Antioxidant Properties of Embelin in Cell Culture. Electrochemistry and Theoretical Mechanism of Scavenging. Potential Scavenging of Superoxide Radical through the Cell Membrane

Abstract

Embelin, a plant natural product found in Lysimachia punctata (Primulaceae), and Embelia ribes Burm (Myrsinaceae) fruit, possesses interesting biological and pharmacological properties. It is a unique chemical species as it includes both quinone and hydroquinone functional groups plus a long hydrophobic tail. By using hydrodynamic voltammetry, which generates the superoxide radical in situ, we show an unusual scavenging capability by embelin. Embelin as a scavenger of superoxide is stronger than the common food additive antioxidant 2,6-bis(1,1-dimethylethyl)-4-20 methylphenol, (butylated hydroxytoluene, BHT). In fact, embelin is even able to completely abolish the superoxide radical in the voltaic cell. Computational results indicate that two different types of embelin scavenging actions may be involved, initially through π–π interaction and followed by proton capture in the cell. A related mechanism describes embelin’s ability to circumvent superoxide leaking by transforming the anion radical into molecular oxygen. In order to confirm its antioxidant properties, its biological activity was tested in a study carried out in THP-1 human leukemic monocytes and BV-2 mice microglia. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, proliferation curves and antioxidant activity by the use of a fluorescent probe showed good antioxidant properties at 24 h. This suggests that embelin’s long alkyl C10 tail may be useful for cell membrane insertion which stimulates the antioxidant defense system, and cytoprotection in microglia. In conclusion, embelin could be an interesting pharmacological tool able to decrease the damage associated with metabolic and neurodegenerative diseases.

Computational studies reveal mechanism by which quinone derivatives can inhibit SARS-CoV-2. Study of embelin and two therapeutic compounds of interest, methyl prednisolone and dexamethasone

“…We have recently described the antioxidant activity of emodin, another quinone plant natural product [ 52 ]. Emodin and embelin possess similar redox properties, and their capture of an electron by the quinone ring are closely related [ 53 ]. The existence of the Cys145 residue at the protease attracted our attention because of a potential strong bond between Cys and the quinone ring.…”

“…1 . Of 10 possible poses, numbers 6 and 9 showed a potential sulfur quinone-centroid approach, resembling embelin interaction with the superoxide anion [ 53 ]. CDocker interaction energy is -36.0 kcal/mol.…”

“…Vitamin K, embelin and coenzyme Q10, are all quinones having long alkyl tails that allow insertion in the host cell membrane, a property recently described for embelin [ 53 ]. Therefore, we also explored coenzyme Q10 to verify its insertion at the protease active site.…”

“…Recently, we demonstrated that, as an antioxidant scavenger of the superoxide radical, embelin acts in an unusual way. Instead of providing an H atom from one of its hydroxyls to the radical as do most polyphenolic antioxidants, it prefers to capture the superoxide electron (effect a ) [ 53 ]. This is accompanied by inserting a proton at one O(carbonyl) of embelin, to form a single C-OH bond (effect b ).…”

Cytoprotective Activity of Natural and Synthetic Antioxidants

“…Embelin, a plant natural product from Lysimachia punctata and Embelia ribes fruit with quinone and hydroquinone functional groups plus a long hydrophobic tail completely abolished the superoxide radical generated in situ with hydrodynamic voltammetry. Moreover, it exhibited cytoprotective activity in THP-1 human leukemic monocytes and BV-2 mice microglia probably thanks to its long alkyl tail enabling its insertion in cell membranes [ 16 ]. The mechanism of anti-inflammatory and antioxidant effects of aspirin on hyperoxia-induced acute lung injury was studied in NF-κB–luciferase transgenic mice.…”