Ethyl Acetate Fraction of Bixa orellana and Its Component Ellagic Acid Exert Antibacterial and Anti-Inflammatory Properties against Mycobacterium abscessus subsp. massiliense

Abstract

Mycobacterium abscessus subsp. massiliense (Mabs) causes chronic infections, which has led to the need for new antimycobacterial agents. In this study, we investigated the antimycobacterial and anti-inflammatory activities of the ethyl acetate fraction of Bixa orellana leaves (BoEA) and ellagic acid (ElAc). In silico analysis predicted that ElAc had low toxicity, was not mutagenic or carcinogenic, and had antimicrobial and anti-inflammatory activities. Apparently, ElAc can interact with COX2 and Dihydrofolate reductase (DHFR) enzymes, which could explain both activities. In vitro analysis showed that BoEA and ElAc exerted antimicrobial activity against Mabs (minimum inhibitory concentration of 1.56, 1.56 mg/mL and bactericidal concentration of 6.25, 3.12 mg/mL, respectively. Clarithromycin showed MIC and MBC of 1 and 6 µg/mL). Treatment with BoEA or ElAc increased survival of Tenebrio molitor larvae after lethal infection with Mabs and reduced carrageenan-induced paw edema in mice, around 40% of edema volume after the fourth hour, similarly to diclofenac. In conclusion, BoEA and ElAc exert antimicrobial effects against Mabs and have anti-inflammatory effects, making them potential sources of antimycobacterial drugs. The biological activities of ElAc may be due to its high binding affinities predicted for COX2 and DHFR enzymes.

A review of <i>Bixa orellana</i> L. (Annatto) leaves as medicinal resource: Use in the population as complementary medicine, phytotherapeutic action and quality parameters

“…(Zarza-García et al, 2017). In a similar trial, the ethyl acetate extract (50 mg/kg) also reduced paw edema by 40%, being comparable to the efficiency of diclofenac (Moraes-Neto et al, 2022). Another work investigated the possible inflammatory mediators inhibited by the aqueous extract of the leaves, and the acute inflammation model was induced in Sprague-Dawley rats through the administration of carrageenan, histamine, serotonin and bradykinin in the hind legs, in addition to verifying to regression of granulomas in the model of chronic inflammation, so that in all models, the extract led to the reduction of inflammation, using doses between 50 and 150 mg/kg (Zuraini et al, 2007).…”

“…The ethyl acetate extract produced an antimicrobial (Minimum inhibitiory concentration (MIC) = 1.56 mg/mL) and bacteriostatic (MIC = 6.25 mg/mL) effect against Mycobacterium abscessus subsp. massiliense (Mabs) (Moraes-Neto et al, 2022). Finally, the methanolic extract presented activity against Pseudomonas aeruginosa, with maximum inhibition halo activity of 17.33 mm (Singh & Vidyasagar, 2017).…”

A Review of the Dietary Intake, Bioavailability and Health Benefits of Ellagic Acid (EA) with a Primary Focus on Its Anti-Cancer Properties

“…Mycobacterium abscessus (Mabs) is a cause of various types of infection including respiratory infection in patients with cystic fibrosis. EA demonstrated antimicrobial activity against Mabs due to its high binding affinity to Dihydrofolate reductase at a minimum inhibitory concentration of 1.56 mg/mL and bactericidal concentration of of 3.12 mg/mL [ 25 ].…”

Myrciaria Genus: Bioactive Compounds and Biological Activities

“…In this way, compounds that act by affecting the functioning of DHFR can cause the death of bacteria. [52] Myricetin acts by inhibiting bacterial enzymes that are essential for bacteria. Studies involving the Escherichia coli species showed that myricetin is able to inhibit DNA gyrase, DNA helicase and RNA polymerase enzymes.…”

“…The antimicrobial activity of ellagic acid is related to its ability to bind with Dihydrofolate reductase (DHFR), this bacterial enzyme acts in important processes related to bacterial multiplication such as nucleic acid synthesis, DNA translation, RNA transcription and replication of proteins. In this way, compounds that act by affecting the functioning of DHFR can cause the death of bacteria [52] . Myricetin acts by inhibiting bacterial enzymes that are essential for bacteria.…”