Analysis of network pharmacological mechanism of Zhenlian Mingmu Capsule in treatment of diabetic retinopathy

BIAN Yun; BAI Hailong; MENG Xiaofeng; LIU Xiao; XUE Chao; LIU Ruixue; CHANG Hongkun; TIAN Fengsheng; CUI Ronggang; SU Yang; LIU mei

doi:10.7619/jcmp.20232153

Journal of Clinical Medicine in Practice > 2023 > 27(18): 75-82. > DOI: 10.7619/jcmp.20232153

BIAN Yun, BAI Hailong, MENG Xiaofeng, LIU Xiao, XUE Chao, LIU Ruixue, CHANG Hongkun, TIAN Fengsheng, CUI Ronggang, SU Yang, LIU mei. Analysis of network pharmacological mechanism of Zhenlian Mingmu Capsule in treatment of diabetic retinopathy[J]. Journal of Clinical Medicine in Practice, 2023, 27(18): 75-82. DOI: 10.7619/jcmp.20232153

Citation:

PDF (2770 KB)

Analysis of network pharmacological mechanism of Zhenlian Mingmu Capsule in treatment of diabetic retinopathy

1.
the Third Department of Diabetes, Cangzhou Hospital of Integrated Chinese and Western Medicine in Hebei Province, Cangzhou, Hebei, 061001
2.
Center of Preventive Treatment of Disease, Cangzhou Hospital of Integrated Chinese and Western Medicine in Hebei Province, Cangzhou, Hebei, 061001
3.
the Second Department of Ultrasound, Cangzhou Hospital of Integrated Chinese and Western Medicine in Hebei Province, Cangzhou, Hebei, 061001
4.
Department of Ophthalmology, Cangzhou Hospital of Integrated Chinese and Western Medicine in Hebei Province, Cangzhou, Hebei, 061001

More Information

Received Date: July 05, 2023
Revised Date: September 03, 2023
Available Online: October 08, 2023

Graphical Abstract

Abstract

Abstract

Objective
To investigate the mechanism of Zhenlian Mingmu Capsule in the treatment of diabetic retinopathy.
Methods
The key targets of Zhenlian Mingmu Capsule in the treatment of diabetic retinopathy were screened by network pharmacology, and the binding sites of active ingredients were predicted by molecular docking. Combined with the results of network pharmacology, a rat model of diabetic retinopathy was established. Sixty rats were randomly divided into normal group, model group, calcium hydroxybenzene sulfonate tablet group and Zhenlian Mingmu Capsule group, with 15 rats in each group. The normal group and the model group were given 2 mL normal saline and gavage once a day; the calcium hydroxybenzene sulfonate tablet group and Zhenlian Mingmu Capsule group were respectively given the corresponding concentration of therapeutic drugs (2 mL), once a day. After 4 weeks of administration, retinal thickness, interleukin (IL) -1β, IL-6, tumor necrosis factor-α (TNF-α) levels, and protein expression levels of vascular endothelial growth factor (VEGF) and nuclear transcription factor-κB (NF-κB) were measured.
Results
A total of 2 367 active ingredients of Zhenlian Mingmu Capsule were identified by network pharmacology, with 248 targets, 3 943 targets related to diabetic retinopathy, and 153 intersection targets. According to the analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), it was mainly involved in biological reaction processes such as signal transduction, inflammation and apoptosis, and mainly involved in the regulation of IL-1β, EGF/EGFR/P13K/AKT, IL-6/STAT3, TP53 and CASP3 signal pathways. The results of molecular docking showed that the main active ingredients obtained by screening had strong binding with the target. Compared with the normal group, retinal thickness in the model group was significantly decreased, and IL-1β, IL-6, TNF-α, VEGF, NF-κB were significantly increased (P < 0.05). Compared with the model group, the retinal thickness of rats in the calcium hydroxybenzene sulfonate tablet group was significantly increased, and IL-1β, IL-6, TNF-α, VEGF, NF-κB were significantly decreased (P < 0.05). Compared with the calcium hydroxybenzene sulfonate tablet group, retinal thickness in the Zhenlian Mingmu Capsule group was significantly increased, and IL-1β, IL-6, TNF-α, VEGF, NF-κB were significantly decreased (P < 0.05).
Conclusion
Zhenlian Mingmu Capsule may have a positive effect in the treatment of diabetic retinopathy, and its mechanism may be related to the regulation of IL-1β, EGF/EGFR/P13K/AKT, IL6/STAT3, TP53 and CASP3 signaling pathways.
- Zhenlian Mingmu Capsule,
- diabetic retinopathy,
- network pharmacology,
- mechanism of action

FullText(HTML)

References (31)

References

[1]	RODRÍGUEZ M L, PÉREZ S, MENA-MOLLÁ S, et al. Oxidative stress and microvascular alterations in diabetic retinopathy: future therapies[J]. Oxid Med Cell Longev, 2019, 2019: 4940825.
[2]	GROENEVELD Y, TAVENIER D, BLOM J W, et al. Incidence of sight-threatening diabetic retinopathy in people with Type 2 diabetes mellitus and numbers needed to screen: a systematic review[J]. Diabet Med, 2019, 36(10): 1199-1208. doi: 10.1111/dme.13908
[3]	ZHANG Y H, AN X D, DUAN L Y, et al. Effect of Chinese patent medicines on ocular fundus signs and vision in calcium dobesilate-treated persons with non-proliferative diabetic retinopathy: a systematic review and meta-analysis[J]. Front Endocrinol, 2022, 13: 799337. doi: 10.3389/fendo.2022.799337
[4]	赵旭芳. 贞莲明目胶囊治疗肝肾阴虚、痰湿瘀阻型NPDR临床疗效观察[D]. 唐山: 华北理工大学, 2021.
[5]	李国建, 尹瑞生, 任崇禧, 等. 贞莲明目胶囊治疗糖尿病视网膜黄斑水肿55例临床观察[J]. 光明中医, 2007, 22(7): 39-42. doi: 10.3969/j.issn.1003-8914.2007.07.029
[6]	孙鹏, 孟岩, 张剑, 等. NGF联合抗VEGF对糖尿病模型大鼠视网膜组织中氧化应激和VEGF表达的影响[J]. 中国老年学杂志, 2022, 42(11): 2773-2776. doi: 10.3969/j.issn.1005-9202.2022.11.050
[7]	戴淑香, 王广梅, 黄德莲, 等. 中药联合全视网膜光凝治疗糖尿病视网膜病变的观察及护理[J]. 实用临床医药杂志, 2017, 21(6): 49-51. doi: 10.7619/jcmp.201706015
[8]	程梅, 方朝晖, 盛凤霞, 等. 盐酸川芎嗪眼部雾化联合耳尖放血对气阴两虚型糖尿病视网膜病变的疗效观察[J]. 实用临床医药杂志, 2021, 25(10): 71-75. doi: 10.7619/jcmp.20211277
[9]	OSHITARI T. Neurovascular impairment and therapeutic strategies in diabetic retinopathy[J]. Int J Environ Res Public Health, 2021, 19(1): 439. doi: 10.3390/ijerph19010439
[10]	BHATWADEKAR A D, SHUGHOURY A, BELAMKAR A, et al. Genetics of diabetic retinopathy, a leading cause of irreversible blindness in the industrialized world[J]. Genes, 2021, 12(8): 1200. doi: 10.3390/genes12081200
[11]	AN X D, JIN D, DUAN L Y, et al. Direct and indirect therapeutic effect of traditional Chinese medicine as an add-on for non-proliferative diabetic retinopathy: a systematic review and meta-analysis[J]. Chin Med, 2020, 15: 99. doi: 10.1186/s13020-020-00380-4
[12]	QIAN S H, QIAN Y J, HUO D X, et al. Tanshinone Ⅱa protects retinal endothelial cells against mitochondrial fission induced by methylglyoxal through glyoxalase 1[J]. Eur J Pharmacol, 2019, 857: 172419. doi: 10.1016/j.ejphar.2019.172419
[13]	CHAI G R, LIU S, YANG H W, et al. Quercetin protects against diabetic retinopathy in rats by inducing heme oxygenase-1 expression[J]. Neural Regen Res, 2021, 16(7): 1344-1350. doi: 10.4103/1673-5374.301027
[14]	SAFARPOUR S, PIRZADEH M, EBRAHIMPOUR A, et al. Protective effect of kaempferol and its nanoparticles on 5-fluorouracil-induced cardiotoxicity in rats[J]. Biomed Res Int, 2022, 2022: 2273000.
[15]	AFIFI S M, AMMAR N M, KAMEL R, et al. β-sitosterol glucoside-loaded nanosystem ameliorates insulin resistance and oxidative stress in streptozotocin-induced diabetic rats[J]. Antioxidants, 2022, 11(5): 1023. doi: 10.3390/antiox11051023
[16]	HE J B, WANG H, LIU Y, et al. Blockade of vascular endothelial growth factor receptor 1 prevents inflammation and vascular leakage in diabetic retinopathy[J]. J Ophthalmol, 2015, 2015: 605946.
[17]	ELEKOFEHINTI O O, OYEDOKUN V O, IWALOYE O, et al. Momordica charantia silver nanoparticles modulate SOCS/JAK/STAT and P13K/Akt/PTEN signalling pathways in the kidney of streptozotocin-induced diabetic rats[J]. J Diabetes Metab Disord, 2021, 20(1): 245-260. doi: 10.1007/s40200-021-00739-w
[18]	张金锋, 徐志龙, 吴梦, 等. 丹参酮ⅡA通过抑制信号通路延缓膝骨关节炎大鼠软骨退变及抑制局部炎症的研究[J]. 中国药学杂志, 2021, 56(23): 1918-1926. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGYX202123008.htm
[19]	HAN X J, XU T S, FANG Q J, et al. Quercetin hinders microglial activation to alleviate neurotoxicity via the interplay between NLRP3 inflammasome and mitophagy[J]. Redox Biol, 2021, 44: 102010. doi: 10.1016/j.redox.2021.102010
[20]	LIU C, LIU H, LU C, et al. Kaempferol attenuates imiquimod-induced psoriatic skin inflammation in a mouse model[J]. Clin Exp Immunol, 2019, 198(3): 403-415. doi: 10.1111/cei.13363
[21]	JAYARAMAN S, DEVARAJAN N, RAJAGOPAL P, et al. β-sitosterol circumvents obesity induced inflammation and insulin resistance by down-regulating IKKβ/NF-κB and JNK signaling pathway in adipocytes of type 2 diabetic rats[J]. Molecules, 2021, 26(7): 2101. doi: 10.3390/molecules26072101
[22]	CHOI S H, KOH D I, CHO S Y, et al. Temporal and differential regulation of KAISO-controlled transcription by phosphorylated and acetylated p53 highlights a crucial regulatory role of apoptosis[J]. J Biol Chem, 2019, 294(35): 12957-12974. doi: 10.1074/jbc.RA119.008100
[23]	GONZALEZ-RELLAN M J, FONDEVILA M F, FERNANDEZ U, et al. O-GlcNAcylated p53 in the liver modulates hepatic glucose production[J]. Nat Commun, 2021, 12(1): 5068. doi: 10.1038/s41467-021-25390-0
[24]	KANAMORI Y, FINOTTI A, MAGNO L D, et al. Enzymatic spermine metabolites induce apoptosis associated with increase of p53, caspase-3 and miR-34a in both neuroblastoma cells, SJNKP and the N-myc-amplified form IMR5[J]. Cells, 2021, 10(8): 1950. doi: 10.3390/cells10081950
[25]	米倚林, 易南星, 许晓彤, 等. 山奈酚抑制软骨凋亡延缓小鼠膝骨关节炎的实验研究[J]. 海南医学院学报, 2022, 28(17): 1299-1306. https://www.cnki.com.cn/Article/CJFDTOTAL-HNYY202217004.htm
[26]	LIU R, HAO D L, XU W Y, et al. β-Sitosterol modulates macrophage polarization and attenuates rheumatoid inflammation in mice[J]. Pharm Biol, 2019, 57(1): 161-168. doi: 10.1080/13880209.2019.1577461
[27]	GREGORIO K C R, LAURINDO C P, MACHADO U F. Estrogen and glycemic homeostasis: the fundamental role of nuclear estrogen receptors ESR1/ESR2 in glucose transporter GLUT4 regulation[J]. Cells, 2021, 10(1): 99. doi: 10.3390/cells10010099
[28]	CHEN Q, HE Y, WANG X F, et al. LncRNA PTGS2 regulates islet β-cell function through the miR-146a-5p/RBP4 axis and its diagnostic value in type 2 diabetes mellitus[J]. Am J Transl Res, 2021, 13(10): 11316-11328.
[29]	张辛宁, 王乐琪, 李莎莎, 等. 丹参从瘀论治抑郁症的潜在靶点及作用机制研究[J]. 中药新药与临床药理, 2021, 32(9): 1300-1308. https://www.cnki.com.cn/Article/CJFDTOTAL-ZYXY202109012.htm
[30]	YI H, PENG H Y, WU X Y, et al. The therapeutic effects and mechanisms of quercetin on metabolic diseases: pharmacological data and clinical evidence[J]. Oxid Med Cell Longev, 2021, 2021: 6678662.
[31]	XIA H T, LIU J Y, YANG W L, et al. Integrated strategy of network pharmacological prediction and experimental validation elucidate possible mechanism of bu-Yang herbs in treating postmenopausal osteoporosis via ESR1[J]. Front Pharmacol, 2021, 12: 654714.

[1]	SHI Xiaoqing, LYU Qunli, XIAO Peihua, WU Jianzhong, HONG Pei. Application value of constructing a prediction model based on nutritional status combined with clinical data for infectious complications after radical gastrectomy for gastric cancer[J]. Journal of Clinical Medicine in Practice, 2025, 29(2): 63-68, 74. DOI: 10.7619/jcmp.20243772
[2]	WANG Shuitang, BU Yunfang, XU Fengying, CAI Xiaoying. Effect of early respiratory rehabilitation combined with nutritional support for patients with acute exacerbation of chronic obstructive pulmonary disease[J]. Journal of Clinical Medicine in Practice, 2022, 26(10): 97-100. DOI: 10.7619/jcmp.20214992
[3]	CHEN Yiliang, ZHANG Yinxu, CHE Zhongguang. Effect of intestinal microecological interventionon complications after operation and during chemotherapy in patients with colon cancer[J]. Journal of Clinical Medicine in Practice, 2021, 25(20): 73-77. DOI: 10.7619/jcmp.20212087
[4]	YANG Yaming, WANG Jianfeng. Effect of enteral nutrition on nutritional status and immune function in patients with chronic obstructive pulmonary disease complicated with respiratory failure by non-invasive ventilation[J]. Journal of Clinical Medicine in Practice, 2019, 23(10): 72-74. DOI: 10.7619/jcmp.201910020
[5]	ZHANG Fang, YU Lijun, ZHAO Rui, LI Na, LIU Ting. Application effect of PDCA in reducing complication incidence of colorectal cancer patients with colostomy[J]. Journal of Clinical Medicine in Practice, 2016, (12): 82-84. DOI: 10.7619/jcmp.201612026
[6]	LI Fang. The influence of nursing intervention on postoperative complications in patients with hepatolobectomy[J]. Journal of Clinical Medicine in Practice, 2014, (8): 58-60. DOI: 10.7619/jcmp.201408019
[7]	LI Jie, ZHANG Zifeng. Application of evidence-based nursing in prevention of complications in young and middle-aged patients with paraplegia[J]. Journal of Clinical Medicine in Practice, 2014, (4): 42-45. DOI: 10.7619/jcmp.201404014
[8]	WU Xiaoli, WANG Fang, JI Jianhong. Influence of gastric lavage monitoring system for detecting liquid input-output balance on complications of gastric lavage[J]. Journal of Clinical Medicine in Practice, 2013, (20): 85-87. DOI: 10.7619/jcmp.201320029
[9]	ZHUANG Zhaorong, YIN Daju. Nursing for gastric cancer patients with early postoperative complications[J]. Journal of Clinical Medicine in Practice, 2013, (12): 14-16,19. DOI: 10.7619/jcmp.201312006
[10]	CHEN Yunlan, QIU Meiling. Nursing for postoperative complications in patients with hysterectomy[J]. Journal of Clinical Medicine in Practice, 2013, (10): 95-97. DOI: 10.7619/jcmp.201310035

Cited By

Cited by

Periodical cited type(3)

1.	赵云霞，王金山，王婷婷，唐斌. 三拗汤合止嗽散加减治疗小儿感染后咳嗽风邪伏肺证的临床观察. 实用中西医结合临床. 2023(04): 37-40 .
2.	史彦超，孙晓旭. 三拗汤加味佐用四子散联合氨溴特罗口服液在慢性咳嗽患儿中的应用效果. 中国民康医学. 2021(08): 76-78 .
3.	许全珍. 儿童慢性咳嗽诊治进展. 系统医学. 2021(15): 195-198 .

Other cited types(1)

Get Citation

PDF

XML

Article views (129) PDF downloads (5) Cited by(4)

Turn off MathJax

Article Contents

Abstract

References

Analysis of network pharmacological mechanism of Zhenlian Mingmu Capsule in treatment of diabetic retinopathy