In vivo Antibacterial Activity of Star Anise (Illicium verum Hook.) Extract Using Murine MRSA Skin Infection Model in Relation to Its Metabolite Profile
Received 9 October 2020
Accepted for publication 12 December 2020
Published 6 January 2021 Volume 2021:14 Pages 33—48
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Sahil Khanna
Mohamed A Salem,1,* Riham A El-Shiekh,2,* Rasha A Hashem,3 Mariam Hassan3
1Department of Pharmacognosy, Faculty of Pharmacy, Menoufia University, Menoufia, Egypt; 2Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 3Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo, Egypt
*These authors contributed equally to this work
Correspondence: Mariam Hassan
Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, Egypt
Tel +20 122 3376326
Introduction: Star anise fruits (Illicium verum Hook.) have been used as an important treatment in traditional Chinese medicine. The previous studies reported the activity of the non-polar fractions as potential sources of antibacterial metabolites, and little was done concerning the polar fractions of star anise.
Methods: The antibacterial activity of the star anise aqueous methanolic (50%) extract against multidrug-resistant Acinetobacter baumannii AB5057 and methicillin-resistant Staphylococcus aureus (MRSA USA300) was investigated in vitro (disc diffusion assay, minimum bactericidal concentration determination, anti-biofilm activity and biofilm detachment activity). The antibacterial activity was further tested in vivo using a murine model of MRSA skin infection. Ultra-performance liquid chromatography coupled to high-resolution mass spectrometry (UPLC/HRMS) approach was applied for the identification of the metabolites responsible for the antibacterial activity. The antioxidant potential was evaluated using five in vitro assays: TAC (total antioxidant capacity), DPPH, ABTS, FRAP (ferric reducing antioxidant power) and iron-reducing power.
Results: In vitro, star anise aqueous methanolic extract showed significant inhibition and detachment activity against biofilm formation by the multidrug-resistant and highly virulent Acinetobacter baumannii AB5057 and MRSA USA300. The topical application of the extract in vivo significantly reduced the bacterial load in MRSA-infected skin lesions. The extract showed strong antioxidant activity using five different complementary methods. More than seventy metabolites from different classes were identified: phenolic acids, phenylpropanoids, sesquiterpenes, tannins, lignans and flavonoids.
Conclusion: This study proposes the potential use of star anise polar fraction in anti-virulence strategies against persistent infections and for the treatment of staphylococcal skin infections as a topical antimicrobial agent. To our knowledge, our research is the first to provide the complete polar metabolome list of star anise in an approach to understand the relationship between the chemistry of these metabolites and the proposed antibacterial activity.
Keywords: Acinetobacter baumannii, antimicrobial resistance, antioxidant, biofilm, metabolome, polar methanolic extract