Journal of Traditional Chinese Medicine ›› 2023, Vol. 43 ›› Issue (5): 1001-1009.DOI: 10.19852/j.cnki.jtcm.20230802.001
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Mechanism of Lingbao Huxin Dan (灵宝护心丹) in the treatment of bradyarrhythmia complicated with coronary heart disease: a network pharmacology analysis
HAN Huagang1, LI Ziqiang2, OUYANG Jingfeng3(
), WANG Tianquan4, DONG Lingyan5, CAO Junling5()
- 1 Department of Traditional Chinese Medicine, Nanyang Medical College, Nanyang 473061, China
2 Oncology Department, Luoyang Hospital of traditional Chinese Medicine, Luoyang 471099, China
3 Morphology Laboratory, Expeimental Research Center, Research and Development Service Base, Beijing Key Laboratory of Research of Chinese Medicine on Prevention and Treatment for Major Diseases, China Academy of Chinese Medical Sciences, Beijing 100700, China
4 Pharmaceutical Department, Dongfang Hospital of Beijing University of Traditional Chinese Medicine, Beijing 100078, China
5 Pharmaceutical Department, Dongzhimen Hospital of Beijing University of Traditional Chinese Medicine, Beijing 100700, China
-
Received:2022-09-12Accepted:2022-12-22Online:2023-10-15Published:2023-08-02 -
Contact:Prof. CAO Junling, Pharmaceutical Department, Dongzhimen Hospital of Beijing University of Traditional Chinese Medicine, Beijing 100078, China.Caojunling72@163.com ; Prof. OUYANG Jingfeng, Morphology Laboratory, Expeimental Research Center, Research and Development Service Base, Beijing Key Laboratory of Research of Chinese Medicine on Prevention and Treatment for Major Diseases, China Academy of Chinese Medical Sciences, Beijing 100700, China.springeltics@163.com . Telephone: +86-10-84013158; +86-10-84015352 -
Supported by:Training Project of National Administration of Traditional Chinese Medicine “Natural Training Project of Backbone of Traditional Chinese Medicine” (SATCM)(2019-128);Fundamental Research Funds for the Central Public Welfare Research Institutes: the Application of Panoramic Tissue Scanning and Quantitative Analysis Systems in the Research of Traditional Chinese Medicine for Disease Prevention and Treatment”(JBGS2021005)
Cite this article
HAN Huagang, LI Ziqiang, OUYANG Jingfeng, WANG Tianquan, DONG Lingyan, CAO Junling. Mechanism of Lingbao Huxin Dan (灵宝护心丹) in the treatment of bradyarrhythmia complicated with coronary heart disease: a network pharmacology analysis[J]. Journal of Traditional Chinese Medicine, 2023, 43(5): 1001-1009.
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Figure 1 Wayne diagram of drugs- diseases -targets and construction of PPI network of common targets A: Wayne diagram of drugs- diseases -targets. The total number of merged and unduplicated targets was 6823. The intersected BA targets (n = 48), CHD targets (n = 6823), and Lingbao Huxin Dan targets (n = 899). A total of 39 targets of BA-CHD were obtained, and 14 core targets were identified when the Lingbao Huxin Dan and BA-CHD were intersected. B: Construction of PPI network of common targets. The area and color of the point represent that point's degree value. The thickness and color of the line represent the closeness between the two points. ACE: angiotensin-converting enzyme; KCNQ1: potassium voltage-gated channel subfamily Q member 1; ADRB1: adrenergic receptor beta-1; CACNA1C: protein tyrosine phosphatase; PTPN11: non-receptor type 11; NOS2: nitric oxide synthase 2; ADRB2: beta-2 adrenergic receptor; RAF1: the proto-oncogene serine/threonine-protein kinase; ABCC9: ATP-binding cassette: sub-family C: member 9; CACNA2D1: voltage-dependent calcium channel subunit alpha-2/delta-1; CYP3A4: cytochrome P450 3A4; ADRA1A: adrenergic receptor alpha-1α; ADRA1B: adrenergic receptor alpha-1β. CHD: coronary heart disease; BA: bradyrhythmia; LBHXD: Lingbao Huxin Dan.
Figure 1 Wayne diagram of drugs- diseases -targets and construction of PPI network of common targets A: Wayne diagram of drugs- diseases -targets. The total number of merged and unduplicated targets was 6823. The intersected BA targets (n = 48), CHD targets (n = 6823), and Lingbao Huxin Dan targets (n = 899). A total of 39 targets of BA-CHD were obtained, and 14 core targets were identified when the Lingbao Huxin Dan and BA-CHD were intersected. B: Construction of PPI network of common targets. The area and color of the point represent that point's degree value. The thickness and color of the line represent the closeness between the two points. ACE: angiotensin-converting enzyme; KCNQ1: potassium voltage-gated channel subfamily Q member 1; ADRB1: adrenergic receptor beta-1; CACNA1C: protein tyrosine phosphatase; PTPN11: non-receptor type 11; NOS2: nitric oxide synthase 2; ADRB2: beta-2 adrenergic receptor; RAF1: the proto-oncogene serine/threonine-protein kinase; ABCC9: ATP-binding cassette: sub-family C: member 9; CACNA2D1: voltage-dependent calcium channel subunit alpha-2/delta-1; CYP3A4: cytochrome P450 3A4; ADRA1A: adrenergic receptor alpha-1α; ADRA1B: adrenergic receptor alpha-1β. CHD: coronary heart disease; BA: bradyrhythmia; LBHXD: Lingbao Huxin Dan.
Figure 2 GO analysis bar chart GO analysis showed that biological processes were primarily related to regulating system processes, blood circulation, circulatory system processes, etc, the cell ingredients were involved in the cation channel complex, ion channel complex, transmembrane transporter complex, transporter complex, etc. and the main molecular functions were related to adrenergic receptor activity, G protein-coupled amine receptor activity, voltage-gated cation channel activity, voltage-gated ion channel activity, etc. GO: gene ontology. BP: biological process; CC: cellular component; MF: molecular function.
Figure 2 GO analysis bar chart GO analysis showed that biological processes were primarily related to regulating system processes, blood circulation, circulatory system processes, etc, the cell ingredients were involved in the cation channel complex, ion channel complex, transmembrane transporter complex, transporter complex, etc. and the main molecular functions were related to adrenergic receptor activity, G protein-coupled amine receptor activity, voltage-gated cation channel activity, voltage-gated ion channel activity, etc. GO: gene ontology. BP: biological process; CC: cellular component; MF: molecular function.
Figure 3 KEGG bubble enrichment diagram and drug-ingredient-target-pathway network A: the KEGG bubble enrichment diagram. More enriched genes were represented as a larger bubble, and smaller P values were redder in color, and smaller P values were redder in color. B: drug-ingredient-target-pathway network. DS (Danshen), Salvia Miltiorrhizae Radix Et Rhizoma; SX (Shexiang), Moschus; NH (Niuhuang), Bovis Calculus; Chansu (CS), Bufonis Venenum; SQ (Sanqi), Notoginseng Radix Et Rhizoma; HS (Hongshen), Ginseng Radix Et Rhizoma. KEGG: Kyoto Encyclopedia of Genes and Genomes; MAPK: mitogen-activated protein kinase; ADRB1: adrenergic receptor beta-1; ACE: angiotensin-converting enzyme; RAF1: Raf-1 proto-oncogene serine/threonine-protein kinase; ADRA1: alpha-1 adrenergic receptor; CACNA2D1: voltage-dependent calcium channel subunit alpha-2/delta-1; KCNQ1: potassium voltage-gated channel subfamily Q member 1; CACNA1C: calcium voltage-gated channel subunit alpha1 C; NOS2: nitric oxide synthase 2; CGMP-PKG: PLAT: Plant; cyclic guanosine 3': 5'-monophosphate- protein kinase G. KEGG: Kyoto Encyclopedia of Genes and Genomes.
Figure 3 KEGG bubble enrichment diagram and drug-ingredient-target-pathway network A: the KEGG bubble enrichment diagram. More enriched genes were represented as a larger bubble, and smaller P values were redder in color, and smaller P values were redder in color. B: drug-ingredient-target-pathway network. DS (Danshen), Salvia Miltiorrhizae Radix Et Rhizoma; SX (Shexiang), Moschus; NH (Niuhuang), Bovis Calculus; Chansu (CS), Bufonis Venenum; SQ (Sanqi), Notoginseng Radix Et Rhizoma; HS (Hongshen), Ginseng Radix Et Rhizoma. KEGG: Kyoto Encyclopedia of Genes and Genomes; MAPK: mitogen-activated protein kinase; ADRB1: adrenergic receptor beta-1; ACE: angiotensin-converting enzyme; RAF1: Raf-1 proto-oncogene serine/threonine-protein kinase; ADRA1: alpha-1 adrenergic receptor; CACNA2D1: voltage-dependent calcium channel subunit alpha-2/delta-1; KCNQ1: potassium voltage-gated channel subfamily Q member 1; CACNA1C: calcium voltage-gated channel subunit alpha1 C; NOS2: nitric oxide synthase 2; CGMP-PKG: PLAT: Plant; cyclic guanosine 3': 5'-monophosphate- protein kinase G. KEGG: Kyoto Encyclopedia of Genes and Genomes.
Figure 4 Immunohistochemical staining of myocardium of each group (magnification, ×200) For immunohistochemical staining, tissues were embedded in paraffin wax, cut into 5 μm-thick sections and mounted on glass slides. Endogenous peroxidase and non-specific binding were both blocked. Subsequently, sections were incubated overnight with primary antibodies (ADRB1, ADRA1A and CACNA1C) at 4 ℃. After rinsing, sections were incubated with the relevant secondary antibodies for 1 h at room temperature. Sections were then rinsed with PBS and color was developed with DAB kits. Sections were examined under a microscope. A, D, G: control group; B, E, H: model group; C, F, I: Lingbao Huxin Dan group. The control and model group were administered with equal amounts of distilled water, while Lingbao Huxin Dan group was administered with Lingbao Huxin Dan group (5 g/mL). Line 1 (A, B and C), Line 2 (D, E and F) and Line 3 (G, H and I) were immunohistochemically stained with primary antibody of ADRB1, ADRA1A and CACNA1C, respectively. ADRB1: adrenergic receptor beta-1; ADRA1A: adrenergic receptor alpha-1α; CACNA1C: protein tyrosine phosphatase.
Figure 4 Immunohistochemical staining of myocardium of each group (magnification, ×200) For immunohistochemical staining, tissues were embedded in paraffin wax, cut into 5 μm-thick sections and mounted on glass slides. Endogenous peroxidase and non-specific binding were both blocked. Subsequently, sections were incubated overnight with primary antibodies (ADRB1, ADRA1A and CACNA1C) at 4 ℃. After rinsing, sections were incubated with the relevant secondary antibodies for 1 h at room temperature. Sections were then rinsed with PBS and color was developed with DAB kits. Sections were examined under a microscope. A, D, G: control group; B, E, H: model group; C, F, I: Lingbao Huxin Dan group. The control and model group were administered with equal amounts of distilled water, while Lingbao Huxin Dan group was administered with Lingbao Huxin Dan group (5 g/mL). Line 1 (A, B and C), Line 2 (D, E and F) and Line 3 (G, H and I) were immunohistochemically stained with primary antibody of ADRB1, ADRA1A and CACNA1C, respectively. ADRB1: adrenergic receptor beta-1; ADRA1A: adrenergic receptor alpha-1α; CACNA1C: protein tyrosine phosphatase.
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