Phytochemical and anti-MRSA constituents of Zanthoxylum nitidum

Biomedicine & Pharmacotherapy

Mei-Ling Xiang¹  Song Chen¹  Yi-Chi Chen²  Huan Wang²  Zhao-Jie Wang³  Xiang-Juan Xu³  Xiao-Dong Luo⁴  Tian-Zhen Xie⁴  Qi Zeng⁴ 

[1] Development of Natural Products;School of Chemical Science and Technology, Yunnan University, Kunming 650091, People’s Republic of China;;Yunnan Province Center for Research &Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education;

关键词: Zanthoxylum nitidum;    Coumarins;    Isoquinoline alkaloids;    Anti-MRSA;    Efflux pump inhibition;    Skin infection;   

DOI  :  

来源: DOAJ

【 摘 要 】

Infectious diseases caused by multidrug-resistant bacteria such as methicillin-resistant Staphylococcus aureus, pose a significant threat to humanity. Persistent and repeated invasive infection with MRSA led to higher morbidity and mortality, and required comprehensive measures in treatment and prevention. Zanthoxylum nitidum (Roxb.) DC. is used as detoxifying, analgesic, and hemostatic herbal medicine for thousands of years. Previously pharmacological studies showed that Z. nitidum had antibacterial bioactivity, but only the MIC of a few compounds, crude extracts, and fractions were reported. In our ongoing endeavor to explore bioactive compounds, two new coumarins, 6-(3-oxo-butyl)-limettin (1) and toddalin I (2), and 24 known compounds were isolated from the roots of Z. nitidum, in which two isoquinoline alkaloids, 6-acetonyl-dihydrofagaridine (16) and 6-acetonyl-dihydrochelerythrine (17) showed anti-MRSA bioactivity in vitro and in vivo. Both 16 and 17 showed synergistic action with ampicillin, which decreased the MIC significantly, and both compounds had a significant ability to destroy bacterial biofilm combined with ampicillin. The combined administration showed a strong scavenging effect on the planktonic bacteria in vitro and cleared skin infection effectively in the model of wound infection in vivo. Furthermore, compound 16 inhibited the efflux of the drug by combining with ampicillin or EtBr, resulting in the MIC decreased obviously. Our investigation supported the traditional use of Z. nitidum in treating infections caused by bacteria, and might provide new natural products to reduce the use of antibiotics and the treatment of drug-resistance bacteria.

【 授权许可】

Unknown