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Identification of the Anti-Atherosclerotic Properties of Benzoinum through Integrative Network Pharmacology and Pharmacological Analyses

Li Zhang1, 2, 3, Yuqing Wang1, Qili Lu1, Fengying Ye1, Qing Zhang2, 3, Feifei Wang2, 3, Shuyao Zhang1,, Feng Wang2, 3,

1Department of Pharmacy, Guangzhou Red Cross Hospital of Jinan University, Guangzhou Guangdong, China

2Key Laboratory of Digital Quality Evaluation of Chinese Materia Medica of State Administration of TCM, School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China

3Engineering & Technology Research Center for Chinese Materia Medica Quality of the Universities of Guangdong Province, School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China

Journal of Food and Nutrition Research. 2022, 10(11), 748-761. DOI: 10.12691/jfnr-10-11-2
Received September 17, 2022; Revised October 23, 2022; Accepted November 03, 2022

Abstract

Benzoinum is a resin derived from Styrax tonkinensis bark that has long been used in clinical settings as a traditional Chinese medicine with cardioprotective properties. The mechanistic basis for these pharmacological properties, however, remains to be demarcated. We used a network pharmacology approach to characterise the mechanism of action that benzoinum used to treat AS. The PharmMapper database was used to find potential benzoin target proteins, and the TCMSP, CTD, TTD, GAD, drug Bank, and pharmGkb databases were used to identify AS-related target genes. Following assessments of pathway enrichment, the functional roles of these genes were discovered, allowing the creation of compound-target and target-pathway networks. HUVEC cells were then used to validate these predicted benzoinum-related mechanisms of action, revealing that an active derivative of this resin was able to modulate signaling activity in TNF-α-exposed HUVECs by regulating the caspase-9 and NF-κB signaling pathways. Overall, our predictive network pharmacology analyses and supporting data highlighted the potential mechanisms whereby benzoinum may exert cardiovascular activity in the context of AS.

Keywords:

network pharmacology, atherosclerosis, cell apoptosis, inflammatory
[1]  Khan, R., Spagnoli, V., Tardif, J. C. & L’Allier, P. L. Novel anti-inflammatory therapies for the treatment of atherosclerosis. Atherosclerosis 240, 497-509 (2015).View Article  PubMed 
 
[2]  Zhou, P. et al. Attenuation of TNF-α-induced inflammatory injury in endothelial cells by ginsenoside Rb1 via inhibiting NF-κB, JNK and p38 signaling pathways. Front. Pharmacol. 8, 1-13 (2017).View Article  PubMed 
 
[3]  Weber, C., Badimon, L., Mach, F. & van Der Vorst, E. P. C. Therapeutic strategies for atherosclerosis and atherothrombosis: Past, present and future. Thromb. Haemost. 117, 1258-1264 (2017).View Article  PubMed 
 
[4]  Zhang, F. et al. Biemamides A-E, Inhibitors of the TGF-β Pathway That Block the Epithelial to Mesenchymal Transition. Org. Lett. 20, 5529-5532 (2018).View Article  PubMed 
 
[5]  Ren, H. et al. Selenium inhibits homocysteine-induced endothelial dysfunction and apoptosis via activation of AKT. Cell. Physiol. Biochem. 38, 871-882 (2016).View Article  PubMed 
 
[6]  Bruikman, C. S., Stoekenbroek, R. M., Hovingh, G. K. & Kastelein, J. P. New Drugs for Atherosclerosis. Can. J. Cardiol. 33, 350-357 (2017).View Article  PubMed 
 
[7]  Choi, E. S. et al. Ligustilide attenuates vascular inflammation and activates Nrf2/HO-1 induction and, NO synthesis in HUVECs. Phytomedicine 38, 12-23 (2018).View Article  PubMed 
 
[8]  Fei-, W. Chemical Constituents of Benzoinum and Its Anti- tumor Activities in Vitro. 1-7 (2020).
 
[9]  Zhang, L. et al. Anti-inflammatory and anti-apoptotic effects of stybenpropol a on human umbilical vein endothelial cells. Int. J. Mol. Sci. 20, (2019).View Article  PubMed 
 
[10]  Paralleloneurum, S. Trzy lignany / neolignany z żywicy benzoinowej. 2, 1000-1004 (2020).
 
[11]  Guo, W. et al. Integrating network pharmacology and pharmacological evaluation for deciphering the action mechanism of herbal formula Zuojin Pill in suppressing hepatocellular carcinoma. Front. Pharmacol. 10, 1-21 (2019).View Article  PubMed 
 
[12]  Huang, D. W., Sherman, B. T. & Lempicki, R. A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc. 4, 44-57 (2009).View Article  PubMed 
 
[13]  Smoot, M. E., Ono, K., Ruscheinski, J., Wang, P. & Ideker, T. Cytoscape 2. 8 : new features for data integration and network visualization. 27, 431-432 (2011).View Article  PubMed 
 
[14]  Zhou, Y. qiang et al. Hyperoside Suppresses Lipopolysaccharide-induced Inflammation and Apoptosis in Human Umbilical Vein Endothelial Cells. Curr. Med. Sci. 38, 222-228 (2018).View Article  PubMed 
 
[15]  Mason, R. P., Dawoud, H., Jacob, R. F., Sherratt, S. C. R. & Malinski, T. Eicosapentaenoic acid improves endothelial function and nitric oxide bioavailability in a manner that is enhanced in combination with a statin. Biomed. Pharmacother. 103, 1231-1237 (2018).View Article  PubMed 
 
[16]  Wu, S. et al. Potent anti-inflammatory effect of dioscin mediated by suppression of TNF-α-induced VCAM-1, ICAM-1 and EL expression via the NF-κB pathway. Biochimie 110, 62-72 (2015).View Article  PubMed 
 
[17]  Guo, S. et al. Role of A20 in cIAP-2 protection against tumor necrosis factor α (TNF-α)-mediated apoptosis in endothelial cells. Int. J. Mol. Sci. 15, 3816-3833 (2014).View Article  PubMed 
 
[18]  Galkina, E. & Ley, K. Vascular adhesion molecules in atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 27, 2292-2301 (2007).View Article  PubMed 
 
[19]  Xu, T. et al. Systematic Understanding of the Mechanism of Baicalin against Ischemic Stroke through a Network Pharmacology Approach. 2018, (2018).View Article  PubMed 
 
[20]  Sun, L., Chen, S., Gao, H., Ren, L. & Song, G. Visfatin induces the apoptosis of endothelial progenitor cells via the induction of pro-inflammatory mediators through the NF-κB pathway. Int. J. Mol. Med. 40, 637-646 (2017).View Article  PubMed 
 
[21]  Gwon, W. G. et al. Sargaquinoic Acid Inhibits TNF-α-Induced NF-κB Signaling, Thereby Contributing to Decreased Monocyte Adhesion to Human Umbilical Vein Endothelial Cells (HUVECs). J. Agric. Food Chem. 63, 9053-9061 (2015).View Article  PubMed 
 
[22]  Wang, M., Wang, Q., Du, Y. & Zhang, X. Network Pharmacology-Based Strategy to Investigate Pharmacological Mechanisms of Qiaoshao Formula for Treatment of Premature Ejaculation. Evidence-based Complement. Altern. Med. 2020, 1-12 (2020).View Article  PubMed 
 
[23]  González, D. et al. Caspase-3 and -9 are activated in human myeloid HL-60 cells by calcium signal. Mol. Cell. Biochem. 333, 151-157 (2010).View Article  PubMed 
 
[24]  Chen, T. L. et al. Protective effects of isorhamnetin on apoptosis and inflammation in TNF-α-induced HUVECs injury. Int. J. Clin. Exp. Pathol. 8, 2311-2320 (2015).
 
[25]  Förstermann, U., Xia, N. & Li, H. Roles of vascular oxidative stress and nitric oxide in the pathogenesis of atherosclerosis. Circ. Res. 120, 713-735 (2017).View Article  PubMed 
 
[26]  Förstermann, U. & Sessa, W. C. Nitric oxide synthases: Regulation and function. Eur. Heart J. 33, 829-837 (2012).View Article  PubMed 
 
[27]  Wang F. et al. Neolignan and phenylpropanoid compounds fromthe resin of Styrax tonkinensis.J. Asian. Nat. Prod. Res.23, 1-8 (2021).View Article  PubMed 
 
[28]  Xie Q. et al. Advances in studies on chemical constituents and pharmacological effects of benzoin. Chin. Med. Mat. 43, 243-248 (2020).
 
[29]  Wang Y. et al. Research progress of pharmacological action of benzoin.Asia-Pacific Traditional Medicine. 11, 3 (2015).