黄连防治鸭病毒性肠炎机制的网络药理学分析及动物试验验证

doi:10.11843/j.issn.0366-6964.2024.07.040

Abstract

Abstract:

To explore the mechanism of Coptidis Rhizoma treating duck viral enteritis (DVE), the active ingredients and targets of Coptidis Rhizoma were firstly screened by the Traditional Chinese Medicine System Pharmacology Analysis Platform (TCMSP), and the DVE related targets and their intersection targets with Coptidis Rhizoma were analyzed and drew using the GeneCards database and Venny and Cytoscape 3.7.2 software, which constructed a "drug component disease target" network. And the protein interaction network (PPI) were established by STRING databases and their GO function and KEGG pathway were analyzed with the DAVID database. Then, the results of network pharmacology were verified by animal experiments which narmol group, virus infection group and drug intervention group, and their tissue samples were collected for histopathological observation and related cytokine determination. The results showed that 14 active components and 212 action targets of Coptidis Rhizoma were selected, including 25 targets that intersect with DVE, involving biological processes such as RNA polymerase Ⅱ promoter transcription, sequence specific DNA binding transcription factor activity, immune response, inflammatory response, and cell apoptosis, enriched in signaling pathways such as Toll like receptor signaling, inflammatory bowel disease, cytokine-cytokine receptor interaction, and herpes simplex virus infection, the core targets are IL-6, IL-10, and STAT1. By animal experiments, there were the varting degrees of pathological damage in liver, spleen and duodenum in virus infection group ducks, and IL-6 content was significantly increased compared to the normal control group ducks (P≤0.05), while the IL-10 and STAT1 contents were significantly reduced (P≤0.05). However, the pathological damage was significantly reduced in drug intervention group ducks, the levels of IL-6, IL-10, and SYAT1 tended to normal levels. These results indicated that Coptidis can effectively alleviate the pathological damage of duck tissues caused by duck viral enteritis, and its mechanism may involves various inflammatory response signaling pathways.

Key words: Coptidis Rhizoma, network pharmacology, duck viral enteritis, mechanism

CLC Number:

S853.74

Anlin WEN, Yunyun YANG, Yongrong LUO, Ying YANG, Zhentao CHENG, Deyuan OU, Ming WEN. Network Pharmacologic Analysis and Experimential Verification on the Mechanism of Coptidis Rhizoma in Preventing Duck Viral Enteritis[J]. Acta Veterinaria et Zootechnica Sinica, 2024, 55(7): 3225-3233.

Figures/Tables 7

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References 19

1	DHAMA K , KUMAR N , SAMINATHAN M , et al. Duck virus enteritis (duck plague)-a comprehensive update[J]. Vet Q, 2017, 37 (1): 57- 80. doi: 10.1080/01652176.2017.1298885
2	ZHANG B , HUANG X J , YANG Y X , et al. Complete genome sequence of an isolate of duck enteritis virus from China[J]. Arch Virol, 2020, 165 (7): 1687- 1689. doi: 10.1007/s00705-020-04594-7
3	KONG J , FENG K Y , ZHAO Q Q , et al. Pathogenicity and transmissibility studies on live attenuated duck enteritis virus vaccine in non-target species[J]. Front Microbiol, 2022, 13, 979368. doi: 10.3389/fmicb.2022.979368
4	KUMAR J , DANDAPAT S , PANICKAN S , et al. Expression profiles of toll like receptors, MHC and cytokine genes along with viral load in organs of ducklings infected with an Indian isolate of duck enteritis virus[J]. Microb Pathol, 2022, 165, 105502. doi: 10.1016/j.micpath.2022.105502
5	LI Y F , HUANG B , MA X L , et al. Molecular characterization of the genome of duck enteritis virus[J]. Virology, 2009, 391 (2): 151- 161. doi: 10.1016/j.virol.2009.06.018
6	付琳, 付强, 李冀, 等. 黄连化学成分及药理作用研究进展[J]. 中医药学报, 2021, 49 (2): 87- 92.
	FU L , FU Q , LI J , et al. Research progress on chemical components and pharmacological effects of Coptis chinensis[J]. Acta Chinese Medicine and Pharmacology, 2021, 49 (2): 87- 92.
7	谢大泽, 湛学军, 舒向荣, 等. 黄连等中药对淋菌耐药菌株体外抗菌活性的研究[J]. 中华医院感染学杂志, 2016, 26 (10): 2193-2195, 2322.
	XIE D Z , ZHAN X J , SU X R , et al. In vitro antibacterial activity of traditional Chinese medicine such as Coptidis rhizome on drug-resistant Neisseria gonorrhoeae[J]. Chinese Journal of Nosocomiology, 2016, 26 (10): 2193-2195, 2322.
8	PARK S M , MIN B G , JUNG J Y , et al. Combination of Pelargonium sidoides and Coptis chinensis root inhibits nuclear factor kappa B-mediated inflammatory response in vitro and in vivo[J]. BMC Complement Altern Med, 2018, 18 (1): 20. doi: 10.1186/s12906-018-2088-x
9	张旭梅, 魏玉荣, 许丞惠, 等. 基于网络药理学和试验验证分析小檗碱治疗鸡沙门菌感染的作用机制[J]. 畜牧兽医学报, 2023, 54 (8): 3557- 3570.
	ZHANG X M , WEI Y R , XU C H , et al. To analyze the mechanism of berberine in the treatment of Salmonella Gallinarum infection based on network pharmacology and experimental verification[J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54 (8): 3557- 3570.
10	王小榛, 刘畅, 宋雪娇, 等. 基于网络药理学分析连翘治疗牛乳房炎的作用机制及体内验证[J]. 中国兽医学报, 2022, 42 (12): 2534- 2542.
	WANG X Z , LIU C , SONG X J , et al. Mechanism of Forsythiae fructus in the treatment of mastitis based on network pharmacology and in vivo pharmacological evaluation[J]. Chinese Journal of Veterinary Science, 2022, 42 (12): 2534- 2542.
11	郝江花, 孙娜, 孙盼盼, 等. 基于网络药理学和分子对接分析苦参碱抗PRRSV的作用机制[J]. 畜牧兽医学报, 2021, 52 (3): 809- 819.
	HAO J H , SUN N , SUN P P , et al. A study on mechanism of matrine against PRRSV based on network pharmacology and molecular docking[J]. Acta Veterinaria et Zootechnica Sinica, 2021, 52 (3): 809- 819.
12	杨霞. 鸭肠炎病毒感染鸭脾脏与肠道代谢组学分析[D]. 贵阳: 贵州大学, 2021.
	YANG X. Metabonomics analysis of duck spleen and intestinal tissues infected by duck enteritis virus[D]. Guiyang: Guizhou University, 2021. (in Chinese)
13	SHAWKY S . Target cells for duck enteritis virus in lymphoid organs[J]. Avian Pathol, 2000, 29 (6): 609- 616. doi: 10.1080/03079450020016869
14	MAYNARD C L , ELSON C O , HATTON R D , et al. Reciprocal interactions of the intestinal microbiota and immune system[J]. Nature, 2012, 489 (7415): 231- 241. doi: 10.1038/nature11551
15	周瑞, 项昌培, 张晶晶, 等. 黄连化学成分及小檗碱药理作用研究进展[J]. 中国中药杂志, 2020, 45 (19): 4561- 4573.
	ZHOU R , XIANG C P , ZHANG J J , et al. Research progress on chemical compositions of Coptidis Rhizoma and pharmacological effects of berberine[J]. China Journal of Chinese Materia Medica, 2020, 45 (19): 4561- 4573.
16	占今舜, 霍俊宏, 詹康, 等. 槲皮素对脂多糖刺激下山羊瘤胃上皮细胞抗氧化和抗炎的影响[J]. 草业科学, 2021, 38 (7): 1393- 1401.
	ZHAN J S , HUO J H , ZHAN K , et al. Effects of quercetin on antioxidant and anti-inflammatory properties of goat rumen epithelial cells stimulated with lipopolysaccharide[J]. Pratacultural Science, 2021, 38 (7): 1393- 1401.
17	张伟洁, 郑宏. IL-6介导免疫炎性反应作用及其与疾病关系的研究进展[J]. 细胞与分子免疫学杂志, 2017, 33 (5): 699- 703.
	ZHANG W J , ZHENG H . Research progress on IL-6 mediated immune inflammatory response and its relationship with diseases[J]. Chinese Journal of Cellular and Molecular Immunology, 2017, 33 (5): 699- 703.
18	郭紫晶, 陈飞, 张志雄, 等. 白细胞介素-10对口蹄疫病毒感染小鼠T细胞增殖及其表达TNF-α、IFN-γ和IL-2的影响[J]. 畜牧兽医学报, 2023, 54 (2): 694- 705.
	GUO Z J , CHEN F , ZHANG Z X , et al. Effects of interleukin-10 on T cell proliferation and its expression of TNF-α, IFN-γ and IL-2 in mice infected with foot-and-mouth disease virus[J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54 (2): 694- 705.
19	GUO W , HUANG J H , WANG N , et al. Integrating network pharmacology and pharmacological evaluation for deciphering the action mechanism of herbal formula Zuojin Pill in suppressing hepatocellular carcinoma[J]. Front Pharmacol, 2019, 10, 1185.

序号 No.	活性成分编号 Mol ID	分子名称 Molecule name	口服生物利用度/% Oral bioavailability	类药性 Drug like properties
1	MOL001458	黄连碱 Coptisine	30.67	0.86
2	MOL000762	掌叶大黄二蒽酮 A Palmidin A	35.36	0.65
3	MOL002894	小蘖红碱 Berberrubine	35.74	0.73
4	MOL002904	小檗浸碱 Berlambine	36.68	0.82
5	MOL001454	小檗碱 Berberine	36.86	0.78
6	MOL002897	表小檗碱 Epiberberine	43.09	0.78
7	MOL013352	奥巴叩酮 Obacunone	43.29	0.77
8	MOL002668	甲基黄连碱 Worenine	45.83	0.87
9	MOL000098	槲皮素 Quercetin	46.43	0.28
10	MOL002903	R-氢化小檗碱(R)-Canadine	55.37	0.77
11	MOL000622	广玉兰内酯 Magnograndiolide	63.71	0.19
12	MOL000785	巴马汀 Palmatine	64.60	0.65
13	MOL008647	穆坪马兜铃酰胺 Moupinamide	86.71	0.26
14	MOL002907	黄麻甙 A Corchoroside A_qt	104.95	0.78

样本名称 Samples	检测指标 Index	组别 Group
样本名称 Samples	检测指标 Index	正常对照组 Normal control group	病毒感染组 Virus infection group	黄连干预组 Drug intervention group
肝 Liver	IL-6	15.13±0.28	26.62±0.12^**	17.22±0.76
	IL-10	38.63±0.20	34.38±0.25	39.54±0.26
	STAT1	237.88±2.96	185.43±4.19^*	204.85±6.27
脾 Spleen	IL-6	15.87±0.41	18.22±0.44^*	16.28±0.35
	IL-10	55.31±0.64	53.11±3.65	57.23±2.81
	STAT1	225.17± 1.27	176.86±7.86^*	217.52±4.82
十二指肠 Duodenum	IL-6	3.92±0.15	10.91±0.12^**	4.79±0.50
	IL-10	45.48±0.06	43.94±0.50	47.44±0.94
	STAT1	176.02± 5.50	146.86±2.14^*	169.68±4.21

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Network Pharmacologic Analysis and Experimential Verification on the Mechanism of Coptidis Rhizoma in Preventing Duck Viral Enteritis

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