Study on the mechanism of Danggui Buxue decoction in the treatment of diabetic retinopathy based on network pharmacology and experiment

doi:10.5246/jcps.2023.07.044

Abstract

Abstract:

In the present study, we investigated the mechanism of action of Danggui Buxue decoction (DBD) in diabetic retinopathy (DR) using network pharmacology and molecular docking combined with experimental validation. GeneCards and DisGeNET were used to collect DR targets. The intersection of the two targets was obtained using Venny 2.1. Cytoscape was used to construct "disease-drug-component-target" and protein-protein interaction (PPI) networks. DAVID database was used to enrich key targets with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). AutoDockVina was used to perform molecular docking of primary active ingredients with key targets. Molecular docking validation was performed with key targets by AutoDockVina. Finally, the network pharmacological results were validated by animal experiments. A total of 84 common targets of DBD and DR were collected, 220 entries were revealed by GO analysis, and 113 signaling pathways were obtained by KEGG enrichment analysis. Molecular docking results showed that the key targets had suitable docking activities with quercetin, dousterol and other active ingredients. Animal experiments showed that DBD could improve retinal tissue morphology, lower blood glucose, increase insulin secretion, reduce VEGF and TNF-α protein expression levels and increase PI3K and Akt1 expression levels in the retinal tissues of DR rats (P < 0.05, P < 0.01). The treatment of DR by DBD had the characteristics of multiple active ingredients, multiple targets and multiple pathways, which could exert therapeutic effects on DR by regulating the core targets of TNF-α, VEGFA, PI3K, and AKT and affecting the signaling pathways of PI3K/AKT and TNF.

Key words: Danggui Buxue decoction, Diabetic retinopathy, Network pharmacology, Molecular docking

Supporting:

Dongyan Wu, Xiaodan Wang, Jinmiao Chai, Qinqing Li, Yue Li, Mei Bi, Wanwei Gui, Huimin Cao. Study on the mechanism of Danggui Buxue decoction in the treatment of diabetic retinopathy based on network pharmacology and experiment[J]. Journal of Chinese Pharmaceutical Sciences, 2023, 32(7): 527-538.

Figures/Tables 11

Table 1. Active components of DBD.

Table 2. The binding energy of the main chemical components in DBD to the core targets.

References 22

[1]	Sabanayagam, C.; Banu, R.; Chee, M.L.; Lee, R.; Wang, Y.X.; Tan, G.; Jonas, J.B.; Lamoureux, E.L.; Cheng, C.Y.; Klein, B.E.K.; Mitchell, P.; Klein, R.; Cheung, C.M.G.; Wong, T.Y. Incidence and progression of diabetic retinopathy: a systematic review. Lancet Diabetes Endocrinol. 2019, 7, 140–149.
[2]	Wan, W.C.; Long, Y. Current research on the epidemiology, etiology and pathogenesis of diabetic retinopathy. New Adv. Ophthalmol. 2022, 42, 673–679.
[3]	Jiao, J.J.; Chang, K.; Yao, W.Y.; Zhang, Q.H.; Li, X.P. Exploring the mechanism of action of resveratrol in the treatment of diabetic retinopathy based on network pharmacology and experimental validation. Modern Drugs Clin. 2022, 37, 942–951.
[4]	Li, D.Y. Discourse on the identification and confusion of internal and external injuries. Beijing: China Medical Science and Technology Press. 2016, 40.
[5]	Sun, X.H.; Qian, K.W.; Zhou, Y.; Gu, H.Y. Study on the efficacy and mechanism of Angelica Sinensis Blood Tonic Tang Plus for diabetic retinopathy. J. Modern Int. Chin. Western Med. 2019, 28, 3152–3155, 3170.
[6]	Tang, Z.Z. Study on the mechanism of protection of BRB in diabetic rats by angelica blood tonic soup through Müller cell pathway. Shanxi Univ. Tradit. Chin. Med. 2021.
[7]	Yang, F.X.; Wang, Y.; Xia, P.F.; Yang, R.J.; Wang, Y.X.; Zhang, J.; Fan, Q.; Zhao, L. Research progress on chemical composition, pharmacological effects, clinical application and predictive analysis of quality markers of angelica blood tonic soup. Chin. J. Tradit. Chin. Med. 2021, 46, 2677–2685.
[8]	Zhang, Y.X. Clinical study on the treatment of non-proliferative diabetic retinopathy with the addition formula of Danggui Buxue decoction. Fujian Univ. Tradi. Chin. Med. 2015.
[9]	Deng, C.; Li, J.; Tang, X.Z. Effect of addition and subtraction of Danggui Buxue decoction on the efficacy of diabetic retinopathy and the effect of serum ICAM-1 and ET-1 levels. Chin. Med. Inform. 2018, 35, 90–93.
[10]	Chai, G.R.; Liu, S.; Yang, H.W.; Chen, X.L. Quercetin protects against diabetic retinopathy in rats by inducing heme oxygenase-1 expression. Neural Regen. Res. 2021, 16, 1344–1350.
[11]	Lupo, G.; Cambria, M.T.; Olivieri, M.; Rocco, C.; Caporarello, N.; Longo, A.; Zanghì, G.; Salmeri, M.; Foti, M.C.; Anfuso, C.D. Anti-angiogenic effect of quercetin and its 8-methyl pentamethyl ether derivative in human microvascular endothelial cells. J. Cell Mol. Med. 2019, 23, 6565–6577.
[12]	Pratiwi, R.; Nantasenamat, C.; Ruankham, W.; Suwanjang, W.; Prachayasittikul, V.; Prachayasittikul, S.; Phopin, K. Mechanisms and neuroprotective activities of stigmasterol against oxidative stress-induced neuronal cell death via sirtuin family. Front. Nutr. 2021, 8, 648995.
[13]	Wang, J.; Gong, H.M.; Zou, H.H.; Liang, L.; Wu, X.Y. Isorhamnetin prevents H₂O₂‑induced oxidative stress in human retinal pigment epithelial cells. Mol. Med. Rep. 2018, 17, 648–652.
[14]	Hu, N.N.; Zhang, X.J. Progress of research on chemical composition and pharmacological effects of Astragalus membranaceus. Chin. Med. Inform. 2021, 38, 76–82.
[15]	Zhang, C.C.; Yin, Y.; Nie, S.Q.; Zheng, Y.J. The effect of inflammation on neurodegenerative changes in diabetic retinopathy. J. Clin. Ophthalmol. 2019, 27, 378–382.
[16]	Yan, P.; Zhang, X.H.; Zhang, L.; Li, J. Study on the relationship between HMW-ADP, TNF-α, VEGF and diabetic retinopathy. Chin. Med. Herald. 2019, 16, 106–109.
[17]	Koleva-Georgieva, D.N.; Sivkova, N.P.; Terzieva, D. Serum inflammatory cytokines IL-1beta, IL-6, TNF-α and VEGF have influence on the development of diabetic retinopathy. Folia Med. 2011, 53, 44–50.
[18]	Le, Y.Z. VEGF production and signaling in Müller glia are critical to modulating vascular function and neuronal integrity in diabetic retinopathy and hypoxic retinal vascular diseases. Vis. Res. 2017, 139, 108–114.
[19]	Wang, Y.R.; Tang, Z.Z.; Li, Y.; Wu, D.Y.; Li, Q.Q.; Chai, J.M. Balancing relationships in diabetic retinopathy based on the theory of yin and yang. Lishizhen Med. Materia Medica Res. 2021, 32, 1704–1706.
[20]	Nian, S.; Lo, A.C.Y.; Mi, Y.; Ren, K.; Yang, D. Neurovascular unit in diabetic retinopathy: pathophysiological roles and potential therapeutical targets. Eye Vis. Lond. Engl. 2021, 8, 15.
[21]	Elsherbiny, N.M.; Abdel-Mottaleb, Y.; Elkazaz, A.Y.; Atef, H.; Lashine, R.M.; Youssef, A.M.; Ezzat, W.; El-Ghaiesh, S.H.; Elshaer, R.E.; El-Shafey, M.; Zaitone, S.A. Carbamazepine alleviates retinal and optic nerve neural degeneration in diabetic mice via nerve growth factor-induced PI3K/Akt/mTOR activation. Front. Neurosci. 2019, 13, 1089.
[22]	Mei, Z.H.; Yang, J.; Wang, W.; Cao, P.; Yang, Y.; Li, P.F.; Zhu, K.F.; Jiang, T.; Zhang, M.T. Exploring the effect of choroidalin injection on early diabetic retinopathy based on PI3K/Akt pathway. J. Chin. Med. Eye Ear Nose Throat. 2020, 10, 6–10.