João Ferreira

Sustained consumption of Western-style diets (WDs), rich in fat and cholesterol, challenges metabolic homeostasis and results in organ-specific alterations, notably hepatic lipid accumulation and adipose tissue dysfunction. Medicinal mushrooms such as Ganoderma lucidum have gained attention for their biological activities; however, the extent to which nutritionally realistic dietary intake of G. lucidum modulates tissue-specific metabolic adaptation under obesogenic conditions remains poorly defined. This exploratory study aimed to evaluate how dietary supplementation with a Ganoderma lucidum extract (GLE) modulates metabolic and organ-specific responses in a WD-fed preclinical mouse model. Forty-seven male C57BL/6J mice were assigned to five groups receiving a control diet (CTR), a cholesterol-enriched WD, or the WD supplemented with increasing concentrations of GLE (0.7%, 1.4%, or 2.8%). Over thirteen weeks, body mass and food and water intake were monitored weekly. Afterwards, mice were euthanized, and tissue and blood samples were collected for further analysis. Fasting glucose was lower in WD+2.8% GLE than in CTR, although no GLE-supplemented group differed significantly from WD and glucose tolerance was unchanged. All GLE-supplemented groups had a lower hepatic genetic damage index than WD. WD+1.4% GLE showed a higher frequency of localized periportal hepatic vacuolar changes than WD, whereas WD+2.8% GLE had lower relative liver weight. GLE supplementation was also associated with depot-specific variation in the occurrence of multilocular adipocytes with a beige-like appearance, without significant changes in final body mass or adiposity. In this preclinical model, subchronic dietary GLE was associated with selected tissue-specific differences, most consistently lower hepatic DNA damage and depot-specific variation in multilocular adipocyte morphology, without consistent systemic metabolic improvements.

Oxidative and nitrosative stress are key contributors to the development and progression of chronic inflammatory disorders, cancer and neurodegenerative diseases (viz., Alzheimer’s disease). Cholinergic dysfunction is a major hallmark of Alzheimer’s disease and is closely associated with these processes. Red seaweeds are rich in bioactive compounds that have been increasingly investigated for their potential to modulate these processes. This review aims to examine the role of major red seaweed-derived metabolites in regulating redox imbalance, immunomodulatory capacity and acetylcholinesterase activity, with emphasis on in vitro studies. An analysis of peer-reviewed literature was conducted, focusing on chemical, biochemical and cell-based assays. Studies assessed antioxidant activity, anti-inflammatory and immunostimulatory effects, and acetylcholinesterase inhibition of isolated compounds/fractions of red seaweed using established methods, including radical scavenging assays, Griess-based nitrite assay and enzyme inhibition assays. Sulfated polysaccharides, oligosaccharides, mycosporine-like amino acids (MAAs), phycoerythrin, bromophenols, phlorotannin and terpenoid-derived metabolites demonstrated antioxidant capacity through radical scavenging, metal chelation and modulation of endogenous antioxidants. They also modulated inflammatory mediators, including nitric oxide and pro-inflammatory cytokines, and inhibited acetylcholinesterase (AChE) activity. In vitro evidence supports red seaweed-derived compounds as promising modulators of redox homeostasis, inflammation and cholinergic function, highlighting their relevance as functional food ingredients, while underscoring the need for in vivo and clinical validation.

Earth hosts a remarkable diversity of life, with oceans covering over 70% of its surface and supporting the greatest abundance and variety of species, including a vast range of seaweeds. Among these, red seaweeds (Rhodophyta) represent the most diverse group and are particularly rich in bioactive compounds. Grateloupia turuturu Yamada and Porphyra umbilicalis Kütz. are two species with significant biotechnological and functional food potential. They contain high levels of phycobiliproteins, sulfated polysaccharides (e.g., carrageenan, agar, porphyran), mycosporine-like amino acids (MAAs), phenols, minerals, and vitamins, including vitamin B12 (rare among non-animal sources). Several analytical methods, such as spectrophotometry, chromatography, and mass spectrometry, have been used to characterize their chemical composition. In vitro and in vivo studies have demonstrated their antioxidant, anti-inflammatory, neuroprotective, immunostimulatory, anti-proliferative, and photoprotective effects. These bioactive properties support its application in the food, pharmaceutical, and cosmetic sectors. Given the growing demand for sustainable resources, these algae species stand out as promising candidates for aquaculture and the development of functional ingredients. Their incorporation into novel food products, such as snacks and fortified dairy and meat products, underscores their potential to support health-promoting diets. This review highlights G. turuturu and P. umbilicalis chemical richness, bioactivities, and applications, reinforcing their value as sustainable marine resources.

Background/Aim: Human papillomavirus (HPV) is the most common sexually transmitted infectious agent and, in cases of persistent infection, may cause cancer. This study evaluated the toxicological and antitumor properties of Mentha spicata extract (MSE) in KP14HPV16 mice, which carry HPV16 oncogenes. Materials and Methods: Thirty-three female FVB/n mice (Mus musculus), including 17 HPV-transgenic and 16 wild-type (WT) mice, were divided into six groups. The control groups received tap water (WT-C, n=5, and HPV-C, n=6), while the treatment groups received either 0.50 mg/ml MSE (WT-50 and HPV-50, n=6) or 0.55 mg/ml MSE (WT-55 and HPV-55, n=5) in drinking water for 28 days. Afterwards, animals were sacrificed, and blood and organs were collected for histopathological and biochemical analysis. Results: The main phenolic compounds in MSE were rosmarinic acid and luteolin-O-glucoronide. MSE did not significantly affect weight gain in WT mice; however, WT-55 gained significantly more weight than HPV-55. MSE demonstrated antioxidant activity as indicated by the modulation of hepatic superoxide dismutase and glutathione S-transferase (GST) activity, as well as renal GST activity, in MSE-treated HPV groups. MSE did not reduce histological lesion incidence or systemic inflammation in HPV16-transgenic mice. Conclusion: In general, while MSE was safe and exhibited antioxidant activity, it did not significantly impact HPV16-induced lesions, warranting further research to assess systemic effects with different concentrations and durations.

Marine macroalgae have been consumed as feed and food for centuries, mainly in East Asian countries. Accordingly, epidemiological studies highlighted a linkage between marine macroalgae consumption and lower incidence of diet-related disorders, such as osteoporosis, diabetes, metabolic syndrome and related cardiovascular disorders, or cancer. For this reason, marine macroalgae have been currently defended as functional foods or ingredients. One of the reported beneficial properties is related with the ability to protect the DNA molecule. Indeed, marine macroalgae have been continually described to possess antioxidant activity, showing also 288antigenotoxic, antimutagenic and antiproliferative actions. The beneficial properties of macroalgae towards the integrity of DNA have been linked to their rich and diverse phytochemical composition. Particularly, sulfated polysaccharides, polyunsaturated fatty acids, phytosterols, pigments, minerals, vitamins, phlorotannins, as well as mycosporine-like amino acids have been associated with those properties. Moreover, the phytochemical profile of macroalgae, and respective bioactive properties, is known to vary due to growing conditions. In this sense, algal farming arises as a controlled and secure growing system and with potential to develop specimens showing higher genoprotective properties.

Sambucus nigra L., popularly known as elderberry, is renowned for its amazing therapeutic properties, as well as its uses as a food source, in nutraceuticals, and in traditional medicine. This study’s aim was to investigate the effects of an elderberry extract (EE) on mice for 29 days, as well as the safety of the extract when used as a natural colorant. Twenty-four FVB/n female mice (n = 6) were randomly assigned to one of four groups: control, 12 mg/mL EE (EE12), 24 mg/mL EE (EE24), or 48 mg/mL EE (EE48). The predominant anthocyanins detected were cyanidin-3-O-sambubioside and cyanidin-3-O-glucoside. Food and drink intake were similar between groups, with the exception of EE48, who drank significantly less compared with the Control. Biochemical analysis of the liver showed that the changes observed in histological analysis had no pathological significance. The EE, at doses of 24 and 48 mg/mL, significantly reduced the oxidative DNA damage compared with the non-supplemented group. The S. nigra extract showed a favorable toxicological profile, affording it potential to be used in the food industry.

Brassica by-products are a source of natural bioactive molecules such as glucosinolates and isothiocyanates, with potential applications in the nutraceutical and functional food industries. However, the effects of oral sub-chronic exposure to broccoli by-product flour (BF) have not yet been evaluated. The objective of this pilot study was to analyse the effects of BF intake in the physiological parameters of FVB/N mice fed a 6.7% BF-supplemented diet for 21 days. Glucosinolates and their derivatives were also quantified in plasma and urine. BF supplementation significantly decreased (p < 0.05) the accumulation of perirenal adipose tissue. Furthermore, mice supplemented with BF showed significantly lower (p < 0.01) microhematocrit values than control animals, but no impact on the general genotoxicological status nor relevant toxic effects on the liver and kidney were observed. Concerning hepatic and renal antioxidant response, BF supplementation induced a significant increase (p < 0.05) in the liver glutathione S-transferase (GST) levels. In BF-supplemented mice, plasma analysis revealed the presence of the glucosinolates glucobrassicin and glucoerucin, and the isothiocyanates sulforaphane and indole-3-carbinol. Overall, these results show that daily intake of a high dose of BF during three weeks is safe, and enables the bioavailability of beneficial glucosinolates and isothiocyanates. These results allow further testing of the benefits of this BF in animal models of disease, knowing that exposure of up to 6.7% BF does not present relevant toxicity.