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1.
Phytomedicine ; 130: 155725, 2024 Jul 25.
Article in English | MEDLINE | ID: mdl-38772181

ABSTRACT

BACKGROUND: Bidirectional communication between the gut microbiota and the brain may play an essential role in the cognitive dysfunction associated with chronic sleep deprivation(CSD). Salvia miltiorrhiza Bunge (Danshen, DS), a famous Chinese medicine and functional tea, is extensively used to protect learning and memory capacities, although the mechanism of action remains unknown. PURPOSE: The purpose of this research was to explore the efficacy and the underlying mechanism of DS in cognitive dysfunction caused by CSD. METHODS: DS chemical composition was analyzed by UPLC-QTOF-MS/MS. Forty rats were randomly assigned to five groups (n = 8): control (CON), model (MOD), low- (1.35 g/kg, DSL), high-dose (2.70 g/kg, DSH) DS group, and Melatonin(100 mg/kg, MT) group. A CSD rat model was established over 21 days. DS's effects and the underlying mechanism were explored using the open-field test(OFT), Morris water-maze(MWM), tissue staining(Hematoxylin and Eosin Staining, Nissl staining, Alcian blue-periodic acid SCHIFF staining, and Immunofluorescence), enzyme-linked immunosorbent assay, Western blot, quantitative real-time polymerase chain reaction(qPCR), and 16S rRNA sequencing. RESULTS: We demonstrated that CSD caused gut dysbiosis and cognitive dysfunction. Furthermore, 16S rRNA sequencing demonstrated that Firmicutes and Proteobacteria were more in fecal samples from model group rats, whereas Bacteroidota and Spirochaetota were less. DS therapy, on the contrary hand, greatly restored the gut microbial community, consequently alleviating cognitive impairment in rats. Further research revealed that DS administration reduced systemic inflammation via lowering intestinal inflammation and barrier disruption. Following that, DS therapy reduced Blood Brain Barrier(BBB) and neuronal damage, further decreasing neuroinflammation in the hippocampus(HP). Mechanistic studies revealed that DS therapy lowered lipopolysaccharide (LPS) levels in the HP, serum, and colon, consequently blocking the TLR4/MyD88/NF-κB signaling pathway and its downstream pro-inflammatory products(IL-1ß, IL-6, TNF-α, iNOS, and COX2) in the HP and colon. CONCLUSION: DS treatment dramatically improved spatial learning and memory impairments in rats with CSD by regulating the composition of the intestinal flora, preserving gut and brain barrier function, and reducing inflammation mediated by the LPS-TLR4 signaling pathway. Our findings provide novel insight into the mechanisms by which DS treats cognitive dysfunction caused by CSD.


Subject(s)
Cognitive Dysfunction , Drugs, Chinese Herbal , Rats, Sprague-Dawley , Salvia miltiorrhiza , Sleep Deprivation , Animals , Salvia miltiorrhiza/chemistry , Sleep Deprivation/complications , Sleep Deprivation/drug therapy , Cognitive Dysfunction/drug therapy , Male , Drugs, Chinese Herbal/pharmacology , Rats , Gastrointestinal Microbiome/drug effects , Disease Models, Animal , Hippocampus/drug effects , Hippocampus/metabolism , NF-kappa B/metabolism , Morris Water Maze Test/drug effects , Maze Learning/drug effects
2.
J Geriatr Psychiatry Neurol ; 32(3): 152-163, 2019 05.
Article in English | MEDLINE | ID: mdl-30885037

ABSTRACT

BACKGROUND: Alzheimer disease (AD) is the most common type of dementia which is becoming a primary problem in the present society, but it lacks effective treatment methods and means of AD. Tanshinone IIA (Tan IIA) has been reported to have neuroprotective effects to restrain the Aß25-35-mediated apoptosis. However, few studies try to understand how Aß1-42 affects hyperphosphorylation of tau and how Tan IIA regulates this process at the molecular level. METHODS: Fifty male Sprague-Dawley rats were randomly divided into 5 groups and infused through the lateral ventricle with Aß1-42 except the control group. Then the rats were treated with Tan IIA through intragastric administration for 4 weeks. After the ability of learning and memory being measured, histomorphological examination and Western blot were used to detect the possible mechanism in the AD-associated model rats. RESULTS: We observed that Aß1-42 infusion could induce spatial learning and memory deficits in rats. Simultaneously, Aß1-42 also could reduce the neuron in cornu ammonis 1 and dentate gyrus of hippocampus, as well as increase the levels of cleaved caspase 3, hyperphosphorylated tau at the sites Ser396, Ser404, and Thr205 with enhancing staining of black granules in brain. We also found that Aß1-42 could increase the activity of extracellular signal-regulated protein kinase (ERK) and glycogen synthase kinase-3ß (GSK-3ß). Meanwhile, these phenomena could be ameliorated when Tan IIA was used. CONCLUSION: We concluded that Tan IIA might have neuroprotective effect and improving learning and memory ability to be a viable candidate in AD therapy with mechanisms involving the ERK and GSK-3ß signal pathway.


Subject(s)
Abietanes/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Glycogen Synthase Kinase 3 beta/drug effects , MAP Kinase Signaling System/drug effects , Memory Disorders/drug therapy , Spatial Learning/drug effects , Abietanes/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Disease Models, Animal , Humans , Male , Rats , Rats, Sprague-Dawley
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