Alzheimer’s disease (AD) is a progressive degenerative disorder of the central nervous system, characterized by neuroinflammation, neurotransmitter deficits, and neurodegeneration, which finally leads to neuronal death. Emerging evidence highlighted that hyperglycemia and brain insulin resistance represent risk factors for AD development, thus suggesting the existence of an additional AD form, associated with glucose metabolism impairment, named type 3 diabetes. Owing to the limited pharmacological options, novel strategies, especially dietary approaches based on the consumption of polyphenols, have been addressed to prevent or, at least, slow down AD progression. Among polyphenols, ferulic acid is a hydroxycinnamic acid derivative, widely distributed in nature, especially in cereal bran and fruits, and known to be endowed with many bioactivities, especially antioxidant, anti-inflammatory and antidiabetic, thus suggesting it could be exploited as a possible novel neuroprotective strategy. Considering the importance of ferulic acid as a bioactive molecule and its widespread distribution in foods and medicinal plants, the aim of the present narrative review is to provide an overview on the existing preclinical and clinical evidence about the neuroprotective properties and mechanisms of action of ferulic acid, also focusing on its ability to modulate glucose homeostasis, in order to support a further therapeutic interest for AD and type 3 diabetes.

Green-tea-based products and their polyphenols, especially epigallocatechin-3-gallate, have attracted great attention over the years as possible nutraceuticals, due to their promising bioactivities, especially antioxidant and anti-inflammatory, which could be exploited in several diseases, including skin ailments. In this context, the present study aimed at reviewing clinical evidence about the benefits of the oral administration of green tea preparations and its polyphenols to relieve skin disorders, to point out the current knowledge, and to suggest possible novel strategies to effectively exploit the properties of green tea, also managing safety risks. To this end, a systematic review of the existing literature was carried out, using the PRISMA method. Few studies, including five focused on UV-induced erythema and skin alterations, three on photoaging, two on antioxidant skin defenses, and one on acne and genodermatosis, were retrieved. Despite several benefits, clinical evidence only supports the use of oral green tea preparations to protect skin from damage induced by ultraviolet radiation; in other cases, conflicting results and methodological limits of clinical trials do not allow one to clarify their efficacy. Therefore, their application as adjuvant or alternative sunscreen-protective interventions could be encouraged, in compliance with the safety recommendations.

Immunomodulation is a key factor in the homeostasis of organisms, both for physiological and inflammatory conditions. In this context, great attention has been devoted to immunomodulant agents, which can boost or modulate the immune system, thus favoring disease relief. The present systematic review is focused on the immunomodulatory properties of plant-based caryophyllane sesquiterpenes, which are unique natural compounds widely studied due to their multiple and pleiotropic bioactivities. Despite lacking clinical evidence, the selected studies highlighted the ability of these substances, especially β-caryophyllene and α-humulene, to modulate the immune system of both in vitro and in vivo models of disease, such as neurodegenerative and inflammatory-based diseases, cancer, and allergies; moreover, some mechanistic hypotheses have been made too. The present overview suggests a further interest in immunomodulation by caryophyllane sesquiterpenes as a possible novel strategy for immune-based diseases or as an adjuvant treatment and encourages further high-quality studies, using high-purity compounds, to better clarify the mechanisms accounting for these properties and to support a further pharmaceutical development.

A combination of anticancer drugs and chemosensitizing agents has been approached as a promising strategy to potentiate chemotherapy and reduce toxicity in aggressive and chemoresistant cancers, like hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and pancreatic ductal adenocarcinoma (PDAC). In the present study, the ability of caryophyllane sesquiterpenes to potentiate sorafenib efficacy was studied in HCC, CCA, and PDAC cell models, focusing on the modulation of STAT3 signaling and ABC transporters; tolerability studies in normal cells were also performed. Results showed that the combination of sorafenib and caryophyllane sesquiterpenes synergized the anticancer drug, especially in pancreatic Bx-PC3 adenocarcinoma cells; a similar trend, although with lower efficacy, was found for the standard ABC transporter inhibitors. Synergistic effects were associated with a modulation of MDR1 (or Pgp) and MRP transporters, both at gene and protein level; moreover, activation of STAT3 cascade and cell migration appeared significantly affected, suggesting that the STAT3/ABC-transporters axis finely regulated efficacy and chemoresistance to sorafenib, thus appearing as a suitable target to overcome drawbacks of sorafenib-based chemotherapy in hepato-biliary-pancreatic cancers. Present findings strengthen the interest in caryophyllane sesquiterpenes as chemosensitizing and chemopreventive agents and contribute to clarifying drug resistance mechanisms in HCC, CCA, and PDAC cancers and to developing possible novel therapeutic strategies.

SPME-GC-MS and PTR-ToF-MS techniques were applied to describe the content of volatile flavor compounds in a craft beer before and after adding spirulina. The obtained results showed that the volatile profile of the two beer samples differed. Furthermore, to chemically characterize biomass spirulina, a derivatization reaction followed by GC-MS analysis was performed, highlighting a high content of molecules belonging to different chemical classes, such as sugars, fatty acids and carboxylic acids. A spectrophotometric analysis of total polyphenols and tannins, investigation into the scavenging activity towards DPPH and ABTS radicals and confocal microscopy of brewer’s yeast cells were carried out. Moreover, the cytoprotective and antioxidant properties towards the oxidative damage induced by tert-butyl hydroperoxide (tBOOH) in human H69 cholangiocytes were investigated. Finally, the modulation of Nrf2 signaling under oxidative stress conditions was also evaluated. Both samples of beer were shown to contain similar levels of total polyphenols and tannins, with slightly increased levels in that containing spirulina 0.25% w/v. Moreover, the beers were found to be endowed with radical scavenging properties towards both DPPH and ABTS radicals, albeit with a weak contribution of spirulina; however, a higher riboflavin content was detected in spirulina-treated yeast cells. Conversely, the addition of spirulina (0.25% w/v) appeared to improve the cytoprotective properties of beer towards tBOOH-induced oxidative damage in H69 cells and reduce intracellular oxidative stress. Accordingly, the cytosolic Nrf2 expression was found to be increased.

Respiratory viral infections continue to pose significant challenges, particularly for more susceptible and immunocompromised individuals. Nutraceutical strategies have been proposed as promising strategies to mitigate their impact and improve public health. In the present study, we developed a mixture of two hydroalcoholic extracts from the aerial parts of Echinacea purpurea (L.) Moench (ECP) and the cones of Humulus lupulus L. (HOP) that can be harnessed in the prevention and treatment of viral respiratory diseases. The ECP/HOP mixture (named ECHOPvir) was characterized for the antioxidant and cytoprotective properties in airway cells. Moreover, the immunomodulating properties of the mixture in murine macrophages against antioxidant and inflammatory stimuli and its antiviral efficacy against the PR8/H1N1 influenza virus were assayed. The modulation of the Nrf2 was also investigated as a mechanistic hypothesis. The ECP/HOP mixture showed a promising multitarget bioactivity profile, with combined cytoprotective, antioxidant, immunomodulating and antiviral activities, likely due to the peculiar phytocomplexes of both ECP and HOP, and often potentiated the effect of the single extracts. The Nrf2 activation seemed to trigger these cytoprotective properties and suggest a possible usefulness in counteracting the damage caused by different stressors, including viral infection. Further studies may strengthen the interest in this product and underpin its future nutraceutical applications.