Qisheng Wan Formula Ameliorates Cognitive Impairment of Alzheimer's Disease Rat Via Inflammation Inhibition and Intestinal Microbiota Regulation

Ethnopharmacology relevance: Qisheng Wan formula (QWF) was first described in the book Sheng Ji Zong Lu in 1117. The book states that QWF can cure forgetfulness, improve the mind, and make people smart. Hence, QWF has been widely used to treat patients with forgetfulness or dementia. QWF, a classic Chinese formulation, comprises seven herbal drugs: the sclerotium of Poria cocos (Schw.) Wolf, bark of Cinnamomum cassia Presl, root of Polygala tenuifolia Willd., root and rhizome of Panax ginseng C. A. Mey., root of Asparagus cochinchinensis (Lour.) Merr., root and rhizome of Acorus tatarinowii Schott, and root bark of Lycium chinense Mill. Aim of the study: This study aimed to utilize modern pharmacological methods to evaluate the therapeutic effects and explore the underlying mechanism of QWF action on rats with Alzheimer's disease (AD). Materials and methods: The chemical profile of QWF was characterized using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The AD rat model was established via a bilateral intraventricular injection of amyloid-beta (1-42) (A beta 1-42). The rats were subsequently treated daily with QWF for 4 weeks. The Morris water maze test was performed to evaluate the cognition processes in the rats, whereas histological changes in the hippocampus were observed using hematoxylin and eosin staining. The expression levels of A beta 1-42, nuclear factor-kappa B (NF-Kappa B), tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 in the hippocampus and colon were assessed. Moreover, the diversity and composition of the intestinal microbiota were analyzed using 16S rDNA gene sequencing. Results: One hundred and fourteen compounds were characterized in QWF. QWF significantly ameliorated the cognition processes and histopathological damages due to AD in rats by decreasing the deposition of A beta 1-42 and downregulating the expression of NF-Kappa B, TNF-alpha, and IL-6. QWF also modulated changes in the diversity and composition of intestinal microbiota to suppress the relative abundance of inflammation-associated microbiota. Conclusion: This study showed that QWF can suppress proinflammatory factors and modulate the intestinal microbiota in AD rats.