5-Lipoxygenase (5-LOX) converts arachidonic acid to lipidic inflammatory mediators such as leukotrienes (LTs). In diseases such as asthma, LTs contribute to a physiopathology that could be reverted by blocking 5-LOX. Natural products with anti-inflammatory potential such as ginger have been used as nutraceuticals since ancient times. 6-Gingerol and 6-shogaol are the most abundant compounds in the ginger rhizome; they possess anti-inflammatory, antioxidant, and chemopreventive properties. In the present study, 6-gingerol and 6-shogaol structures were analyzed and compared with two commercial 5-LOX inhibitors (zileuton and atreleuton) and with other inhibitor candidates (3f, NDGA, CP 209, caffeic acid, and caffeic acid phenethyl ester (CAPE)). The pharmacokinetics and toxicological properties of 6-gingerol, 6-shogaol, and the other compounds were evaluated. Targeted molecular coupling was performed to identify the optimal catalytic pocket for 5-LOX inhibition. The results showed that 6-gingerol and 6-shogaol follow all of the recommended pharmacokinetic parameters. These compounds could be inhibitors of 5-LOX because they present specific interactions with the residues involved in molecular inhibition. The current study demonstrated the potential of 6-gingerol and 6-shogaol as anti-inflammatory agents that inhibit 5-LOX, as they present a high level of performance in the toxicological analysis and could be catabolized by the cytochrome p450 enzymatic complex; however, 6-gingerol was superior in safety compared to 6-shogaol.

Lichens are an important source of diverse and unique secondary metabolites with recognized biological activities through experimental and computational procedures. The objective of this study is to investigate the metabolomic profile of the ethanolic extract of the Antarctic lichen Gondwania regalis and evaluate its antioxidant and antidiabetic activities with in vitro, in silico, and molecular dynamics simulations. Twenty-one compounds were tentatively identified for the first time using UHPLC/ESI/QToF/MS in negative mode. For antioxidant activity, the DPPH assay showed an IC₅₀ value of 2246.149 µg/mL; the total phenolic content was 31.9 mg GAE/g, the ORAC assay was 13.463 µmol Trolox/g, and the FRAP assay revealed 6.802 µmol Trolox/g. Regarding antidiabetic activity, enzyme inhibition yielded IC₅₀ values of 326.4513 µg/mL for pancreatic lipase, 19.49 µg/mL for α-glucosidase, and 585.216 µg/mL for α-amylase. Molecular docking identified sekikaic acid as the most promising compound, with strong binding affinities to catalytic sites, while molecular dynamics confirmed its stability and interactions. Toxicological and pharmacokinetic analyses supported its drug-like potential without significant risks. These findings suggest that the ethanolic extract of Gondwania regalis is a promising source of bioactive compounds for developing natural antioxidant and antidiabetic therapies.

Bacterial aggregation and adhesion are ruled by specific and nonspecific adhesion mechanisms. In the case of the probiotic strain Lactobacillus plantarum 299v (Lp299v) the biochemistry of adhesion has been previously studied and s-layer proteins have been identified. However, physic-chemical mechanisms which ruled the aggregation and adhesion phenomena able to change through the time under different pH conditions have not been completely elucidated. The non-specific adhesion mechanisms (hydrophobicity, zeta potential and morphology) of Lp299v auto-aggregates over time (24 h) at different pH levels (from 5.0 to 9.0) on starvation were described. Auto-aggregation resulted in greater dependency on time. The Lp299v cell surface showed a higher level of affinity with chloroform than n-hexadecane, while the zeta potential was a negative charge in all cases. Size and shape parameters were found to be dependent on time and pH. A strong Pearson correlation (0.991) was observed between circularity and auto-aggregation. In conclusion, Lp299v’s nonspecific adhesion mechanism was found to be more related to time than pH levels, indicating that Van der Waals and hydrophobic forces and shape parameters have the potential to dominate the autoaggregation of Lp299v. However, the predictive model presented shows that lower pH may promote auto-aggregation and thus facilitate the colonization at the upper level of the digestive system. La agregación bacteriana se rige por mecanismos de adhesión específicos e inespecíficos. En el caso de Lactobacillus plantarum 299v (Lp299v), la bioquímica de la adhesión ha sido previamente estudiada y se han identificado algunas proteínas de la capa superficial. Sin embargo, los mecanismos fisicoquímicos que rigen los fenómenos de agregación y adhesión capaces de cambiar a lo largo del tiempo en diferentes condiciones de pH no han sido dilucidados. Se describieron los mecanismos de adhesión no específicos de los agregados a lo largo del tiempo (24 h) a diferentes niveles de pH (de 5.0 a 9.0) en la inanición. La auto-agregación resultó dependiente del tiempo. La superficie celular de Lp299v mostró un mayor nivel de afinidad con el cloroformo que el n-hexadecano, mientras que el potencial zeta presentó carga negativa. Los parámetros de tamaño y forma dependieron del tiempo y el pH. Se observó una fuerte correlación de Pearson (0.991) entre la circularidad y la auto-agregación. En conclusión, el mecanismo de adhesión inespecífica de Lp299v se relacionó más con el tiempo que los niveles de pH, lo que indica que las fuerzas hidrofóbicas y los parámetros de forma de Van der Waals pueden dominar la auto-agregación de Lp299v en las distintas condiciones. Sin embargo, el modelo presentado en este estudio sugiere que el pH a bajos niveles puede influir positivamente en la auto-agregación facilitando la colonización en la parte superior del sistema digestivo.