基于高脂血症斑马鱼模型和网络药理学探讨黄鳝肽抗高脂血症的作用机制

doi:10.3976/j.issn.1002-4026.20230120

Abstract

Abstract:

This study aimed to explore the material basis and mechanism of action of Monopterus albus peptides against hyperlipidemia using hyperlipidemic zebrafish model and network pharmacology. Analysis of the ameliorating effects of Monopterus albus peptides on hyperlipidemia was conducted by constructing a hyperlipidemic zebrafish model and measuring the dye staining signal intensity of triglyceride and cholesterol fluorescence intensity changes. Monopterus albus peptides and disease targets were filtered using BIOPEP-UWM, SwissTargetPrediction, GeneCards, STRING, and other databases. Target GO functional enrichment analysis and KEGG pathway enrichment analysis were performed using the DAVID bioinformatics software, and the Monopterus albus peptides-potential target-signaling pathway network and theprotein-protein interaction (PPI) network were constructed. The results showed that Monopterus albus peptides at mass concentrations of 62.5 μg/mL and 125.0 μg/mL significantly reduced the intensity of the triglyceride staining signal (p<0.01) and cholesterol fluorescence intensity (p<0.001) in the vasculature of hyperlipidemic zebrafish. The results of network pharmacology showed that there were 35 potentially active peptide sequences in Monopterus albus peptides, and 21 core targets were obtained by protein interaction analysis. GO and KEGG enrichment analyses indicated that Monopterus albus peptides were mainly involved in biological processes such asregulation of lipid metabolic processes, and exertan antihyperlipidemia effect viainflammation regulation, insulin resistance, and lipid and atherosclerosis channels. Initially, this study confirmed that Monopterus albus peptides have an antihyperlipidemia effect, and revealed that Monopterus albus peptides have multiple active peptide fragments, multiple targets, and multiple channels in the biological process of reducing blood lipid levels, which will provide a theoretical basis and reference for further in-depth research on the material basis of Monopterus albus peptides and their role and application in countering hyperlipidemia.

Key words: Monopterus albus peptides, hyperlipidemia, zebrafish, network pharmacology, mechanism of action

CLC Number:

R285

MA Shijing, HE Chunyan, GUAN Tianzhu, YAO Xueshuang, ZHANG Junpeng. Exploration of antihyperlipidemia mechanism of Monopterus albus peptides based on hyperlipidemic zebrafish model and network pharmacology[J].Shandong Science, 2024, 37(3): 27-38.

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References 21

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实验组	质量浓度/(μg·mL^-1)	死亡数/尾	死亡率/%	表型
正常对照组	未添加	0	0	未见明显异常
	62.5	0	0	与正常对照组状态相似
	125.0	0	0	与正常对照组状态相似
黄鳝肽	250.0	30	100	—
	500.0	30	100	—
	1 000.0	30	100	—

实验组	质量浓度/(μg·mL^-1)	尾部血管染色强度/像素	甘油三酯抑制率/%
正常对照组	未添加	459±39^***
模型对照组	未添加	13 464±814
阿伐他汀钙组	11.6	4 050±294^***	69.9
黄鳝肽低剂量组	31.2	11 732±399	12.9
黄鳝肽中剂量组	62.5	6 915±234^***	48.6
黄鳝肽高剂量组	125.0	7 351±374^***	45.4

实验组	质量浓度/(μg·mL^-1)	尾部血管胆固醇荧光强度/像素	胆固醇抑制率/%
正常对照组	未添加	15 640±946^***
模型对照组	未添加	47 552±3 555
阿伐他汀钙组	11.6	33 087±2 906^**	30.4
黄鳝肽低剂量组	31.2	35 188±2 935	26.0
黄鳝肽中剂量组	62.5	29 848±2 422^**	37.2
黄鳝肽高剂量组	125.0	28 914±2 370^**	39.2

肽段序列	肽活性评分	血脑屏障通透性	分子疏水常数	生物利用度评分
PGPLGPYFL	0.96	NO	-1.39	0.17
PGPM	0.95	NO	-0.77	0.55
FSAPGGGF	0.95	—	-2.91	0.17
PGPGMP	0.94	—	-1.60	0.17
PGPLGPM	0.93	—	-1.55	0.17
PGPGPM	0.93	—	-1.60	0.17
GPPVPGPLGP	0.93	—	-2.75	0.17
PDPGPGPM	0.93	—	-2.83	0.11
LPGPGACGKF	0.92	—	-3.51	0.17
PGPLGPL	0.92	—	-1.36	0.17
PDPGPGMP	0.92	—	-2.83	0.11
PGLPGPM	0.91	—	-1.55	0.17
PGPLGMP	0.91	—	-1.55	0.17
PGLPGACGKF	0.91	—	-3.51	0.17
GPPSGGFK	0.90	—	-3.60	0.17
PVPGLPGPM	0.90	—	-2.00	0.17
SSGPPVPGPL	0.88	—	-4.34	0.17
PGPLGPMT	0.88	—	-2.66	0.17
PGLPCGAGKF	0.87	—	-3.51	0.17
AGGPLGPR	0.86	—	-3.51	0.17
PVPGPM	0.85	—	-0.98	0.17
VPGLPGPM	0.85	—	-1.76	0.17
VPPGPM	0.85	—	-0.98	0.17
GPAPP	0.85	—	-1.29	0.55
GPGR	0.84	—	-2.42	0.17
WDPGPQ	0.84	—	-2.72	0.11
GPAGSFGPVGK	0.84	—	-5.12	0.17
PGGGFDL	0.84	—	-2.50	0.11
PGLPGP	0.84	—	-1.39	0.17
GPAGPHGPVG	0.83	—	-4.80	0.17
PAGPL	0.82	—	-1.06	0.55
SGPPAP	0.82	—	-2.55	0.17
GPAGGPAGSF	0.81	—	-4.71	0.17
GPVGPM	0.81	—	-1.60	0.17
GPAGPR	0.80	—	-2.88	0.17

核心靶点名称	中间度值	接近度值	节点度值	核心靶点名称	中间度值	接近度值	节点度值
TNF	1 094.86	0.009 3	54	DPP4	220.39	0.006 6	16
EGFR	444.02	0.008 1	40	CASP3	212.92	0.008 1	38
PPARA	385.85	0.007 2	25	PLG	196.49	0.007 2	27
ACE	336.95	0.007 7	32	FOS	176.27	0.007 7	33
REN	284.97	0.007 3	29	MMP2	139.78	0.007 5	32
F2	278.27	0.006 9	22	SERPINE1	139.33	0.007 4	28
APP	263.44	0.007 3	27	PIK3CA	120.40	0.006 4	23
CCND1	254.93	0.007 6	33	SIRT1	108.19	0.007 4	28
HSP90AA1	249.20	0.007 2	29	MAPK8	102.92	0.007 4	30
MMP9	232.55	0.008 3	41	PTGS2	93.59	0.007 7	34
PPARG	227.57	0.007 6	32

Exploration of antihyperlipidemia mechanism of Monopterus albus peptides based on hyperlipidemic zebrafish model and network pharmacology

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