PMID- 28848992 OWN - NLM STAT- MEDLINE DCOM- 20180515 LR - 20231213 IS - 1791-244X (Electronic) IS - 1107-3756 (Linking) VI - 40 IP - 4 DP - 2017 Oct TI - Antimicrobial activity and synergism of ursolic acid 3-O-alpha-L-arabinopyranoside with oxacillin against methicillin-resistant Staphylococcus aureus. PG - 1285-1293 LID - 10.3892/ijmm.2017.3099 [doi] AB - The objective of the present study was to investigate the antibacterial activity of a single constituent, ursolic acid 3-O-alpha-L-arabinopyranoside (URS), isolated from the leaves of Acanthopanax henryi (Oliv.) Harms, alone and in combination with oxacillin (OXA) against methicillin-resistant Staphylococcus aureus (MRSA). A broth microdilution assay was used to determine the minimal inhibitory concentration (MIC). The synergistic effects of URS and OXA were determined using a checkerboard dilution test and time-kill curve assay. The mechanism of action of URS against MRSA was analyzed using a viability assay in the presence of a detergent and an ATPase inhibitor. Morphological changes in the URS-treated MRSA strains were evaluated via transmission electron microscopy (TEM). In addition, the producing penicillin-binding protein 2a (PBP2a) protein level was analyzed using western blotting. The MIC value of URS against MRSA was found to be 6.25 microg/ml and there was a partial synergistic effect between OXA and URS. The time-kill growth curves were suppressed by OXA combined with URS at a sub-inhibitory level. Compared to the optical density at 600 nm (OD600) value of URS alone (0.09 microg/ml), the OD600 values of the suspension in the presence of 0.09 microg/ml URS and 0.00001% Triton X-100 or 250 microg/ml N,N'-dicyclohexylcarbodiimide reduced by 56.6 and 85.9%, respectively. The TEM images of MRSA indicated damage to the cell wall, broken cell membranes and cell lysis following treatment with URS and OXA. Finally, an inhibitory effect on the expression of PBP2a protein was observed when cells were treated with URS and OXA compared with untreated controls. The present study suggested that URS was significantly active against MRSA infections and revealed the potential of URS as an effective natural antibiotic. FAU - Zhou, Tian AU - Zhou T AD - Department of Oriental Pharmacy, College of Pharmacy and Wonkwang-Oriental Medicines Research Institute, Institute of Biotechnology, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea. FAU - Li, Zhi AU - Li Z AD - School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan 410-208, P.R. China. FAU - Kang, Ok-Hwa AU - Kang OH AD - Department of Oriental Pharmacy, College of Pharmacy and Wonkwang-Oriental Medicines Research Institute, Institute of Biotechnology, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea. FAU - Mun, Su-Hyun AU - Mun SH AD - Department of Oriental Pharmacy, College of Pharmacy and Wonkwang-Oriental Medicines Research Institute, Institute of Biotechnology, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea. FAU - Seo, Yun-Soo AU - Seo YS AD - Department of Oriental Pharmacy, College of Pharmacy and Wonkwang-Oriental Medicines Research Institute, Institute of Biotechnology, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea. FAU - Kong, Ryong AU - Kong R AD - Department of Oriental Pharmacy, College of Pharmacy and Wonkwang-Oriental Medicines Research Institute, Institute of Biotechnology, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea. FAU - Shin, Dong-Won AU - Shin DW AD - Department of Oriental Medicine Resources, College of Bio Industry Science, Sunchon National University, Sunchon, Jeonnam 540-742, Republic of Korea. FAU - Liu, Xiang-Qian AU - Liu XQ AD - School of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan 410-208, P.R. China. FAU - Kwon, Dong-Yeul AU - Kwon DY AD - Department of Oriental Pharmacy, College of Pharmacy and Wonkwang-Oriental Medicines Research Institute, Institute of Biotechnology, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea. LA - eng PT - Journal Article DEP - 20170814 PL - Greece TA - Int J Mol Med JT - International journal of molecular medicine JID - 9810955 RN - 0 (Anti-Bacterial Agents) RN - 0 (Drug Combinations) RN - 0 (Glycosides) RN - 0 (Plant Extracts) RN - 0 (Triterpenes) RN - UH95VD7V76 (Oxacillin) SB - IM MH - Anti-Bacterial Agents/isolation & purification/*pharmacology MH - Cell Wall/*drug effects/metabolism/ultrastructure MH - Drug Combinations MH - Drug Synergism MH - Eleutherococcus/chemistry MH - Glycosides/isolation & purification/*pharmacology MH - Methicillin-Resistant Staphylococcus aureus/*drug effects/growth & development/metabolism/ultrastructure MH - Microbial Sensitivity Tests MH - Microscopy, Electron, Transmission MH - Oxacillin/*pharmacology MH - Plant Extracts/chemistry MH - Plant Leaves/chemistry MH - Triterpenes/isolation & purification/*pharmacology MH - Ursolic Acid EDAT- 2017/08/30 06:00 MHDA- 2018/05/16 06:00 CRDT- 2017/08/30 06:00 PHST- 2017/02/07 00:00 [received] PHST- 2017/07/28 00:00 [accepted] PHST- 2017/08/30 06:00 [pubmed] PHST- 2018/05/16 06:00 [medline] PHST- 2017/08/30 06:00 [entrez] AID - 10.3892/ijmm.2017.3099 [doi] PST - ppublish SO - Int J Mol Med. 2017 Oct;40(4):1285-1293. doi: 10.3892/ijmm.2017.3099. Epub 2017 Aug 14.