背景:在治疗抑郁症时,肠道中残留的抗抑郁药与微生物组相互作用,导致多重耐药(MDR)突变体的出现,这对感染性并发症的治疗提出了挑战。需要战略来解决这个问题。刺梨(ATR,石芋根茎,天南星科),中药,在我国已广泛应用于神经系统疾病和消化道疾病的治疗。这里,在氟西汀诱导的大肠杆菌中,ATR被证明具有出色的MDR预防作用(E.大肠杆菌)。
目的:本研究旨在揭示ATR及其信号级联在预防氟西汀诱导的多药耐药中的有效作用。
方法:将ATR的水提取物与亚最低抑制浓度(100mg/l)的氟西汀在大肠杆菌中共同应用,以评估其抗MDR潜力。通过二氯二氢荧光素二乙酸盐测定和实时PCR检测细菌中活性氧(ROS)的形成和MDR相关基因的表达。分别。两种荧光染料,1-N-苯基萘胺和3,3'-二丙基硫二甲己花青用于分析大肠杆菌的外膜通透性和内膜去极化。通过HPLC测定氟西汀在处理的大肠杆菌中的积累。鉴定了ATR的活性部分。
结果:ATR水提物显著降低氟西汀诱导的MDR突变体数量,对氯霉素和四环素的半数有效浓度(EC50)为55.5μg/ml和16.8μg/ml,分别。ATR强烈逆转了氟西汀诱导的大肠杆菌超氧化物反应和膜损伤。此外,ATR的加入显著降低了氟西汀在大肠杆菌中的积累。进一步分馏后,ATR的多糖被证明是具有最显著的抗MDR活性的部分。
结论:这是第一份研究ATR预防MDR效果的报告。这项研究的结果表明,ATR是一种预防MDR问题的优秀草药产品,如氟西汀诱导的,有可能减少抑郁症药物治疗期间的副作用。
BACKGROUND: In treating depression, the residual anti-depressant in gut interacts with the microbiome, leading to the appearance of multiple drug resistant (MDR) mutants, which poses a challenge for the treatment of infectious complications. Strategy is needed to combat this issue. Acori Tatarinowii Rhizoma (ATR, rhizome of Acorus tatarinowii Schott, Araceae), a traditional Chinese medicine, has been widely used for treatment of neurological disorders and gastrointestinal digestive disease in China. Here, ATR was demonstrated an excellent MDR-preventing effect in fluoxetine-induced Escherichia coli (E. coli).
OBJECTIVE: This study aimed to reveal the effective role of ATR and its signaling cascades involved in preventing fluoxetine-induced MDR.
METHODS: The water extract of ATR was co-applied with sub-minimum inhibitory concentration (100 mg/l) of fluoxetine in E. coli to evaluate its anti-MDR potential. Formation of reactive oxygen species (ROS) and expression of MDR-related genes in bacteria were measured by dichloro-dihydro-fluorescein diacetate assay and real-time PCR, respectively. Two fluorescent dyes, 1-N-phenylnapthylamine and 3,3\'-dipropylthiadicarbocyanine were used to analyze the outer membrane permeability and inner membrane depolarization of E. coli. The accumulation of fluoxetine in the treated E. coli was determined via HPLC. The active fraction of ATR was identified.
RESULTS: The water extract of ATR significantly decreased the number of MDR mutants induced by fluoxetine and had half effective concentrations (EC50) of 55.5 μg/ml and 16.8 μg/ml for chloramphenicol and tetracycline, respectively. ATR robustly reversed the fluoxetine-induced superoxide response and membrane damage in E. coli. In addition, the inclusion of ATR significantly reduced the accumulation of fluoxetine in E. coli. After further fractionation, the polysaccharide of ATR was demonstrated as the fraction with the most significant anti-MDR activity.
CONCLUSIONS: This is the first report to investigate the MDR-preventing effect of ATR. The results of this study proposed ATR as an excellent herbal product to prevent MDR issues, as induced by fluoxetine, with the potential to reduce the side effects during the drug therapy of depression.