College of Pharmacy, Medicinal Chemistry Laboratory, Jiamusi University, 154007, Jiamusi, China.
Heilongjiang Provincial Key Laboratory of New Drug Development and Pharmacotoxicological Evaluation, Jiamusi University, 154007, Jiamusi, China.
J Ethnopharmacol. 2023 Nov 15;316:116716. doi: 10.1016/j.jep.2023.116716. Epub 2023 Jun 8.
ETHNOPHARMACOLOGICAL RELEVANCE: Paeonia lactiflora Pall. (PL) has been commonly used to de-stressing the liver and relieve depression in traditional Chinese medicine for over a thousand years. Recently, it has been widely used in studies on anti-depressant, anti-inflammatory and regulation of intestinal flora. However, the polysaccharide component has received less attention than the saponin component of PL. AIM OF THE STUDY: This study aimed to elucidate the effects of Paeonia lactiflora polysaccharide (PLP) on depressive behavior in mice in a chronic unpredictable mild stress (CUMS) model and its possible action mechanisms. MATERIALS AND METHODS: A model of chronic depression induced by the CUMS approach. Behavioral experiments were used to assess the success of the CUMS model and the therapeutic impact of PLP. Then the extent of damage to the colonic mucosa was assessed by H&E staining; the extent of neuronal damage was assessed by Nissler staining. Inflammatory factor expression was assessed at different sites in the mouse by enzyme-linked immunoassay (Elisa). The alterations of faecal microflora were detected by 16S rRNA gene sequencing. In the colonic tissues, NLRP3, ASC and Caspase-1 mRNA and protein levels detected by quantitative real-time PCR (qRT-PCR) and Western blot(WB). RUSULTS: PLP can improve depressive behavior in CUMS mice, and colonic mucosal and neuronal damage. Elisa assay showed that PLP could reduce interleukin-1β (IL-1β), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) levels, and increase 5-Hydroxytryptamine(5-HT) levels in CUMS mice. 16S sequencing analysis showed that PLP could regulate the intestinal flora of CUMS mice and increase their species richness. In addition, PLP significantly inhibited NLRP3/ASC/Caspase-1 signalling pathways activation in the colonic tissues of CUMS mice. CONCLUSIONS: PLP modulates depression-related intestinal ecological dysregulation, increases species richness, and inhibits inflammatory factors levels and NLRP3 inflammasome activation to reduce colonic mucosal and neurons damage, thereby improving depression-like behavior and neurotransmitter release in CUMS mice.
民族药理学相关性：白芍（PL）在中医药中已被广泛用于舒缓肝脏和缓解抑郁，已有一千多年的历史。最近，它已被广泛应用于抗抑郁、抗炎和调节肠道菌群的研究中。然而，与 PL 的皂苷成分相比，多糖成分受到的关注较少。
研究目的：本研究旨在阐明白芍多糖（PLP）在慢性不可预测轻度应激（CUMS）模型中对小鼠抑郁行为的影响及其可能的作用机制。
材料和方法：采用 CUMS 方法诱导慢性抑郁模型。行为实验用于评估 CUMS 模型的成功和 PLP 的治疗效果。然后通过 H&E 染色评估结肠黏膜损伤程度；通过尼氏染色评估神经元损伤程度。通过酶联免疫吸附测定（ELISA）评估小鼠不同部位的炎症因子表达。通过 16S rRNA 基因测序检测粪便微生物群的变化。在结肠组织中，通过定量实时 PCR（qRT-PCR）和 Western blot（WB）检测 NLRP3、ASC 和 Caspase-1 的 mRNA 和蛋白水平。
结果：PLP 可改善 CUMS 小鼠的抑郁行为，并改善结肠黏膜和神经元损伤。ELISA 检测显示，PLP 可降低白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）水平，并增加 CUMS 小鼠 5-羟色胺（5-HT）水平。16S 测序分析表明，PLP 可调节 CUMS 小鼠的肠道菌群，增加其物种丰富度。此外，PLP 可显著抑制 CUMS 小鼠结肠组织中 NLRP3/ASC/Caspase-1 信号通路的激活。
结论：PLP 调节与抑郁相关的肠道生态失调，增加物种丰富度，抑制炎症因子水平和 NLRP3 炎性小体激活，减轻 CUMS 小鼠结肠黏膜和神经元损伤，从而改善抑郁样行为和神经递质释放。
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