Review

Authors: Giovanni Schepici, Placido Bramanti, Emanuela Mazzon...

Sulforaphane (SFN) is a phytocompound belonging to the isothiocyanate family. Although it was also found in seeds and mature plants, SFN is mainly present in sprouts of many cruciferous vegetables, including cabbage, broccoli, cauliflower, and Brussels sprouts. SFN is produced by the conversion of glucoraphanin through the enzyme myrosinase, which leads to the formation of this isothiocyanate. SFN is especially characterized by antioxidant, anti-inflammatory, and anti-apoptotic properties, and for this reason, it aroused the interest of researchers. The aim of this review is to summarize the experimental studies present on Pubmed that report the efficacy of SFN in the treatment of neurodegenerative disease, including Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). Therefore, thanks to its beneficial effects, SFN could be useful as a supplement to counteracting neurodegenerative diseases.

Topics: Anti-Inflammatory Agents; Antioxidants; Apoptosis; Humans; Isothiocyanates; Neurodegenerative Diseases; Sulfoxides

PubMed: 33207780
DOI: 10.3390/ijms21228637

Review

Authors: Raymond A Otoo, Antiño R Allen

Sulforaphane (SFN) is a naturally occurring compound found in cruciferous vegetables such as broccoli and cauliflower. It has been widely studied for its potential as a neuroprotective and anticancer agent. This review aims to critically evaluate the current evidence supporting the neuroprotective and anticancer effects of SFN and the potential mechanisms through which it exerts these effects. SFN has been shown to exert neuroprotective effects through the activation of the Nrf2 pathway, the modulation of neuroinflammation, and epigenetic mechanisms. In cancer treatment, SFN has demonstrated the ability to selectively induce cell death in cancer cells, inhibit histone deacetylase, and sensitize cancer cells to chemotherapy. SFN has also shown chemoprotective properties through inhibiting phase I metabolizing enzymes, modulating phase II xenobiotic-metabolizing enzymes, and targeting cancer stem cells. In addition to its potential as a therapeutic agent for neurological disorders and cancer treatment, SFN has shown promise as a potential treatment for cerebral ischemic injury and intracranial hemorrhage. Finally, the ongoing and completed clinical trials on SFN suggest potential therapeutic benefits, but more research is needed to establish its effectiveness. Overall, SFN holds significant promise as a natural compound with diverse therapeutic applications.

Topics: Neuroprotection; Isothiocyanates; Sulfoxides; Histone Deacetylases

PubMed: 37836745
DOI: 10.3390/molecules28196902

Review

Authors: Yoko Yagishita, Jed W Fahey, Albena T Dinkova-Kostova...

There is robust epidemiological evidence for the beneficial effects of broccoli consumption on health, many of them clearly mediated by the isothiocyanate sulforaphane. Present in the plant as its precursor, glucoraphanin, sulforaphane is formed through the actions of myrosinase, a β-thioglucosidase present in either the plant tissue or the mammalian microbiome. Since first isolated from broccoli and demonstrated to have cancer chemoprotective properties in rats in the early 1990s, over 3000 publications have described its efficacy in rodent disease models, underlying mechanisms of action or, to date, over 50 clinical trials examining pharmacokinetics, pharmacodynamics and disease mitigation. This review evaluates the current state of knowledge regarding the relationships between formulation (e.g., plants, sprouts, beverages, supplements), bioavailability and efficacy, and the doses of glucoraphanin and/or sulforaphane that have been used in pre-clinical and clinical studies. We pay special attention to the challenges for better integration of animal model and clinical studies, particularly with regard to selection of dose and route of administration. More effort is required to elucidate underlying mechanisms of action and to develop and validate biomarkers of pharmacodynamic action in humans. A sobering lesson is that changes in approach will be required to implement a public health paradigm for dispensing benefit across all spectrums of the global population.

Topics: Animals; Anti-Infective Agents; Antineoplastic Agents, Phytogenic; Biomarkers, Tumor; Brassica; Clinical Trials as Topic; Humans; Isothiocyanates; Molecular Structure; Plant Extracts; Sulfoxides

PubMed: 31590459
DOI: 10.3390/molecules24193593

Randomized Controlled Trial

Authors: Kanwaljit Singh, Susan L Connors, Eric A Macklin...

Autism spectrum disorder (ASD), characterized by both impaired communication and social interaction, and by stereotypic behavior, affects about 1 in 68, predominantly males. The medico-economic burdens of ASD are enormous, and no recognized treatment targets the core features of ASD. In a placebo-controlled, double-blind, randomized trial, young men (aged 13-27) with moderate to severe ASD received the phytochemical sulforaphane (n = 29)--derived from broccoli sprout extracts--or indistinguishable placebo (n = 15). The effects on behavior of daily oral doses of sulforaphane (50-150 µmol) for 18 wk, followed by 4 wk without treatment, were quantified by three widely accepted behavioral measures completed by parents/caregivers and physicians: the Aberrant Behavior Checklist (ABC), Social Responsiveness Scale (SRS), and Clinical Global Impression Improvement Scale (CGI-I). Initial scores for ABC and SRS were closely matched for participants assigned to placebo and sulforaphane. After 18 wk, participants receiving placebo experienced minimal change (<3.3%), whereas those receiving sulforaphane showed substantial declines (improvement of behavior): 34% for ABC (P < 0.001, comparing treatments) and 17% for SRS scores (P = 0.017). On CGI-I, a significantly greater number of participants receiving sulforaphane had improvement in social interaction, abnormal behavior, and verbal communication (P = 0.015-0.007). Upon discontinuation of sulforaphane, total scores on all scales rose toward pretreatment levels. Dietary sulforaphane, of recognized low toxicity, was selected for its capacity to reverse abnormalities that have been associated with ASD, including oxidative stress and lower antioxidant capacity, depressed glutathione synthesis, reduced mitochondrial function and oxidative phosphorylation, increased lipid peroxidation, and neuroinflammmation.

Topics: Adolescent; Adult; Child Development Disorders, Pervasive; Humans; Isothiocyanates; Male; Placebos; Social Behavior; Sulfoxides; Treatment Outcome; Young Adult

PubMed: 25313065
DOI: 10.1073/pnas.1416940111

Randomized Controlled Trial

Authors: Martin Magner, Kateřina Thorová, Veronika Župová...

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder with repetitive behaviour which affects interaction and communication. Sulforaphane (SFN), an isothiocyanate abundant in the seeds and sprouts of cruciferous vegetables, has been shown to be effective in alleviating autistic behaviour. We performed a prospective double-blind placebo-controlled study to examine the possible effect of SFN in a paediatric cohort aged three to seven years based on measurements of the Autism Diagnostic Observation Schedule-2 (ADOS-2), the Social Responsiveness Scale-2 (SRS-2), and the Aberrant Behaviour Checklist (ABC). The study consisted of three visits over the duration of 36 weeks (baseline, 18 weeks, and 36 weeks). Twenty-eight of the 40 randomized children completed the study. The mean total raw scores on ABC and SRS-2 improved in both groups, but none of the changes reached statistical significance (ABC: 0 weeks = 0.2742, 18 weeks = 0.4352, and 36 weeks 0.576; SRS-2: 0 weeks = 0.5235, 18 weeks = 0.9176, and 36 weeks 0.7435). Changes in the assessment of the ADOS-2 subscale scores also did not differ between the two study cohorts (ADOS-2: 0 weeks = 0.8782, 18 weeks = 0.4788, and 36 weeks 0.9414). We found no significant clinical improvement in the behavioural outcome measures evaluated in children with ASD aged 3-7 years that were treated with sulforaphane.

Topics: Humans; Child; Autistic Disorder; Autism Spectrum Disorder; Double-Blind Method; Prospective Studies; Isothiocyanates

PubMed: 36771424
DOI: 10.3390/nu15030718

Review

Authors: Xin Jiang, Ye Liu, Lixin Ma...

Cancer is one of the major causes of morbidity and mortality in the world. Carcinogenesis is a multistep process induced by genetic and epigenetic changes that disrupt pathways controlling cell proliferation, apoptosis, differentiation, and senescence. In this context, many bioactive dietary compounds from vegetables and fruits have been demonstrated to be effective in cancer prevention and intervention. Over the years, sulforaphane (SFN), found in cruciferous vegetables, has been shown to have chemopreventive activity in vitro and in vivo. SFN protects cells from environmental carcinogens and also induces growth arrest and/or apoptosis in various cancer cells. In this review, we will discuss several potential mechanisms of the chemopreventive activity of SFN, including regulation of Phase I and Phase II drug-metabolizing enzymes, cell cycle arrest, and induction of apoptosis, especially via regulation of signaling pathways such as Nrf2-Keap1 and NF-κB. Recent studies suggest that SFN can also affect the epigenetic control of key genes and greatly influence the initiation and progression of cancer. This research may provide a basis for the clinical use of SFN for cancer chemoprevention and enable us to design preventive strategies for cancer management, reduce cancer development and recurrence, and thus improve patient survival.

Topics: Animals; Anticarcinogenic Agents; Apoptosis; Cell Cycle Checkpoints; Cell Proliferation; Humans; Isothiocyanates; Metabolic Detoxication, Phase I; Metabolic Detoxication, Phase II; Neoplasms; Sulfoxides

PubMed: 30254420
DOI: 10.2147/DDDT.S100534

Review

Authors: Dushani L Palliyaguru, Jian-Min Yuan, Thomas W Kensler...

Isothiocyanates from cruciferous vegetables have been studied extensively in cells and in animals for their disease preventive and therapeutic effects. However, translating their utility to human populations has been both limited and challenging. Herein, clinical trials employing two isothiocyanates, sulforaphane (SFN; 1-isothiocyanato-4-(methylsulfinyl) butane) and phenethyl isothiocyanate (PEITC; 2-isothiocyanatoethylbenzene) that are isolated principally from broccoli and watercress, respectively, are summarized and discussed. Both of these compounds have been used in small human clinical trials, either within food matrices or as single agents, against a variety of diseases ranging from cancer to autism. Results suggest an opportunity to incorporate them, or more likely preparations derived from their source plants, into larger human disease mitigation efforts. The context for the applications of these compounds and plants in evidence-based food and nutritional policy is also evaluated.

Topics: Brassica; Cardiovascular Diseases; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Humans; Isothiocyanates; Neoplasms; Skin Diseases; Sulfoxides; Treatment Outcome; Vegetables

PubMed: 29468815
DOI: 10.1002/mnfr.201700965

Review

Authors: Yu-Yao Wu, Yan-Ming Xu, Andy T Y Lau...

(), which belongs to the Moringaceae family, is a common herb, rich in plant compounds. It has a variety of bioactive compounds that can act as antioxidants, antibiotics, anti-inflammatory and anti-cancer agents, etc., which can be obtained in different body parts of . Isothiocyanates (ITCs) from are one class of these active substances that can inhibit cancer proliferation and promote cancer cell apoptosis through multiple signaling pathways, thus curbing cancer migration and metastasis, at the same time they have little adverse effect on normal cells. There are multiple variants of ITCs in , but the predominant phytochemical is 4-(α-L-rhamnosyloxy)benzyl isothiocyanate, also known as moringa isothiocyanate (MIC-1). Studies have shown that MIC-1 has the possibility to be used clinically for the treatment of diabetes, neurologic diseases, obesity, ulcerative colitis, and several cancer types. In this review, we focus on the molecular mechanisms underlying the anti-cancer and anti-chronic disease effects of MIC-1, current trends, and future direction of MIC-1 based treatment strategies. This review combines the relevant literature of the past 10 years, in order to provide more comprehensive information of MIC-1 and to fully exploit its potentiality in the clinical settings.

Topics: Anti-Inflammatory Agents; Anti-Obesity Agents; Anti-Ulcer Agents; Antineoplastic Agents, Phytogenic; Humans; Hypoglycemic Agents; Isothiocyanates; Moringa oleifera

PubMed: 34946594
DOI: 10.3390/molecules26247512

Authors: Camille Bowen-Forbes, Edward Armstrong, Audric Moses...

Our research group previously found that broccoli sprouts possess neuroprotective effects during pregnancy. The active compound has been identified as sulforaphane (SFA), obtained from glucosinolate and glucoraphanin, which are also present in other crucifers, including kale. Sulforaphene (SFE), obtained from glucoraphenin in radish, also has numerous biological benefits, some of which supersede those of sulforaphane. It is likely that other components, such as phenolics, contribute to the biological activity of cruciferous vegetables. Notwithstanding their beneficial phytochemicals, crucifers are known to contain erucic acid, an antinutritional fatty acid. The aim of this research was to phytochemically examine broccoli, kale, and radish sprouts to determine good sources of SFA and SFE to inform future studies of the neuroprotective activity of cruciferous sprouts on the fetal brain, as well as product development. Three broccoli: Johnny's Sprouting Broccoli (JSB), Gypsy F1 (GYP), and Mumm's Sprouting Broccoli (MUM), one kale: Johnny's Toscano Kale (JTK), and three radish cultivars: Black Spanish Round (BSR), Miyashige (MIY), and Nero Tunda (NT), were analyzed. We first quantified the glucosinolate, isothiocyanate, phenolics, and DPPH free radical scavenging activity (AOC) of one-day-old dark- and light-grown sprouts by HPLC. Radish cultivars generally had the highest glucosinolate and isothiocyanate contents, and kale had higher glucoraphanin and significantly higher sulforaphane content than the broccoli cultivars. Lighting conditions did not significantly affect the phytochemistry of the one-day-old sprouts. Based on phytochemistry and economic factors, JSB, JTK, and BSR were chosen for further sprouting for three, five, and seven days and subsequently analyzed. The three-day-old JTK and radish cultivars were identified to be the best sources of SFA and SFE, respectively, both yielding the highest levels of the respective compound while retaining high levels of phenolics and AOC and markedly lower erucic acid levels compared to one-day-old sprouts.

Topics: Glucosinolates; Brassica; Raphanus; Isothiocyanates; Free Radicals

PubMed: 37298743
DOI: 10.3390/molecules28114266

Review

Authors: Yuting Zhang, Huiting Huang, Libo Jin...

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, accounting for about 90% of cases. Sorafenib, lenvatinib, and the combination of atezolizumab and bevacizumab are considered first-line treatments for advanced HCC. However, clinical application of these drugs has also caused some adverse reactions such as hypertension, elevated aspartate aminotransferases, and proteinuria. At present, natural products and their derivatives have drawn more and more attention due to less side effects as cancer treatments. Isothiocyanates (ITCs) are one type of hydrolysis products from glucosinolates (GLSs), secondary plant metabolites found exclusively in cruciferous vegetables. Accumulating evidence from encouraging in vitro and in vivo animal models has demonstrated that ITCs have multiple biological activities, especially their potentially health-promoting activities (antibacterial, antioxidant, and anticarcinogenic effects). In this review, we aim to comprehensively summarize the chemopreventive, anticancer, and chemosensitizative effects of ITCs on HCC, and explain the underlying molecular mechanisms.

Topics: Animals; Anticarcinogenic Agents; Carcinoma, Hepatocellular; Liver Neoplasms; Isothiocyanates

PubMed: 36430307
DOI: 10.3390/ijms232213834