In vitro antibacterial activity of nimbolide against Helicobacter pylori.
In vitro antibacterial activity of nimbolide against Helicobacter pylori.
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DOI：
10.1016/j.jep.2021.114828
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发表时间：
2022-03-01
影响因子：
5.4
通讯作者：
Merrell DS
中科院分区：
文献类型：
--
作者：
Wylie MR;Windham IH;Blum FC;Wu H;Merrell DS
宁波利特是印楝树中已被确认的数百种植物化学物质之一。作为一种原产于印度次大陆的常青树，印楝树的成分在数千年的传统医学中已被用于治疗牙科、胃肠道、尿路和血液相关疾病、溃疡、头痛、胃灼热和糖尿病。在现代，人们发现天然的印楝油和提取物对包括人类病原体在内的各种微生物都有抑制作用。幽门螺杆菌是一种流行的胃部病原体，对抗生素的耐药性越来越高。因此，对治疗慢性感染的新疗法的需求越来越大。印甸油提取物对幽门螺杆菌的体外抗菌活性已被鉴定并发现具有杀菌作用。鉴于印印油提取物中发现了大量的植物化学物质，本研究旨在定义和表征具有抗幽门螺杆菌杀菌活性的特定化合物。对印木提取物中常见的印楝素、葛豆素和宁波莱德进行了抑菌活性测试，并测定了9株H.Nimbolide对幽门螺杆菌G27菌株的特性进行了进一步表征。考察了其杀菌动力学、可逆性、低pH下的杀菌效果和抑菌效果。同时测定了尼伯来特的溶血活性。最后，与常用的抗幽门螺杆菌感染的抗生素进行了比较，考察了印缅油提取物和尼美拉特对幽门螺杆菌生物被膜的抑制作用。对9株受试菌的最低抑菌浓度(MIC)和最低抑菌浓度(MBCs)分别为1.2 5~5μg/m L和2.5~10μg/m L。印缅油提取物和尼美拉特对幽门螺杆菌生物被膜均有一定的抑制作用。宁波利特在生物相关浓度下没有明显的溶血活性。尼波莱德的杀菌活性具有时间和剂量依赖性，与幽门螺杆菌的生长无关，且在低pH条件下具有协同作用。此外，高浓度(80μg/mL，作用2小时，40μg/mL，作用8小时)诱导的幽门螺杆菌细胞死亡是不可逆的。宁波利特对幽门螺杆菌具有显著的杀菌活性，既能杀死自由生活的细菌细胞，也能杀死生物膜内的细胞。此外，缺乏溶血活性、在低pH下的协同活性以及对处于生长停滞状态的细菌的杀菌性能都是潜在新药的理想药理和生物相关特性。这项研究强调了印属油提取物或宁波利特作为未来治疗幽门螺杆菌感染的潜在药物的潜力。
Nimbolide is one of hundreds of phytochemicals that have been identified within the neem tree (Azadirachta indica A. Juss). As an evergreen tree native to the Indian subcontinent, components of the neem tree have been used for millennia in traditional medicine to treat dental, gastrointestinal, urinary tract, and blood-related ailments, ulcers, headaches, heartburn, and diabetes. In modern times, natural oils and extracts from the neem tree have been found to have activities against a variety of microorganisms, including human pathogens. Helicobacter pylori, a prevalent gastric pathogen, shows increasing levels of antibiotic resistance. Thus, there is an increasing demand for novel therapeutics to treat chronic infections. The in vitro activity of neem oil extract against H. pylori was previously characterized and found to be bactericidal. Given the numerous phytochemicals found in neem oil extract, the present study was designed to define and characterize specific compounds showing bactericidal activity against H. pylori. Azadirachtin, gedunin, and nimbolide, which are all common in neem extracts, were tested for antimicrobial activity; the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined for nine strains of H. pylori. The specific properties of nimbolide were further characterized against H. pylori strain G27. Bactericidal kinetics, reversibility, effectiveness at low pH, and activity under bacteriostatic conditions were examined. The hemolytic activity of nimbolide was also measured. Finally, neem oil extract and nimbolide effectiveness against H. pylori biofilms were examined in comparison to common antibiotics used to treat H. pylori infection. Nimbolide, but not azadirachtin or gedunin, were effective against H. pylori; MICs and MBCs against the nine tested strains ranged between 1.25–5 μg/mL and 2.5–10 μg/mL, respectively. Additionally, neem oil extract and nimbolide were both effective against H. pylori biofilms. Nimbolide exhibited no significant hemolytic activity at biologically relevant concentrations. The bactericidal activity of nimbolide was time- and dose-dependent, independent of active H. pylori growth, and synergistic with low pH. Furthermore, nimbolide-mediated H. pylori cell death was irreversible after exposure to high nimbolide concentrations (80 μg/mL, after 2 hours of exposure time and 40 μg/mL after 8 hours of exposure). Nimbolide has significant bactericidal activity against H. pylori, killing both free living bacterial cells as well as cells within a biofilm. Furthermore, the lack of hemolytic activity, synergistic activity at low pH and bactericidal properties even against bacteria in a state of growth arrest are all ideal pharmacological and biologically relevant properties for a potential new agent. This study underscores the potential of neem oil extract or nimbolide to be used as a future treatment for H. pylori infection.
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影响因子：
6.1
作者：
Anchi, Pratibha;Swamy, Veerabhadra;Godugu, Chandraiah
通讯作者：
Godugu, Chandraiah
影响因子：
5.6
作者：
Bansod, Sapana;Godugu, Chandraiah
通讯作者：
Godugu, Chandraiah
影响因子：
5.8
作者：
Chattopadhyay, Ishita;Nandi, Bithi;Banerjee, Ranajit K.
通讯作者：
Banerjee, Ranajit K.
影响因子：
5.2
作者：
Erah, PO;Goddard, AF;Spiller, RC
通讯作者：
Spiller, RC
影响因子：
5.4
作者：
Fabry, W;Okemo, PO;Ansorg, R
通讯作者：
Ansorg, R