Maytenus octogona Superoxide Scavenging and Anti-Inflammatory Caspase-1 Inhibition Study Using Cyclic Voltammetry and Computational Docking Techniques.

The relationship between oxidative stress and inflammation is well known, and exogenous antioxidants, primarily phytochemical natural products, may assist the body's endogenous defense systems in preventing diseases due to excessive inflammation. In this study, we evaluated the antioxidant properties of ethnomedicines from Peru that exhibit anti-inflammatory activity by measuring the superoxide scavenging activity of ethanol extracts of Maytenus octogona aerial parts using hydrodynamic voltammetry at a rotating ring-disk electrode (RRDE). The chemical compositions of these extracts are known and the interactions of three methide-quinone compounds found in Maytenus octogona with caspase-1 were analyzed using computational docking studies. Caspase-1 is a critical enzyme triggered during the activation of the inflammasome and its actions are associated with excessive release of cytokines. The most important amino acid involved in active site caspase-1 inhibition is Arg341 and, through docking calculations, we see that this amino acid is stabilized by interactions with the three potential methide-quinone Maytenus octogona inhibitors, hydroxytingenone, tingenone, and pristimerin. These findings were also confirmed after more rigorous molecular dynamics calculations. It is worth noting that, in these three compounds, the methide-quinone carbonyl oxygen is the preferred hydrogen bond acceptor site, although tingenone's other carbonyl group also shows a similar binding energy preference. The results of these calculations and cyclovoltammetry studies support the effectiveness and use of anti-inflammatory ethnopharmacological ethanol extract of Maytenus octogona (L'Héritier) DC.

Antioxidant properties of bee propolis and an important component, galangin, described by X-ray crystal structure, DFT-D and hydrodynamic voltammetry.

Propolis is produced by honeybees and used to seal their hives for defensive purposes and has been used in ethnopharmacology since ancient times. It is a lipophilic material containing a large collection of naturally produced plant organic molecules, including flavonoids. The flavonoid galangin is consistently found in propolis, independent of the hive geographical location and its X-ray crystal and molecular structure is reported. The antioxidant scavenging of superoxide by galangin and propolis is here presented. Using a cyclic voltammetry technique developed in our lab, we show that galangin is an excellent scavenger of the superoxide radical, perhaps even better than quercetin. Our results show that galangin displays a Superoxide Dismutase (SOD) function. This is described experimentally and theoretically (DFT). Two modes of scavenging superoxide are seen for galangin: (1) superoxide radical extraction of H atom from the hydroxyl moieties located in position 3 and 5 of galangin, which are also associated with proton incorporation defining the SOD action; (2) π-π interaction among several superoxide radicals and the galangin polyphenol ring that evolve towards release of O2 and H2O2. We describe these two actions separately as their relative sequence, and/or combination, cannot be defined; all these processes are thermodynamically spontaneous, or subjected to mild barriers.

Interrelated Mechanism by Which the Methide Quinone Celastrol, Obtained from the Roots of Tripterygium wilfordii, Inhibits Main Protease 3CLpro of COVID-19 and Acts as Superoxide Radical Scavenger.

We describe the potential anti coronavirus disease 2019 (COVID-19) action of the methide quinone inhibitor, celastrol. The related methide quinone dexamethasone is, so far, among COVID-19 medications perhaps the most effective drug for patients with severe symptoms. We observe a parallel redox biology behavior between the antioxidant action of celastrol when scavenging the superoxide radical, and the adduct formation of celastrol with the main COVID-19 protease. The related molecular mechanism is envisioned using molecular mechanics and dynamics calculations. It proposes a covalent bond between the S(Cys145) amino acid thiolate and the celastrol A ring, assisted by proton transfers by His164 and His41 amino acids, and a π interaction from Met49 to the celastrol B ring. Specifically, celastrol possesses two moieties that are able to independently scavenge the superoxide radical: the carboxylic framework located at ring E, and the methide-quinone ring A. The latter captures the superoxide electron, releasing molecular oxygen, and is the feature of interest that correlates with the mechanism of COVID-19 inhibition. This unusual scavenging of the superoxide radical is described using density functional theory (DFT) methods, and is supported experimentally by cyclic voltammetry and X-ray diffraction.