Neural Regeneration Research
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2019
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IF 2.472
Yu-Min Xu,Xin-Chen Wang,Ting-Ting Xu,Hong-Ying Li,Shang-Yan Hei,Na-Chuan Luo,Hong Wang,Wei Zhao,Shu-Huan Fang,Yun-Bo Chen,Li Guan,Yong-Qi Fang,Shi-Jie Zhang,Qi Wang,Wei-Xiong Liang
Kai Xin San (KXS, containing ginseng, hoelen, polygala, and acorus), a traditional Chinese herbal compound, has been found to regulate cognitive dysfunction; however, its mechanism of action is still unclear. In this study, 72 specific-pathogen-free male Kunming mice aged 8 weeks were randomly divided into a vehicle control group, scopolamine group, low-dose KXS group, moderate-dose KXS group, high-dose KXS group, and positive control group. Except for the vehicle control group and scopolamine groups (which received physiological saline), the doses of KXS (0.7, 1.4 and 2.8 g/kg per day) and donepezil (3 mg/kg per day) were gastrointestinally administered once daily for 2 weeks. On day 8 after intragastric treatment, the behavioral tests were carried out. Scopolamine group and intervention groups received scopolamine 3 mg/kg per day through intraperitoneal injection. The effects of KXS on spatial learning and memory, pathological changes of brain tissue, expression of apoptosis factors, oxidative stress injury factors, synapse-associated protein, and cholinergic neurotransmitter were measured. The results confirmed the following. (1) KXS shortened the escape latency and increased residence time in the target quadrant and the number of platform crossings in the Morris water maze. (2) KXS increased the percentage of alternations between the labyrinth arms in the mice of KXS groups in the Y-maze. (3) Nissl and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining revealed that KXS promoted the production of Nissl bodies and inhibited the formation of apoptotic bodies. (4) Western blot assay showed that KXS up-regulated the expression of anti-apoptotic protein Bcl-2 and inhibited the expression of pro-apoptotic protein Bax. KXS up-regulated the expression of postsynaptic density 95, synaptophysin, and brain-derived neurotrophic factor in the cerebral cortex and hippocampus. (5) KXS increased the level and activity of choline acetyltransferase, acetylcholine, superoxide dismutase, and glutathione peroxidase, and reduced the level and activity of acetyl cholinesterase, reactive oxygen species, and malondialdehyde through acting on the cholinergic system and reducing oxidative stress damage. These results indicate that KXS plays a neuroprotective role and improves cognitive function through reducing apoptosis and oxidative stress, and regulating synapse-associated protein and cholinergic neurotransmitters.
研究领域:
神经科学
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药理学
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中医药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Ya-Nan Tang,Yun-Feng Bai,Ai Dong,Qin-Ling Rao,Hong-Hua Wu,Chun-Guo Wang,Yan-Tong Xu
Ethnopharmacological relevance Kai-Xin-San (KXS) is a classic prescription for treating affective disorders in traditional Chinese medicine (TCM) over millennium. Although antidepressant effects of KXS have been demonstrated in both clinical and preclinical studies, antidepressant constituents and action mechanisms of KXS remain unclear. Aim of the study To reveal antidepressant constituents and action mechanisms of KXS using the method of “fraction-spectrum-effect-mechanism”. Materials and methods Homologous fractions of KXS were isolated through solvent extraction combined with macroporous resin chromatography methods. The quantification of the fractions was performed using chemical chromogenic methods. Antidepressant effects of the homologous fractions were assessed using tail suspension test (TST), forced swimming test (FST) and open field test (OFT) in mice. Two major fractions of total phenols (TP) and total saponins (TS) were chosen for further studies. The constituents of TP and TS were identified using UPLC-Q-Exactive Orbitrap-MS (UPLC-MS) method, and their antidepressant effects were verified on chronic restraint stress (CRS) model in mice by behavioral evaluations including sucrose preference test (SPT), TST, FST and OFT. Network pharmacology was used to predict antidepressant mechanisms of TP and TS based on the homologous constituents determined in UPLC-MS analysis. Proteomic analyses were undertaken with tissues of hippocampus (HP) and prefrontal cortex (PFC) in CRS mice treated by TP and TS. Western blot (WB) was employed to verify the findings in network pharmacology and proteomic analyses. Results Five homologous fractions of essential oils (EO), TP, TS, oligosaccharides (OL) and polysaccharides (PO) were isolated from KXS with homologous contents exceeding 50 %. Results of TST and FST indicated that all the five fractions significantly decreased the immobility time of mice, while OFT results exhibited that their locomotor activities remained unchanged. A total of 50 constituents and 114 constituents were identified in the TP and TS, respectively. CRS tests demonstrated that both TP and TS significantly increased the percent of sucrose consumption and decreased the immobility time in the TST and FST, without affecting their locomotor activities. Results of both network pharmacology and proteomic analyses primarily pointed to similar contents highly related to depression. GO analysis on TP and TS principally enriched in synaptic structures and functions, as well as neural metabolic and gene expression processes. KEGG analysis on TP and TS principally enriched in pathways of neurodegeneration-multiple diseases, as well as neurotrophin signaling pathway in HP and PFC. Results of WB verified that TP and TS significantly reversed the decrease in signature proteins of synaptic plasticity including presynaptic SYN1, postsynaptic PSD95 and GRIA1, as well as the underlying mechanism of BDNF/TrkB/Akt pathway in the HP and PFC induced by CRS. Conclusion This is the first study on antidepressant constituents and action mechanisms of KXS guided by the method of “fraction-spectrum-effect-mechanism”. Albeit the findings are still preliminary, it provides an example in methodology for unraveling the complicated chemical system and action mechanisms of TCM prescriptions.
研究领域:
药理学
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神经科学
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民族药理学
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中医药学
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精神药理学
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蛋白质组学
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网络药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Jiahui Wu,Xin Li,Xiaoning Huang,Yun Zhu,Hongquan Yu,Yingjie Xia,Suisui Guo,Xiaoyang Wang,Tingxia Dong,Karl Wah Keung Tsim,Yue Zhu
Ethnopharmacological relevance The gut microbiome plays a crucial role in the pathology of depression. The intestinal dysbiosis associated with prolonged use of antidepressants, such as fluoxetine, can adversely affect the efficacy of these medications. Kai-Xin-San (KXS), a traditional Chinese herbal decoction, has been utilized to treat mental disorders with a long history in China. The modulation of the gut microbiome by KXS could underlie its antidepressant effect. In the context of combining with fluoxetine, KXS could potentially mitigate fluoxetine-associated intestinal side effects during depression treatment. Aim of the study This study investigates the impact of KXS on the gut of depressive mice, with a particular emphasis on its potential to mitigate fluoxetine-induced intestinal side effects. Materials and methods A high dose of fluoxetine was applied to the chronic unpredictable mild stress (CUMS)-induced mice, alone or in combination with KXS. Behavior tests were conducted to confirm the anti-depressant efficiencies. The feces of mice were collected and subjected to 16S rDNA and metagenomic sequencing. The gastrointestinal morphology and functions were assessed. The potential mechanistic action of KXS on alleviating the intestinal dysbiosis was probed. Results Notable imbalance of microbiome and disruption of intestinal barrier were observed in CUMS mice. The intake of fluoxetine exacerbated the dysbiosis, as evidenced by the increased ratio of Firmicutes/Bacteroidetes and the elevated abundance of antibiotic-resistant genes in the gut microbiome. In addition, fluoxetine treatment further compromised the intestinal integrity and functions. Significantly, KXS treatment effectively mitigated the impairment of intestinal barrier induced by fluoxetine. These protective effects appeared to be mediated through multiple mechanisms, including the restoration of microbial homeostasis and the direct cytoprotective action on intestinal epithelial cells. Conclusions These findings particularly provide support for the combined usage of KXS and fluoxetine in depression treatment.
研究领域:
民族药理学
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微生物学
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神经科学
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药理学
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整合医学
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胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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