Liang Hui-Qing, Chen Shao-Dong, Wang Yu-Jie, Zheng Xiao-Ting, Liu Yao-Yu, Guo Zhen-Ying, Zhang Chun-Fang, Zhuang Hong-Li, Cheng Si-Jie, Gu Xiao-Hong
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, China.
Hepatology Unit, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian Province, 361009, China.
Chin J Integr Med. 2024 Aug 13. doi: 10.1007/s11655-024-3802-9.
To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis.
Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats.
Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05).
The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.
确定陈皮主要成分橙皮苷对抑郁行为的药理作用，并阐明橙皮苷治疗抑郁症的机制，重点关注肠-脑轴。
采用随机数字表将54只雄性Sprague Dawley大鼠随机分为6组，包括对照组、模型组、橙皮苷组、益生菌组、氟西汀组和陈皮组。除对照组外，其余5组大鼠接受慢性不可预测轻度应激（CUMS）刺激21天，并单笼饲养。通过蔗糖偏好试验（SPT）、强迫游泳试验（FST）中的不动时间和旷场试验（OFT）中的活动次数来测量大鼠的行为变化。采用酶联免疫吸附测定法测定脑组织中5-羟色胺（5-HT）和脑源性神经营养因子（BDNF）的水平，并进行组织病理学检查以评估结肠组织的变化，同时对粪便16S rRNA基因的V3-V4区域进行测序，以探究大鼠肠道菌群的变化。
与对照组相比，模型组大鼠体重、蔗糖偏好率和旷场试验活动次数显著降低（P<0.01）。发现橙皮苷可改善CUMS诱导的抑郁，表现为体重、蔗糖偏好试验、强迫游泳试验不动时间和旷场试验活动次数的改善（P<0.05或P<0.01）。关于神经递质，发现橙皮苷以50 mg/kg剂量治疗可上调抑郁大鼠的5-HT和BDNF水平（P<0.05）。与对照组相比，模型组结肠组织炎症细胞浸润更明显，杯状细胞和隐窝数量明显减少，橙皮苷治疗后显著改善。同时，给予橙皮苷对接受CUMS处理的大鼠肠道微生物群有积极影响，如香农指数增加、辛普森指数降低（P<0.01），而橙皮苷处理组中变形菌门和拟杆菌门的丰度增加（P<0.05）。
橙皮苷对大鼠抑郁行为有益作用的机制可能与抑制BDNF和5-HT的表达以及维持肠道微生物群有关。
