槐花通过抑制PI3K/AKT通路减轻炎症反应治疗银屑病

doi:10.12122/j.issn.1673-4254.2025.09.18

摘要/Abstract

摘要：

目的采用网络药理学、分子对接技术及实验验证，探讨槐花治疗银屑病的作用机制。方法通过TCMSP、GeneCards、OMIM、DisGeNET以及String数据库获得槐花活性成分、作用靶点以及银屑病相关疾病靶点，采用Cytoscape 3.8.0软件绘制“药物—有效成分—关键靶点—信号通路—疾病”网络图以及GO、KEGG通路富集分析；使用Discovery Studio 2019软件进行分子对接。体外实验采用咪喹莫特（IMQ）诱导的银屑病BALB/c小鼠模型，分为正常组、模型组、槐花高剂量组（3.00 g/kg）、中剂量组（1.50 g/kg）、低剂量组（0.75 g/kg）和阳性药组，6只/组。提前给药1周并于造模期间给药物干预。通过体质量变化、脾脏系数、银屑病皮损面积及严重程度指数（PASI）评分和皮肤病理变化进行效果评价；运用免疫组化和Western blotting技术检测p-PI3K、p-AKT蛋白水平。结果共筛选出10个活性成分和110个关键靶点，GO和KEGG通路富集分析显示槐花可能通过调控PI3K/AKT信号通路、TNF信号通路、IL-17信号通路等改善银屑病。分子对接结果显示，槲皮素和山奈酚均与AKT1、TNF等位点结合紧密。动物实验结果显示，槐花低剂量组小鼠体质量增加，PASI评分下降，改善银屑病病理症状（P<0.05），降低PI3K、AKT蛋白的磷酸化水平（P<0.05）。结论槐花能够通过多成分、多靶点、多通路治疗银屑病，其作用机制可能与下调p-PI3K、p-AKT蛋白的表达，进而影响PI3K/AKT信号通路有关。

关键词: 槐花, 银屑病, 网络药理学, 分子对接, PI3K/AKT信号通路

Abstract:

Objective To explore the therapeutic mechanism of Flos Sophorae (FS) for treatment of psoriasis. Methods The active ingredients, targets and psoriasis-related disease targets of FS were obtained from TCMSP, GeneCards, OMIM, DisGeNET and String databases, and Cytoscape 3.8.0 software was used to construct the "FS -active ingredient-key target-signaling pathway-psoriasis" network. GO and KEGG enrichment analyses of the key targets were conducted, and molecular docking was performed using Discovery Studio 2019. In a BALB/c mouse model of imiquimod-induced psoriasis, the effects of vaseline, FS at high, medium and low doses (3.00, 1.50 and 0.75 g/kg, respectively) and a positive drug, given 1 week before and during modeling, were evaluated on body weight changes, spleen coefficient, psoriasis area and severity index (PASI) score and skin pathological changes. Phosphorylation levels of PI3K and AKT proteins were detected using immunohistochemistry and Western blotting. Results A total of 10 active components and 110 key targets were screened. GO and KEGG pathway enrichment analysis suggested that FS improved psoriasis primarily through the PI3K/AKT, TNF, and IL-17 signaling pathways. Molecular docking showed that both quercetin and kaempferol could spontaneously bind to AKT1, TNF and other sites. In the mouse model of psoriasis, treatment with low-dose FS significantly improved epidermal thickening, increased body weight, lowered PASI score, and reduced phosphorylation levels of PI3K and AKT proteins. Conclusion The therapeutic mechanism of FS for psoriasis involves multiple components, targets, and pathways that mediate the inhibition of the phosphorylation levels of PI3K and AKT proteins to suppress the activation of the PI3K/AKT signaling pathway.

Key words: Flos Sophorae, psoriasis, network pharmacology, molecular docking, PI3K/AKT signaling pathway

饶璐, 丁家和, 魏江平, 阳勇, 张小梅, 王计瑞. 槐花通过抑制PI3K/AKT通路减轻炎症反应治疗银屑病[J]. 南方医科大学学报, 2025, 45(9): 1989-1996.

Lu RAO, Jiahe DING, Jiangping WEI, Yong YANG, Xiaomei ZHANG, Jirui WANG. Flos Sophorae improves psoriasis in mice by inhibiting the PI3K/AKT pathway[J]. Journal of Southern Medical University, 2025, 45(9): 1989-1996.

图/表 7

图1 槐花成分网络药理学分析

Fig.1 Network pharmacological analysis of the components of Flos Sophorae. A: PPI network diagram of the core targets of Flos Sophorae for treatment of psoriasis. B: Degree values of the targets in the PPI network. C: KEGG pathway enrichment analysis. D: GO enrichment analysis. E: Traditional Chinese Medicine-Active Ingredients-Key Targets-Signalling Pathways-Disease pathway network.

图2 槐花活性成分与蛋白分子的对接3D模型

Fig.2 3D modelling of docking of Flos Sophorae active ingredients with the protein molecules. A: Docking results of IL-6 with quercetin. B: Docking results of AKT1 with quercetin. C: Docking results of AKT1 with kaempferol. D: Docking results of TNF with quercetin. E: Docking results of TNF with kaempferol. F: Docking results of IL-1Β with quercetin. G: Docking results of TP53 with quercetin.

图3 槐花改善IMQ诱导的银屑病小鼠病症情况

Fig.3 Flos Sophorae ameliorates IMQ-induced psoriasis in mice. A: Schematic diagram of IMQ modeling in mice. B: Changes in body weight of the mice of each group. C: Morphological changes in the spleen. D: Spleen index. E: Morphological characteristics of dorsal skin lesions in each group on the 15th day of modelling. F: Skin PASI scores of the mice in each group. G: HE staining of the dorsal skin of the mice in each group (scale bar=100 μm). H: Skin thickness. ****P<0.05 vs Normal; ##P<0.01 vs Model group. The black arrow indicate the stratum corneum, and the blue arrow indicate the infiltrating inflammatory cells. FS-L/M/H: Flos Sophorae low/medium/high; QDCC: Qingdai compound capsule; MTX: Methotrexate.

表1 银屑病样小鼠PASI评分表

Tab.1 PASI scale for psoriasis-like mice

Score	Severity	Erythema	Epidermal flaking	Plaque thickness
0	Asymptomatic	None	None	Flush with normal skin
1	Mild symptom	Patch of pale red colour	Epidermal flaking	Slightly higher than normal skin
2	Moderate symptomatology	Red patch	Covered with flaky epidermal flakes	Moderate bulge
3	Severe symptoms	Dark red patches	Thick, stratified epidermal flakes	Bulge
4	Extremely severe symptoms	Very dark red patches	There is thick, stratified epidermal flaking	Marked thickening of the bulge

表2 槐花中有效成分信息

Tab.2 General information of active ingredients of Flos Sophorae

Mol ID	Compound	OB (%)	DL
MOL000131	Linoleic acid (EIC)	41.90	0.14
MOL000354	isorhamnetin	49.60	0.31
MOL000357	Sitogluside	20.63	0.62
MOL000358	beta-sitosterol	36.91	0.75
MOL000422	kaempferol	41.88	0.24
MOL000432	linolenic acid	45.01	0.15
MOL005935	N-[6-(9-acridinylamino) hexyl]benzamide	41.70	0.78
MOL005940	quercetin-3'-methyl ether	46.44	0.3
MOL000098	quercetin	46.43	0.28
MOL000415	rutin	3.20153	-

表3 靶点的筛选及对接结果

Tab.3 Target screening and docking results

Gene	Uniprot ID	PDB	Refinement resolution	Docking molecule	CDOCKER-ENERGY
IL-6	P05231	1ALU	1.9A	quercetin	35.587 4
AKT1	P31749	1UNQ	0.98A	quercetin	51.894 3
AKT1	P31749	1UNQ	0.98A	kaempferol	68.900 4
TNF	P01375	5UUI	1.4A	quercetin	26.816 3
TNF	P01375	5UUI	1.4A	kaempferol	34.701 2
IL-1β	P01584	5R8Q	1.23A	quercetin	47.096 9
TP53	P04637	5MHC	1.2A	quercetin	59.838 6

图4 银屑病小鼠皮肤组织PI3K/AKT的表达

Fig.4 Expression of PI3K and AKT in the skin tissue of psoriasis mice. A: results of immunohistochemistry (×20). B, C: AOD diagram. D, F: Results of Western blotting for p-PI3K, PI3K, p-AKT, and AKT. E, G: Quantitative analysis of the protein expressions. **P<0.01, ****P<0.0001 vs Normal; #P<0.05, ##P<0.01, ###P<0.001, ####P<0.0001 vs Model.

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