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Lv Q, Chen L, Du Y, Yang P, Chen Q, Qin F, Zhang H, Li Y. Network pharmacology and in vitro experiments based strategy to explore the effects of Jujuboside A on the proliferation and migration ability of glioma cells. Brain Res 2025; 1855:149570. [PMID: 40090447 DOI: 10.1016/j.brainres.2025.149570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2024] [Revised: 03/06/2025] [Accepted: 03/10/2025] [Indexed: 03/18/2025]
Abstract
OBJECTIVE This study predicted and verified the effects of Jujuboside A (JuA) on the proliferation and migration ability of glioma cells to developing new therapies for glioma treatment. METHODS The druggability of JuA was determined by using cheminformatics. Network pharmacology was used to analyse common targets, biological function and metabolic pathways of JuA against glioma. The core targets of JuA against glioma were validated by using molecular docking. The biological functions of JuA were verified by in vitro experiments. RESULTS Cheminformatics results showed that JuA is possible to be a drug. Network pharmacology revealed 294 shared targets between JuA and glioma, which were associated with proliferation, migration, and multiple signalling pathways. A total of 16 core targets related to the signalling pathways were verified by molecular docking. The in vitro experiments showed that JuA could inhibit cell proliferation and migration, decrease cell numbers and alter cell morphology. CONCLUSION The results of network pharmacology and in vitro experiments indicate that JuA has significant toxic effects on glioma cells, and can play a therapeutic role in treating glioma by inhibiting the proliferation and migration of glioma cells.
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Affiliation(s)
- Quanzhou Lv
- Pharmaceutical School, Jilin Medical University, Jilin, Jilin 132013, China
| | - Lin Chen
- Pharmaceutical School, Jilin Medical University, Jilin, Jilin 132013, China
| | - Yuan Du
- Pharmaceutical School, Jilin Medical University, Jilin, Jilin 132013, China
| | - Peng Yang
- Pharmaceutical School, Jilin Medical University, Jilin, Jilin 132013, China
| | - Quanying Chen
- Pharmaceutical School, Jilin Medical University, Jilin, Jilin 132013, China
| | - Fayu Qin
- Pharmaceutical School, Jilin Medical University, Jilin, Jilin 132013, China
| | - Hongxia Zhang
- Pharmaceutical School, Jilin Medical University, Jilin, Jilin 132013, China
| | - Yan Li
- Basic Medical School, Jilin Medical University, Jilin, Jilin 132013, China.
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Li J, Zhao Y, Liu G, Li T. Fast urine metabolomics for the assessment of Zopiclone effects on insomnia. J Pharmacol Toxicol Methods 2025:107745. [PMID: 40348733 DOI: 10.1016/j.vascn.2025.107745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2024] [Revised: 03/05/2025] [Accepted: 04/26/2025] [Indexed: 05/14/2025]
Abstract
Insomnia is a common symptom of many diseases and is closely associated with neurodegenerative diseases. Zopiclone is one of several clinical hypnotics for treating insomnia. However, some patients are sensitive to this drug treatment, whereas others are not, and the underlying mechanisms remain unclear, causing confusion for making therapeutic regimens and prolong the course of the disease. In present work, we developed a fast urine metabolomics' method for evaluating the sensitivity of insomnia patients to Zopiclone treatment. Firstly, we extracted urine metabolome using methanol-water solutions of different ratios. Secondly, the extracts were either directly injected into LC-MS analysis or dried and resuspended using methanol-water solutions of different concentrations for LC-MS analysis. Then, the total abundance and chromatographic behaviors of urine metabolome from different extraction methods were compared with each other. The optimal extraction method is to mix 50 μl of urine with an equal volume of methanol and 150 μl of water for LC-MS analysis. Finally, the developed method was applied to a metabolomics study of urine from patients with insomnia to evaluate the effectiveness of Zopiclone in treating insomnia. The results showed that there were significant statistical differences in the levels of acylcarnitines, β-hydroxybutyrate (BHB), 4-hydroxybutyric acid (GHB), 3-hydroxyisovaleric acid, citrate, leucine, isoleucine, and valine between the sensitive and insensitive groups treated with Zopiclone. Furthermore, alterations in levels of GHB, valine, and isoleucine were closely correlated with Pittsburgh Sleep Quality Index (PSQI) scores, which may be potential biomarkers for assessing the sensitivity of insomnia patients to Zopiclone treatment, and guiding therapy adjustment.
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Affiliation(s)
- Jun Li
- Inspection Department, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China
| | - Yang Zhao
- Psychology Department, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Guifang Liu
- Psychology Department, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China
| | - Tao Li
- Psychology Department, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China.
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Zhang B, Wang Q, Zhang Y, Wang H, Kang J, Zhu Y, Wang B, Feng S. Treatment of Insomnia With Traditional Chinese Medicine Presents a Promising Prospect. Phytother Res 2025. [PMID: 40251853 DOI: 10.1002/ptr.8495] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 04/01/2025] [Accepted: 04/02/2025] [Indexed: 04/21/2025]
Abstract
Insomnia, a prevalent sleep disorder, significantly impacts global health. While Western medications provide temporary relief, their risks of dependency and cognitive impairment have spurred the search for safer alternatives. Traditional Chinese Medicine (TCM) offers a promising approach to treating insomnia by focusing on harmonizing the balance of Yin and Yang and the functions of internal organs. This review explores recent research advances in TCM for insomnia treatment, integrating classical theories with modern scientific understanding of key pathological mechanisms, including neurotransmitter regulation (GABA, monoamines), immune-inflammatory responses, the HPA axis, and interactions with the gut microbiota. Growing clinical evidence supports the effectiveness of classical TCM prescriptions and treatments like acupuncture in improving sleep quality, particularly when combined with Western medications to enhance efficacy and reduce dependency. However, TCM also has its limitations. Future research directions should focus on modernizing TCM applications, addressing comorbidities associated with insomnia, exploring the role of gut microbiota, and optimizing medicinal and edible homologous products. By integrating traditional knowledge with cutting-edge technologies, TCM holds great potential for advancing personalized and effective insomnia treatments globally.
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Affiliation(s)
- Boyi Zhang
- Medical College, Henan University of Chinese Medicine, Zhengzhou, China
| | - Qianqian Wang
- Medical College, Henan University of Chinese Medicine, Zhengzhou, China
- Henan Engineering Research Center for Chinese Medicine Foods for Special Medical Purpose, Zhengzhou, China
| | - Yuhang Zhang
- Medical College, Henan University of Chinese Medicine, Zhengzhou, China
| | - Hanyu Wang
- Medical College, Henan University of Chinese Medicine, Zhengzhou, China
| | - Jingyu Kang
- Medical College, Henan University of Chinese Medicine, Zhengzhou, China
| | - Yandi Zhu
- Medical College, Henan University of Chinese Medicine, Zhengzhou, China
| | - Baiyan Wang
- Medical College, Henan University of Chinese Medicine, Zhengzhou, China
- Henan Engineering Research Center for Chinese Medicine Foods for Special Medical Purpose, Zhengzhou, China
| | - Shuying Feng
- Medical College, Henan University of Chinese Medicine, Zhengzhou, China
- Henan Engineering Research Center for Chinese Medicine Foods for Special Medical Purpose, Zhengzhou, China
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Fan R, Jia Y, Chen Z, Li S, Qi B, Ma A. Foods for Sleep Improvement: A Review of the Potential and Mechanisms Involved. Foods 2025; 14:1080. [PMID: 40238208 PMCID: PMC11988850 DOI: 10.3390/foods14071080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2025] [Revised: 03/14/2025] [Accepted: 03/19/2025] [Indexed: 04/18/2025] Open
Abstract
Insomnia affects one-third of the world's population; the negative effects of insomnia are significant, and traditional insomnia medications have numerous side effects and cause considerable suffering. This has aroused interest in obtaining sleep-improving substances from foods. This study conducted a comprehensive literature review using Web of Science and PubMed with keywords like "sleep", "insomnia", and "food". A subsequent summary of the literature revealed that certain foods, including milk, Ziziphus jujuba, Lactuca sativa, ginseng, Schisandra chinensis, and Juglans regia, etc., are purported to enhance sleep quality by prolonging sleep duration, reducing sleep latency, and alleviating anxiety. The mechanisms of these foods' effects mainly occur via the central nervous system, particularly the gamma-aminobutyric acid (GABA)ergic and 5-hydroxytryptamine (5-HT)ergic systems. Although this review supports the fact that they have potential, further research is needed. There are also issues such as more limited foods, fewer mechanisms, fewer pharmacokinetic studies, and more traditional research models being involved. These need to be addressed in the future to adequately address the problem of insomnia. It is hoped that this study will contribute to research into foods with sleep-improving properties and, in the future, provide an effective natural alternative for those seeking medication.
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Affiliation(s)
- Rui Fan
- School of Food and Health, Beijing Technology and Business University, Beijing 100048, China; (R.F.); (Y.J.); (Z.C.); (S.L.)
| | - Yingmin Jia
- School of Food and Health, Beijing Technology and Business University, Beijing 100048, China; (R.F.); (Y.J.); (Z.C.); (S.L.)
| | - Zhou Chen
- School of Food and Health, Beijing Technology and Business University, Beijing 100048, China; (R.F.); (Y.J.); (Z.C.); (S.L.)
| | - Siting Li
- School of Food and Health, Beijing Technology and Business University, Beijing 100048, China; (R.F.); (Y.J.); (Z.C.); (S.L.)
| | - Bing Qi
- Hebei Key Laboratory of Walnut Nutritional Function and Processing Technology, Hengshui 053000, China;
| | - Aijin Ma
- School of Food and Health, Beijing Technology and Business University, Beijing 100048, China; (R.F.); (Y.J.); (Z.C.); (S.L.)
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Yan Y, Zhao N, Liu J, Zhang S, Zhang Y, Qin X, Zhai K, Du C. Ziziphi Spinosae Semen Flavonoid Ameliorates Hypothalamic Metabolism and Modulates Gut Microbiota in Chronic Restraint Stress-Induced Anxiety-like Behavior in Mice. Foods 2025; 14:828. [PMID: 40077533 PMCID: PMC11898499 DOI: 10.3390/foods14050828] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2025] [Revised: 02/15/2025] [Accepted: 02/22/2025] [Indexed: 03/14/2025] Open
Abstract
Ziziphi Spinosae Semen (ZSS), a homology of medicine and a type of seed, has been widely used to improve sleep quality. The present study aimed to assess the effects of ZSS flavonoid (ZSSF) extracted and isolated from ZSS on gut microbiota and hypothalamus metabolomic profiles in a chronic restraint stress (CRS)-induced anxiety mouse model. ZSSF was prepared using microporous resin chromatography, and seven compounds were determined by UPLC-MS. ZSSF treatment dramatically reduced anxiety-like behaviors, exerted sedative-hypnotic effects, increased hippocampal 5-HT and 5-HTP, and enhanced intestinal barrier function through inhibiting colon ZO-1, Claudin-1, and Occludin expression and reducing TNF-α, IL-6, and IL-1β levels. Compared with the CRS group, the diversity of gut microbiota in ZSSF-group mice was increased, with an increase in Bacteroidetes and a decrease in Firmicutes, and it was accompanied by an increase in fecal SCFAs. Hypothalamus metabolomics and lipidomics were performed to achieve 25 differential metabolites and 44 lipids, respectively. Serum metabolomics showed a total of 13 metabolites associated with anxiety were remarkably regulated by ZSSF. Weighted correlation network analysis (WGCNA) showed that glycerophospholipids (GPs) as well as phenylalanine, tyrosine, and L-tryptophan in peripheral and central parts were significant metabolites, which contributed to the pharmacological action of ZSSF. The mRNA expression of TPH2 and DDC key enzymes associated with tryptophan metabolism were upregulated, and PLA2G12A, LACT, and PLA2G6 key enzymes associated with GP metabolism were downregulated in ZSSF compared with CRS. Briefly, ZSSF improved tryptophan and GP metabolism and regulated the gut microbiome. This study may lay a theoretical basis for potentially developing ZSSF as a natural functional food ingredient for the improvement of anxiety and sleep disorders.
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Affiliation(s)
- Yan Yan
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, China; (Y.Y.); (N.Z.); (J.L.); (Y.Z.); (X.Q.)
| | - Ni Zhao
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, China; (Y.Y.); (N.Z.); (J.L.); (Y.Z.); (X.Q.)
| | - Jiaying Liu
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, China; (Y.Y.); (N.Z.); (J.L.); (Y.Z.); (X.Q.)
| | - Shengmei Zhang
- School of Traditional Chinese Materia Medica, Shanxi University of Chinese Medicine, Taiyuan 030619, China;
| | - Yinjie Zhang
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, China; (Y.Y.); (N.Z.); (J.L.); (Y.Z.); (X.Q.)
| | - Xuemei Qin
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, China; (Y.Y.); (N.Z.); (J.L.); (Y.Z.); (X.Q.)
| | - Kefeng Zhai
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, China; (Y.Y.); (N.Z.); (J.L.); (Y.Z.); (X.Q.)
- Engineering Research Center for Development and High Value Utilization of Genuine Medicinal Materials in North Anhui Province, School of Biological and Food Engineering, Suzhou University, Suzhou 234000, China
| | - Chenhui Du
- School of Traditional Chinese Materia Medica, Shanxi University of Chinese Medicine, Taiyuan 030619, China;
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Liu L, Zhu JW, Wu JL, Li MZ, Lu ML, Yu Y, Pan L. Insomnia and intestinal microbiota: a narrative review. Sleep Breath 2024; 29:10. [PMID: 39589434 DOI: 10.1007/s11325-024-03206-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Revised: 09/11/2024] [Accepted: 09/23/2024] [Indexed: 11/27/2024]
Abstract
PURPOSE The intestinal microbiota and insomnia interact through the microbiota-gut-brain axis. The purpose of this review is to summarize and analyze the changes of intestinal microbiota in insomnia, the interaction mechanisms between intestinal microbiota and insomnia and the treatment methods based on the role of microbiota regulation in insomnia, in order to reveal the feasibility of artificial intervention of intestinal microbiota to improve insomnia. METHODS Pubmed/ Embase were searched through March 2024 to explore the relevant studies, which included the gut microbiota characteristics of insomnia patients, the mechanisms of interaction between insomnia and gut microbiota, and the relationship between gut microbiota and insomnia treatment. RESULTS Numerous studies implicated insomnia could induce intestinal microbiota disorder by activating the immune response, the hypothalamic-pituitary-adrenal axis, the neuroendocrine system, and affecting bacterial metabolites, resulting in intestinal ecological imbalance, intestinal barrier destruction and increased permeability. The intestinal microbiota exerted an influence on the central nervous system through its interactions with intestinal neurons, releasing neurotransmitters and inflammatory factors, which in turn, can exacerbate symptoms of insomnia. Artificial interventions of gut microbiota included probiotics, traditional Chinese medicine, fecal microbiota transplantation, diet and exercise, whose main pathway of action is to improve sleep by affecting the release of neurotransmitters and gut microbial metabolites. CONCLUSION There is an interaction between insomnia and gut microbiota, and it is feasible to diagnose and treat insomnia by focusing on changes in the gut microbiota of patients with insomnia. Large cross-sectional studies and fecal transplant microbiota studies are still needed in the future to validate its safety and efficacy.
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Affiliation(s)
- Lu Liu
- Department of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou, Shandong, 256603, China
| | - Ji-Wei Zhu
- Department of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou, Shandong, 256603, China
| | - Jing-Lin Wu
- Department of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou, Shandong, 256603, China
| | - Ming-Zhen Li
- Department of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou, Shandong, 256603, China
| | - Man-Lu Lu
- Department of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou, Shandong, 256603, China
| | - Yan Yu
- Department of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou, Shandong, 256603, China.
| | - Lei Pan
- Department of Respiratory and Critical Care Medicine, Binzhou Medical University Hospital, Binzhou Medical University, Binzhou, Shandong, 256603, China.
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Ma J, Huang S, Shi L, Shen Y, Gao S, Wu Z. Research progress on the effect of medicine and food homology resources for sleep improvement. Heliyon 2024; 10:e40067. [PMID: 39583811 PMCID: PMC11584607 DOI: 10.1016/j.heliyon.2024.e40067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 10/31/2024] [Accepted: 10/31/2024] [Indexed: 11/26/2024] Open
Abstract
Insomnia can have a negative impact on people's life or even cause mental or physical diseases. In China, the usage of medicine food homology herbal resources to treat insomnia has a long history. This review, which is based on the theory of traditional Chinese medicine (TCM), summarizes the research progress of medicine and food homology (MFH) resources in treating insomnia. Through literature search from the last 8 years, we compared the understanding of insomnia between TCM and modern pharmacology, found 21 kinds of MFH plants and 15 kinds of prescriptions containing MFH plants that have the effect of improving sleep and summarized the mechanism of their treatment of insomnia. Our study will provide theoretical support for the development and utilization of MFH plant resources with sleep-enhancing properties and provide positive insights and direction references for more effective treatment of insomnia disease.
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Affiliation(s)
- Jingxuan Ma
- College of Food Science, Shenyang Agricultural University, Shenyang, Liaoning, 110866, China
| | - Shan Huang
- College of Food Science, Shenyang Agricultural University, Shenyang, Liaoning, 110866, China
| | - Lin Shi
- College of Food Science, Shenyang Agricultural University, Shenyang, Liaoning, 110866, China
| | - Yixiao Shen
- College of Food Science, Shenyang Agricultural University, Shenyang, Liaoning, 110866, China
| | - Shiyu Gao
- College of Food Science, Shenyang Agricultural University, Shenyang, Liaoning, 110866, China
| | - Zhaoxia Wu
- College of Food Science, Shenyang Agricultural University, Shenyang, Liaoning, 110866, China
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Wang Z, Li D, Chen M, Yu X, Chen C, Chen Y, Zhang L, Shu Y. A comprehensive study on the regulation of Compound Zaoren Granules on cAMP/CREB signaling pathway and metabolic disorder in CUMS-PCPA induced insomnia rats. JOURNAL OF ETHNOPHARMACOLOGY 2024; 332:118401. [PMID: 38815875 DOI: 10.1016/j.jep.2024.118401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 05/07/2024] [Accepted: 05/27/2024] [Indexed: 06/01/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Compound Zaoren Granules (CZG), an optimized herbal formulation based on the traditional Chinese medicine prescription Suanzaoren decoction, are designed specifically for insomnia treatment. However, the mechanisms underlying its efficacy in treating insomnia are not yet fully understood. AIM OF THE STUDY The research investigated the mechanisms of CZG's improvement in insomnia by regulating cAMP/CREB signaling pathway and metabolic profiles. METHODS The main components of CZG were characterized by liquid chromatography-mass spectrometry (LC-MS). Subsequently, these validated components were applied to network pharmacological analysis to predict signaling pathways associated with insomnia. We evaluated the effect of CZG on BV-2 cells in vitro. We also evaluated the behavioral indexes of CUMS combined with PCPA induced insomnia in rats. HE staining and Nissl staining were used to observe the pathological damage of hippocampus. ELISA was used to detect the levels of various neurotransmitters, orexins, HPA axis, and inflammatory factors in insomnia rats. Then we detected the expression of cAMP/CREB signaling pathway through ELISA, WB, and IHC. Finally, the metabolomics was further analyzed by using UHPLC-QTOF-MS/MS to investigate the changes in the hippocampus of insomnia rats and the possible metabolic pathways were also speculated. RESULTS The results of CZG in vitro experiments showed that CZG has protective and anti-inflammatory effects on LPS induced BV-2 cells. A total of 161 chemical components were identified in CZG. After conducting network pharmacology analysis through these confirmed components, we select the cAMP/CREB signaling pathway for further investigate. The behavioral research results on insomnia rats showed that CZG significantly prolonged sleep time, mitigated brain tissue pathological damage, and exhibited liver protective properties. CZG treats insomnia by regulating the content of various neurotransmitters, reducing levels of orexin, HPA axis, and inflammatory factors. It can also treat insomnia by upregulating the expression of the cAMP/CREB signaling pathway. Hippocampus metabolomics analysis identified 69 differential metabolites associated with insomnia. The metabolic pathways related to these differential metabolites have also been predicted. CONCLUSION These results indicate that CZG can significantly prolong sleep time. CZG is used to treat insomnia by regulating various neurotransmitters, HPA axis, inflammatory factors, cAMP/CREB signaling pathways, and metabolic disorders.
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Affiliation(s)
- Zekun Wang
- Affiliated Hospital of Nanjing University of Chinese Medicine & Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, China
| | - Danting Li
- Affiliated Hospital of Nanjing University of Chinese Medicine & Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, China; Key laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Min Chen
- Affiliated Hospital of Nanjing University of Chinese Medicine & Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, China
| | - Xiaocong Yu
- Affiliated Hospital of Nanjing University of Chinese Medicine & Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, China
| | - Chen Chen
- Nanjing Women and Children's Healthcare Hospital, 210029, China
| | - Yajun Chen
- Nanjing Women and Children's Healthcare Hospital, 210029, China
| | - Lingfeng Zhang
- School of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing, 211198, China
| | - Yachun Shu
- Affiliated Hospital of Nanjing University of Chinese Medicine & Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, China; Jiangsu Province Seaside Rehabilitation Hospital, Lianyungang, 222042, China.
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Song Y, Wei D, Wang Q, Guo J, Zhu Y, Shang E, Duan JA. Luteoloside mitigates premature age-related macular degeneration by suppressing p53-p21-Rb1 axis: Insights from transcriptomic analysis, serum metabolomics and gut microbiota analysis. J Pharm Biomed Anal 2024; 248:116296. [PMID: 38878454 DOI: 10.1016/j.jpba.2024.116296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 06/02/2024] [Accepted: 06/07/2024] [Indexed: 07/20/2024]
Abstract
Transcriptomics of dry age-related macular degeneration (AMD) patients with premature aging revealed the upregulated pathways involved in glycerolipid metabolism, tyrosine metabolism, and pentose and glucuronate interconversion. To investigate natural strategies for modulating these implicated pathways, we examined the impact and underlying mechanism of luteoloside on premature AMD using a stress-induced premature senescence (SIPS)-associated AMD animal model in middle-aged mice that mimicked the dysregulated pathways observed in dry AMD patients with premature aging. Luteoloside supplementation resulted in a significant reduction in serum levels of the pro-inflammatory cytokine IL-1β and lipofuscin, along with increased serum activity of the antioxidant enzyme superoxide dismutase (SOD) and elevated levels of pigment epithelium-derived factor (PEDF), and preserved retinal thickness and structure in AMD mice. Furthermore, luteoloside supplementation effectively reversed the abnormal serum levels of metabolites, particularly by reducing harmful lysophosphatidylcholine (LysoPC) and increasing beneficial 4-guanidinobutanoic acid. In addition to its impact on metabolites, luteoloside modulated the composition of gut microbiota, promoting the enrichment of beneficial bacterial populations, including Lactobacillus, while reducing the abundance of harmful bacterial populations, including Bacteroides. Overall, our findings highlight the potential of luteoloside supplementation in regulating the dysregulated intestinal microbiota and metabolites in premature AMD, thereby reducing ocular levels of senescence-associated secretory phenotype (SASP) factors through the suppression of the p53-p21-retinoblastoma protein 1 (Rb1) axis.
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Affiliation(s)
- Yuhan Song
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Dandan Wei
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China.
| | - Qi Wang
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Jianming Guo
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Yue Zhu
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Erxin Shang
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China
| | - Jin-Ao Duan
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China.
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Ren H, Kong X, Zhang Y, Deng F, Li J, Zhao F, Li P, Pei K, Tan J, Cheng Y, Wang Y, Zhang L, Wang Y, Hao X. The therapeutic potential of Ziziphi Spinosae Semen and Polygalae Radix in insomnia management: Insights from gut microbiota and serum metabolomics techniques. JOURNAL OF ETHNOPHARMACOLOGY 2024; 330:118255. [PMID: 38670402 DOI: 10.1016/j.jep.2024.118255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/11/2023] [Revised: 04/17/2024] [Accepted: 04/23/2024] [Indexed: 04/28/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Ziziphi Spinosae Semen and Polygalae Radix (ZSS-PR) constitute a traditional Chinese herbal combination with notable applications in clinical and experimental settings due to their evident sedative and calming effects. Aligned with traditional Chinese medicine principles, Ziziphi Spinosae Semen supports cardiovascular health, nourishes the liver, and induces mental tranquillity. Simultaneously, Polygalae Radix elicits calming effects, fosters clear thinking, and reinstates proper coordination between the heart and kidneys. ZSS-PR is commonly employed as a therapeutic intervention for various insomnia types, demonstrating distinct clinical efficacy. Our previous study findings provide evidence that ZSS-PR administration significantly reduces sleep onset latency, increases overall sleep duration, and improves abnormal neurotransmitter levels in a murine insomnia model. AIM OF STUDY This investigation aimed to scrutinize the intrinsic regulatory mechanism of ZSS-PR in managing insomnia using gut microbiota and serum metabolomics techniques. MATERIALS AND METHODS Mice were given DL-4-Chlorophenylalanine to induce insomnia and then treated with ZSS-PR. The open-field test assessed the animals' spontaneous activity. Concentrations of neurotransmitters, endocrine hormones, and cytokines in the duodenum were measured using enzyme linked immunosorbent assay, and brain histopathology was evaluated with H&E staining. The impact of ZSS-PR on the metabolic profile was examined by liquid chromatography couped to high resolution mass spectrometry, and 16S rDNA sequencing was used to study the influence of ZSS-PR on the gut microbiota. Additionally, the content of short-chain fatty acids (SCFAs) was analyzed by GC-MS. Finally, correlation analysis investigated relationships between biochemical markers, metabolites, SCFAs, and gut microbiota. RESULTS ZSS-PR treatment significantly increased movement time and distance in mice with insomnia and improved pathological impairments in the cerebral cortex and hippocampus. It also restored abnormal levels of biochemical markers in the gut of insomnia-afflicted mice, including 5-hydroxytryptamine, dopamine, gastrin, melatonin, tumour necrosis factor-α, and interleukin-1β. Metabolomics findings showed that ZSS-PR had a significant restorative effect on 15 endogenous metabolites in mice with insomnia. Furthermore, ZSS-PR primarily influenced five metabolic pathways, such as phenylalanine, tyrosine, and tryptophan biosynthesis, glutamine, and glutamate metabolism. Additionally, gut microbiota analysis revealed notable alterations in both diversity and microbial composition after ZSS-PR treatment. These changes were primarily attributed to the relative abundances of microbiota, including Firmicutes, Bacteroidota, Fusobacteriota, Muribaculaceae_unclassified, and Ligilactobacillus. The results of SCFAs analysis demonstrated that ZSS-PR effectively restored abnormal levels of acetic acid, propionic acid, isobutyric acid, butyric acid, isovaleric acid, and valeric acid in insomniac mice. Subsequent correlation analysis revealed that microbiota show obvious correlations with both biochemical markers and metabolites. CONCLUSIONS The results provide compelling evidence that ZSS-PR effectively mitigates abnormal activity, reduces cerebral pathological changes, and restores abnormal levels of neurotransmitters, endocrine hormones, and cytokines in mice with insomnia. The underlying mechanism is intricately linked to the modulation of gut microbiota and endogenous metabolic pathways.
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Affiliation(s)
- Haiqin Ren
- Institute of Pharmaceutical & Food Engineering, Shanxi University of Chinese Medicine, 121 Daxue Road, Yuci District, Jinzhong, 030619, China
| | - Xiangpeng Kong
- Institute of Pharmaceutical & Food Engineering, Shanxi University of Chinese Medicine, 121 Daxue Road, Yuci District, Jinzhong, 030619, China
| | - Yue Zhang
- Institute of Pharmaceutical & Food Engineering, Shanxi University of Chinese Medicine, 121 Daxue Road, Yuci District, Jinzhong, 030619, China
| | - Fanying Deng
- Institute of Pharmaceutical & Food Engineering, Shanxi University of Chinese Medicine, 121 Daxue Road, Yuci District, Jinzhong, 030619, China
| | - Jianli Li
- Institute of Pharmaceutical & Food Engineering, Shanxi University of Chinese Medicine, 121 Daxue Road, Yuci District, Jinzhong, 030619, China
| | - Fuxia Zhao
- Institute of Pharmaceutical & Food Engineering, Shanxi University of Chinese Medicine, 121 Daxue Road, Yuci District, Jinzhong, 030619, China
| | - Pei Li
- Institute of Pharmaceutical & Food Engineering, Shanxi University of Chinese Medicine, 121 Daxue Road, Yuci District, Jinzhong, 030619, China
| | - Ke Pei
- Institute of Pharmaceutical & Food Engineering, Shanxi University of Chinese Medicine, 121 Daxue Road, Yuci District, Jinzhong, 030619, China
| | - Jinyan Tan
- Institute of Pharmaceutical & Food Engineering, Shanxi University of Chinese Medicine, 121 Daxue Road, Yuci District, Jinzhong, 030619, China
| | - Yangang Cheng
- Institute of Pharmaceutical & Food Engineering, Shanxi University of Chinese Medicine, 121 Daxue Road, Yuci District, Jinzhong, 030619, China
| | - Yan Wang
- Institute of Pharmaceutical & Food Engineering, Shanxi University of Chinese Medicine, 121 Daxue Road, Yuci District, Jinzhong, 030619, China
| | - Lu Zhang
- Affiliated Hospital of Shanxi University of Traditional Chinese Medicine, No. 75, section 1, Jinci Road, WanBailin District, Taiyuan, 030024, China
| | - Yingli Wang
- Institute of Pharmaceutical & Food Engineering, Shanxi University of Chinese Medicine, 121 Daxue Road, Yuci District, Jinzhong, 030619, China.
| | - Xuliang Hao
- Affiliated Hospital of Shanxi University of Traditional Chinese Medicine, No. 75, section 1, Jinci Road, WanBailin District, Taiyuan, 030024, China.
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11
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Yin C, Zhang M, Cheng L, Ding L, Lv Q, Huang Z, Zhou J, Chen J, Wang P, Zhang S, You Q. Melatonin modulates TLR4/MyD88/NF-κB signaling pathway to ameliorate cognitive impairment in sleep-deprived rats. Front Pharmacol 2024; 15:1430599. [PMID: 39101143 PMCID: PMC11294086 DOI: 10.3389/fphar.2024.1430599] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Accepted: 07/05/2024] [Indexed: 08/06/2024] Open
Abstract
Sleep deprivation (SD) is commonplace in today's fast-paced society. SD is a severe public health problem globally since it may cause cognitive decline and even neurodegenerative disorders like Alzheimer's disease. Melatonin (MT) is a natural chemical secreted by the pineal gland with neuroprotective effects. The purpose of this study was to investigate the protective effect and mechanism of MT on chronic sleep deprivation-induced cognitive impairment. A 3-week modified multi-platform method was used to create the SD rat model. The Morris water maze test (MWM), Tissue staining (including Hematoxylin and Eosin (H & E) staining, Nissl staining, and immunofluorescence), Western blot, Enzyme-linked immunosorbent assay (ELISA), and Quantitative real-time polymerase chain reaction (qPCR) were used to investigate the protective effect and mechanism of MT in ameliorating cognitive impairment in SD rats. The results showed that MT (50 and 100 mg/kg) significantly improved cognitive function in rats, as evidenced by a shortening of escape latency and increased time of crossing the platform and time spent in the quadrant. Additionally, MT therapy alleviated hippocampus neurodegeneration and neuronal loss while lowering levels of pathogenic factors (LPS) and inflammatory indicators (IL-1β, IL-6, TNF-α, iNOS, and COX2). Furthermore, MT treatment reversed the high expression of Aβ42 and Iba1 as well as the low expression of ZO-1 and occludin, and inhibited the SD-induced TLR4/MyD88/NF-κB signaling pathway. In summary, MT ameliorated spatial recognition and learning memory dysfunction in SD rats by reducing neuroinflammation and increasing neuroprotection while inhibiting the TLR4/MyD88/NF-κB signaling pathway. Our study supports the use of MT as an alternate treatment for SD with cognitive impairment.
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Affiliation(s)
- Chao Yin
- School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China
- Engineering Research Center of TCM Protection Technology and New Product Development for the Elderly Brain Health, Ministry of Education, Hubei University of Chinese Medicine, Wuhan, China
- Hubei Shizhen Laboratory, Hubei University of Chinese Medicine, Wuhan, China
| | - Meiya Zhang
- School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China
- Engineering Research Center of TCM Protection Technology and New Product Development for the Elderly Brain Health, Ministry of Education, Hubei University of Chinese Medicine, Wuhan, China
- Hubei Shizhen Laboratory, Hubei University of Chinese Medicine, Wuhan, China
| | - Li Cheng
- School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China
| | - Li Ding
- School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China
- Engineering Research Center of TCM Protection Technology and New Product Development for the Elderly Brain Health, Ministry of Education, Hubei University of Chinese Medicine, Wuhan, China
- Hubei Shizhen Laboratory, Hubei University of Chinese Medicine, Wuhan, China
| | - Qing Lv
- School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China
| | - Zixuan Huang
- School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China
| | - Jiaqi Zhou
- School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China
| | - Jianmei Chen
- School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China
| | - Ping Wang
- Engineering Research Center of TCM Protection Technology and New Product Development for the Elderly Brain Health, Ministry of Education, Hubei University of Chinese Medicine, Wuhan, China
- Hubei Shizhen Laboratory, Hubei University of Chinese Medicine, Wuhan, China
| | - Shunbo Zhang
- School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China
| | - Qiuyun You
- School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China
- Engineering Research Center of TCM Protection Technology and New Product Development for the Elderly Brain Health, Ministry of Education, Hubei University of Chinese Medicine, Wuhan, China
- Hubei Shizhen Laboratory, Hubei University of Chinese Medicine, Wuhan, China
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12
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Du C, Han R, Wu J, Zhao N, Pei X, Qin X, Yan Y. Study on the antidepressive effects and mechanism of raw and fried Ziziphi Spinosae Semen via metabolomics and gut microbiota analysis. Biomed Chromatogr 2024; 38:e5873. [PMID: 38587039 DOI: 10.1002/bmc.5873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Revised: 03/09/2024] [Accepted: 03/14/2024] [Indexed: 04/09/2024]
Abstract
Ziziphi Spinosae Semen (ZSS) and fried ZSS (FZSS) have been used for treating insomnia and depression in China. However, the potential influence of chemical variations on their efficacy remains unclear. This study demonstrated that compared with ZSS, FZSS exhibited an increase in the content of seven compounds, while the fatty oil content decreased. Both ZSS and FZSS exhibited antidepressive effects in a chronic unpredictable mild stress rat model, indicating a synergistic regulation of deficiencies in 5-hydroxytryptamine in the brain and the hyperactivation of severe peripheral inflammation. ZSS demonstrated a superior modulatory effect compared with FZSS, as indicated by integrated pharmacodynamic index, metabolic profile, and relative distance value. The potential mechanism underlying their antidepressive effects involved the modulation of gut microbiota structure to alleviate excessive inflammatory responses and imbalanced tryptophan metabolism. Correlation analysis indicated that the higher fatty oil contents should be comprehensively considered as the main reason for ZSS's superior antidepressive effects, achieved through the regulation of pyroglutamic acid levels.
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Affiliation(s)
- Chenhui Du
- School of Traditional Chinese Materia Medica, Shanxi University of Chinese Medicine, Taiyuan, China
| | - Rui Han
- School of Traditional Chinese Materia Medica, Shanxi University of Chinese Medicine, Taiyuan, China
| | - Jiang Wu
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China
| | - Ni Zhao
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China
| | - Xiangping Pei
- School of Traditional Chinese Materia Medica, Shanxi University of Chinese Medicine, Taiyuan, China
| | - Xuemei Qin
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China
| | - Yan Yan
- Modern Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan, China
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Li B, Yang Y, Song Z, Tang Z. Comparative Analysis of the Sedative and Hypnotic Effects among Various Parts of Zizyphus spinosus Hu and Their Chemical Analysis. Pharmaceuticals (Basel) 2024; 17:413. [PMID: 38675375 PMCID: PMC11054641 DOI: 10.3390/ph17040413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Revised: 03/18/2024] [Accepted: 03/19/2024] [Indexed: 04/28/2024] Open
Abstract
Zizyphus spinosus Hu (ZS), as a "medicinal and food-homologous" plant, has been used for a long history. The study was to assess the sedative and hypnotic effects among various parts of ZS. The model, diazepam (DZP), ZS kernel (ZSS), ZS flesh (ZSF), and ZS husk (ZSKS) group occurred subsequent to the successful establishment of the para-chlorophenylalanine induced insomnia model via intraperitoneal injection. The latency and duration of sleep in mice in each group were recorded. The substance basis of various parts of ZS was analyzed by the UPLC-QTOF-MS technique. The results showed that relative to the model group, DZP, ZSS, ZSF, and ZSKS groups demonstrated shortened sleep latency (p < 0.05) and extended sleep duration (p < 0.01). The GABA, 5-HT, and BDNF levels were significantly upregulated in the brain tissues of the mice in the DZP, ZSF, and ZSS groups (p < 0.01). However, the improvement in ZSKS was non-significant. Additionally, the mRNA and protein expression levels of 5-HT1AR, GABAARα1, and BDNF in mice in the DZP, ZSS, and ZSF groups were significantly enhanced (p < 0.01). However, the improvement in the ZSKS group was insignificant (p < 0.05). The examination of the substance composition across different parts revealed that the shared chemical basis contributing to the sedative and hypnotic potency of different parts of ZS may involve the presence of compounds such as (1) magnoflorine, (8) betulinic acid, (9) ceanothic acid, and (10) alphitolic acid. It provides a basis for further elucidation of the substance basis responsible for the functional and medicinal effects of ZS.
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Affiliation(s)
- Baojian Li
- Shaanxi Collaborative Innovation Center of Chinese Medicine Resources Industrialization, State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi Innovative Drug Research Center and College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang 712046, China; (B.L.); (Z.S.)
| | - Yuangui Yang
- Shaanxi Collaborative Innovation Center of Chinese Medicine Resources Industrialization, State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi Innovative Drug Research Center and College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang 712046, China; (B.L.); (Z.S.)
| | - Zhongxing Song
- Shaanxi Collaborative Innovation Center of Chinese Medicine Resources Industrialization, State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi Innovative Drug Research Center and College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang 712046, China; (B.L.); (Z.S.)
| | - Zhishu Tang
- Shaanxi Collaborative Innovation Center of Chinese Medicine Resources Industrialization, State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), Shaanxi Innovative Drug Research Center and College of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang 712046, China; (B.L.); (Z.S.)
- China Academy of Chinese Medical Sciences, Beijing 100700, China
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14
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Zuo WF, Pang Q, Yao LP, Zhang Y, Peng C, Huang W, Han B. Gut microbiota: A magical multifunctional target regulated by medicine food homology species. J Adv Res 2023; 52:151-170. [PMID: 37269937 PMCID: PMC10555941 DOI: 10.1016/j.jare.2023.05.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 05/27/2023] [Accepted: 05/28/2023] [Indexed: 06/05/2023] Open
Abstract
BACKGROUND The relationship between gut microbiota and human health has gradually been recognized. Increasing studies show that the disorder of gut microbiota is related to the occurrence and development of many diseases. Metabolites produced by the gut microbiota are responsible for their extensive regulatory roles. In addition, naturally derived medicine food homology species with low toxicity and high efficiency have been clearly defined owing to their outstanding physiological and pharmacological properties in disease prevention and treatment. AIM OF REVIEW Based on supporting evidence, the current review summarizes the representative work of medicine food homology species targeting the gut microbiota to regulate host pathophysiology and discusses the challenges and prospects in this field. It aims to facilitate the understanding of the relationship among medicine food homology species, gut microbiota, and human health and further stimulate the advancement of more relevant research. KEY SCIENTIFIC CONCEPTS OF REVIEW As this review reveals, from the initial practical application to more mechanism studies, the relationship among medicine food homology species, gut microbiota, and human health has evolved into an irrefutable interaction. On the one hand, through affecting the population structure, metabolism, and function of gut microbiota, medicine food homology species maintain the homeostasis of the intestinal microenvironment and human health by affecting the population structure, metabolism, and function of gut microbiota. On the other hand, the gut microbiota is also involved in the bioconversion of the active ingredients from medicine food homology species and thus influences their physiological and pharmacological properties.
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Affiliation(s)
- Wei-Fang Zuo
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Qiwen Pang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Lai-Ping Yao
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Yang Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Cheng Peng
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Wei Huang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Bo Han
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
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15
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Liu D, Wang Q, Li Y, Yuan Z, Liu Z, Guo J, Li X, Zhang W, Tao Y, Mei J. Fructus gardeniae ameliorates anxiety-like behaviors induced by sleep deprivation via regulating hippocampal metabolomics and gut microbiota. Front Cell Infect Microbiol 2023; 13:1167312. [PMID: 37377643 PMCID: PMC10291143 DOI: 10.3389/fcimb.2023.1167312] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Accepted: 05/25/2023] [Indexed: 06/29/2023] Open
Abstract
Fructus gardeniae (FG) is a traditional Chinese medicine and health food for thousands of years of application throughout Chinese history and is still widely used in clinical Chinese medicine. FG has a beneficial impact on anxiety, depression, insomnia, and psychiatric disorders; however, its mechanism of action requires further investigation. This study aimed to investigate the effects and mechanisms of FG on sleep deprivation (SD)-induced anxiety-like behavior in rats. A model of SD-induced anxiety-like behavior in rats was established by intraperitoneal injection of p-chlorophenylalanine (PCPA). This was accompanied by neuroinflammation and metabolic abnormalities in the hippocampus and disturbance of intestinal microbiota. However reduced SD-induced anxiety-like behavior and decreased levels of pro-inflammatory cytokines including TNF-α and IL-1β were observed in the hippocampus of rats after 7 days of FG intervention. In addition, metabolomic analysis demonstrated that FG was able to modulate levels of phosphatidylserine 18, Phosphatidylinositol 18, sn-glycero-3-phosphocholine, deoxyguanylic acid, xylose, betaine and other metabolites in the hippocampus. The main metabolic pathways of hippocampal metabolites after FG intervention involve carbon metabolism, glycolysis/gluconeogenesis, pentose phosphate, and glycerophospholipid metabolism. 16S rRNA sequencing illustrated that FG ameliorated the dysbiosis of gut microbiota in anxious rats, mainly increased the abundance of Muribaculaceae and Lactobacillus, and decreased the abundance of Lachnospiraceae_NK4A136_group. In addition, the correlation analysis demonstrated that there was a close relationship between hippocampal metabolites and intestinal microbiota. In conclusion, FG improved the anxiety behavior and inhibited of neuroinflammation in sleep-deprived rats, and the mechanism may be related to the FG regulation of hippocampal metabolites and intestinal microflora composition.
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Affiliation(s)
- Dong Liu
- Department of Emergency, The First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
- Department of Traditional Chinese Medicine, Hebei General Hospital, Shijiazhuang, Hebei, China
| | - Qianfei Wang
- Department of Emergency, The First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Ying Li
- Department of Pharmacy, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China
| | - Zhenshuang Yuan
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China
| | - Zhiliang Liu
- Department of Emergency, Hebei Yiling Hospital, Shijiazhang, Hebei, China
| | - Junli Guo
- Department of Emergency, The First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Xin Li
- Department of Emergency, The First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Weichao Zhang
- Department of Emergency, The First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Yulei Tao
- Department of Emergency, The First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
| | - Jianqiang Mei
- Department of Emergency, The First Affiliated Hospital of Hebei University of Chinese Medicine, Shijiazhuang, Hebei, China
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16
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Yang M, Ma Y, Si X, Liu X, Geng X, Wen X, Li G, Zhang L, Yang C, Zhang Z. Analysis of the Glycoside Hydrolase Family 1 from Wild Jujube Reveals Genes Involved in the Degradation of Jujuboside A. Genes (Basel) 2023; 14:1135. [PMID: 37372316 DOI: 10.3390/genes14061135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 05/17/2023] [Accepted: 05/19/2023] [Indexed: 06/29/2023] Open
Abstract
Jujubosides are the major medicinal ingredients of Ziziphi Spinosae Semen (the seed of wild jujube). To date, a complete understanding of jujuboside's metabolic pathways has not been attained. This study has systematically identified 35 β-glucosidase genes belonging to the glycoside hydrolase family 1 (GH1) using bioinformatic methods based on the wild jujube genome. The conserved domains and motifs of the 35 putative β-glucosidases, along with the genome locations and exon-intron structures of 35 β-glucosidase genes were revealed. The potential functions of the putative proteins encoded by the 35 β-glucosidase genes are suggested based on their phylogenetic relationships with Arabidopsis homologs. Two wild jujube β-glucosidase genes were heterologously expressed in Escherichia coli, and the recombinant proteins were able to convert jujuboside A (JuA) into jujuboside B (JuB). Since it has been previously reported that JuA catabolites, including JuB and other rare jujubosides, may play crucial roles in the jujuboside's pharmacological activity, it is suggested that these two proteins can be used to enhance the utilization potential of jujubosides. This study provides new insight into the metabolism of jujubosides in wild jujube. Furthermore, the characterization of β-glucosidase genes is expected to facilitate investigations involving the cultivation and breeding of wild jujube.
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Affiliation(s)
- Mingjun Yang
- School of Life Science and Engineering, Lanzhou University of Technology, Lanzhou 730050, China
| | - Yimian Ma
- National Engineering Laboratory for Breeding of Endangered Medicinal Materials, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China
| | - Xupeng Si
- School of Life Science and Engineering, Lanzhou University of Technology, Lanzhou 730050, China
| | - Xiaofeng Liu
- School of Life Science and Engineering, Lanzhou University of Technology, Lanzhou 730050, China
| | - Xin Geng
- National Engineering Laboratory for Breeding of Endangered Medicinal Materials, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China
| | - Xin Wen
- National Engineering Laboratory for Breeding of Endangered Medicinal Materials, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China
| | - Guoqiong Li
- National Engineering Laboratory for Breeding of Endangered Medicinal Materials, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China
| | - Liping Zhang
- National Engineering Laboratory for Breeding of Endangered Medicinal Materials, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China
| | - Chengmin Yang
- National Engineering Laboratory for Breeding of Endangered Medicinal Materials, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China
| | - Zheng Zhang
- National Engineering Laboratory for Breeding of Endangered Medicinal Materials, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, China
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He J, Fang J, Wang Y, Ge C, Liu S, Jiang Y. Discovery of Small-Molecule Antagonists of Orexin 1/2 Receptors from Traditional Chinese Medicinal Plants with a Hypnotic Effect. Pharmaceuticals (Basel) 2023; 16:ph16040542. [PMID: 37111298 PMCID: PMC10146837 DOI: 10.3390/ph16040542] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2023] [Revised: 03/25/2023] [Accepted: 03/31/2023] [Indexed: 04/29/2023] Open
Abstract
Insomnia is an important public health problem. The currently available treatments for insomnia can cause some adverse effects. Orexin receptors 1 (OX1R) and 2 (OX2R) are burgeoning targets for insomnia treatment. It is an effective approach to screening OX1R and OX2R antagonists from traditional Chinese medicine, which contains abundant and diverse chemical components. This study established an in-home ligand library of small-molecule compounds from medicinal plants with a definite hypnotic effect, as described in the Chinese Pharmacopoeia. Molecular docking was applied to virtually screen potential orexin receptor antagonists using molecular operating environment software, and surface plasmon resonance (SPR) technology was used to detect the binding affinity between potential active compounds and orexin receptors. Finally, the results of virtual screening and SPR analysis were verified through in vitro assays. We successfully screened one potential lead compound (neferine) as an orexin receptor antagonist from the in-home ligand library, which contained more than 1000 compounds. The screened compound was validated as a potential agent for insomnia treatment through comprehensive biological assays. This research enabled the discovery of a potential small-molecule antagonist of orexin receptors for the treatment of insomnia, providing a novel screening approach for the detection of potential candidate compounds for corresponding targets.
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Affiliation(s)
- Jia He
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, China
- Institute for Rational and Safe Medication Practices, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Jing Fang
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, China
- Institute for Rational and Safe Medication Practices, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Yuxin Wang
- College of Pharmacy, Dali University, Dali 671000, China
| | - Chengyu Ge
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, China
- Institute for Rational and Safe Medication Practices, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Shao Liu
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, China
- Institute for Rational and Safe Medication Practices, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
| | - Yueping Jiang
- Department of Pharmacy, Xiangya Hospital, Central South University, Changsha 410008, China
- Institute for Rational and Safe Medication Practices, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China
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Feng W, Yang Z, Liu Y, Chen R, Song Z, Pan G, Zhang Y, Guo Z, Ding X, Chen L, Wang Y. Gut microbiota: A new target of traditional Chinese medicine for insomnia. Biomed Pharmacother 2023; 160:114344. [PMID: 36738504 DOI: 10.1016/j.biopha.2023.114344] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 01/20/2023] [Accepted: 01/29/2023] [Indexed: 02/05/2023] Open
Abstract
All species have a physiological need for sleep, and sleep is crucial for the preservation and restoration of many physiological processes in the body. Recent research on the effects of gut microbiota on brain function has produced essential data on the relationship between them. It has been discovered that dysregulation of the gut-brain axis is related to insomnia. Certain metabolites of gut microbiota have been linked to insomnia, and disturbances in gut microbiota can worsen insomnia. Traditional Chinese medicine (TCM) has unique advantages for the treatment of insomnia. Taking the gut microbiota as the target and determining the scientific relevance of TCM to the prevention and treatment of insomnia may lead to new concepts for the treatment of sleep disorders and improve the therapeutic effect of sleep. Taking the gut microbiota as an entry point, this paper reviews the relationship between gut microbiota and TCM, the relationship between gut microbiota and insomnia, the mechanism by which gut microbiota regulate sleep, and the mechanism by which TCM regulates gut microbiota for insomnia prevention and treatment. This review provides new ideas for the prevention and treatment of insomnia through TCM and new ideas for drug development.
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Affiliation(s)
- Wanying Feng
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
| | - Zhihua Yang
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
| | - Yangxi Liu
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin 300381, China.
| | - Rui Chen
- College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
| | - Zhihui Song
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
| | - Guiyun Pan
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
| | - Yuhang Zhang
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
| | - Zehui Guo
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
| | - Xinya Ding
- First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin 300381, China.
| | - Lu Chen
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
| | - Yi Wang
- State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
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Wang Z, An X, Chitrakar B, Li J, Yuan Y, Liu K, Nie X, Zhang Y, Zhao X, Zhao Z, Liu M, Ao C. Spatial and Temporal Distribution of Phenolic and Flavonoid Compounds in Sour Jujube (Ziziphus. Acidojujuba Cheng et Liu) and Their Antioxidant Activities. PLANT FOODS FOR HUMAN NUTRITION (DORDRECHT, NETHERLANDS) 2023; 78:46-51. [PMID: 36279034 DOI: 10.1007/s11130-022-01015-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Revised: 09/15/2022] [Accepted: 09/19/2022] [Indexed: 06/16/2023]
Abstract
In order to comprehensively analyze the antioxidant substances in sour jujube, total phenolic content (TPC) and total flavonoids contents (TFC) in different organs, including stem, leaf, flower, fruit pulp, and seed were analyzed for their contents and antioxidant activities. The results showed that leaves possessed significantly higher TPC and TFC (20.4 and 20.5 mg/g, respectively) than the other organs and have the highest antioxidant activity, which were also higher than the wild blueberry (A well-known for its high TPC). Subsequently, the variations in the antioxidant content and antioxidant activity of leaves were analyzed during leaf development. TPC in leaves sampled in may and august were significantly higher than that in other months, while the highest one was found in may. The n-hexane, ethyl acetate, n-butanol, and water fractions obtained from the main methanol extract of sour jujube leaves were evaluated for TPC and TFC and their antioxidant activity and it was found that ethyl acetate fraction displayed the highest TPC and TFC (184.5 and 193.3 mg/g, respectively), as well as the best antioxidant activity. In addition, using LC-MS and HPLC, ethyl acetate fraction was analyzed from qualitative and quantitative aspects; 31-one phenolic compounds, including catechin (33.0 mg/g), epigallocatechin (15.3 mg/g), quercetin 3-O-glucoside (11.4 mg/g), naringenin (6.7 mg/g), esculetin (4.8 mg/g), and chlorogenic acid (4.6 mg/g) were identified. Catechin, esculetin, epigallocatechin, chlorogenic acid, quercetin 3-O-glucoside, and naringenin exhibited high antioxidant activity. These results provide a theoretical basis for further study and utilization of flavonoid and polyphenols in sour jujube.
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Affiliation(s)
- Zijuan Wang
- College of Food Science and Technology, Hebei Agricultural University, 071000, Baoding, China
| | - Xiaowen An
- College of Food Science and Technology, Hebei Agricultural University, 071000, Baoding, China
| | - Bimal Chitrakar
- College of Food Science and Technology, Hebei Agricultural University, 071000, Baoding, China
| | - Jiamin Li
- College of Food Science and Technology, Hebei Agricultural University, 071000, Baoding, China
| | - Ye Yuan
- College of Horticulture, Hebei Agricultural University, 071000, Baoding, China
| | - Kexin Liu
- College of Food Science and Technology, Hebei Agricultural University, 071000, Baoding, China
| | - Xinyu Nie
- College of Food Science and Technology, Hebei Agricultural University, 071000, Baoding, China
| | - Yifan Zhang
- College of Food Science and Technology, Hebei Agricultural University, 071000, Baoding, China
| | - Xin Zhao
- College of Horticulture, Hebei Agricultural University, 071000, Baoding, China
| | - Zhihui Zhao
- College of Horticulture, Hebei Agricultural University, 071000, Baoding, China
| | - Mengjun Liu
- College of Horticulture, Hebei Agricultural University, 071000, Baoding, China
| | - Changwei Ao
- College of Food Science and Technology, Hebei Agricultural University, 071000, Baoding, China.
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Ganmaidazao Decoction Alleviated Cognitive Impairment on Alzheimer's Disease Rats by Regulating Gut Microbiota and Their Corresponding Metabolites. ARAB J CHEM 2023. [DOI: 10.1016/j.arabjc.2023.104688] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/17/2023] Open
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21
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Zheng HL, Li MT, Zhou T, Wang YY, Shang EX, Hua YQ, Duan JA, Zhu Y. Protective effects of Lycium barbarum L. berry extracts against oxidative stress-induced damage of the retina of aging mouse and ARPE-19 cells. Food Funct 2023; 14:399-412. [PMID: 36512065 DOI: 10.1039/d2fo02788g] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
In this study, we investigated the preventive effect of Lycium barbarum L. berry extract on age-related macular degeneration (AMD) and the main components responsible for its antioxidant activity. An AMD mouse model was developed by feeding 18-month-old mice with a 1% hydroquinone diet. Meanwhile, the model mice were treated with water extract (LBW) and alcohol extract (LBE) of L. barbarum berries respectively for 3 months. It was found that the retinal structural abnormalities were improved and the oxidation stress and inflammatory imbalance were both attenuated in model mice treated with the extracts of L. barbarum berries. According to the metabolomics analysis of the serum of model mice, LBW regulated the metabolism of unsaturated fatty acids and sphingolipids, while LBE extracts tended to regulate taurine metabolism. On sodium iodate induced oxidative injury of ARPE-19 cells, water extracts of L. barbarum berries eluted with 95% ethanol (LBW-95E) on AB-8 macroporous resin significantly improved the cell viability and attenuated oxidative stress by increasing the superoxide dismutase (SOD) activity and glutathione (GSH) content, decreasing the reactive oxygen species (ROS) content, promoting the entry of nuclear factor erythroid-derived 2-like 2 (Nrf2) into the nucleus and up-regulating the heme oxygenase-1 (HO-1) expression. Scopoletin, N-trans-feruloyltyramine and perlolyrine were identified as the main components of LBW-95E. These results demonstrated that L. barbarum berry extracts protected the retina of aging AMD model mice from degeneration and LBW-95E was the vital antioxidant activity fraction of LBW. These findings suggest that L. barbarum berry extracts might be an excellent natural source for the development of retinal protection-related drugs or dietary supplements.
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Affiliation(s)
- Hui-Li Zheng
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China.
| | - Meng-Ting Li
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China.
| | - Tong Zhou
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China.
| | - Ying-Yi Wang
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China.
| | - Er-Xin Shang
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China.
| | - Yong-Qing Hua
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China.
| | - Jin-Ao Duan
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China.
| | - Yue Zhu
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China.
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22
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Qiao T, Wang Y, Liang K, Zheng B, Ma J, Li F, Liu C, Zhu M, Song M. Effects of the Radix Ginseng and Semen Ziziphi Spinosae drug pair on the GLU/GABA-GLN metabolic cycle and the intestinal microflora of insomniac rats based on the brain-gut axis. Front Pharmacol 2022; 13:1094507. [PMID: 36618926 PMCID: PMC9811267 DOI: 10.3389/fphar.2022.1094507] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2022] [Accepted: 12/02/2022] [Indexed: 12/24/2022] Open
Abstract
Introduction: To explore the mechanism of action of appling Radix Ginseng and Semen Ziziphi Spinosae Drug pair (R-S) in the treatment of insomnia by investigating the effect of R-S on GLU/GABA-GLN metabolic cycle and intestinal microflora of rats with insomnia. Methods: Rats were intraperitoneally injected with 4-chloro-DL-phenylalanine (PCPA) to make sleep deprivation (SD) models. The rats were divided into 6 groups, with 8 rats in each group. The general status of the rats was observed and the pentobarbital sodium sleep synergy experiment was performed. The contents of GABA, GLU, GLN, GAD65, and GS in hippocampus of rats were determined by ELISA. The expressions of GABAARα1mRNA, mGluR5mRNA, NR1mRNA and GluR1mRNA in rats' hippocampal tissue were determined by Realtime PCR. 16SrRNA gene sequencing was used to analyze the intestinal microflora of insomnia rats. Results: In PCPA-induced insomnia rats, the state of insomnia was relieved, the sleep rate was improved, the duration of sleep latency was shortened and the sleep duration was prolonged in each dose group of R-S (p < 0.05, p < 0.01) compared with the model group. The contents of GABA, GLN, GAD65 and GS were increased (p < 0.05, p < 0.01) while GLU content was decreased (p < 0.01) in both medium and high dose groups, especially in the high dose group. The expression of GABAARα1mRNA was increased (p < 0.01), and the expressions of mGluR5mRNA, NR1mRNA and GluR1mRNA were decreased (p < 0.01) in hippocampal tissue of rats in R-S groups, especially in the high dose group. At the same time, the various dose groups of R-S could improve the species diversity, microflora abundance of insomnia rats and regulate the KEGG metabolic pathway related to sleep. Discussion: R-S can improve the sleep of PCPA-induced insomnia rats by regulating GLU/GABA-GLN metabolic cycle and intestinal microflora, which provides experimental basis for appling R-S in the treatment of insomnia.
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Affiliation(s)
- Tie Qiao
- Liaoning Academy of Traditional Chinese Medicine Sciences, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China,Guangdong Xin-Huangpu Joint Innovation Institute of Traditional Chinese Medicine, Guangzhou, Guangdong, China,*Correspondence: Tie Qiao,
| | - Yuan Wang
- Liaoning Academy of Traditional Chinese Medicine Sciences, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China
| | - Ke Liang
- Liaoning Academy of Traditional Chinese Medicine Sciences, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China
| | - Bingyuan Zheng
- Liaoning Academy of Traditional Chinese Medicine Sciences, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China
| | - Jin Ma
- The Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China
| | - Fangxiao Li
- Liaoning Academy of Traditional Chinese Medicine Sciences, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China
| | - Chi Liu
- Liaoning Academy of Traditional Chinese Medicine Sciences, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China
| | - Mingdan Zhu
- Liaoning Academy of Traditional Chinese Medicine Sciences, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China
| | - Meng Song
- Liaoning Academy of Traditional Chinese Medicine Sciences, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China
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Liu H, Yang L, Wan C, Li Z, Yan G, Han Y, Sun H, Wang X. Evaluation of the pharmacological effects and exploration of the mechanism of traditional Chinese medicine preparation Ciwujia tablets in treating insomnia based on ethology, energy metabolism, and urine metabolomic approaches. Front Pharmacol 2022; 13:1009668. [PMID: 36545309 PMCID: PMC9760683 DOI: 10.3389/fphar.2022.1009668] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Accepted: 11/14/2022] [Indexed: 12/11/2022] Open
Abstract
Ciwujia Tablets (CWT) are produced by concentrating and drying the extract solution of the dried rhizome of Eleutherococcus senticosus (Rupr. & Maxim.) Maxim [Araliaceae; E. senticosus radix et rhizoma]. Besides, CWT is included in the 2020 edition of Chinese Pharmacopoeia and is widely used in the treatment of insomnia. It mainly contains eleutheroside B, eleutheroside E, isofraxidin, eleutheroside C, ciwujiatone, and chlorogenic acid, as well as other chemical components. Although the clinical efficacy of CWT in treating insomnia has been confirmed, its functions and pharmacological effects have not been systematically evaluated and its mechanism of action in the treatment of insomnia remains unclear. Therefore, in this study, behavioral, energy metabolism, and metabonomics methods were applied to systematically evaluate the effect of CWT on insomnia. Additionally, urine metabonomics based on UPLC-Q-TOF-MS/MS were utilized to identify potential endogenous biomarkers of insomnia, detect the various changes before and after CWT treatment, explore the metabolic pathway and potential target of CWT, and reveal its pharmacological mechanism. Results revealed that CWT increased inhibitory neurotransmitter (5-HT and GABA) content and reduced the content of excitatory neurotransmitters (DA and NE). Moreover, CWT enhanced autonomous behavioral activity, stabilized emotions, and promoted the return of daily basic metabolic indexes of insomniac rats to normal levels. The urine metabolomics experiment identified 28 potential endogenous biomarkers, such as allysine, 7,8-dihydroneopterin, 5-phosphonooxy-L-lysine, and N-acetylserotonin. After CWT treatment, the content of 22 biomarkers returned to normal levels. The representative markers included N-acetylserotonin, serotonin, N-methyltryptamine, and 6-hydroxymelatonin. Additionally, the metabolic pathways in rats were significantly reversed, such as tryptophan metabolism, folate biosynthesis, phenylalanine metabolism, and tyrosine metabolism. Ultimately, it is concluded that CWT regulated tryptophan metabolism, folate biosynthesis, phenylalanine metabolism, and other metabolic levels in the body. This drug has been confirmed to be effective in the treatment of insomnia by regulating the content of serotonin, 6-hydroxymelatonin, N-acetylserotonin, and N-methyltryptamine to a stable and normal level in tryptophan metabolism.
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Affiliation(s)
- Hongda Liu
- National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Le Yang
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou, University of Chinese Medicine, Guangzhou, China
| | - Chunlei Wan
- National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Zhineng Li
- National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Guangli Yan
- National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Ying Han
- National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Hui Sun
- National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Harbin, China,*Correspondence: Hui Sun, ; Xijun Wang,
| | - Xijun Wang
- National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Harbin, China,State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou, University of Chinese Medicine, Guangzhou, China,State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macao, China,*Correspondence: Hui Sun, ; Xijun Wang,
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A Combination of Rosa Multiflora and Zizyphus Jujuba Enhance Sleep Quality in Anesthesia-Induced Mice. Int J Mol Sci 2022; 23:ijms232214177. [PMID: 36430653 PMCID: PMC9696267 DOI: 10.3390/ijms232214177] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Revised: 11/15/2022] [Accepted: 11/15/2022] [Indexed: 11/18/2022] Open
Abstract
Sleep is an essential component of quality of life. The majority of people experience sleep problems that impact their quality of life. Melatonin is currently a representative sleep aid. However, it is classified as a prescription drug in most countries, and consumers cannot purchase it to improve their sleep. This sleep induction experiment in mice aimed to identify a natural combination product (NCP) that can create synergistic sleep-promoting effects. Based on the mechanism of action of sleep, we investigated whether phenomenological indicators of sleep quality change according to the intake of NCP. The sleep onset and sleep time of the mice that consumed the NCP found by this study were improved compared to the existing sleep aids. The mean melatonin level in the blood increased by 197% compared to the control. To our knowledge, this is the first study to demonstrate that Rosa multiflora Thunb. (Yeongsil) can promote sleep similarly to Zizyphus jujuba Miller (Sanjoin). The results indicate a preclinical study of NCPs containing Rosa multiflora Thunb and Zizyphus jujuba Miller developed by us showed significant differences in sleep incubation and duration depending on melatonin concentrations. Our results also suggest that increased melatonin concentrations in the blood are likely to improve sleep quality, especially regarding incubation periods.
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Fazil M, Nikhat S. Therapeutic and palliative role of a Unani herbal decoction in COVID-19 and similar respiratory viral illnesses: Phytochemical & pharmacological perspective. JOURNAL OF ETHNOPHARMACOLOGY 2022; 297:115526. [PMID: 35843408 PMCID: PMC9281408 DOI: 10.1016/j.jep.2022.115526] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 06/22/2022] [Accepted: 07/06/2022] [Indexed: 06/15/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Outbreaks of respiratory viral infections like Severe Acute Respiratory Syndrome, Middle-East Respiratory Syndrome, and Coronavirus Disease-2019 have been a regular occurrence in the past 100 years. A significant proportion of the morbidity and mortality in influenza is attributed to the co-morbidities and complications induced by the disease, involving the vital organs and physiological functions. In this context, traditional medicines offer effective protective, palliative, and therapeutic benefits, as observed in several studies on various types of influenza, including COVID-19. The Unani herbal decoction comprising of 'Unnāb (Ziziphus jujuba Mill. fruit), Sapistān (Cordia dichotoma G. Forst. fruit), and Behīdāna (Cydonia oblonga Mill. seed) was originally prescribed by Hakim Ajmal Khan (1868-1927 AD) for various respiratory ailments as a bronchodilator, anti-inflammatory, and for clearing the respiratory tract. During COVID-19, the decoction was prescribed by the Ministry of Ayurveda, Yoga, Unani, Siddha, and Homeopathy (AYUSH), Government of India, for mild patients in home isolation, and also as a self-care drink for healthy people. Preliminary studies are of the view that the decoction could reduce COVID-19 incidence and prevent severe disease in the population where it was administered. AIMS OF THE STUDY We intend to review the pharmacological activity of the Unani decoction ingredients, i.e., Z. jujuba, C. dichotoma, and C. oblonga, in context with respiratory viral infections and their co-morbidities, to develop an understanding of its action mechanism. METHODOLOGY We reviewed Unani classical textbooks for information on the therapeutic activity of the decoction ingredients. Scientific studies published in English from the year 2000 onwards on leading scientific websites (PubMed, MEDLINE, Scopus, and Springer) were searched for information regarding the efficacy of the drugs in influenza and its common complications. Non-English language articles, or those published prior to 2000, and those which included plant parts other than those traditionally included in the decoction were excluded. OBSERVATIONS A wide range of therapeutic and palliative effects have been observed in the three herbs included in the Unani decoction, including anti-viral, anti-bacterial, immuno-modulatory, anti-inflammatory, hepato-, and nephroprotective, anti-atherosclerotic, anti-tussive, broncho-dilatory, and regulation of gut microbiota. Together, these effects can help to mitigate and prevent most of the complications caused as a result of respiratory viral infections. CONCLUSION The combined effects of ingredients in this Unani herbal decoction can potentially help to mitigate most of the pathological changes and complications caused by influenza viruses. With further clinical research, the decoction may be potentially utilized as a prophylactic and therapeutic against viral influenza.
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Affiliation(s)
- Mohammad Fazil
- Hakim Ajmal Khan Institute for Literary and Historical Research in Unani Medicine, CCRUM, Jamia Millia Islamia Campus, New Delhi, India.
| | - Sadia Nikhat
- Dept. of Ilaj bit Tadbeer, School of Unani Medical Education and Research, Jamia Hamdard, New Delhi, India.
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Ren H, Gao S, Wang S, Wang J, Cheng Y, Wang Y, Wang Y. Effects of Dangshen Yuanzhi Powder on learning ability and gut microflora in rats with memory disorder. JOURNAL OF ETHNOPHARMACOLOGY 2022; 296:115410. [PMID: 35640741 DOI: 10.1016/j.jep.2022.115410] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Revised: 05/24/2022] [Accepted: 05/26/2022] [Indexed: 06/15/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Yuanzhi Powder is a commonly used traditional Chinese medical formulae for its potency in enhancing memory and learning. In clinical practice, Yuanzhi Powder is a classic formula in TCM to treat amnesia of the type "deficiency of Qi, turbid phlegm harasses the head and eyes, and stagnation of phlegm converting into the fire". Our previous study showed that Yuanzhi Power, used together with Codonopsis Radix (Dangshen Yuanzhi Power, DYP), could improve learning and memory ability in animals with memory disorder (MD) and its efficacy is superior or equivalent to that of the Yuanzhi Power. AIM OF STUDY This study aimed to explore the regulatory mechanism of DYP through the "bacteria-gut-brain axis". MATERIALS AND METHODS The SD rats were divided randomly into control, model, positive, DYP-L, and DYP-H groups. Except for the control group, the rats were intraperitoneally injected with D-Gal (400 mg/kg) and gavaged with aluminum chloride (200 mg/kg) every day for 50 days. The rats in the DYP group were gavaged with DYP (6.67 and 13.34 g/kg, respectively) from the 15th day, once a day. The rats in the positive group were similarly administrated with piracetam (0.5 g/kg). The rats' bodyweight was recorded from the 16th day. The learning and memory ability of animals was tested by Morris water maze. The levels of MCP-1, NF-L, NSE, and TNF-α in serum were determined by Elisa kit, while the histopathology of duodenum and colon tissues was examined by H & E staining. The diversity of intestinal flora was sequenced and analyzed. In order to reveal the role of intestinal flora in DYP treatment of MD, the intestinal flora composition and the correlation analysis of intestinal flora and the above biochemical indexes were investigated. The intestinal flora function and biological metabolic pathways were predicted and analyzed by the KEGG database. RESULTS The MD animals' learning and spatial memory ability decreased significantly, compared with the normal group, accompanied by weight increase and intestinal flora disorder. DYP can improve the learning and memory ability of MD animals, and its efficacy may exert through the following ways: (i) callback the abnormal biochemical indexes of MCP-1, NF-L, NSE, and TNF-α; (ii) decreasing the relative ratio of Firmicutes/Bacteroidetes and repairing the pathology of MD animal intestinal mucosa; and (iii) the regulation of DYP on biochemical blood indexes of MD animals was significantly correlated with the regulation of intestinal flora; (iv) DYP rats showed a strong correlation between cognitive ability improvement and bodyweight loss; (v) besides, DYP could also regulate the metabolic pathways of carbohydrate, amino acid, nucleotide, and energy by affecting related biological functions. CONCLUSIONS The results supported that DYP can improve MD animals' learning and memory ability by restoring the intestinal flora disorder and callback the abnormal biochemical indexes in serum, closely related to the "bacteria-gut-brain axis".
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Affiliation(s)
- Haiqin Ren
- Institute of Pharmaceutical & Food Engineering, Shanxi University of Chinese Medicine, 121 Daxue Road, Yuci District, Jinzhong, 030619, China
| | - Shouqin Gao
- Institute of Pharmaceutical & Food Engineering, Shanxi University of Chinese Medicine, 121 Daxue Road, Yuci District, Jinzhong, 030619, China
| | - Shihui Wang
- Institute of Pharmaceutical & Food Engineering, Shanxi University of Chinese Medicine, 121 Daxue Road, Yuci District, Jinzhong, 030619, China
| | - Jiamin Wang
- Institute of Pharmaceutical & Food Engineering, Shanxi University of Chinese Medicine, 121 Daxue Road, Yuci District, Jinzhong, 030619, China
| | - Yangang Cheng
- Institute of Pharmaceutical & Food Engineering, Shanxi University of Chinese Medicine, 121 Daxue Road, Yuci District, Jinzhong, 030619, China
| | - Yan Wang
- Institute of Pharmaceutical & Food Engineering, Shanxi University of Chinese Medicine, 121 Daxue Road, Yuci District, Jinzhong, 030619, China
| | - Yingli Wang
- Institute of Pharmaceutical & Food Engineering, Shanxi University of Chinese Medicine, 121 Daxue Road, Yuci District, Jinzhong, 030619, China.
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Liu H, Yang L, Wan C, Li Z, Yan G, Han Y, Sun H, Wang X. Exploring potential mechanism of ciwujia tablets for insomnia by UPLC-Q-TOF-MS/MS, network pharmacology, and experimental validation. Front Pharmacol 2022; 13:990996. [PMID: 36110515 PMCID: PMC9468710 DOI: 10.3389/fphar.2022.990996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Accepted: 08/08/2022] [Indexed: 11/24/2022] Open
Abstract
Insomnia, whether chronic or intermittent, is a common central nervous system disease. Ciwujia Tablet (CWT) is a well-known traditional Chinese medicine (TCM) made from the extract of Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. This medication is commonly used for treating insomnia in China, but the lack of in-depth research focused on the chemical ingredients of CWT creates a gap in knowledge regarding its effective constituents against insomnia. Considering that the therapeutic material basis, targets, and pathways related to this drug have not been fully investigated by scholars in the field, the focus of this study is on identifying the chemical ingredients or structural characteristics of CWT by the UPLC-Q-TOF-MS/MS technique. Besides, concepts of network pharmacology were also used to investigate the targets and pathways of CWT. An insomnia rat model was established by intraperitoneal injection of p-chlorophenylalanine, and the results were verified through various experiments. A total of 46 ingredients were identified in CWT, such as eleutheroside B, eleutheroside E, isofraxidin, and chlorogenic acid. Among them, 17 ingredients with good solubility, favorable gastrointestinal absorption, and high bioavailability were selected for network pharmacological analysis. It was concluded that CWT participated in the regulation of neurotransmitter levels, modulation of ion transport, neurotransmitter receptor activity, synaptic transmission, dopaminergic transmission and other essential processes. Results from the animal experiments showed that CWT can increase the content of inhibitory neurotransmitters 5-HT and GABA in the brain, reduce the synthesis of excitatory escalating transmitters DA and NE, shorten the sleep latency and prolong the sleep duration of insomnia rats. Furthermore, CWT could significantly alleviate the symptoms of insomnia in model rats. Identifying the chemical ingredients of CWT in this experiment is of great significance for exploring its potential curative effects, which provides a solid basis for further understanding the therapeutic value of this medication.
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Affiliation(s)
- Hongda Liu
- National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Le Yang
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Chunlei Wan
- National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Zhineng Li
- National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Guangli Yan
- National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Ying Han
- National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Hui Sun
- National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Xijun Wang
- National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Harbin, China
- State Key Laboratory of Dampness Syndrome of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
- State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau SAR, China
- *Correspondence: Xijun Wang,
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Neuromodulatory and Protective Effects Induced by the Association of Herbal Extracts from Valeriana officinalis, Ziziphus jujuba, and Humulus lupulus with Melatonin: An Innovative Formulation for Counteracting Sleep Disorders. Processes (Basel) 2022. [DOI: 10.3390/pr10081609] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Background: The use of herbal extracts could represent an advantageous approach for treating sleeping disorders, especially in mild-to-moderate conditions, before the onset of a specific therapy with first-line drugs. Specifically, the focus was posed about the use of extracts from Valeriana officinalis, Ziziphus jujuba, and Humulus lupulus. Multiple studies demonstrated the efficacy of these medicinal plants to positively manage insomnia symptoms. Additionally, their efficacy in the treatment of sleeping disorders could also be improved by their pharmacological association. In the present study, extracts from Valeriana officinalis, Ziziphus jujuba, Humulus lupulus, melatonin, and their pharmacological association, Vagonotte® MEL, were studied for potential application in the treatment of insomnia. Methods: The extracts and melatonin were tested on hypothalamic neurons and tissue for evaluating biocompatibility and protective and neuromodulatory effects. The neuromodulatory effects were evaluated as orexin A gene expression and serotonin steady state level, in the hypothalamus. Results: The extracts and melatonin, although with evident differences, were effective as antioxidant and anti-inflammatory agents; additionally, they were also able to reduce the hypothalamic gene expression of orexin A and the steady state level of serotonin, playing master roles in wakefulness. It is noteworthy that the formulation displayed all the effects of the single ingredients, without any sign of toxicity and pharmacological interference in the hypothalamus. Conclusions: Concluding, the present study explored the biological effects of melatonin and herbal extracts with phytotherapy interest in V. officinalis, Z. jujuba, and H. lupulus. The study demonstrated their intrinsic scavenging/reducing activity, together with protective and neuromodulatory effects in the hypothalamus, with a significant reduction of both orexin A gene expression and serotonin steady state level. Additionally, the study also considered their pharmacological association, which displayed an overall pharmacological spectrum mirroring, including all the effects of the single ingredients, without showing any sign of toxicity in the brain and interference between the extracts and melatonin.
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Hua Y, Xu XX, Guo S, Xie H, Yan H, Ma XF, Niu Y, Duan JA. Wild Jujube ( Ziziphus jujuba var. spinosa): A Review of Its Phytonutrients, Health Benefits, Metabolism, and Applications. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2022; 70:7871-7886. [PMID: 35731918 DOI: 10.1021/acs.jafc.2c01905] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Wild jujube, Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou, as a food and health supplement worldwide, has rich nutritional value. It contains nutrients such as nucleosides, amino acids, polysaccharides, and fatty oils. The fruits, seeds, and leaves of wild jujube can all be used for food, medicine, or health care purposes. Among these, the fruits play many roles, such as antioxidant, antibacterial, and anti-inflammatory functions, and can be used as a natural nutritional supplement to prevent aging. Simultaneously, the mature seed of wild jujube exhibits beneficial effects on central nervous system diseases and is often used for the treatment of insomnia and as a functional food for improving sleep quality and enhancing learning and memory. This review presents an overview of research progress relevant to the phytonutrients, biological functions, metabolism of bioactive compounds, and applications of wild jujube and aims to provide a scientific reference for the development and utilization of this plant.
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Affiliation(s)
- Yue Hua
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of Traditional Chinese Medicine Formulae, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China
| | - Xiao-Xue Xu
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of Traditional Chinese Medicine Formulae, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China
| | - Sheng Guo
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of Traditional Chinese Medicine Formulae, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China
| | - Hong Xie
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of Traditional Chinese Medicine Formulae, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China
| | - Hui Yan
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of Traditional Chinese Medicine Formulae, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China
| | - Xin-Fei Ma
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of Traditional Chinese Medicine Formulae, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China
| | - Yang Niu
- Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan, Ningxia 750004, China
| | - Jin-Ao Duan
- National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Key Laboratory for High Technology Research of Traditional Chinese Medicine Formulae, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China
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Sun Y, Wang Z, Hou J, Shi J, Tang Z, Wang C, Zhao H. Shuangxinfang Prevents S100A9-Induced Macrophage/Microglial Inflammation to Improve Cardiac Function and Depression-Like Behavior in Rats After Acute Myocardial Infarction. Front Pharmacol 2022; 13:832590. [PMID: 35814253 PMCID: PMC9263923 DOI: 10.3389/fphar.2022.832590] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Accepted: 05/06/2022] [Indexed: 01/07/2023] Open
Abstract
Background: Depression is a common complication of cardiovascular disease, which deteriorates cardiac function. Shuangxinfang (psycho-cardiology formula, PCF) was reported to alleviate myocardial ischemia injury and improve depression-like behavior. Interestingly, our previous proteomics study predicted that the protein S100A9 appeared as an important target, and macrophage/microglial inflammation might be involved in the process of PCF improving depression induced by acute myocardial infarction (AMI). This study aims to validate the proteomics results. Methods: AMI rat models were established in vivo, followed by the administration of PCF or ABR-215757 (also named paquinimod, inhibiting S100A9 binding to TLR4) for 5 days. Forced swimming test (FST) and open field test (OFT) were applied to record depression-like behavior, and echocardiography was employed to evaluate cardiac function. Morphological changes of cardiomyocytes were assessed by HE staining and TUNEL staining on day 7 after cardiac surgery, as well as Masson trichrome staining on day 21. Hippocampal neurogenesis was determined by Nissl staining, while 5-hydroxytryptamine (5-HT), tryptophan/kynurenine ratio, and brain-derived neurotrophic factor (BDNF) in the hippocampus were analyzed as biochemical indicators of depression. We employed RT-qPCR, western blotting, and immunofluorescence to detect the expression of pathway-related genes and proteins. Myocardial and hippocampal expression of inflammatory factors were performed by ELISA. The activation of macrophage and microglia was assessed via immunoreaction using CD68 and Iba1, respectively. For in vitro confirmation, BV2 cells were primed with recombinant protein S100A9 and then treated with PCF serum or ferulic acid to determine alterations in microglial inflammation. Results: Rats in the AMI group showed heart function deterioration and depression-like behavior. Coronary ligation not only brought about myocardial inflammation, cell apoptosis, and fibrosis but also reduced the neurogenesis, elevated the tryptophan/kynurenine ratio, and decreased the content of 5-HT. PCF could ameliorate the pathological and phenotypic changes in the heart and brain and inhibit the expression of the S100A9 protein, the activation of the microglial cell, and the secretion of IL-1β and TNF-α raised by AMI. ABR-215757 showed therapeutic effect and molecular biological mechanisms similar to PCF. Treatment with PCF serum or ferulic acid in vitro was proved to efficiently block the hyperactivation of BV2 cells and increment of cytokine contents induced by recombinant protein S100A9. Conclusion: We identify S100A9 as a novel and potent regulator of inflammation in both the heart and brain. Macrophage/microglia inflammation mediated by S100A9 is considered a pivotal pathogenic in depression after AMI and a major pathway for the treatment of PCF, suggesting that PCF is a promising therapeutic candidate for psycho-cardiology disease.
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Affiliation(s)
- Yize Sun
- Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Zheyi Wang
- Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Jiqiu Hou
- Oriental Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Jinyu Shi
- Oriental Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Zhuoran Tang
- Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Chao Wang
- Oriental Hospital, Beijing University of Chinese Medicine, Beijing, China
- *Correspondence: Chao Wang, ; Haibin Zhao,
| | - Haibin Zhao
- Oriental Hospital, Beijing University of Chinese Medicine, Beijing, China
- *Correspondence: Chao Wang, ; Haibin Zhao,
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Bian Z, Zhang W, Tang J, Fei Q, Hu M, Chen X, Su L, Fei C, Ji D, Mao C, Tong H, Yuan X, Lu T. Mechanisms Underlying the Action of Ziziphi Spinosae Semen in the Treatment of Insomnia: A Study Involving Network Pharmacology and Experimental Validation. Front Pharmacol 2022; 12:752211. [PMID: 35002696 PMCID: PMC8740267 DOI: 10.3389/fphar.2021.752211] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Accepted: 11/25/2021] [Indexed: 01/13/2023] Open
Abstract
Purpose: This study aimed to investigate the potential mechanisms and related bioactive components of ZSS for the treatment of insomnia. Method: The insomnia model of rat induced by PCPA was established. After oral administration of ZSS extract, the general morphological observation, pentobarbital sodium-induced sleep test and histopathological evaluation were carried out. Network pharmacology, assisted by UHPLC-Q-Exactive-MS/MS analysis, was developed to identify the targets of ZSS in the treatment of insomnia, as well as the corresponding signaling pathways. In addition, we validated the identified targets and pathways by RT-qPCR and immunohistochemical analysis. Results: The pentobarbital sodium-induced sleep test, determination of 5-HT and GABA levles in hypothalamic tissues and HE staining showed that ZSS extract was an effective treatment for insomnia. Network pharmacology analysis identified a total of 19 candidate bioactive ingredients in ZSS extract, along with 433 potentially related targets. Next, we performed protein-protein interaction (PPI), MCODE clustering analysis, GO functional enrichment analysis, KEGG pathway enrichment analysis, and ingredient-target-pathway (I-T-P) sub-networks analysis. These methods allowed us to investigate the synergistic therapeutic effects of crucial pathways, including the serotonergic and GABAergic synapse pathways. Our analyses revealed that palmitic acid, coclaurine, jujuboside A, N-nornuciferine, caaverine, magnoflorine, jujuboside B, and betulinic acid, all played key roles in the regulation of these crucial pathways. Finally, we used the PCPA-induced insomnia in rats to validate the data generated by network pharmacology; these in vivo experiments clearly showed that pathways associated with the serotonergic and GABAergic system were activated in the rats model. Furthermore, ZSS treatment significantly suppressed high levels of HTR1A, GABRA1, and GABRG2 expression in the hypothalamus and reduced the expression levels of HTR2A. Conclusion: Based on the combination of comprehensive network pharmacology and in vivo experiments, we successfully identified the potential pharmacological mechanisms underlying the action of ZSS in the treatment of insomnia. The results provide a theoretical basis for further development and utilization of ZSS, and also provide support for the development of innovative drugs for the treatment of insomnia.
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Affiliation(s)
- Zhenhua Bian
- College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China.,Department of Pharmacy, Wuxi TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Wuxi, China
| | - Wenming Zhang
- Department of Pharmacy, Wuxi TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Wuxi, China
| | - Jingyue Tang
- Department of Pharmacy, Wuxi TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Wuxi, China
| | - Qianqian Fei
- Department of Pharmacy, Wuxi TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Wuxi, China
| | - Minmin Hu
- Department of Pharmacy, Wuxi TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Wuxi, China
| | - Xiaowei Chen
- Department of Pharmacy, Wuxi TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Wuxi, China
| | - Lianlin Su
- College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Chenghao Fei
- College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - De Ji
- College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Chunqin Mao
- College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Huangjin Tong
- College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
| | - Xiaohang Yuan
- Department of Pharmacy, Wuxi TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Wuxi, China
| | - Tulin Lu
- College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, China
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