葛根秦连煎剂通过调节肠道微环境缓解CUMS大鼠的抑郁样行为

IF 3.3 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE
Yaqin Peng, Yao Du, Yuanyuan Zhang, Ze Wang, Tao Hu, Yuning Mai, Hongxiu Song, Weichao Pan, Qinglong Cai, Feifei Ge, Yu Fan, Hee Young Kim, Dekang Liu, Xiaowei Guan
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引用次数: 0

摘要

背景:格根秦连煎(GQD)是一种经典的传统中药配方,主要用于治疗肠道疾病。在临床和动物实验中,GQD 通过靶向肠道微生物对多种疾病具有治疗效果。我们最近的研究还发现,GQD 通过调节肠道微生物组和代谢,有效缓解了甲基苯丙胺致瘾小鼠的焦虑。鉴于多项研究表明肠道微生物组与抑郁症的发生有关,我们在此尝试探讨 GQD 是否能通过靶向肠道微生物组来控制抑郁症:通过慢性不可预测轻度应激(CUMS)诱导大鼠抑郁样模型,并使用蔗糖偏好试验(SPT)测定抑郁水平。针对大鼠的抑郁样行为,采用了口服 GQD 的方法。结肠微生物组和代谢物模式分别通过 16s rRNA 测序和非靶向代谢组学进行测定:结果:我们发现 6 周的 CUMS 可诱导大鼠抑郁样行为,而 4 周的 GQD 治疗可显著缓解抑郁样行为。GQD还能改善CUMS大鼠结肠的组织学病变。然后,CUMS 增加了肠道微生物的丰度,而 GQD 治疗可以将其恢复到较低水平。我们进一步发现,在 CUMS 处理后,19 种细菌的属级丰度发生了变化,其中反刍球菌、舔舔菌、 Pygmaiobacter、Bacteroides、假单胞菌和假单胞菌 Family_XIII_AD3011_group 的丰度在 GQD 处理后有所降低。此外,我们还发现了 36 种结肠代谢物的水平在 CUMS 处理后发生了变化,其中包括筋骨草酸 B、精胺、醋酸氟氢可的松、α-酮戊二酸、α-酮戊二酸、α-酮戊二酸、α-酮戊二酸、α-酮戊二酸、α-酮戊二酸、α-酮戊二酸和α-酮戊二酸、2-氧代戊二酸、N'-(苯甲酰氧基)-2-(2,2-二氯环丙基)乙脒、N6-琥珀酰腺苷 齐墩果酸、KQH、Ergosta-5,7,9(11),22-四烯-3-beta-Ol、龙胆二酸、4-羟基维甲酸、FAHFA(3:0/16:0)、亮氨酸-脑啡肽和 N-乳酰基-苯丙氨酸可通过 GQD 治疗得到恢复。结论我们的研究结果为 GQD 在缓解 CUMS 大鼠抑郁样行为方面的疗效提供了证据支持,GQD 可能对结肠细菌(尤其是反刍球菌和乳酸杆菌的丰度)和代谢产物(尤其是齐墩果酸的水平)具有靶向作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Gegen Qinlian decoction alleviates depression-like behavior by modulating the gut microenvironment in CUMS rats.

Background: Gegen Qinlian Decoction (GQD) is a classical traditional Chinese medicine (TCM) formula primarily utilized for treating gut disorders. GQD showed therapeutic effects on several diseases in clinical and animal studies by targeting gut microbes. Our recent studies also found that GQD efficiently alleviated anxiety in methamphetamine-withdrawn mice via regulating gut microbiome and metabolism. Given that various studies have indicated the link between the gut microbiome and the development of depression, here we endeavor to explore whether GQD can manage depression disorders by targeting the gut microbiome.

Methods and materials: The depression-like model was induced in rats through chronic unpredictable mild stress (CUMS) and the depression levels were determined using the sucrose preference test (SPT). To address the depression-like behavior in rats, oral administration of GQD was employed. The colon microbiome and metabolite patterns were determined by 16s rRNA sequencing and untargeted metabolomics, respectively.

Results: We found 6 weeks of CUMS can induce depression-like behavior in rats and 4 weeks of GQD treatment can significantly alleviate the depression-like behavior. GQD treatment can also ameliorate the histological lesions in the colon of CUMS rats. Then, CUMS increased the abundance of gut microbes, while GQD treatment can restore it to a lower level. We further discovered that the abundances of 19 bacteria at the genus level were changed with CUMS treatment, among which the abundances of Ruminococcus, Lachnoclostridium, Pygmaiobacter, Bacteroides, Pseudomonas, and Pseudomonas Family_XIII_AD3011_group were stored by GQD treatment. Besides, we identified the levels of 36 colon metabolites were changed with CUMS treatment, among which the levels of Fasciculic acid B, Spermine, Fludrocortisone acetate, alpha-Ketoglutaric acid, 2-Oxoglutaric acid, N'-(benzoyloxy)-2-(2,2-dichlorocyclopropyl) ethanimidamide, N6-Succinyl Adenosine Oleanolic acid, KQH, Ergosta-5,7,9(11),22-Tetraen-3-beta-Ol, Gentisic acid, 4-Hydroxyretinoic Acid, FAHFA (3:0/16:0), Leucine-enkephalin and N-lactoyl-phenylalanine can be restored by GQD treatment.

Conclusion: Our findings provide evidence supporting the therapeutic efficacy of GQD in alleviating depression-like behavior in CUMS rats, potentially being targeted on colon bacteria (especially the abundance of Ruminococcus and Bacteroides) and metabolites (especially the level of Oleanolic acid).

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来源期刊
BMC Complementary Medicine and Therapies
BMC Complementary Medicine and Therapies INTEGRATIVE & COMPLEMENTARY MEDICINE-
CiteScore
6.10
自引率
2.60%
发文量
300
审稿时长
19 weeks
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