期刊：
Journal of Ethnopharmacology,2024年326:117972 ISSN：0378-8741
通讯作者：
Liu, Lumei;Zhang, Wei;He, Qinghu
作者机构：
[Fu, Xinying; He, Qinghu; Li, Wanyu] College of Integrated Chinese and Western Medicine, Hunan Provincial Key Laboratory for Prevention and Treatment of Heart and Brain Diseases with Integrated Traditional Chinese and Western Medicine, Hunan University of Traditional Chinese Medicine, Hunan, 410208, China;[Fu, Xinying; He, Qinghu] College of Integrated Chinese Medicine, Hunan University of Traditional Chinese Medicine, Hunan, 410208, China;[Fu, Xinying] Hunan University of Medicine, Huaihua, Hunan, 418000, China;[Yan, Siyang] The First Affiliated Hospital of Hunan University of Traditional Chinese Medicine, Changsha, Hunan, 410007, China;[Sheng, Wen; Kuang, Shida; Hu, Zongren] College of Integrated Chinese Medicine, Hunan University of Traditional Chinese Medicine, Hunan, 410208, China
通讯机构：
[He, Qinghu] H;[Zhang, Wei; Liu, Lumei] C;College of Integrated Chinese and Western Medicine, Hunan Provincial Key Laboratory for Prevention and Treatment of Heart and Brain Diseases with Integrated Traditional Chinese and Western Medicine, Hunan University of Traditional Chinese Medicine, Hunan, 410208, China. Electronic address:;Hunan University of Medicine, Huaihua, Hunan, 418000, China. Electronic address:
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: Guhan Yangsheng Jing (GHYSJ) is a traditional Chinese patent medicine, that has the function of nourishing the kidney and replenishing the essence, invigorating the brain and calming the mind. It is often used to treat dizziness, memory loss, sleep disorders, fatigue, and weakness, etc. However, its mechanism for improving sleep has not yet been determined. AIM OF THE STUDY: This study aims to explore the effects of GHYSJ on Sleep Deprivation (SD)-induced hippocampal neuronal pyroptotic injury, learning and cognitive abilities, and sleep quality in mice. METHODS: In this study, a PCPA-induced SD mouse model was established. We assessed the influence of GHYSJ on sleep quality and mood by using the pentobarbital-induced sleep test (PIST) and sucrose preference test (SPT). The pharmacological effects of GHYSJ on learning and memory impairment were evaluated by the Morris Water Maze (MWM) and Open Field Test (OFT). Pathological changes in the hippocampal tissue of the SD rats were observed via HE staining and Nissl staining. The severity of neuronal damage was evaluated by detecting the expression of the neuronal marker Microtubule-associated protein 2 (MAP2), via immunohistochemistry and immunofluorescence. Furthermore, the levels of neurotransmitter 5-hydroxytryptophan (5-HTP), 5-hydroxy tryptamine (5-HT), γ-aminobutyric acid (GABA), and Glutamic acid (Glu) in hippocampal tissues, as well as the expression of inflammatory factors Interleukin-1β (IL-1β) and Interleukin-18 (IL-18) in serum, were determined by ELISA. The expressions of mRNA and protein NOD-like receptor thermal protein domain associated protein 3 (NLRP3), Gasdermin D (GSDMD), Cysteinyl aspartate specific proteinase1 (Caspase1), High mobility group box-1 protein (HMGB1) and Apoptosis-associated speck-like protein containing CARD (ASC) related to the cellular ferroptosis pathway were tested and analyzed by RT-PCR and WB respectively. RESULTS: PCPA significantly diminishes the sleep span of experimental animals by expediting the expenditure of 5-HT, consequently establishing an essentially direct SD model. The intervention of GHYSJ displays remarkable efficacy in mitigating insomnia symptoms, encompassing difficulties in initiating sleep and insufficient sleep duration. Likewise, it ameliorates memory function impairments induced by sleep deprivation, along with symptoms such as fatigue and depletion of vitality. GHYSJ exerts a protective influence on hippocampal neurons facilitated by inhibiting the down regulation of MAP2 and maintaining the equilibrium of neurotransmitters (5-HTP, 5-HT, GABA, and Glu). It diminishes the expression of intracellular pyroptosis-associated inflammatory factors (IL-1β and IL-18) and curbs the activation of the NLRP3/Caspase1/GSDMD pyroptosis-related signaling pathways, thereby alleviating the damage caused by hippocampal neuronal pyroptosis.
期刊：
CURRENT MOLECULAR MEDICINE,2024年 ISSN：1566-5240
作者机构：
[Xiong, Wu] Department of Burns and Plastic Surgery, the First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, 410007, China;[Zhang, Xi] Clinical Medical School of Hunan University of Chinese Medicine, Hunan Brain Hospital, Changsha, 410007, China;[Zou, Xiao-Ling] Department of Endocrinology, the First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, 410007, China;[Peng, Sai; Lei, Hua-Juan] Department of Anesthesiology, the First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, 410007, China;[Liu, Xiang-Nan] College of Acupuncture & Tuina and Rehabilitation, Hunan University of Chinese Medicine, Changsha, 410208, China
摘要：
BACKGROUND: Chronic hyperglycemia in diabetes induces oxidative stress, leading to damage to the vascular system. In this study, we aimed to evaluate the effects and mechanisms of AS-IV-Exos in alleviating endothelial oxidative stress and dysfunction caused by high glucose (HG). METHODS: Histopathological changes were observed using HE staining, and CD31 expression was assessed through immunohistochemistry (IHC). Cell proliferation was evaluated through CCK8 and EDU assays. The levels of ROS, SOD, and GSH-Px in the skin tissues of each group were measured using ELISA. Cell adhesion, migration, and tube formation abilities were assessed using adhesion, Transwell, and tube formation experiments. ROS levels in HUVEC cells were measured using flow cytometry. The levels of miR-210 and Nox2 were determined through quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The expression of Nox2, SOD, GSH-Px, CD63, and CD81 was confirmed using WB. RESULTS: The level of miR-210 was reduced in diabetes-induced skin damage, while the levels of Nox2 and ROS increased. Treatment with AS-IV increased the level of miR-210 in EPC-Exos. Compared to Exos, AS-IV-Exos significantly reduced the proliferation rate, adhesion number, migration speed, and tube-forming ability of HGdamaged HUVEC cells. AS-IV-Exos also significantly decreased the levels of SOD and GSH-Px in HG-treated HUVEC cells and reduced the levels of Nox2 and GSH-Px. However, ROS levels and Nox2 could reverse this effect. CONCLUSION: AS-IV-Exos effectively alleviated endothelial oxidative stress and dysfunction induced by HG through the miR-210/Nox2/ROS pathway.
关键词：
Acute toxicity;Behavioral analysis;Danggui Shaoyao San;Danio rerio;Histopathological alteration index
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: Although the Traditional Chinese Medicine (TCM) prescription of Danggui Shaoyao San (DSS) presents substantial clinical efficacy and promising clinical prospects, the safety of DSS and its extracts have been inadequately investigated. The larva-adult duality of the zebrafish model offers a more efficient approach for evaluating the safety of herbal preparations in the fields of toxicology and pharmacology. AIM OF THE STUDY: To investigate the acute toxicity of the extract derived from Danggui Shaoyao San, a traditional Chinese medicine preparation, on both Danio rerio embryos and adult organisms. MATERIALS AND METHODS: The components of DSS were identified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The hatching rate of Danio rerio juveniles with different concentrations of DSS was calculated and the morphological changes of juveniles after administration were observed through a microscope. The behavioral trajectory of the adult fish was recorded by the observation tower of the automated Danio rerio analysis system, and DSS's effects on the behavior was analyzed. The pathological changes of Danio rerio gills, livers, kidneys, intestines and spermaries were examined using HE staining. RESULTS: Compared with the control group, 25, 50 and 100mg/L of DSS did not elicit any significant impacts on the hatching rate and morphology. Both 200mg/L and the propylene glycol 2% reduced the hatching rate and caused the morphological teratogenic changes of the juvenile fish. The dosage of DSS below 100mg/L had no discernible effect on the behavior of the adult fish, whereas the application of propylene glycol 2% was found to stimulate the adult fish, resulting in a notable increase in high-speed movement distance. 100mg/L DSS group was not observed to cause any noticeable damage to the gills, livers, intestines and spermaries of Danio rerio, only mild nephrotoxicity was detected. The propylene glycol 2% group was found to result in pathological changes such as hyperplasia of epithelial cells on secondary lamellae, liver cell outline loss or atypia, tubal disorganization, goblet cell hypertrophy and irregularly arranged spermatozoa. CONCLUSION: A viable approach for conducting toxicological studies on TCM preparations was developed and tested in this research. The findings showed that Danggui Shaoyao San has minimal acute toxicity to embryos and adult organisms at concentrations up to 100mg/L. These results indicate that Danggui Shaoyao San is a safe TCM preparation.
