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Sleep-improving mechanisms of Jiu Wei Bu Xue Oral Liquid on regulating Glu/GABA balance in insomnia rats based on network pharmacology and experimental verification
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Jie WEI1, Xiao-dong LAN2, Dong-mei LI1, Jun-hui HE3, Zhen MENG2, Dong-mei WEI1, Yi LI1, Fu-quan PENG2, Gui-ning WEI1, Ruo-gan HUANG2, *
Acta Pharmaceutica Sinica | 2023, 58(6) : 1484 - 1495
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Acta Pharmaceutica Sinica | 2023, 58(6): 1484-1495
Special Reports: Research on Modernization of Traditional Chinese Medicine Based on Integrative Pharmacology
Sleep-improving mechanisms of Jiu Wei Bu Xue Oral Liquid on regulating Glu/GABA balance in insomnia rats based on network pharmacology and experimental verification
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Jie WEI1, Xiao-dong LAN2, Dong-mei LI1, Jun-hui HE3, Zhen MENG2, Dong-mei WEI1, Yi LI1, Fu-quan PENG2, Gui-ning WEI1, Ruo-gan HUANG2, *
Affiliations
  • 1. Guangxi Institute of Chinese Medicine and Pharmaceutical Science, Nanning 530022, China
  • 2. Guangxi Baiyunshan Yingkang Pharmaceutical Co., Ltd., Nanning 530002, China
  • 3. Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards, Nanning 530022, China
Published: 2023-06-12 doi: 10.16438/j.0513-4870.2022-0878
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This study aimed to investigate the mechanism of Jiu Wei Bu Xue Oral Liquid on insomnia rats combining the methods of network pharmacology, molecular docking and experimental verification. UPLC-Q-TOF-MS/MS method and TCMIP, TCMSP databases were used to collect the ingredients and targets of Jiu Wei Bu Xue Oral Liquid. Protein-protein interactions and network analysis were performed to screen the key network targets and putative active ingredients of Jiu Wei Bu Xue Oral Liquid in treatment of insomnia, and then following by biological function and KEGG pathway analysis. Then binding ability for key network targets and putative active ingredients were predicted with molecular docking. The prediction targets were validated in para-chlorophenylalanine (PCPA) induced insomnia rats with administration of Jiu Wei Bu Xue Oral Liquid (2, 4, 8 mL·kg-1) for 7 days. Pentobarbital sodium induced sleeping test were performed to evaluate the synergistic sleep-aiding effect of Jiu Wei Bu Xue Oral Liquid. Then glutamic acid (Glu), γ-aminobutyrate (GABA) content and glutamate decarboxylase 1 (GAD67) activity in hypothalamus or hippocampus were evaluated, and the expressions of GAD67, γ-aminobutyric acid receptor subunit α1 (GABRA1) and γ-aminobutyric acid receptor subunit β2 (GABRB2) in hippocampus were detected by qRT-PCR and Western blot methods. Animal experiments were approved by the Institutional Committee on Animal Care of Guangxi Institute of Chinese Medicine & Pharmaceutical Science (the number of permission: 2022060802). Results showed that 16 key network targets and 16 putative active ingredients were obtained by analyzing the herbs-ingredients-targets network of Jiu Wei Bu Xue Oral Liquid in treatment of insomnia. Network pharmacology and molecular docking all indicated these active ingredients, for example atractylenolide Ⅲ, showed better binding ability with GABRA1 and GABRB2. Animal study indicated that, compared to PCPA-induced insomnia model, Jiu Wei Bu Xue Oral Liquid remarkably shortened the sleeping latency and increased the sleeping duration, increased GAD67 activity and the production of GABA in hippocampus of insomnia rats, as well as the expressions of GAD67, GABRA1 and GABRB2, while decreased Glu content in hypothalamus, leading to decreasing of Glu/GABA ratio and recovery of Glu-GABA balance. These results indicated that Jiu Wei Bu Xue Oral Liquid improved insomnia symptoms and helped maintain the Glu-GABA balance within hypothalamus and hippocampus, and reduced the excitatory neurotoxicity within brain. The mechanism may due to the elevation of GAD67 expression and enzyme activity, and the enhancement of type-A GABA receptor (GABAAR)-mediated neurons inhibition.

Jiu Wei Bu Xue Oral Liquid  /  insomnia  /  para-chlorophenylalanine  /  pentobarbital sodium  /  network pharmacology  /  molecular docking  /  γ-aminobutyrate
Jie WEI, Xiao-dong LAN, Dong-mei LI, Jun-hui HE, Zhen MENG, Dong-mei WEI, Yi LI, Fu-quan PENG, Gui-ning WEI, Ruo-gan HUANG. Sleep-improving mechanisms of Jiu Wei Bu Xue Oral Liquid on regulating Glu/GABA balance in insomnia rats based on network pharmacology and experimental verification[J]. Acta Pharmaceutica Sinica, 2023 , 58 (6) : 1484 -1495 . DOI: 10.16438/j.0513-4870.2022-0878
Year 2023 volume 58 Issue 6
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Article Info
doi: 10.16438/j.0513-4870.2022-0878
  • Receive Date:2022-07-18
  • Online Date:2025-11-21
  • Published:2023-06-12
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History
  • Received:2022-07-18
  • Revised:2022-09-06
Funding
Affiliations
    1. Guangxi Institute of Chinese Medicine and Pharmaceutical Science, Nanning 530022, China
    2. Guangxi Baiyunshan Yingkang Pharmaceutical Co., Ltd., Nanning 530002, China
    3. Guangxi Key Laboratory of Traditional Chinese Medicine Quality Standards, Nanning 530022, China
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表12种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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