Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China.
Jiangsu Key Laboratory for High Technology Research of TCM Formulae and Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nan Jing, Jiangsu Province, China.
Phytomedicine. 2024 Jan;123:155232. doi: 10.1016/j.phymed.2023.155232. Epub 2023 Nov 19.
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).
This study aimed to reveal the effective role of ATR and its signaling cascades involved in preventing fluoxetine-induced MDR.
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.
The water extract of ATR significantly decreased the number of MDR mutants induced by fluoxetine and had half effective concentrations (EC) 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.
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.
在治疗抑郁症时，肠道中残留的抗抑郁药与微生物群相互作用，导致出现多种耐药（MDR）突变体，这给治疗感染并发症带来了挑战。需要采取策略来应对这一问题。石菖蒲（Acori Tatarinowii Rhizoma，ATR，天南星科菖蒲属植物石菖蒲的根茎）是一种传统中药，在中国被广泛用于治疗神经紊乱和胃肠道消化疾病。在这里，ATR 被证明在氟西汀诱导的大肠杆菌（E. coli）中具有出色的 MDR 预防作用。
本研究旨在揭示 ATR 的有效作用及其参与预防氟西汀诱导的 MDR 的信号级联反应。
将 ATR 的水提取物与低于最小抑菌浓度（100mg/L）的氟西汀共同应用于大肠杆菌中，以评估其抗 MDR 潜力。通过二氯二氢荧光素二乙酸酯测定法和实时 PCR 分别测量细菌中活性氧物种（ROS）的形成和 MDR 相关基因的表达。使用两种荧光染料，1-N-苯基萘基胺和 3,3'-二丙基噻二碳菁，分析大肠杆菌的外膜通透性和内膜去极化。通过 HPLC 测定处理后的大肠杆菌中氟西汀的积累量。鉴定 ATR 的有效成分。
ATR 的水提取物显著降低了氟西汀诱导的 MDR 突变体的数量，对氯霉素和四环素的半有效浓度（EC）分别为 55.5μg/ml 和 16.8μg/ml。ATR 可有效逆转氟西汀诱导的大肠杆菌中超氧化物的反应和膜损伤。此外，ATR 的加入显著减少了大肠杆菌中氟西汀的积累。进一步分离后，ATR 的多糖被证明是具有最显著抗 MDR 活性的成分。
这是首次研究 ATR 对 MDR 的预防作用。本研究结果表明，ATR 是一种预防氟西汀诱导的 MDR 问题的优秀草药产品，有望降低抑郁症药物治疗过程中的副作用。
