Antibiotic resistance poses a serious threat to the current healthcare system, negatively impacting the effectiveness of many antimicrobial treatments. The situation is exacerbated by the widespread overuse and abuse of available antibiotics, accelerating the evolution of resistance. Thus, there is an urgent need for novel approaches to therapy to overcome established resistance mechanisms. Plants produce molecules capable of inhibiting bacterial growth in various ways, offering promising paths for the development of alternative antibiotic medicine. This review emphasizes the necessity of research efforts on plant-derived chemicals in the hopes of finding and creating novel drugs that can successfully target resistant bacterial populations. Investigating these natural chemicals allows us to improve our knowledge of novel antimicrobial pathways and also expands our antibacterial repertoire with novel molecules. Simultaneously, it is still necessary to utilize present antibiotics sparingly; prudent prescribing practices must be encouraged to extend the effectiveness of current medications. The combination of innovative drug research and responsible drug usage offers an integrated strategy for managing the antibiotic resistance challenge.

Oleacein (Olea) and Oleocanthal (Oleo) are two phenolic compounds found in olive oil. Cell and animal studies have shown these two compounds can modulate inflammation, cancer, and neurodegenerative diseases. Unfortunately, the study of the pharmacokinetics of these two compounds appears difficult due to their high reactivity with primary amines. Indeed, the presence of primary amines in culture media and biological fluids raises the question as to whether the observed biological effects are attributable to the parent compounds or to their amine derivatives. In the present work, we investigated the adduct formation between Olea or Oleo and tris(hydroxymethyl)aminomethane (Tris), a well-known primary amine used primarily as a buffer system, showing that the reaction kinetics were extremely rapid. In addition, we assessed whether the newly formed Tris adducts, i.e., Olea-Tris and Oleo-Tris, retained their antioxidant capacity by means of the ABTS and DPPH radical scavenging assays, showing that their activity was partially maintained. Finally, we evaluated the anti-inflammatory activity of these adducts on murine BV-2 microglial cells stimulated with lipopolysaccharide (LPS) and kept in an amine-free culture medium, showing how the biological response varied as the compound was degraded. Taken together, these data demonstrate that the biological effects reported in the literature are mainly due to the amino-derivatives of Olea and Oleo rather than the polyphenols derived from their breakdown (tyrosol and hydroxytyrosol).

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease marked by progressive degeneration of motor neurons and skeletal muscle. Gene expression analysis of the spinal cord and gastrocnemius of the SOD1-G93A ALS mouse model revealed a strong increase in inflammatory pathways and, specifically in the ALS gastrocnemius, a decrease in mitochondrial transcription and an increase in ribosomal protein expression. Treatment of ALS mice with the polyamine spermidine (SPD), a promising molecule in combating neurodegeneration and muscle atrophy, is able to partially restore the expression of more than four thousand genes in gastrocnemius tissue, including the mitochondrial regulator Pgc1α, as well as all the mitochondrial encoded genes and a large class of ribosomal proteins. SPD enhanced mitochondrial bioenergetics, as evidenced by Seahorse experiments, and delayed muscle weakness in vivo, as shown by grip strength records. These findings suggest that SPD can act as a potential supplement in the therapeutic strategy for ALS, offering a foundation for further research to improve patient outcomes.

Olive oil polyphenols are a valuable help for human health and producing high‐quality extra virgin olive oil rich in these polyphenols is a key objective for many farmers. In this work, we evaluated the impact of addition of salts to the milling process to increase the polyphenolic content of olive oil. The procedure proved successful, with efficacy dependent on the specific salt used and its concentration. The use of salts, in both laboratory and industrial settings, has increased not only the polyphenol content within the oil but also the yield and the qualitative–quantitative, sensory and nutritional characteristics of olive oil by impacting the amount of other minor constituents of olive oil, such as volatile compounds, chlorophyll, and carotenoids. Using the same approach, and by utilizing wastewater as a source of bioactives, we also successfully enriched other seed oils with olive oil polyphenols minimizing the waste of these substances and valorizing them. This enabled us to obtain a new class of seed oils enriched in antioxidant and anti‐inflammatory compounds, potentially representing a new frontier in nutraceuticals.

Endocannabinoids are lipid mediators consisting of esters, amides and ethers of long-chain polyunsaturated fatty acids. In this work, attention was focused on N-arachidonoyl tyrosine (NA-Tyr) and N-arachidonoyl dopamine (NADA), the amides of arachidonic acid with tyrosine and dopamine, respectively. NADA is an endogenous ligand of both type 1 cannabinoid receptors and type 1 vanilloid channel receptors. NADA is considered an endogenous compound with capsaicin-like activity and is distributed in several brain areas. The metabolic fate of endocannabinoids involves numerous enzymatic activities, which are only partially characterized. In particular, the biological activity of these biomolecules is terminated by enzymes with hydrolytic or oxygenase/oxidase activity. As part of this problem, we studied the oxidation of NADA and NA-Tyr mediated by mushroom tyrosinase. Our experimental data show that tyrosinase can oxidize both NADA and NA-Tyr. The oxidation of these biomolecules was also carried out in the presence of cysteine, allowing us to observe the formation of endocannabinoid/endovanilloid adducts with cysteine. These results were derived from chromatographic analyses and mass spectral experiments. During the tyrosinase-mediated oxidation in the presence of cysteine, it was possible to observe the production of a melanin-like pigment. The spectral characteristics of this pigment are consistent with those of pheomelanin, the pigment that contributes to the structure of neuromelanin. While mushroom tyrosinase serves here as a convenient biomimetic model to investigate the oxidative susceptibility of NADA and NA-Tyr, extrapolating these in vitro findings to mammalian physiology requires caution. Nevertheless, considering the neuronal distribution of these precursors and the documented, albeit debated, presence of tyrosinase-like activity in the central nervous system (CNS), these results offer a chemical rationale to further investigate whether similar oxidative pathways occur in vivo and potentially contribute to neurodegenerative mechanisms.

This study presents the successful expression, purification, and functional characterization of the human TRPM8 ion channel, a key player in temperature sensing and pain modulation. Using a modified bacterial expression protocol and DDM-based solubilization, TRPM8 was purified via HPLC-SEC and analyzed for its membrane-binding properties. FRET-based assays with synthetic lipid rafts revealed a strong and selective affinity of TRPM8 for cholesterol-containing membranes, suggesting cholesterol’s role in modulating TRPM8 localization and activity. These findings provide quantitative in vitro evidence of TRPM8–cholesterol interactions and establish a robust model system for future structural and functional studies of membrane-associated proteins.