Danggui-Shaoyao-San Attenuates Cognitive Impairment via the Microbiota–Gut–Brain Axis With Regulation of Lipid Metabolism in Scopolamine-Induced Amnesia

Abstract

Danggui-Shaoyao-San (DSS) has a long history of being used as a traditional medicine (TCM) and has been reported to show therapeutic effects in alleviating the symptoms of cognitive impairment. The purpose of this study was to investigate whether DSS treatment attenuates cognitive impairment via the microbiota–gut–brain axis in scopolamine-induced amnesia. In this work, we first performed the Morris water maze (MWM) test and novel object recognition (NOR) test to evaluate the memory function of treated C57BL/6N mice. Then we evaluated 16S rRNA for gut microbiota analysis, as well as assessment of blood–brain barrier function and intestinal barrier function and lipid metabolism analysis on tissues from different groups. We hypothesised that DSS may affect brain function and behavior through the gut–brain axis in a bidirectional interplay with both top-down and bottom-up regulation. Furthermore, in order to confirm whether intestinal flora plays a crucial role in scopolamine-induced amnesia, C57BL/6N mice were treated with fecal microbial transplantation (FMT), and then behavioral tests were performed. The mice’s feces were simultaneously evaluated by 16S rRNA analysis. The result supported that the FMT-induced improvement in cognitive function highlights the role of the gut microbiota–brain axis to mediate cognitive function and behavior. Besides theses works, more findings indicated that DSS altered lipid metabolism by activating LXR-PPAR-γ and repaired mucosal barrier dysfunction assessed with a broad range of techniques, which attenuated cognitive impairment via the microbiota–gut–brain axis.

Using network pharmacology to explore the mechanism of Danggui-Shaoyao-San in the treatment of diabetic kidney disease

“…In this study, we reported that DSS regulates a variety of metabolic pathways including PPAR signaling pathway. Consistently, Liu et al (2022) also demonstrated that DSS regulates lipid metabolism though PPARG in scopolamineinduced amnesia. These findings indicated that DSS may play a reno-protective role in DKD through metabolism pathways by targeting PPARG, which is worthy to be validated by experiments in the future.…”

Modulation of the Gut Microbiota in Memory Impairment and Alzheimer’s Disease via the Inhibition of the Parasympathetic Nervous System

“…Scopolamine injections have been demonstrated to positively correlate with Clostridium, Bifidobacterium, Ruminococcaceae_unclassified, Lachnospiraceae_unclassified, and Lactobacillus while being negatively related to Desulfovibrio, Akkermansia , and Blautia [ 23 ]. Scopolamine injections increase the intestinal permeability and induce memory impairment [ 23 , 24 ]. The present study also showed similar changes in the gut microbiota and memory function.…”

“…The primary gut bacteria in the different groups can be determined by LDA, which identifies the bacteria that are more abundant in one group than another, adopting a principle of analysis closely related to the principal component analysis and linear regression analysis [ 24 ]. The present study demonstrated that only Escherichia was selected with a high LDA score in the AD group.…”

Literature review on the interdisciplinary biomarkers of multi-target and multi-time herbal medicine therapy to modulate peripheral systems in cognitive impairment

“…Furthermore, antimicrobial therapy, as used in the prevention and treatment of AD, induces the suppression of pro-inflammatory cytokines and Aβ aggregation. Treatment with DSS and HLJDD attenuated cognitive impairment through their actions on the microbiome-gut-brain axis, such as reduced alterations in the gut microbiome ( Gu et al, 2021 ; Liu et al, 2022 ). In addition, Gu et al (2021) indicated that the combination of inflammatory cytokines (interleukin-6 and interferon-gamma), phosphatidylcholines, and SCFA-producing bacteria were expected to be early diagnostic biomarkers for AD.…”