Pharmaceuticals
·
2025
·Vol. 18
·期 3
·426
·
IF 4.8
Zhimin Song,Meijing Li,Ziwei Zhou,Xiaomeng Guo,Qi Wang,Zekuan Zhang,Keshu Wang,Qixiang Zheng,Wenjing Gou,Sha Wu,Hui Zhao,Muxin Gong
Background:Chronic migraine (CM) is a common complex nervous system disease, often accompanied by symptoms of the digestive tract that interact with each other, leading to prolonged and difficult-to-cure migraines. These symptoms are associated with abnormalities in 5-HT and its receptors. Wuzhuyu decoction (WZYD) is a traditional Chinese medicine prescription commonly used in clinics to treat CM; it relieves gastrointestinal symptoms, such as nausea and vomiting; however, its mechanism is still unclear. Investigating the differences in the role of WZYD compared to existing drugs targeting 5-HT receptors in the treatment of CM not only helps elucidate its pathogenesis but also provides possibilities for the development of new therapeutic approaches.Methods:An inflammation soup (IS)-induced CM male rat model was established. Based on a preliminary experiment, the target of WZYD in treating CM was determined by network pharmacology, and verified by molecular docking. ELISA, immunofluorescence, western blot, and real-time quantitative polymerase chain reaction (RT-qPCR) were used to evaluate the expression levels of CM-related indicators (5-HT, calcitonin gene-related peptide (CGRP), and c-Fos) to ensure the successful establishment of the CM model and the effectiveness of the drug. On this basis, the protein expression levels of 5-HT1A/3A receptors and their cAMP-response element binding protein (CREB) signaling pathway were detected by western blot and immunohistochemistry. The role of 5-HT1A/3A receptors in the treatment of CM by WZYD was validated using a 5-HT1A receptor antagonist (WAY 100635) and a 5-HT3A receptor agonist (SR 57227).Results:The results showed that WZYD increased the expression of 5-HT in the brain, decreased the expression of CGRP, c-Fos, ionized calcium-binding adapter molecule 1 (Iba1), and relieved CM. At the same time, WZYD also increased the expression of the 5-HT1A receptor and decreased the expression of the 5-HT3A receptor in the brain and colon of CM rats. Subsequently, WZYD further exerted its brain-gut integrated therapeutic effects by regulating the CREB signaling pathway mediated by 5-HT1A/3A receptors in the brain and colon of CM rats.Conclusions:WZYD not only regulates neurotransmitters in the brain and colon at the same time, but also specifically regulates 5-HT1A/3A receptors in the brain and colon, which explains the characteristics and advantages of WZYD from a new perspective. While effectively relieving headache symptoms, it also improves related gastrointestinal symptoms, which is more conducive to the treatment of CM.
研究领域:
神经科学
·
药理学
·
中医药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2023
·
IF 7.9
Yuanyuan Wei,Yimeng Fan,Sijuan Huang,Jianyu Lv,Yannan Zhang,Zhihui Hao
Background Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common functional gastrointestinal disease. Besides, baizhu shaoyao decoction (BSD) is an effective treatment for IBS-D; however, its mechanism of action remains unclear. Purpose This study aims to assess the ability of BSD to therapy IBS-D and to elucidate the underlying mechanism. Methods First, comprehensive analyses, including ADME (absorption, distribution, metabolism, excretion) screening, Venn analysis, Gene Ontology (GO) analysis, and network construction, were performed to characterize IBS-D-related pathways and explore the synergistic effects of BSD active compounds. Next, an IBS-D model was constructed using a three-factor superposition method of neonatal maternal separation, chronic immobilization stress stimulation, and Sennae folium aqueous extract lavage. Moreover, the impact of BSD was assessed based on the body weight, fecal water content, and abdominal withdrawal reflex (AWR), and the results of the open field test, sucrose preference test, intestinal permeability assessment, transmission electron microscopy, and TdT-mediated dUTP nick-end labeling (TUNEL) analysis. The factors that regulate the BSD effects on IBS-D were estimated using immunoblotting, quantitative reverse transcription polymerase chain reaction (q-RTPCR), immunohistochemistry, and transcriptome sequencing analyses. Results We found that BSD improved depressive behavior, brain–gut peptide levels, and intestinal permeability induced by IBS-D by increasing the abundance of intestinal tight junctions. In addition, BSD reduced secretory immunoglobulin A levels and the number of intestinal mast cells in IBS-D rats. Network pharmacology and transcriptome sequencing analysis further revealed that the forkhead box O (FoxO) signaling pathway contributed to the BSD-induced alleviation of IBS-D, as BSD regulated the protein and mRNA levels of FoxO1, glycogen synthase kinase 3β, and FoxO3a. Importantly, a FoxO1 inhibitor effectively alleviated IBS-D symptoms in rats, whereas a FoxO3a agonist had the opposite effects. Conclusion These results demonstrate that BSD alleviates depression and intestinal symptoms by regulating brain–gut peptide expression and restoring the intestinal barrier function via the FoxO signaling pathway. Furthermore, our study uses serum pharmacochemistry technology to analyze the in vivo components of TCM formula under effective condition, solving the problem of the discovery of the effective components of TCM to some extent.
研究领域:
药理学
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胃肠病学
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神经科学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Zhiwei Li,Guodong Zheng,Chaoping Fang,Jingtao Mei,Hanji Liang,Licong Yang
The brain-gut axis plays an important role in regulating cognitive ability in obesity-related Alzheimer's disease (AD). In this study, we aimed to investigate the correlation between the barrier penetration ability of the DMY nanodelivery system in vivo and the regulation of the gut-brain axis to alleviate cognitive impairment. Brain-targeted peptide (TGN: TGNYKALHPHNG) and DMY loaded chitosan (CS)/sodium tripolyphosphate (TPP) nanoparticles (TGN-DMY-CS/TPP-NPs) and ovalbumin (OVA)/sodium carboxymethylcellulose (CMC) nanoparticles (TGN-DMY-OVA/CMC-NPs) were prepared. TGN-DMY-CS/TPP-NPs demonstrated superior mucus penetration and BBB targeting ability compared to TGN-DMY-OVA/CMC-NPs, while the latter showed notable intestinal accumulation. TGN-DMY-CS/TPP-NPs treatment significantly increased the relative abundance of Alistipes and Rikenellaceae_RC9_gut_group , and TGN-DMY-OVA/CMC-NPs treatment obviously enhanced the relative abundance of Lactobacillus . Furthermore, both nanoparticles alleviated lipid metabolism disorder, oxidative stress, and inflammation in the liver, reduced oxidative stress and neuroinflammation in the brain, inhibited neuronal apoptosis, and enhanced mitochondrial biogenesis and synaptic plasticity in obesity-related AD mice. Despite different mucus penetration and biodistribution, their similar efficacy in improving obesity-related AD is attributed to the gut-brain bidirectional connection.
研究领域:
神经科学
·
药理学
·
生物医学工程
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微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Xu Zhang,Xiaotong Wang,Rui Shi,Xiaoku Ran,Xiahong He,Deqiang Dou
Ethnopharmacological relevance Red ginseng (RG), a processed product of ginseng (GS), is a generally used qi -tonifying medicine in Traditional Chinese Medicine (TCM). According to the TCM principle, RG is also generally applied to spleen-deficiency syndrome (SDS) clinically for its warmer property. However, the effective substances and mechanism of RG on SDS have not been well investigated. Aim of the study The aim of this study was to explore the effective substances and their mechanism of RG on SDS. Materials and methods The SDS model was established with a compound factor method involving an irregular diet, excessive fatigue and sennae folium with a bitter-cold property. The medicine of RG was split by multi-mode separation methods and analyzed by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). The appearance indexes such as body weight, body temperature, swimming endurance, urine output, and water content of fecal were determined. The biochemical indexes such as D-xylose, SP , VIP and AChE in the digestive system, CRH, ACTH, CORT, E, T3, T4, T, E2 and 5-HT in the endocrine system, CS, NCR , IDH1 , COX and Na + -K + -ATPase in the metabolism of substance and energy, cAMP and cGMP in the cyclic nucleotide system were analyzed by Enzyme-linked immunosorbent assay (ELISA) kits and biochemical kits. The serum metabolites were analyzed by UPLC-QTOF/MS. Furthermore, the gut microbiota and short-chain fatty acids (SCFAs) in feces were analyzed by 16S rRNA sequencing and headspace gas chromatography-mass method. Results The pharmacological experiments showed that total saponin fraction (RGTSF), less polar fraction (RGLPF), and polysaccharides faction (RGPSF) significantly modulated the “brain-gut” axis-related indexes (the levels of VIP, AChE, and 5-HT). Besides, RGTSF also significantly modulated the hypothalamic-pituitary-adrenal (HPA) axis-related indexes as well as the substance and energy metabolism-related indexes (the levels of ACTH, CORT, A, Na + -K + -ATPase, COX, NCR and CS). RGPSF also significantly modulated the hypothalamus-pituitary-thyroid (HPT) axis-related indexes (the levels of T3 and T4). Secondly, metabolomics indicated that RGTSF could significantly regulate the abnormal metabolic pathways associated with the development of SDS, which involved steroid hormone biosynthesis, taurine and hypotaurine metabolism, primary bile acid biosynthesis, and amino acid metabolism. Subsequently, the study of gut microbiota indicated that RGLPF could increase the diversities of the gut microbiota and the relative abundance of Firmicutes in rats with SDS, while RGWEF significantly increased the relative abundance of Bacteroidetes . At the genus level, RGLPF could increase the relative abundance of Lactobacillus in rats with SDS and decrease that of Akkermansia . Meanwhile, the water-eluted fraction (RGWEF) showed a stronger regulation in SCFAs. Conclusion It is for the first time that the effective substances of red ginseng on spleen-deficiency syndrome were studied systematically, and the different mechanisms of the RG fractions involved in substance and energy metabolism as well as the “brain-gut” axis were revealed. The present study demonstrated that RGTSF, RGPSF, and RGLPF were the effective substances of red ginseng for ameliorating spleen-deficiency syndrome, indicating that ginsenosides composed of primary and secondary saponins as well as polysaccharides were the main effective substances for red ginseng in ameliorating spleen-deficiency syndrome.
研究领域:
民族药理学
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中医药学
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药理学
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代谢组学
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微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Jingjing Shao,Linlin Qu,Yao Liu,Jingjing Zhang,Yannan Liu,Jianjun Deng,Xiaoxuan Ma,Daidi Fan
Depression is a neuropsychiatric disease that significantly impacts the physical and mental health of >300 million people worldwide and places a major burden on society. Ginsenosides are the main active ingredient in ginseng and have been proven to have various pharmacological effects on the nervous system. Herein, we investigated the antidepressant effect of ginsenoside Rk3 and its underlying mechanism in a murine model of depression. Rk3 significantly improved depression-like behavior in mice, ameliorated the disturbance of the hypothalamus–pituitary–adrenal axis, and alleviated neuronal damage in the hippocampus and prefrontal cortex of mice. Additionally, Rk3 improved the abnormal metabolism of tryptophan in brain tissue by targeting tryptophan hydroxylase, thereby reducing neuronal apoptosis and synaptic structural damage in the mouse hippocampus and prefrontal cortex. Furthermore, Rk3 reshaped the composition of the gut microbiota of mice and regulated intestinal tryptophan metabolism, which alleviated intestinal barrier damage. Thus, this study provides valuable insights into the role of Rk3 in the tryptophan metabolic cycle along the brain–gut axis, suggesting that Rk3 may have the potential for treating depression.
研究领域:
神经科学
·
药理学
·
微生物学
·
行为科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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