Division of Life Science and Center for Chinese Medicine, The Hong Kong University of Science and Technology, Hong Kong, China; Shenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Shenzhen, China.
Shenzhen Key Laboratory of Edible and Medicinal Bioresources, HKUST Shenzhen Research Institute, Shenzhen, China.
Phytomedicine. 2022 Nov;106:154421. doi: 10.1016/j.phymed.2022.154421. Epub 2022 Aug 27.
The medication of synthetic chemical is one of the main treatments for depressive disorders. Different lines of evidence reveal that a long-term exposure to anti-depressants, e.g., fluoxetine, is causing multiple-drug resistance (MDR) of gut microbiomes. The MDR bacterial strains in gut pose a threat to intestinal balance and treatment of future microbial infection. Effective strategies are thus in urgent need to prevent the anti-depressant-mediated MDR of gut microbes.
We aimed to investigate the potential role of Aloe vera (L.) Burm. f. (aloe; Liliaceae family) to prevent MDR of E. coli being co-cultured with fluoxetine.
The extract of A. vera was co-cultured with E. coli and fluoxetine to analyze the preventive effect of MDR. To figure out the mechanistic action, the formation of reactive oxygen species (ROS) and the expression of key biomarkers, including outer membrane proteins (OmpF and OmpC), superoxidative stress activator (SoxS) and efflux pumps (AcrA/B-TolC), were determined in E. coli being treated with fluoxetine and aloe extract. In addition, the genetic mutation of transcriptional factors of these biomarkers was determined in the fluoxetine-treated E. coli.
The water extract of A. vera showed considerable potential to reduce the number of fluoxetine-mediated MDR colonies. The extract robustly suppressed the formation of ROS in E. coli. However, thiourea and N-acetylcysteine, two well-known antioxidants, showed no activity in preventing the formation of bacterial MDR. Additionally, A. vera extract directly affected the fluoxetine-triggered early stress response of E. coli and the expression of downstream genes. Meanwhile, A. vera extract was able to inhibit the genetic mutation of SoxR gene in E. coli, as induced by co-cultured with fluoxetine. By fractionation of the aloe extract, the ethanol precipitate, composing mainly polysaccharides, showed robust activity in preventing the fluoxetine-mediated MDR.
This study therefore suggested that the extract of A. vera could be an adjuvant agent to combat bacterial MDR during anti-depressant treatment.
合成化学药物是治疗抑郁症的主要方法之一。不同的证据表明，长期暴露于抗抑郁药（如氟西汀）会导致肠道微生物群的多药耐药性（MDR）。肠道中的 MDR 菌株对肠道平衡和未来微生物感染的治疗构成威胁。因此，迫切需要有效的策略来防止抗抑郁药介导的肠道微生物 MDR。
我们旨在研究库拉索芦荟（L.）Burm. f.（芦荟；百合科）提取物预防氟西汀共培养的大肠杆菌 MDR 的潜力。
将库拉索芦荟提取物与大肠杆菌和氟西汀共培养，分析 MDR 的预防作用。为了弄清楚其作用机制，测定了氟西汀和芦荟提取物处理的大肠杆菌中外膜蛋白（OmpF 和 OmpC）、超氧化物应激激活剂（SoxS）和外排泵（AcrA/B-TolC）等关键生物标志物的活性氧（ROS）形成和表达。此外，还测定了氟西汀处理的大肠杆菌中这些生物标志物的转录因子的基因突变。
库拉索芦荟的水提取物显示出很大的潜力，可以减少氟西汀介导的 MDR 菌落数量。提取物强烈抑制了大肠杆菌中 ROS 的形成。然而，硫脲和 N-乙酰半胱氨酸这两种众所周知的抗氧化剂在预防细菌 MDR 的形成方面没有活性。此外，芦荟提取物直接影响了氟西汀诱导的大肠杆菌早期应激反应和下游基因的表达。同时，芦荟提取物能够抑制大肠杆菌 SoxR 基因在与氟西汀共培养时的基因突变。通过芦荟提取物的分级分离，主要由多糖组成的乙醇沉淀显示出很强的预防氟西汀介导的 MDR 的活性。
因此，本研究表明，芦荟提取物可以作为一种辅助剂，用于对抗抗抑郁药治疗期间的细菌 MDR。
