Sulforaphane (SFN), a bioactive compound derived from glucoraphanin in cruciferous vegetables such as broccoli, has been extensively studied for its therapeutic potential across diverse disease categories. SFN exerts its effects through well-characterised pathways, including the Keap1/Nrf2 axis, which regulates phase II detoxification enzymes, and epigenetic mechanisms such as histone deacetylase inhibition. This review evaluates clinical trials registered on ClinicalTrials.gov, focusing on those using SFN or broccoli-derived extracts.

As a result, we identified 84 trials, of which 39 have been published. Results suggest SFN’s potential in regulating redox and inflammatory pathways, improving metabolic and cardiovascular outcomes, and exerting anti-cancer and neuroprotective effects. For healthy subjects, SFN enhanced detoxification and reduced inflammation. In cancer patients, SFN showed promise in early-stage prostate and breast cancer, particularly in GSTM1-positive individuals, but had limited effects in advanced cases. For brain disorders, SFN demonstrated symptomatic improvements in autism spectrum disorder and cognitive benefits in schizophrenia but lacked robust biomarker integration. SFN had minimal impact on respiratory diseases but showed supportive roles in allergic rhinitis therapy. Metabolic disease studies revealed glycaemic control improvements in type 2 diabetes but no benefits for hypertension. Approximately 50% of completed trials remain unpublished, raising concerns about publication bias. While published results highlight SFN’s therapeutic potential, limited sample sizes and inconsistent outcomes underscore the need for more extensive, stratified trials. This review emphasises the importance of integrating mechanistic insights and precision medicine approaches to maximise SFN’s clinical utility.

Overnutrition during before and pregnancy can cause maternal obesity and raise the risk of maternal metabolic diseases during pregnancy, and in offspring. Lentinus edodes may prevent or reduce obesity. This study aimed to to assess Lentinus edodes fermented products effects on insulin sensitivity, glucose and lipid metabolism in maternal and offspring, and explore its action mechanism. A model of overnutrition during pregnancy and lactation was developed using a 60 % kcal high-fat diet in C57BL6/J female mice. Fermented Lentinus edodes (FLE) was added to the diet at concentrations of 1 %, 3 %, and 5 %. The results demonstrated that FLE to the gestation diet significantly reduced serum insulin levels and homeostatic model assessment for insulin resistance (HOMA-IR) in pregnant mice. FLE can regulate maternal lipid metabolism and reduce fat deposition. Meanwhile, the hepatic phosphoinositide-3-kinase-protein kinase (PI3K/AKT) signaling pathway was significantly activated in the maternal mice. There is a significant negative correlation between maternal FLE supplementation doses and offspring body fat percentage and visceral fat content. Furthermore, FLE supplementation significantly increased offspring weaning litter weight, significantly reduced fasting glucose level, serum insulin level, HOMA-IR and serum glucose level, significantly activated liver PI3K/AKT signaling pathway in offspring, and upregulated the expression of liver lipolytic genes adipose triglyceride lipase, hormone-sensitive lipase and carnitine palmitoyltransferase 1 mRNA. Overall, FLE supplementation can regulate maternal lipid metabolism and reduce fat deposition during pregnancy and lactation, and it may improve insulin sensitivity in pregnant mothers and offspring at weaning through activation of the PI3K/AKT signaling pathway.

Kombucha is a fermented beverage rich in bioactive compounds. This beverage has demonstrated high antioxidant capacity in vitro and experimental animal studies. In this sense, this study aimed to evaluate the effect of daily consumption of green tea kombucha on oxidative stress and endothelial health in individuals with excess body weight. This is a randomized controlled clinical trial, lasting 10 weeks, during which the control group followed a healthy −500 kcal/d energy-restricted diet. In contrast, the kombucha group, in addition to the energy-restricted diet, consumed 200 ml of kombucha green tea daily. This study included men and women aged 18–45 years without chronic diseases. At the beginning and end of the study, fasting blood was collected, and colorimetric assays and immunoassay protocols evaluated markers of oxidative stress and endothelial health. Compared to the control group, kombucha consumption significantly reduced hydrogen peroxide (H2O2) levels (P = 0·007). Initial and final values were as follows: Control group (16·5 v. 15·09 µmol/ml; n 29) and Kombucha group (18·14 v. 14·67 µmol/ml; n 30). The other markers that were evaluated did not change after the kombucha consumption. In conclusion, daily consumption of 200 ml of green tea kombucha for 10 weeks reduces one pro-oxidant marker, without altering other markers of oxidative stress and endothelial health in individuals with excess body weight. Reducing a pro-oxidant marker suggests that kombucha is an antioxidant beverage with promising implications for human health. However, further studies are needed to elucidate other possible beneficial effects on health.

Osteoarthritis (OA), a disease with a multifactorial aetiology and an enigmatic root cause, affects the quality of life of many elderly patients. Even though there are certain medications utilised to reduce the symptomatic effects, a reliable treatment method to reverse the disease is yet to be discovered. Zinc is a cofactor of over 3000 proteins and is the only metal found in all six classes of enzymes. We explored zinc’s effect on the immune system and the bones as OA affects both. We also discussed zinc-dependent enzymes, highlighting their significant role in the disease’s pathogenesis. It is important to note that both excessive and deficient zinc levels can negatively affect bone health and immune function, thereby exacerbating OA. The purpose of this review is to offer a better understanding of zinc’s impact on OA pathogenesis and to provide clarity regarding its beneficial and detrimental outcomes. We searched thoroughly systematic reviews, meta-analysis, review articles, research articles and randomised controlled trials to ensure a comprehensive review. In brief, using zinc supplementation in the treatment of OA may act as a doubled-edged sword, offering potential benefits but also posing risks.

Nuclear and chemical weapons of mass destruction share both a tragic and beneficial legacy in mankind’s history and health. The horrific health effects of ionizing radiation and mustard gas exposures unleashed during disasters, wars, and conflicts have been harnessed to treat human health maladies. Both agents of destruction have been transformed into therapies to treat a wide range of cancers. The discovery of therapeutic uses of radiation and sulfur mustard was largely due to observations by clinicians treating victims of radiation and sulfur mustard gas exposures. Clinicians identified vulnerability of leukocytes to these agents and repurposed their use in the treatment of leukemias and lymphomas. Given the overlap in therapeutic modalities, it goes to reason that there may be common mechanisms to target as protective strategies against their damaging effects. This commentary will highlight oxidative stress as a common mechanism shared by both radiation and sulfur mustard gas exposures and discuss potential therapies targeting oxidative stress as medical countermeasures against the devastating lung diseases wrought by these agents.

Glaucoma and uveitis are non-vascular ocular diseases which are among the leading causes of blindness and visual loss. These conditions have distinct characteristics and mechanisms but share a multifactorial and complex nature, making their management challenging and burdensome for patients and clinicians. Furthermore, the lack of symptoms in the early stages of glaucoma and the diverse aetiology of uveitis hinder timely and accurate diagnoses, which are a cause of poor visual outcomes under both conditions. Although current treatment is effective in most cases, it is often associated with low patient adherence and adverse events, which directly impact the overall therapeutic success. Therefore, long-lasting alternatives with improved safety and efficacy are needed. Gene therapy, particularly utilising adeno-associated virus (AAV) vectors, has emerged as a promising approach to address unmet needs in these diseases. Engineered capsids with enhanced tropism and lower immunogenicity have been proposed, along with constructs designed for targeted and controlled expression. Additionally, several pathways implicated in the pathogenesis of these conditions have been targeted with single or multigene expression cassettes, gene editing and silencing approaches. This review discusses strategies employed in AAV-based gene therapies for glaucoma and non-infectious uveitis and provides an overview of current progress and future directions.

Cardiac hypertrophy is the enlargement of cardiomyocytes in response to persistent release of catecholamine which further leads to cardiac fibrosis. Chrysin, flavonoid from honey, is well known for its multifarious properties like antioxidant, anti-inflammatory, anti-fibrotic and anti-apoptotic. To investigate the cardioprotective potential of chrysin against isoproterenol (ISO), cardiac hypertrophy and fibrosis are induced in rats. Acclimatised male albino Wistar rats were divided into seven groups (n 6): normal (carboxymethyl cellulose at 0·5 % p.o.; as vehicle), hypertrophy control (ISO 3 mg/kg, s.c.), CHY15 + H, CHY30 + H & CHY60 + H (chrysin; p.o.15, 30 and 60 mg/kg respectively + ISO at 3 mg/kg, s.c.), CHY60 (chrysin 60 mg/kg in per se) and LST + H (losartan 10 mg/kg p.o. + ISO 3 mg/kg, s.c.) were treated for 28 d. After the dosing schedule on day 29, haemodynamic parameters were recorded, after that blood and heart were excised for biochemical, histological, ultra-structural and molecular evaluations. ISO administration significantly increases heart weight:body weight ratio, pro-oxidants, inflammatory and cardiac injury markers. Further, histopathological, ultra-structural and molecular studies confirmed deteriorative changes due to ISO administration. Pre-treatment with chrysin of 60 mg/kg reversed the ISO-induced damage to myocardium and prevent cardiac hypertrophy and fibrosis through various anti-inflammatory, anti-apoptotic, antioxidant and anti-fibrotic pathways. Data demonstrated that chrysin attenuated myocardial hypertrophy and prevented fibrosis via activation of transforming growth factor-beta (TGF-β)/Smad signalling pathway.

Table olives, a product of olive tree (Olea europaea L.), is an important fermented product of the Mediterranean Diet. Agronomical factors, particularly the cultivar, the ripening stage and the processing method employed are the main factors influencing the nutritional and non-nutritional composition of table olives and their organoleptic properties. The important nutritional value of this product is due to its richness in monounsaturated fat (MUFA), mainly oleic acid, fibre and vitamin E together with the presence of several phytochemicals. Among these, hydroxytyrosol (HT) is the major phenolic compound present in all types of table olives. There is a scarcity of in vitro, in vivo and human studies of table olives. This review focused comprehensively on the nutrients and bioactive compound content as well as the health benefits assigned to table olives. The possible health benefits associated with their consumption are thought to be primarily related to effects of MUFA on cardiovascular health, the antioxidant (AO) capacity of vitamin E and its role in protecting the body from oxidative damage and the anti-inflammatory and AO activities of HT. The influence of multiple factors on composition of the end product and the potential innovation in the production of table olives through the reduction of its final salt content was also discussed.

The present study was conducted to test the hypothesis that dietary supplementation with a nano chitosan–zinc complex (CP–Zn, 100 mg/kg Zn) could alleviate weaning stress in piglets challenged with enterotoxigenic Escherichia coli K88 by improving growth performance and intestinal antioxidant capacity. The in vivo effects of CP–Zn on growth performance variables (including gastrointestinal digestion and absorption functions and the levels of key proteins related to muscle growth) and the antioxidant capacity of the small intestine (SI) were evaluated in seventy-two weaned piglets. The porcine jejunal epithelial cell line IPEC-J2 was used to further investigate the antioxidant mechanism of CP–Zn in vitro. The results showed that CP–Zn supplementation increased the jejunal villus height and decreased the diarrhoea rate in weaned piglets. CP–Zn supplementation also improved growth performance (average daily gain and average daily feed intake), increased the activity of carbohydrate digestion-related enzymes (amylase, maltase, sucrase and lactase) and the mRNA expression levels of nutrient transporters (Na+-dependent glucose transporter 1, glucose transporter type 2, peptide transporter 1 and excitatory amino acid carrier 1) in the jejunum and up-regulated the expression levels of mammalian target of rapamycin (mTOR) pathway-related proteins (insulin receptor substrate 1, phospho-mTOR and phospho-p70S6K) in muscle. In addition, CP–Zn supplementation increased glutathione content, enhanced total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-px) activity, and reduced malondialdehyde (MDA) content in the jejunum. Furthermore, CP–Zn decreased the content of MDA and reactive oxygen species, enhanced the activity of T-SOD and GSH-px and up-regulated the expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) pathway-related proteins (Nrf2, NAD(P)H:quinone oxidoreductase 1 and haeme oxygenase 1) in lipopolysaccharide-stimulated IPEC-J2 cells. Collectively, these findings indicate that CP–Zn supplementation can improve growth performance and the antioxidant capacity of the SI in piglets, thus alleviating weaning stress.

Deep-fried vegetable oils are reused multiple times to save costs, and their chronic consumption may cause organ dysfunction. In this study, we assessed the modulatory effects of lipid-solubles from ginger and turmeric that may migrate to oils during heating, on the cardio-hepatic antioxidant defence response and blood pressure in rats. Male Wistar rats were fed with: (1) control (native rapeseed (N-CNO) or native sunflower (N-SFO)) oil, (2) heated (heated rapeseed (H-CNO) or heated sunflower (H-SFO)) oil and (3) heated oil with ginger or turmeric (heated rapeseed oil with ginger (H-CNO + GI) or heated rapeseed oil with turmeric (H-CNO + TU), heated sunflower oil with ginger (H-SFO + GI) or heated sunflower oil with turmeric (H-SFO + TU)) for 120 d. Oxidative stress (OS) markers, antioxidant enzymes, nitric oxide synthase-2 (NOS-2), intercellular adhesion molecule-1 (ICAM-1), nuclear factor erythroid 2-related factor 2 (NRF-2), markers of hepatic and cardiac function and blood pressure were assessed. Feeding heated oils (H-CNO or H-SFO) (1) increased OS markers, NOS-2 and ICAM-1 expression; (2) decreased antioxidant enzyme activity and NRF-2 level; (3) increased marker enzymes of hepatic and cardiac function and (4) increased systolic and diastolic blood pressure significantly (P < 0·05), when compared with respective native oils (N-CNO or N-SFO). However, feeding oils heated with ginger or turmeric positively countered the changes induced by heated oils. Consumption of repeatedly heated oil causes cardio-hepatic dysfunction by inducing OS through NRF-2 down-regulation. Lipid-solubles from ginger and turmeric that may migrate to oil during heating prevent the oxidative stress and blood pressure triggered by heated oils in rats.

Se is a micronutrient essential for human health. Sub-optimal Se status is common, occurring in a significant proportion of the population across the world including parts of Europe and China. Human and animal studies have shown that Se status is a key determinant of the host response to viral infections. In this review, we address the question whether Se intake is a factor in determining the severity of response to coronavirus disease 2019 (COVID-19). Emphasis is placed on epidemiological and animal studies which suggest that Se affects host response to RNA viruses and on the molecular mechanisms by which Se and selenoproteins modulate the inter-linked redox homeostasis, stress response and inflammatory response. Together these studies indicate that Se status is an important factor in determining the host response to viral infections. Therefore, we conclude that Se status is likely to influence human response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and that Se status is one (of several) risk factors which may impact on the outcome of SARS-CoV-2 infection, particularly in populations where Se intake is sub-optimal or low. We suggest the use of appropriate markers to assess the Se status of COVID-19 patients and possible supplementation may be beneficial in limiting the severity of symptoms, especially in countries where Se status is regarded as sub-optimal.

Limb remote ischemic conditioning (LRIC) provides a physiologic strategy for harnessing the body’s endogenous protective capabilities against injury induced by ischemia–reperfusion in the central nervous system. The aim of the present study was to determine if LRIC played a role in protecting the retina from ischemia–reperfusion injury. A total of 81 adult male Sprague-Dawley rats were randomly assigned to sham and ischemia/reperfusion with or without remote LRIC arms. The retinal ischemic model was generated through right middle cerebral artery occlusion (MCAO) and pterygopalatine artery occlusion for 60 min followed by 1, 3, and 7 days of subsequent reperfusion. LRIC was conducted immediately following MCAO by tightening a tourniquet around the upper thigh and releasing for three cycles. Paraffin sections were stained with hematoxylin and eosin in order to quantify the number of cells in retinal ganglion cells (RGCs) layer throughout the duration of the study. Cellular expression of glial fibrillary acidic protein (GFAP) was detected and examined through immunohistochemistry. Protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) was also analyzed by Western blot techniques. Our study demonstrated that the loss of cells in RGC layer was attenuated by LRIC treatment at 3 and 7 days following reperfusion (P < 0.05). Immunohistochemistry studies depicted a gradual increase (P < 0.05) in GFAP levels from day 1 through day 7 following ischemia and subsequent reperfusion, whereas LRIC reduced GFAP levels at 1, 3, and 7 days postreperfusion. In addition, LRIC increased the expression of Nrf2 and HO-1 at day 1 and 3 following ischemia/reperfusion. This particular study is the first remote conditioning study applicable to retinal ischemia. Our results strongly support the position that LRIC may be used as a noninvasive neuroprotective strategy, which provides retinal protection from ischemia–reperfusion injury through the upregulation of antioxidative stress proteins, such as Nrf2 and HO-1.

We investigate the cytoprotective effects and the molecular mechanism of genistein in oxidative stress-induced injury using an endothelial cell line (EA.hy926). An oxidative stress model was established by incubating endothelial cells with H2O2. According to the present results, genistein pretreatment protected endothelial cells against H2O2-induced decreases in cell viability and increases in apoptosis. Genistein also prevented the inhibition of B-cell lymphoma 2 and the activation of caspase-3 induced by H2O2. Genistein increased superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) levels and attenuated the decrease in these antioxidants during oxidative stress. We also found that genistein induced the promoter activity of both nuclear factor erythroid 2-related factor 2 (Nrf2) and PPARγ. Additionally, genistein induced the nuclear translocation of Nrf2 and PPARγ. While genistein caused the up-regulation of both Nrf2 and PPARγ, it also activated and up-regulated the protein expression and transcription of a downstream protein, haem oxygenase-1 (HO-1). Moreover, the use of Nrf2 small interfering RNA transfection and HO-1- or PPARγ-specific antagonists (Znpp and GW9662, respectively) blocked the protective effects of genistein on endothelial cell viability during oxidative stress. Therefore, we conclude that oxidative stress-induced endothelial cell injury can be attenuated by treatment with genistein, which functions via the regulation of the Nrf2 and PPARγ signalling pathway. Additionally, the endogenous antioxidants SOD, CAT and GSH appear to play a role in the antioxidant activity of genistein. The present findings suggest that the beneficial effects of genistein involving the activation of cytoprotective antioxidant genes may represent a novel strategy in the prevention and treatment of cardiovascular endothelial damage.