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首页> 外文期刊>BMC Complementary and Alternative Medicine >Use of Pinus sylvestris L. ( Pinaceae ), Origanum vulgare L. ( Lamiaceae ) , and Thymus vulgaris L. ( Lamiaceae ) essential oils and their main components to enhance itraconazole activity against azole susceptibleot-susceptible Cryptococcus neoformans strains
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Use of Pinus sylvestris L. ( Pinaceae ), Origanum vulgare L. ( Lamiaceae ) , and Thymus vulgaris L. ( Lamiaceae ) essential oils and their main components to enhance itraconazole activity against azole susceptibleot-susceptible Cryptococcus neoformans strains

机译:使用樟子松(Pinaceae),牛至(Origanum vulgare L.(Lamiaceae)和百里香(Lyaceae)精油及其主要成分来增强伊曲康唑对唑敏感/不敏感的新型隐球菌菌株的活性。

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Cryptococcal infections, besides being a problem for immunocompromised patients, are occasionally being a problem for immunocompetent patients. In addition, the lower susceptibility of this yeast to azoles is a growing problem in health care. To date, there are very few molecules with any activity towards Cryptococcus neoformans, leading to heightened interest in finding new alternatives or adjuvants to conventional drugs for the treatment of mycosis caused by this yeast. Since the essential oils (EOs) are considered as a potential rich source of bioactive antimicrobial compounds, we evaluated the antifungal activity of Origanum vulgare (oregano), Pinus sylvestris (pine), and Thymus vulgaris (thyme red) EOs, and their components (α-pinene, carvacrol, thymol) compared with fluconazole, itraconazole, and voriconazole, against C.neoformans clinical strains. Then, we investigated the effect of EOs and components in combination with itraconazole. EO composition was analysed by Gas chromatography-mass spectrometry (GC-MS). A broth microdilution method was used to evaluate the susceptibility of C.neoformans to azoles, EOs and components. Checkerboard tests, isobolograms and time-kill assays were carried out for combination studies. Six C.neoformans isolates were susceptible to azoles, while one C.neoformans exhibited a reduced susceptibility to all tested azole drugs. All EOs exerted a good inhibitory activity against all C.neoformans strains. Pine EO was the most effective. Among components, thymol exerted the most remarkable activity. By checkerboard testing and isobolographic analysis, combinations of itraconazole with oregano, pine, or thyme EOs, and carvacrol were found to be synergistic (FICI≤0.5) against azole susceptible C.neoformans. Regarding the azole not susceptible C.neoformans strain, the synergistic effect with itraconazole was observed with thyme EO (chemotype: thymol 26.52%; carvacrol 7.85%), and carvacrol. Time-kill assays confirmed the synergistic effects of itraconazole and oregano or thyme EO against azole susceptible C.neoformans. Binary mixtures of itraconazole/thyme EO or carvacrol yielded additive effects on the azole not susceptible C.neoformans. Our findings highlight the potential effectiveness of thyme, oregano EOs, and carvacrol as natural and cost-effective adjuvants when used in combination with itraconazole. Identification of EOs exerting these effects could be one of the feasible ways to overcome drug resistance, reducing drug concentration and side effects.
机译:隐球菌感染除了是免疫功能低下患者的问题外,有时也是免疫能力强的患者的问题。另外,该酵母对唑类的较低敏感性在卫生保健中是一个日益严重的问题。迄今为止,几乎没有任何分子对新隐球菌具有活性,从而引起了人们对于寻找新的替代品或佐剂来治疗这种酵母菌引起的真菌病的兴趣。由于香精油(EOs)被认为是生物活性抗微生物化合物的潜在丰富来源,因此我们评估了牛至,牛樟子松(pine)和百里香(百里香红)EOs及其成分的抗真菌活性( α-pine烯,香芹酚,百里酚)与氟康唑,伊曲康唑和伏立康唑的抗药性比较。然后,我们研究了伊曲康唑与EOs和组分的作用。通过气相色谱-质谱法(GC-MS)分析EO组成。肉汤微稀释法用于评估新福寿螺对吡咯,EOs和组分的敏感性。进行了棋盘格测试,等效线图和时间杀伤试验以进行组合研究。六种新孢子虫隔离株对唑类敏感,而一种新孢子虫对所有测试的唑类药物的敏感性降低。所有EO均对所有新孢子虫菌株表现出良好的抑制活性。松油油最有效。在组分中,百里酚发挥最显着的活性。通过棋盘测试和等效线描记法分析,发现伊曲康唑与牛至,松树或百里香油EO和香芹酚的组合对于易受唑类影响的新福建梭菌具有协同作用(FICI≤0.5)。关于对唑不敏感的新孢子虫菌株,在百里香EO(化学型:百里酚26.52%;香芹酚7.85%)和香芹酚中观察到与伊曲康唑的协同作用。时间杀灭试验证实了伊曲康唑和牛至或百里香EO对吡咯敏感的新福尔摩斯氏菌的协同作用。伊曲康唑/百里香EO或香芹酚的二元混合物对不易感新孢子虫的唑产生加性作用。我们的发现强调了百里香,牛至EOs和香芹酚作为与伊曲康唑组合使用的天然且具成本效益的佐剂的潜在功效。鉴定具有这些作用的EO可能是克服耐药性,降低药物浓度和副作用的可行方法之一。

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