a sulfur-containing amino acid present in garlic and exhibits a wide range of biological activities such as antioxidant, anti-inflammatory, and anticancer agent. An earlier study demonstrated that SAC ameliorates oxidative damage in a model of experimental stroke. However, the antioxidant property of SAC does not suffice to explain its beneficial effects in terms of the underlying mechanisms. Endoplasmic reticulum (ER) stress and ER stress-induced cell death have been shown to be involved in various neurological diseases such as brain ischemia, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and Huntington's disease. We have previously demonstrated that SAC exerts significant protective effects against ER stress-induced neurotoxicity in cultured rat hippocampal neurons and organotypic hippocampal slice cultures. Recently, we demonstrated that these results are due to the direct suppression of calpain activity via the binding of SAC to this enzyme's Ca 2+-binding domain. We also found that the protective effects of the side-chain-modified SAC derivatives, S-ethyl-L-cysteine (SEC) and S-propyl-L-cysteine (SPC), against ER stress-induced neurotoxicity were more potent than those of SAC in cultured rat hippocampal neurons. In addition, SAC, SEC and SPC have been shown to decrease the production of amyloid-β peptide in the brains of mice with D-galactose-induced aging. These three hydrophilic cysteine-containing compounds have also been shown to exert neuroprotective effects against dopaminergic neuron injury in a murine model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In this review, we aim to provide a current overview of the protective actions of SAC and the SAC-related compounds, SEC and SPC, in neurodegenerative disease and discuss the promise of SAC as a prototype for developing novel therapeutic drugs for neurological diseases. Contents 1. Introduction 2. Protective effects of SAC against neuronal death due to ER stress 3. Calpain is a probable target molecule for SAC 4. Analogs of SAC 5. Conclusions and future perspectives

S‐Allyl cysteine in garlic (Allium sativum): Formation, biofunction, and resistance to food processing for value‐added product development

“…Through an Nrf2‐dependent antioxidant response component, SAC has been shown to exhibit neuroprotective effects in ischemic nerve injury, retinal protection against kainate neurotoxicity, protection of dopamine neurons from the toxic effects of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP), and repair of β‐amyloid‐induced brain damage (Kosuge, 2019; Zarezadeh et al., 2017). A master transcription factor that regulates phase 2 enzyme production, Nrf2, is inactive under normal settings because it binds to Kelch‐like ECH‐associated protein 1 (KEAP1).…”

S-Methylcysteine (SMC) Ameliorates Intestinal, Hepatic, and Splenic Damage Induced by Cryptosporidium parvum Infection Via Targeting Inflammatory Modulators and Oxidative Stress in Swiss Albino Mice

“…Interestingly, several previous reports have documented a wide range of activities of garlic and its components, particularly SMC, for treatment of various physiological and pathological conditions [ 24 , 25 , 26 ]. In this regard, some previous reports revealed that garlic, SMC, and other organosulfur compounds of raw or extracted garlic showed anticancer [ 27 ], antioxidant [ 28 ], anti-inflammatory [ 29 ], antidiabetic [ 30 ], cardioprotective [ 24 ], neuroprotective [ 31 ], hypocholesterolemic [ 30 ], antiinfective [ 32 , 33 ], and hepatoprotective effects [ 34 , 35 , 36 ]. To the authors’ knowledge, no former investigations assessed the effect of SMC against C. parvum either in vitro or in vivo.…”

Allium sativum, a potential phytopharmacological source of natural medicine for better health

“…Active component N-α-[1-deoxy-D-fructos-1-yl]-L-arginine [FruArg] from AGE alleviated neuroinflammation by inhibiting the production of NO and regulating the expression of multiple protein targets related to oxidative stress in lipopolysaccharide activated murine BV-2 microglial cells [130]. S-allyl-L-cysteine [SAC] exerts significant protective effects against endoplasmic reticulum stress-induced neurotoxicity in cultured rat hippocampal neurons and organotypic hippocampal slice cultures [131]. SAC and FruArg are prototype for developing novel therapeutic drugs for neurological diseases.…”