Journal of Traditional Chinese Medicine ›› 2022, Vol. 42 ›› Issue (6): 956-964.DOI: 10.19852/j.cnki.jtcm.20220902.001
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Compound Gaoziban tablet (复方高滋斑片) alleviates depression via toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-kappa B pathway
ZOU Xinshuang1, SHI Lei1, YIN Hailong2, LI Haiping1, WANG Mengheng1, SONG Wanci1, LUO Laichun1, WU Hezhen1, YANG Yanfang1, ZAN Junfeng1, LIU Yanwen1, DAN Hanxiong1, YIN Qiang2(
), YOU Pengtao1()
- 1 Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, Hubei University of Chinese Medicine, Hubei 430065, China
2 Xinjiang Uygur Pharmaceutical Co., Ltd., Urumqi 830001, China
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Received:2021-10-14Accepted:2022-01-11Online:2022-12-15Published:2022-09-02 -
Contact:YIN Qiang,YOU Pengtao -
About author:YOU Pengtao, Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine, Hubei University of Chinese Medicine, Hubei 430065, China, tptyou@hbtcm.edu.cn,Telephone: +86-27-88920834
YIN Qiang, Xinjiang Uygur Pharmaceutical Co., Ltd., Urumqi 830001, China, yinqiang@renfu.com.cn;
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Supported by:Scientific Research Project of Education Department of Hubei Province: Synthesis and Anti-hepatocellular Carcinoma Effect of Novel NMT1 Inhibitors(D20192003)
Cite this article
ZOU Xinshuang, SHI Lei, YIN Hailong, LI Haiping, WANG Mengheng, SONG Wanci, LUO Laichun, WU Hezhen, YANG Yanfang, ZAN Junfeng, LIU Yanwen, DAN Hanxiong, YIN Qiang, YOU Pengtao. Compound Gaoziban tablet (复方高滋斑片) alleviates depression via toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-kappa B pathway[J]. Journal of Traditional Chinese Medicine, 2022, 42(6): 956-964.
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Figure 1 CGZBT reduced depressive-like behaviours in rats Schematic representation of the experimental procedure for CUMS in rat (A). Effects of CGZBT treatment on the sucrose consumption coefficient of rats at 0, 2, 4, and 6 weeks (B). Effects of CGZBT treatment on the movement traces of rats (C); Control group, Model group, 0.4 g/kg CGZBT group, 0.8 g/kg CGZBT group, 1.6 g/kg CGZBT group and Fluoxetine group (C1-C6, respectively). Effects of CGZBT treatment on distance of movement (D), distance through the center (E), and number of grid crossings (F) in the open field test. Effects of CGZBT treatment on immobility time in the forced swimming test after CUMS (G). The Control group was only treated with normal saline. The Model group was treated with normal saline after CUMS.CUMS consists of the following steps: food deprivation/water deprivation, cold swimming, cage shaking, electric foot shocks, tail clamp, light/dark reversal, and cage housing tilting. 0.4 g/kg CGZBT group, 0.8 g/kg CGZBT group, 1.6 g/kg CGZBT group and Fluoxetine group (3.69 mg/kg) were given the corresponding dose of drugs after CUMS for two weeks. CGZBT: compound Gaoziban tablet; CUMS: chronic unpredictable mild stress; FST: forced swimming test; OFT: open field test; SPT: sucrose preference test. Data are presented as mean ± standard deviation. aP < 0.01 vs Control group; bP < 0.01 vs Model group.
Figure 1 CGZBT reduced depressive-like behaviours in rats Schematic representation of the experimental procedure for CUMS in rat (A). Effects of CGZBT treatment on the sucrose consumption coefficient of rats at 0, 2, 4, and 6 weeks (B). Effects of CGZBT treatment on the movement traces of rats (C); Control group, Model group, 0.4 g/kg CGZBT group, 0.8 g/kg CGZBT group, 1.6 g/kg CGZBT group and Fluoxetine group (C1-C6, respectively). Effects of CGZBT treatment on distance of movement (D), distance through the center (E), and number of grid crossings (F) in the open field test. Effects of CGZBT treatment on immobility time in the forced swimming test after CUMS (G). The Control group was only treated with normal saline. The Model group was treated with normal saline after CUMS.CUMS consists of the following steps: food deprivation/water deprivation, cold swimming, cage shaking, electric foot shocks, tail clamp, light/dark reversal, and cage housing tilting. 0.4 g/kg CGZBT group, 0.8 g/kg CGZBT group, 1.6 g/kg CGZBT group and Fluoxetine group (3.69 mg/kg) were given the corresponding dose of drugs after CUMS for two weeks. CGZBT: compound Gaoziban tablet; CUMS: chronic unpredictable mild stress; FST: forced swimming test; OFT: open field test; SPT: sucrose preference test. Data are presented as mean ± standard deviation. aP < 0.01 vs Control group; bP < 0.01 vs Model group.
Figure 2 CGZBT restores the levels of neurotransmitters in the hippocampus A-E: levels of 5-HT (A), DA (B), NE (C) and 5-HIAA (D) in the hippocampus after CUMS measured by LC-MS. The Control group was only treated with normal saline. The Model group was treated with normal saline after CUMS. CUMS consists of the following steps: food deprivation/water deprivation, cold swimming, cage shaking, electric foot shocks, tail clamp, light/dark reversal, and cage housing tilting. 0.4 g/kg CGZBT group, 0.8 g/kg CGZBT group, 1.6 g/kg CGZBT group and Fluoxetine group (3.69 mg/kg) were given the corresponding dose of drugs after CUMS for two weeks. CGZBT: compound Gaoziban tablet; CUMS: chronic unpredictable mild stress; 5-HT: 5-hydroxytryptamine; DA: dopamine; NE: norepinephrine; 5-HIAA: 5-hydroxyindoleacetic acid. Data are presented as mean ± standard deviation. aP < 0.01 vs control group; bP < 0.01 vs Model group.
Figure 2 CGZBT restores the levels of neurotransmitters in the hippocampus A-E: levels of 5-HT (A), DA (B), NE (C) and 5-HIAA (D) in the hippocampus after CUMS measured by LC-MS. The Control group was only treated with normal saline. The Model group was treated with normal saline after CUMS. CUMS consists of the following steps: food deprivation/water deprivation, cold swimming, cage shaking, electric foot shocks, tail clamp, light/dark reversal, and cage housing tilting. 0.4 g/kg CGZBT group, 0.8 g/kg CGZBT group, 1.6 g/kg CGZBT group and Fluoxetine group (3.69 mg/kg) were given the corresponding dose of drugs after CUMS for two weeks. CGZBT: compound Gaoziban tablet; CUMS: chronic unpredictable mild stress; 5-HT: 5-hydroxytryptamine; DA: dopamine; NE: norepinephrine; 5-HIAA: 5-hydroxyindoleacetic acid. Data are presented as mean ± standard deviation. aP < 0.01 vs control group; bP < 0.01 vs Model group.
Figure 3 CGZBT reversed serum levels of inflammatory factors Levels of serum TNF-α (A); IL-1β (B); IL-6 (C); IL-4 (D); IL-10 (E) were quantified by ELISA. The Control group was only treated with normal saline. The Model group was treated with normal saline after CUMS. CUMS consists of the following steps: food deprivation/water deprivation, cold swimming, cage shaking, electric foot shocks, tail clamp, light/dark reversal, and cage housing tilting. 0.4 g/kg CGZBT group, 0.8 g/kg CGZBT group, 1.6 g/kg CGZBT group and Fluoxetine group (3.69 mg/kg) were given the corresponding dose of drugs after CUMS for two weeks. CGZBT: compound Gaoziban tablet; CUMS: chronic unpredictable mild stress; TNF-α: tumor necrosis factor-alpha; IL: interleukin; ELISA: enzyme-linked immunosorbent assay. Data are presented as mean ± standard deviation. aP < 0.01 vs Control group; bP < 0.01 vs Model group.
Figure 3 CGZBT reversed serum levels of inflammatory factors Levels of serum TNF-α (A); IL-1β (B); IL-6 (C); IL-4 (D); IL-10 (E) were quantified by ELISA. The Control group was only treated with normal saline. The Model group was treated with normal saline after CUMS. CUMS consists of the following steps: food deprivation/water deprivation, cold swimming, cage shaking, electric foot shocks, tail clamp, light/dark reversal, and cage housing tilting. 0.4 g/kg CGZBT group, 0.8 g/kg CGZBT group, 1.6 g/kg CGZBT group and Fluoxetine group (3.69 mg/kg) were given the corresponding dose of drugs after CUMS for two weeks. CGZBT: compound Gaoziban tablet; CUMS: chronic unpredictable mild stress; TNF-α: tumor necrosis factor-alpha; IL: interleukin; ELISA: enzyme-linked immunosorbent assay. Data are presented as mean ± standard deviation. aP < 0.01 vs Control group; bP < 0.01 vs Model group.
Figure 4 CGZBT alleviated depression via the TLR4/MyD88/NF-κB pathway A: the CA1 region we observed is shown in the black box; B: effects of CGZBT treatment on TLR4 (b1), MyD88 (b2), p-NF-κB (b3), COX-2 (b4) and IBA-1 (b5) in the hippocampus of rats by immunohistochemical staining (x 200 magnification; x 400 in the red box); C: Western blot analysis of TLR4, MyD88, and p-NF-κB proteins in the hippocampus; D: relative density of proteins. The Control group was only treated with normal saline. The Model group was treated with normal saline after CUMS. CUMS consists of the following steps: food deprivation/water deprivation, cold swimming, cage shaking, electric foot shocks, tail clamp, light/dark reversal, and cage housing tilting.0.4 g/kg CGZBT group, 0.8 g/kg CGZBT group, 1.6 g/kg CGZBT group and Fluoxetine group (3.69 mg/kg) were given the corresponding dose of drugs after CUMS for two weeks. DG: dentate gyrus; CGZBT: compound Gaoziban tablet; CUMS: chronic unpredictable mild stress; TLR4: toll-like receptor 4; MyD88: myeloid differentiation factor 88; p-NF-κB: phospho-nuclear factor-kappa B; COX-2: cyclooxygenase-2; IBA-1: ionized calcium binding adapter molecule-1. Data are presented as mean ± standard deviation. aP < 0.01 vs Control group; bP < 0.01 vs Model group.
Figure 4 CGZBT alleviated depression via the TLR4/MyD88/NF-κB pathway A: the CA1 region we observed is shown in the black box; B: effects of CGZBT treatment on TLR4 (b1), MyD88 (b2), p-NF-κB (b3), COX-2 (b4) and IBA-1 (b5) in the hippocampus of rats by immunohistochemical staining (x 200 magnification; x 400 in the red box); C: Western blot analysis of TLR4, MyD88, and p-NF-κB proteins in the hippocampus; D: relative density of proteins. The Control group was only treated with normal saline. The Model group was treated with normal saline after CUMS. CUMS consists of the following steps: food deprivation/water deprivation, cold swimming, cage shaking, electric foot shocks, tail clamp, light/dark reversal, and cage housing tilting.0.4 g/kg CGZBT group, 0.8 g/kg CGZBT group, 1.6 g/kg CGZBT group and Fluoxetine group (3.69 mg/kg) were given the corresponding dose of drugs after CUMS for two weeks. DG: dentate gyrus; CGZBT: compound Gaoziban tablet; CUMS: chronic unpredictable mild stress; TLR4: toll-like receptor 4; MyD88: myeloid differentiation factor 88; p-NF-κB: phospho-nuclear factor-kappa B; COX-2: cyclooxygenase-2; IBA-1: ionized calcium binding adapter molecule-1. Data are presented as mean ± standard deviation. aP < 0.01 vs Control group; bP < 0.01 vs Model group.
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