Institute of Pharmaceutical & Food Engineering, Shanxi University of Chinese Medicine, 121 Daxue Road, Yuci District, Jinzhong, 030619, China.
Institute of Pharmaceutical & Food Engineering, Shanxi University of Chinese Medicine, 121 Daxue Road, Yuci District, Jinzhong, 030619, China.
J Ethnopharmacol. 2022 Oct 5;296:115410. doi: 10.1016/j.jep.2022.115410. Epub 2022 May 29.
Yuanzhi Powder is a commonly used traditional Chinese medical formulae for its potency in enhancing memory and learning. In clinical practice, Yuanzhi Powder is a classic formula in TCM to treat amnesia of the type "deficiency of Qi, turbid phlegm harasses the head and eyes, and stagnation of phlegm converting into the fire". Our previous study showed that Yuanzhi Power, used together with Codonopsis Radix (Dangshen Yuanzhi Power, DYP), could improve learning and memory ability in animals with memory disorder (MD) and its efficacy is superior or equivalent to that of the Yuanzhi Power.
This study aimed to explore the regulatory mechanism of DYP through the "bacteria-gut-brain axis".
The SD rats were divided randomly into control, model, positive, DYP-L, and DYP-H groups. Except for the control group, the rats were intraperitoneally injected with D-Gal (400 mg/kg) and gavaged with aluminum chloride (200 mg/kg) every day for 50 days. The rats in the DYP group were gavaged with DYP (6.67 and 13.34 g/kg, respectively) from the 15th day, once a day. The rats in the positive group were similarly administrated with piracetam (0.5 g/kg). The rats' bodyweight was recorded from the 16th day. The learning and memory ability of animals was tested by Morris water maze. The levels of MCP-1, NF-L, NSE, and TNF-α in serum were determined by Elisa kit, while the histopathology of duodenum and colon tissues was examined by H & E staining. The diversity of intestinal flora was sequenced and analyzed. In order to reveal the role of intestinal flora in DYP treatment of MD, the intestinal flora composition and the correlation analysis of intestinal flora and the above biochemical indexes were investigated. The intestinal flora function and biological metabolic pathways were predicted and analyzed by the KEGG database.
The MD animals' learning and spatial memory ability decreased significantly, compared with the normal group, accompanied by weight increase and intestinal flora disorder. DYP can improve the learning and memory ability of MD animals, and its efficacy may exert through the following ways: (i) callback the abnormal biochemical indexes of MCP-1, NF-L, NSE, and TNF-α; (ii) decreasing the relative ratio of Firmicutes/Bacteroidetes and repairing the pathology of MD animal intestinal mucosa; and (iii) the regulation of DYP on biochemical blood indexes of MD animals was significantly correlated with the regulation of intestinal flora; (iv) DYP rats showed a strong correlation between cognitive ability improvement and bodyweight loss; (v) besides, DYP could also regulate the metabolic pathways of carbohydrate, amino acid, nucleotide, and energy by affecting related biological functions.
The results supported that DYP can improve MD animals' learning and memory ability by restoring the intestinal flora disorder and callback the abnormal biochemical indexes in serum, closely related to the "bacteria-gut-brain axis".
远志粉是一种常用的中药方剂,因其增强记忆和学习的功效而被广泛使用。在临床实践中,远志粉是中医治疗“气虚、痰浊扰头目、痰火转化”型健忘的经典方剂。我们之前的研究表明,远志粉与党参(党参远志粉,DYP)合用,可改善记忆障碍(MD)动物的学习和记忆能力,其疗效优于或等同于远志粉。
本研究旨在通过“细菌-肠道-大脑轴”探讨 DYP 的调节机制。
SD 大鼠随机分为对照组、模型组、阳性组、DYP-L 组和 DYP-H 组。除对照组外,大鼠每天腹腔注射 D-半乳糖(400mg/kg)和氯化铝(200mg/kg),连续 50 天。DYP 组大鼠从第 15 天开始分别灌胃 DYP(6.67 和 13.34g/kg,每天一次)。阳性组大鼠同样灌胃吡拉西坦(0.5g/kg)。从第 16 天开始记录大鼠体重。通过 Morris 水迷宫测试动物的学习和记忆能力。用 Elisa 试剂盒测定血清中 MCP-1、NF-L、NSE 和 TNF-α 的水平,用 H&E 染色观察十二指肠和结肠组织的组织病理学变化。对肠道菌群进行测序和分析。为了揭示肠道菌群在 DYP 治疗 MD 中的作用,对肠道菌群组成以及肠道菌群与上述生化指标的相关性进行了研究。利用 KEGG 数据库对肠道菌群功能和生物代谢途径进行预测和分析。
与正常组相比,MD 动物的学习和空间记忆能力明显下降,体重增加,肠道菌群紊乱。DYP 可改善 MD 动物的学习和记忆能力,其作用机制可能是:(i)回调 MCP-1、NF-L、NSE 和 TNF-α 等异常生化指标;(ii)降低 Firmicutes/Bacteroidetes 的相对比值,修复 MD 动物肠道黏膜病理;(iii)DYP 对 MD 动物生化血液指标的调节与肠道菌群的调节呈显著正相关;(iv)DYP 大鼠认知能力的改善与体重的减轻呈显著正相关;(v)此外,DYP 还可以通过影响相关生物学功能来调节碳水化合物、氨基酸、核苷酸和能量的代谢途径。
研究结果支持 DYP 通过恢复肠道菌群紊乱和回调血清中异常生化指标来改善 MD 动物的学习和记忆能力,这与“细菌-肠道-大脑轴”密切相关。