Active Compounds in Zingiber officinale as Possible Redox Inhibitors of 5-Lipoxygenase Using an In Silico Approach

Abstract

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.

Phytochemical Characterization and In Vitro and In Silico Biological Studies from Ferns of Genus Blechnum (Blechnaceae, Polypodiales)

“…The partition coefficient (cLogP), the number of hydrogen bond donors, the number of hydrogen bond acceptors, the molecular mass of the compounds, the topological polar surface area (TPSA) and the number of rotable bonds were calculated to determine the violations of the Lipinski’s rules that the compounds could present and to predict which compounds will have a good bioavailability and absorption through their possible oral administration. To evaluate the absorption in each of the compounds, the percentage of absorption (% ABS) (equation 1) was calculated using the calculated values of TPSA in each of the compounds [ 19 , 20 ]: % ABS = 109 − (0.345 ×TPSA) …”

“…The Osiris Data Warrior computational tool was used to determine the toxicological behavior of the compounds extracted from Blechnum . The toxicological risks that were evaluated were mutagenicity, tumorigenicity, irritation and reproductive effect [ 19 ]. The toxicological comparison of the compounds extracted from Blechnum with known inhibitors of cholinesterases was made.…”

Prospects for Pharmaceutical of Zingiber officinale Extracts and Fractions by Analysis of the Chemical Markers, Safety Profile, Anti-Lipoxygenase, and Analgesic Activity

“…The in-silico method determined that these two active compounds in ZO inhibit 5-LOX due to their specific interactions with residues involved in molecular inhibition. 23 Research also suggested that the primary ginger components, 6-gingerol, and 6-shogaol, are responsible for the diverse effects. Furthermore, it has been found that, in many cases, the bioactivity of shogaols is more potent than gingerols.…”

Antioxidant and antidiabetic activity and phytoconstituents of lichen extracts with temperate and polar distribution

“…The topological polar surface area and the percentage absorption (% ABS) (Eq. 1) were also calculated using the values calculated from TPSA in each of the compounds (Zhao et al, 2002;Ley-Martínez et al, 2022):…”