生理病理状态下荭草活性物质对转运体表达的影响

doi:10.3976/j.issn.1002-4026.2025089

山东科学 ›› 2026, Vol. 39 ›› Issue (5): 9-20.doi: 10.3976/j.issn.1002-4026.2025089

生理病理状态下荭草活性物质对转运体表达的影响

罗秋芸^1a^,^1b^,²(), 孙佳^1a, 刘东辉^1a^,^1b, 李勇军^1a, 薛维娜^1a^,^1b^,^1c^,^*()

¹ 贵州医科大学 a.药学院中药功效成分发掘与利用全国重点实验室;b.贵州省现代中药创制全省重点实验室民族药与中药开发应用教育部工程研究中心;c.医药卫生管理学院, 贵州贵安新区 561113
² 贵州省第三人民医院药剂科, 贵州贵阳 550008

收稿日期:2025-08-29 修回日期:2025-11-05 出版日期:2026-10-20 上线日期:2026-04-30
通信作者: *薛维娜,女,副教授,硕士生导师,研究方向为药理学。E-mail: xwn824@126.com
作者简介:罗秋芸(1988—),女,硕士研究生,研究方向为药理学。E-mail:luoqiuyun817@163.com
基金资助:
贵州省科技重大专项项目(黔科合重大专项字[2024]015);贵州省现代中药创制全省重点实验室(黔科合平台ZSYS[2025]019)

Effects of active constituents from Polygonum orientale L. on the expression of transporters under physiological and pathological conditions

LUO Qiuyun^1a^,^1b^,²(), SUN Jia^1a, LIU Donghui^1a^,^1b, LI Yongjun^1a, XUE Weina^1a^,^1b^,^1c^,^*()

¹ a. State Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmacy;b. Guizhou Provincial Key Laboratory of Modern Traditional Chinese Medicine Creation, Engineering Research Center for Development and Application of Ethnic Medicine and Traditional Chinese Medicine (Ministry of Education); c. School of Pharmaceutical and Health Administration,Guizhou Medical University, Gui'an New Area 561113, China
² Department of Pharmacy, The Third People’s Hospital of Guizhou Province, Guiyang 550008, China

Received:2025-08-29 Revised:2025-11-05 Published:2026-10-20 Online:2026-04-30

摘要/Abstract

摘要：

荭草具有明确的抗心肌缺血作用,且其活性成分在生理和病理状态下的代谢过程存在显著差异,鉴于转运体在心肌缺血病理过程和外源物代谢中的作用,本研究拟探讨荭草活性物质在生理及病理状态下对大鼠肝脏转运体表达的影响。采用网络药理学筛选心肌缺血相关靶点,利用蛋白质相互作用(PPI)分析、基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析,结合文献调研,筛选与心肌缺血相关的肝脏转运体及通路;运用分子对接技术预测荭草活性成分与转运体调控蛋白的结合;并建立大鼠心肌缺血模型,采用实时荧光定量逆转录聚合酶链反应(qRT-PCR)和蛋白免疫印迹法(Western blot)检测荭草提取物对肝脏转运体表达的影响。结果显示,网络药理学分析发现428个心肌缺血与转运蛋白的共同靶基因;PPI分析筛选出36个节点,GO和KEGG分析表明这些靶点显著富集于炎症反应、ABC转运蛋白及PPAR信号通路等,结合文献调研,发现BCRP、MRP、P-gp等7个肝脏转运体与心肌缺血相关;分子对接提示荭草活性成分与转运体上游调控蛋白具有较高亲和力。动物实验表明,在正常大鼠中荭草提取物可上调MRP1、MRP2、OATP2、OCT1、OCT2和P-gp的表达,而在心肌缺血模型大鼠中则下调BCRP、MRP2、OATP2、OCT1、OCT2和P-gp的蛋白表达。结果表明,在生理病理状态下,荭草活性成分具有调控肝脏转运体的能力,其机制可能与活性成分结合肝脏转运体上游调控蛋白有关。

关键词: 荭草, 心肌缺血, 转运体, 网络药理学, 分子对接, 实时荧光定量逆转录聚合酶链反应, 蛋白免疫印迹法

Abstract:

Polygonum orientale L. has an anti-myocardial ischemia effect, and the metabolic processes of its active constituents exhibits considerable differences under physiological and pathological conditions. Considering the role of transporters in the pathological process of myocardial ischemia and the metabolism of xenobiotics, this study aims to investigate the effects of the active constituents in Polygonum orientale L. on the expressions of liver transporters in rats under physiological and pathological conditions.Network pharmacology was used to screen myocardial ischemia-related targets, followed by protein-protein interaction (PPI) analysis, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Based on a literature review, hepatic transporters and pathways related to myocardial ischemia were identified. Morever, molecular docking was used to predict the binding affinity between the active constituents of Polygonum orientale L. and regulatory proteins of transporters. A rat model of myocardial ischemia was established, and the effects of Polygonum orientale L. extract on the expressions of hepatic transporters were detected using quantitative real-time PCR (qRT-PCR) and western blot. Results revealed that network pharmacology analysis identified 428 common target genes associated with myocardial ischemia and transport proteins. PPI analysis yielded 36 key nodes, and GO and KEGG analyses revealed substantial enrichment of these targets in inflammatory responses, ABC transporters, PPAR signaling pathway, among others. Based on the literature review, seven hepatic transporters, including BCRP, MRP, and P-gp, were observed to be associated with myocardial ischemia. Molecular docking suggested high binding affinity between active constituents of Polygonum orientale L. and upstream regulatory proteins of transporters. Furthermore, animal experiments revealed that Polygonum orientale L. extract upregulated the expressions of MRP1, MRP2, OATP2, OCT1, OCT2, and P-gp in normal rats, and downregulated the protein expressions of BCRP, MRP2, OATP2, OCT1, OCT2, and P-gp in rats with myocardial ischemia. These results indicate that the active constituents of Polygonum orientale L. can regulate hepatic transporters under physiological and pathological conditions, and their mechanism may be related to their binding to upstream regulatory proteins of hepatic transporters.

Key words: Polygonum orientale L., myocardial ischemia, transporters, network pharmacology, molecular docking, qRT-PCR, Western blot

中图分类号:

罗秋芸, 孙佳, 刘东辉, 李勇军, 薛维娜. 生理病理状态下荭草活性物质对转运体表达的影响[J]. 山东科学, 2026, 39(5): 9-20.

LUO Qiuyun, SUN Jia, LIU Donghui, LI Yongjun, XUE Weina. Effects of active constituents from Polygonum orientale L. on the expression of transporters under physiological and pathological conditions[J]. Shandong Science, 2026, 39(5): 9-20.

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参考文献 31

[1]	王皎. 室性期前收缩性心肌病诊疗进展[J]. 心血管病学进展, 2020, 41(6): 563-566. DOI:10.16806/j.cnki.issn.1004-3934.2020.06.001.
[2]	Sagris M, Apostolos A, Theofilis P, et al. Myocardial ischemia-reperfusion injury: Unraveling pathophysiology, clinical manifestations, and emerging prevention strategies[J]. Biomedicines, 2024, 12(4): 802. DOI:10.3390/biomedicines12040802.
[3]	Duan Xuewen, Hu Meiling, Yang Linshan, et al. IRG1 prevents excessive inflammatory responses and cardiac dysfunction after myocardial injury[J]. Biochemical Pharmacology, 2023, 213: 115614. DOI:10.1016/j.bcp.2023.115614.
[4]	Bhatt A S, Ambrosy A P, Velazquez E J. Adverse remodeling and reverse remodeling after myocardial infarction[J]. Current Cardiology Reports, 2017, 19(8): 71. DOI:10.1007/s11886-017-0876-4.
[5]	贵州省药品监督管理局. 贵州省中药材、民族药材质量标准[S]. 贵阳: 贵州科学技术出版社, 2003.
[6]	Liu Chunhua, He Yu, Wang Mingjin, et al. Regulation of the SIRT3/SOD2 signaling pathway by a compound mixture from Polygonum orientale L. for myocardial damage[J]. Pharmaceuticals, 2024, 17(10): 1288. DOI:10.3390/ph17101288.
[7]	Fu Changli, Wang Mingjin, Lu Yuan, et al. Polygonum orientale L. alleviates myocardial ischemia-induced injury via activation of MAPK/ERK signaling pathway[J]. Molecules, 2023, 28(9): 3687. DOI:10.3390/molecules28093687.
[8]	刘春花, 王明金, 杨淑婷, 等. 基于外翻肠囊模型研究荭草提取物在正常和心肌缺血模型大鼠中的肠吸收特征[J]. 中国中药杂志, 2021, 46(1): 196-205. DOI:10.19540/j.cnki.cjcmm.20201010.201.
[9]	陆苑, 黎娜, 刘春花, 等. 基于在体肠袢模型研究荭草活性成分在正常及心肌缺血模型大鼠的肠吸收特性[J]. 中国药理学通报, 2020, 36(8): 1146-1151. DOI:10.3969/j.issn.1001-1978.2020.08.021.
[10]	Lu Yuan, Li Na, Zhu Xiaoqin, et al. Comparative analysis of excretion of six major compounds of Polygonum orientale L. extract in urine, feces and bile under physiological and myocardial ischemia conditions in rats using UPLC-MS/MS[J]. Biomedical Chromatography, 2021, 35(10): e5174. DOI:10.1002/bmc.5174.
[11]	Du Bingxin, Fu Qiang, Yang Qin, et al. Different types of cell death and their interactions in myocardial ischemia-reperfusion injury[J]. Cell Death Discovery, 2025, 11: 87. DOI:10.1038/s41420-025-02372-5.
[12]	Schumacher T, Benndorf R A. ABC transport proteins in cardiovascular disease-a brief summary[J]. Molecules, 2017, 22(4): 589. DOI:10.3390/molecules22040589.
[13]	Tiriticco V, Codotto G, Blarasin B, et al. Rat liver perfusion and primary hepatocytes isolation: An old procedure crucial for cutting-edge 3D organoids culture[J]. Journal of Visualized Experiments, 2024(213):e66857. DOI:10.3791/66857.
[14]	Morris M E, Rodriguez-Cruz V, Felmlee M A. SLC and ABC transporters: Expression, localization, and species differences at the blood-brain and the blood-cerebrospinal fluid barriers[J]. The AAPS Journal, 2017, 19(5): 1317-1331. DOI:10.1208/s12248-017-0110-8.
[15]	Meissner K, Heydrich B, Jedlitschky G, et al. The ATP-binding cassette transporter ABCG2 (BCRP), a marker for side population stem cells, is expressed in human heart[J]. Journal of Histochemistry & Cytochemistry, 2006, 54(2): 215-221. DOI:10.1369/jhc.5a6750.2005.
[16]	陆苑, 黎娜, 吕婷, 等. UPLC-MS/MS研究荭草提取物的H9c2细胞药代动力学[J]. 中国中药杂志, 2021, 46(18): 4833-4840. DOI:10.19540/j.cnki.cjcmm.20210618.202.
[17]	王明金, 刘春花, 孙佳, 等. UHPLC-PDA法同时测定荭草药材中不同类型化学成分的含量[J]. 中药材, 2022, 45(2): 392-396. DOI:10.13863/j.issn1001-4454.2022.02.023.
[18]	Yang Jianxin, Bai Xue, Liu Guiqin, et al. A transcriptional regulatory network of HNF4α and HNF1α involved in human diseases and drug metabolism[J]. Drug Metabolism Reviews, 2022, 54(4): 361-385. DOI:10.1080/03602532.2022.2103146.
[19]	Tajiri A, Hirota T, Kawano S, et al. Regulation of organic anion transporting polypeptide 2B1 expression by microRNA in the human liver[J]. Molecular Pharmaceutics, 2020, 17(8): 2821-2830. DOI:10.1021/acs.molpharmaceut.0c00193.
[20]	Arruda A C, Perilhão M S, Santos W A, et al. PPARα-dependent modulation by metformin of the expression of OCT-2 and MATE-1 in the kidney of mice[J]. Molecules, 2020, 25(2): 392. DOI:10.3390/molecules25020392.
[21]	Zhang Xinyue, Su Tianhong, Wu Yifan, et al. N6-methyladenosine reader YTHDF1 promotes stemness and therapeutic resistance in hepatocellular carcinoma by enhancing NOTCH1 expression[J]. Cancer Research, 2024, 84(6): 827-840. DOI:10.1158/0008-5472.CAN-23-1916.
[22]	Mo Dongqing, Liu Chenglin, Chen Yao, et al. The mitochondrial ribosomal protein mRpL4 regulates Notch signaling[J]. EMBO Reports, 2023, 24(6): EMBR202255764. DOI:10.15252/embr.202255764.
[23]	Paggi J M, Pandit A, Dror R O. The art and science of molecular docking[J]. Annual Review of Biochemistry, 2024, 93(1): 389-410. DOI:10.1146/annurev-biochem-030222-120000.
[24]	Alizadeh S R, Ali Ebrahimzadeh M. Quercetin derivatives: Drug design, development, and biological activities, a review[J]. European Journal of Medicinal Chemistry, 2022, 229: 114068. DOI:10.1016/j.ejmech.2021.114068.
[25]	Long Qiu, Ma Ting, Wang Ye, et al. Orientin alleviates the inflammatory response in psoriasis like dermatitis in BALB/c mice by inhibiting the MAPK signaling pathway[J]. International Immunopharmacology, 2024, 134: 112261. DOI:10.1016/j.intimp.2024.112261.
[26]	Li Hao, Yuan Li, Li Xueyi, et al. Isoorientin attenuated the pyroptotic hepatocyte damage induced by benzo [a]pyrene via ROS/NF-κB/NLRP3/caspase-1 signaling pathway[J]. Antioxidants, 2021, 10(8): 1275. DOI:10.3390/antiox10081275.
[27]	Shi Shaojun, Li Yunqiao. Interplay of drug-metabolizing enzymes and transporters in drug absorption and disposition[J]. Current Drug Metabolism, 2014, 15(10): 915-941. DOI:10.2174/1389200216666150401110610.
[28]	杨玉洁, 刘蕾, 徐苗, 等. 调控肝脏转运体对肝脏疾病防治的意义[J]. 华西药学杂志, 2020, 35(3): 316-324. DOI:10.13375/j.cnki.wcjps.2020.03.018.
[29]	师少军. 肝脏“代谢-转运互作”及其对药物药代动力学、疗效和毒性影响的研究进展[J]. 中国医院药学杂志, 2020, 40(5): 579-585. DOI:10.13286/j.1001-5213.2020.05.21.
[30]	孟强, 刘克辛. 转运体介导药物相互作用的研究现状及展望[J]. 中国临床药理学与治疗学, 2021, 26(8): 876-888. DOI:10.12092/j.issn.1009-2501.2021.08.004.
[31]	武新安. 药物转运体基础与应用[M]. 北京: 科学出版社, 2017.

基因名称	正向引物	反向引物
BCRP	AGAGAGAAGCCAATAATAGA	CACCAATAATCAGTCCCAGTAT
MRP1	CGACGGGAAGACAAGTTCAT	AGGTTTCCTCTGGTCCTGGT
MRP2	TTGACAGAGAGCGGATTCCT	GGCATCCCTGATGAAGAACT
OATP2	TGAACAACAGCACTCACCA	GTTGTTGAACCAGGCAAAGGC
OCT1	TCCTGCGAAACCTCAGTGAT	TGCTGCTTCCTGGTCCTAAA
OCT2	CATCGGTGCTATGATGATTGGC	AGCCCAACAAATTCTGTAATCA
P-gp	CAACGGCACAGTCAAGGGCAAGTT	CTCAGCACCCCATCAGCATCAC
GAPDH	TATGCCAACACCCTCAGTGC	CTGCTTGCTGGTACTCATCC

RT反应体系	用量
5×gDNA Eraser Buffer	2.0 μL
gDNA Eraser	1.0 μL
total RNA	1.0 μg
PrimeScript RT Enzyme Mix I	1.0 μL
RT Primer Mix	1.0 μL
5×PrimeScript Buffer 2(for Real Time)	4.0 μL
RNase Free ddH₂O	up to 20.0 μL
Total	20.0 μL

PCR反应体系	用量/μL
cDNA	2.0
SYBR Premix Ex Taq II (2×)	10.0
PCR Forward Primer(20 μmol/L)	0.4
PCR Reverse Primer(20 μmol/L)	0.4
ddH₂O	7.2
Total	20.0

	过程	温度	时间	循环次数
Stage 1	预变性	95 ℃	30 s	循环1次
		95 ℃	5 s
Stage 2	PCR反应	60 ℃	30 s	循环40次
		72 ℃	30 s
		Plate read
Stage 3	Melt Curve Stage

活性成分	调控蛋白结合能/(kcal·mol^-1)
活性成分	Notch1	HNF4α	PPARα
原儿茶酸	-5.01	-5.08	-6.88
异荭草素	-8.54	-6.82	-7.25
荭草素	-5.85	-7.25	-7.87
牡荆素	-6.32	-5.43	-6.67
山柰素-3-O-β-D-葡萄糖苷	-7.21	-6.88	-7.63
槲皮素	-6.87	-6.42	-8.18

生理病理状态下荭草活性物质对转运体表达的影响

Effects of active constituents from Polygonum orientale L. on the expression of transporters under physiological and pathological conditions

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