PMID- 37739234 OWN - NLM STAT- MEDLINE DCOM- 20231023 LR - 20231106 IS - 1873-2747 (Electronic) IS - 0361-9230 (Linking) VI - 203 DP - 2023 Oct 15 TI - The Anxiolytic Effect of Polysaccharides from Stellariae Radix through Monoamine Neurotransmitters, HPA Axis, and ECS/ERK/CREB/BDNF Signaling Pathway in Stress-induced Male Rats. PG - 110768 LID - S0361-9230(23)00193-4 [pii] LID - 10.1016/j.brainresbull.2023.110768 [doi] AB - BACKGROUND: Stellaria dichotoma L. var. lanceolata Bge. is renowned for its efficacy in "clearing deficiency heat" and represents a significant traditional Chinese medicine (TCM) resource. Modern pharmacology has demonstrated the anti-anxiety effects of Stellaria dichotoma L. var. lanceolata Bge. polysaccharides (SDPs). SDPs are one of the active constituents of Stellaria dichotoma L. var. lanceolata Bge. This study presents the first extraction of SDPs and investigates their potential molecular mechanisms and anxiolytic effects that are not previously reported. METHODS: First, SDPs were obtained by water extraction and alcohol precipitation and analyzed for their monosaccharide composition by high performance liquid chromatography (HPLC). Male SD rats were subjected to a two-week indeterminate empty bottle stress procedure and a three-day acute restraint stress procedure, during which diazepam (DZP) (1 mg/kg) and SDPs (50, 100 and 200 mg/kg, intragastrically) were administered. A number of behavioral tests, including the elevated plus maze test (EPM), the open field test (OFT) and the light/dark box test (LDB), were used to assess the anti-anxiety potential of SDPs. Serum levels of Corticosterone (CORT) and Adrenocorticotropic hormone (ACTH), as well as the levels of Dopamine (DA) and serotonin (5-HT) found in the hippocampus and frontal cortex, were quantified using commercially available enzyme-linked immunosorbent assay (ELISA) kits. In addition, protein levels of key proteins cAMP-response element binding protein (CREB), phospho-CREB (p-CREB), brain-derived neurotrophic factor (BDNF), ERK(1/2), p-ERK(1/2), and GAPDH expression in rat hippocampus were measured by Western blot analysis, and modulation of the endocannabinoid system was assessed by immunohistochemistry. RESULTS: Following administration of SDPs (50, 100, 200 mg/kg) and diazepam 1 mg/kg, anxiolytic activity was exhibited through an increase in the percentage of arm opening times and arm opening time of rats in the elevated plus maze. Additionally, there was an increase in the number of times and time spent in the open field center, percentage of time spent in the open box, and shuttle times in the LDB. Furthermore, tissue levels of DA and 5-HT were increased in the hippocampus and frontal cortex of rats after treatment with SDPs. In addition, SDPs significantly decreased serum levels of CORT and ACTH in rats. SDPs also effectively regulated the phosphorylation of the extracellular regulated protein kinases (ERK) and CREB-BDNF pathway in the hippocampus. Moreover, the expression levels of CB1 and CB2 proteins were heightened due to SDPs treatment in rats. CONCLUSIONS: The study verified that SDPs alleviate anxiety in the EBS and ARS. The neuroregulatory behavior is accomplished by regulating the Monoamine neurotransmitter, HPA axis, and ECB-ERK-CREB-BDNF signaling pathway. CI - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Ma, Miao AU - Ma M AD - School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China. FAU - Quan, Hongfeng AU - Quan H AD - School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China. FAU - Chen, Shujuan AU - Chen S AD - School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China. FAU - Fu, Xueyan AU - Fu X AD - School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China; Ningxia Collaborative Innovation Center of Regional Characteristic Traditional Chinese Medicine, Yinchuan 750004, China; Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education (Ningxia Medical University), Yinchuan 750004, China. FAU - Zang, Lingling AU - Zang L AD - Hainan Health Vocational College, Haikou 813099, China. FAU - Dong, Lin AU - Dong L AD - School of Pharmacy, Ningxia Medical University, Yinchuan 750004, China; Ningxia Collaborative Innovation Center of Regional Characteristic Traditional Chinese Medicine, Yinchuan 750004, China; Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education (Ningxia Medical University), Yinchuan 750004, China. Electronic address: donglinnxmu@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230921 PL - United States TA - Brain Res Bull JT - Brain research bulletin JID - 7605818 RN - 0 (Anti-Anxiety Agents) RN - 0 (Brain-Derived Neurotrophic Factor) RN - EC 2.7.- (Protein Kinases) RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 333DO1RDJY (Serotonin) RN - VTD58H1Z2X (Dopamine) RN - 9002-60-2 (Adrenocorticotropic Hormone) RN - Q3JTX2Q7TU (Diazepam) RN - 0 (Neurotransmitter Agents) SB - IM MH - Rats MH - Male MH - Animals MH - *Anti-Anxiety Agents/pharmacology/metabolism MH - Brain-Derived Neurotrophic Factor/metabolism MH - Rats, Sprague-Dawley MH - Protein Kinases/metabolism MH - Cyclic AMP Response Element-Binding Protein/metabolism MH - Serotonin/metabolism MH - Hypothalamo-Hypophyseal System/metabolism MH - Pituitary-Adrenal System/metabolism MH - Signal Transduction MH - Hippocampus/metabolism MH - Dopamine/metabolism MH - Adrenocorticotropic Hormone MH - Diazepam/pharmacology MH - Neurotransmitter Agents/metabolism OTO - NOTNLM OT - Anxiety OT - ECS/ERK/CREB/BDNF OT - Stellaria dichotoma L. var. lanceolata Bge. polysaccharides COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/09/23 11:42 MHDA- 2023/10/23 01:18 CRDT- 2023/09/22 19:17 PHST- 2023/06/19 00:00 [received] PHST- 2023/09/05 00:00 [revised] PHST- 2023/09/20 00:00 [accepted] PHST- 2023/10/23 01:18 [medline] PHST- 2023/09/23 11:42 [pubmed] PHST- 2023/09/22 19:17 [entrez] AID - S0361-9230(23)00193-4 [pii] AID - 10.1016/j.brainresbull.2023.110768 [doi] PST - ppublish SO - Brain Res Bull. 2023 Oct 15;203:110768. doi: 10.1016/j.brainresbull.2023.110768. Epub 2023 Sep 21.