Research Paper Volume 15, Issue 22 pp 13239—13264
Qi Fu Yin ameliorates neuroinflammation through inhibiting RAGE and TLR4/NF-κB pathway in AD model rats
- 1 School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China
- 2 Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China
- 3 Baoshan College of Traditional Chinese Medicine, Baoshan, Yunnan 678000, China
- 4 Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine, Foshan, Guangdong 528000, China
Received: July 10, 2023 Accepted: October 23, 2023 Published: November 22, 2023
https://doi.org/10.18632/aging.205238How to Cite
Copyright: © 2023 He et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
The purpose of this study is to investigate the therapeutic effect of Qi Fu Yin (QFY) on Alzheimer’s disease (AD) both computationally and experimentally. Network pharmacology analysis and molecular docking were conducted to identify potential targets and signaling pathways involved in QFY treating AD. Streptozotocin-induced AD rat model was used to verify important targets and predicted pathways. The components of QFY were identified using liquid chromatography-tandem mass spectrometry. The results indicate that the potential targets of QFY are highly enriched for anti-inflammatory pathways. Molecular docking analysis revealed stable structures formed between QFY’s active compounds, including stigmasterol, β-sitosterol, and isorhamnetin, and the identified targets. In vivo, QFY improved cognitive memory in AD rats and reduced the mRNA expression levels of toll-like receptor 4 (TLR4), the receptor for advanced glycation end products (AGER), and the inflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the brains of AD rats. Furthermore, QFY effectively reduced nuclear translocation of nuclear factor-kappa B (NF-κB) and inhibited NF-κB and microglia activation. In conclusion, QFY can ameliorate neuroinflammation in AD model rats, partly via the inhibition of TLR4 and RAGE/NF-κB pathway and microglia activation, thereby enhancing learning and memory in AD model rats.
Abbreviations
AchE: acetylcholinesterase; AD: Alzheimer’s disease; AGER/RAGE: the receptor of advanced glycation endproducts; AGEs: advanced glycation end products; AKT: protein kinase B; ANOVA: one-way analysis of variance; AP: anterior-posterior; AR: androgen receptor; Aβ: beta-amyloid; BATMAN-TCM: Bioinformatics Analysis Tool For Molecular Mechanism Of Traditional Chinese Medicine; BAX: Bcl-2-associated X-protein; BBB: blood-brain barrier; BCHE: butyrylcholinesterase; BZ: Atractylodis Macrocephalae Rhizoma (Atractylodes macrocephala Koidz., Baizhu); CALM1: calmodulin 1; CASP3: caspase 3; CCND1: cyclin D1; CDK5: cyclin-dependent kinase 5; COX2: cyclooxygenase-2; DAMPs: damage-associated molecular patterns; DG: Angelicae Sinensis Radix (Angelica sinensis (Oliv.) Diels: Danggui); DL: drug-likeness; DV: dorsal-ventral; ERK: extracellular signal-regulated kinase; ESR1: estrogen receptor 1; FDA: Food and Drug Administration; GABA: γ-aminobutyric acid; GDAs: gene-disease associations; GO: Gene Ontology; GSK3B: glycogen synthase kinase 3 beta; GWAS: Genome-wide association studies; H-QFY: H-QFY high-dose group; Iba1: ionized calcium binding adapter molecule 1; ICV: intracerebroventricular injection; IL-1β: interleukin-1β; iNOS: inducible nitric oxide synthase; KEGG: Kyoto Encyclopedia of Genes and Genomes; L-QFY: QFY low-dose group; LC-MS/MS: liquid chromatography-tandem mass spectrometry; MAPK14: mitogen-activated protein kinase 14; MCP-1: monocyte chemoattractant protein-1; Mino: minocycline; ML: medial-lateral; M-QFY: QFY medium-dose group; MWM: Morris Water Maze; MyD88: myeloid differentiation primary response protein 88; NF-κB: nuclear factor-κB; NMDA: N-Methyl-D-aspartic acid; NOS2: nitric oxide synthase 2; OB: oral bioavailability; PI3K: phosphoinositide 3-kinase; PPARG: peroxisome proliferator-activated receptor gamma; PPI: protein-protein interaction; PTGS1: Prostaglandin-endoperoxide synthase 1; PTGS2: prostaglandin-endoperoxide synthase 2; PVDF: polyvinylidene difluoride; QFY: Qi Fu Yin; RELA: reticuloendotheliosis viral oncogene homolog A; Rg3: ginsenoside Rg3; RS: Ginseng Radix Et Rhizoma (Panax ginseng C.A. Mey., Renshen); RT-Qpcr: real-time quantitative polymerase chain reaction; SD: Rehmanniae Radix Praeparata (Rehmannia glutinosa (Gaertn) DC., Shudi); SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel electrophoresis; SPF SD: specific pathogen-free Sprague Dawley; STAT3: signal transducer and activator of transcription 3; STZ: Streptozotocin; SZR: Ziziphi Spinosae Semen (Ziziphus jujuba Mill., Suanzaoren); T2DM: type 2 diabetes mellitus; TCM: Traditional Chinese medicine; TCMSP: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform; TLR4: toll-like receptor 4; TNF-α: tumor necrosis factor-α; VD: vascular dementia; VDAC1: voltage-dependent anion channel 1; YZ: Polygalae Radix (Polygala tenuifolia Willd., Yuanzhi); ZGC: Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle (Glycyrrhiza uralensis Fisch. ex DC., Zhigancao).