SHORT COMMUNICATION Inhibitory Activity of Brown Propolis Extracts on a Norfloxacin-Resistant Strain of Staphylococcus aureus Vanessa Moreira Frota 1 & Francisco Matheus F. Dias 1 & Mariana Ferreira do Nascimento 1 & Lavosyer da Silva Mendonça 1 & Emanuella Cristina dos Santos Moita 1 & Laressa Cristyne dos Santos Gomes 2 & Antonio Linkoln Alves Borges Leal 3 & Humberto Medeiros Barreto 3 & Maria Francilene Souza Silva 4 & Raquel Oliveira dos Santos Fontenelle 2 & Geovany Amorim Gomes 1 & Jean Parcelli C. do Vale 1 & Murilo Sérgio da Silva Julião 1 & Paulo Nogueira Bandeira 1 & Cláudia do Ó. Pessoa 4 & Hélcio Silva dos Santos 1 & Guilherme Julião Zocolo 5 & Tigressa Helena S. Rodrigues 1 Received: 21 October 2020 /Accepted: 2 April 2021 # Sociedade Brasileira de Farmacognosia 2021 Abstract Brown propolis from northern Ceará, Brazil, was found to contain predominantly sesquiterpenes in its volatile profile. The ethanolic propolis extract yielded a substantial apolar fraction (80.07 ± 1.47%) after liquid–liquid partitioning, which explains the low phenolic content (41.33 ± 1.68 mg GAE g EXT -1 ). Phenolics, such as p-coumaric (0.13 ± 0.04 mg g EPE -1 ), ferulic (1.07 ± 0.09 mg g EPE -1 ), and trans-cinnamic (0.41 ± 0.02 mg g EPE -1 ) acids, were detected in the EtOH-soluble extract. The apolar fraction was rich in triterpenes such as cycloartenol (12.85 ± 2.80%), α-amyrenyl acetate (4.37 ± 0.69%), and α-amyrin (3.89 ± 0.62%). Despite the lack of a direct antibacterial activity against Staphylococcus aureus 1199-B, both fractions exhibited potentiating effects in combination with norfloxacin; these effects could be attributed to efflux pump inhibition. The apolar fraction was more effective than the EtOH-soluble one at reducing the minimum inhibitory concentration, producing similar results to chlorpromazine and ethidium bromide. The EtOH-soluble fraction exhibited cytostatic properties at lower concentra- tions, while the apolar fraction demonstrated better selectivity for PC3 and HL60 tumor cells. The findings highlight the biological potential of Brazilian brown propolis for application as a complementary agent in the treatment of S. aureus infections and as an alternative therapy for cancer treatment. Keywords Phenolics . Volatiles . Non-volatile compounds . Efflux pump inhibitors . Cytotoxicity Introduction Propolis plays an important role in honeybee communities where it is used as a building material and defensive sub- stance. Many properties, such as antibacterial, antifungal, an- tiviral, cytotoxic, antioxidant, anti-inflammatory, and immu- nomodulatory properties, have been attributed to propolis, in- cluding the types found in Brazil, leading to its use in com- plementary medicine (Andrade et al. 2017; Xavier et al. 2017; Olegário et al. 2019). Propolis contains secondary plant me- tabolites, including polyphenolics, volatiles, and non-vola- tiles, determined by the flora at the collection site (Pellati et al. 2013). In this sense, the composition of propolis is not uniform throughout the world (Pellati et al. 2013; Olegário et al. 2019). Although the phenolic composition of propolis has been the most widely investigated, some studies have reported the * Tigressa Helena S. Rodrigues tigressa_helena@uvanet.br 1 Centro de Ciências Exatas e Tecnologia, Curso de Química, Universidade Estadual Vale do Acaraú, Avenida da Universidade 850, Sobral, Ceará 62.040-370, Brazil 2 Centro de Ciências Agrárias e Biológicas, Curso de Ciências Biológicas, Universidade Estadual Vale do Acaraú, Avenida da Universidade 850, Sobral, Ceará 62.040-370, Brazil 3 Departamento de Parasitologia e Microbiologia, Universidade Federal do Piauí, Campus Ministro Petronio Portella, Teresina, Piauí 64.049-550, Brazil 4 Departamento de Fisiologia e Farmacologia da Faculdade de Medicina, Universidade Federal do Ceará, Rua Coronel Nunes de Melo 1127, Fortaleza, Ceará 60.430-275, Brazil 5 Embrapa Agroindústria Tropical, Rua Doutora Sara Mesquita 2270, Fortaleza, Ceará 60.020-181, Brazil https://doi.org/10.1007/s43450-021-00150-9 / Published online: 21 April 2021 Revista Brasileira de Farmacognosia (2021) 31:249–255