Exploring the antihypertensive mechanism of Prunella vulgaris through integrated network pharmacology analysis

doi:10.5246/jcps.2024.11.077

Journal of Chinese Pharmaceutical Sciences ›› 2024, Vol. 33 ›› Issue (11): 1068-1081.DOI: 10.5246/jcps.2024.11.077

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Exploring the antihypertensive mechanism of Prunella vulgaris through integrated network pharmacology analysis

Na Sun^*(), Yujing Wang, Caihong Zhou, Huanhuan Kang, Shuo Ma, Yu Zhang, Yuhan Yuan, Xin Zhang, Linxuan Jin, Wenqian Li, Xinru Wu, Penghua Shu^*()

Food and Pharmacy College, Xuchang University, Xuchang 461000, Henan, China

Received:2024-04-25 Revised:2024-05-10 Accepted:2024-07-12 Online:2024-12-10 Published:2024-12-10
Contact: Na Sun, Penghua Shu
Supported by:
National Natural Science Foundation of China (Grant No. 21702178), the Training Plan of Young Backbone Teachers in Universities of Henan Province (Grant No. 2021GGJS144), the Key Scientific Research Program in Universities of Henan Province (Grant No. 22A350009 and 23A350012), the National Undergraduate Training Program for Innovation and Entrepreneurship (Grant No. 202410480007 and 202310480020), the Undergraduate Training Program for Innovation and Entrepreneurship of Henan Province (Grant No. 202210480020 and 202210480021), the Scientific Research Innovation Team of Xuchang University (Grant No. 2022CXTD007), the Horizontal Cooperation Project (Grant No. 2023HX181), and the Undergraduate Training Program for Innovation and Entrepreneurship of Xuchang University (Grant No. X202210480016).

Abstract

Abstract:

Prunella vulgaris, a traditional Chinese medicine (TCM), exerts a significant hypotensive effect, particularly in managing various forms of hypertension. Nonetheless, the precise antihypertensive constituents and their respective targets remain elusive. This study endeavored to identify the hypotensive components of P. vulgaris and elucidated its mode of action based on hypotensive targets. Utilizing the Systematic Pharmacology of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), UniProt, GeneCards, STRING, RCSB, and the Human Genome Annotation and Analysis Database (Metascape), we conducted a screening of active ingredients and hypotensive targets. The Network Analyzer software Cytoscape 3.9.0 facilitated a comprehensive analysis of the active ingredients. Molecular docking was executed employing Sybyl-X 2.0 and Discovery Studio 2019. Predictions and analyses of the pharmacokinetics and toxicity of active ingredients were performed using the ADMETlab 2.0 online platform. Eight active compounds (1–8) and 11 hypotensive targets were identified, with IL1B and PPARG exhibiting a high degree of correlation. Dominant biological processes included negative regulation of apoptotic processes, positive regulation of gene expression, response to xenobiotic stimulus, and response to hypoxia. KEGG analysis unveiled core pharmacological mechanisms, notably fluid shear stress and atherosclerosis, lipid and atherosclerosis, P13K-Akt, MAPK, and relaxin signaling pathways. Compounds 5–8 demonstrated robust interactions with multiple targets through hydrogen bonds, van der Waals forces, and pi-alkyl interactions, which serve as primary stabilizers of docking complexes. Notably, compound 7 exhibited promising ADMET prediction results, suggesting its potential for drug molecule development. Our findings underscored the synergistic effects of P. vulgaris on multiple targets and pathways in hypertension treatment, reflecting the characteristic multi-component and multi-target effects of TCM.

Key words: Prunella vulgaris L., Anti-hypertension, Traditional Chinese medicine targets, Natural active ingredients

Supporting: /attached/file/20241208/20241208163838_778.pdf

Na Sun, Yujing Wang, Caihong Zhou, Huanhuan Kang, Shuo Ma, Yu Zhang, Yuhan Yuan, Xin Zhang, Linxuan Jin, Wenqian Li, Xinru Wu, Penghua Shu. Exploring the antihypertensive mechanism of Prunella vulgaris through integrated network pharmacology analysis[J]. Journal of Chinese Pharmaceutical Sciences, 2024, 33(11): 1068-1081.

Figures/Tables 13

Table 1. The compounds screened out in the Traditional Chinese Medicines Database.

Table 2. The data of the top 20 KEGG pathways.

Table 3. ADMET prediction results of compounds 1–8.

References 32

[1]	Kjeldsen, S.E. Hypertension and cardiovascular risk: general aspects. Pharmacol. Res. 2018, 129, 95–99.
[2]	Messerli, F.H.; Williams, B.; Ritz, E. Essential hypertension. Lancet. 2007, 370, 591–603.
[3]	Yuan, M.Z.; Li, F.; Fang, Q.; Wang, W.; Peng, J.J.; Qin, D.Y.; Wang, X.F.; Liu, G.W. Research on the cause of death for severe stroke patients. J. Clin. Nurs. 2018, 27, 450–460.
[4]	Vaněčková, I.; Maletínská, L.; Behuliak, M.; Nagelová, V.; Zicha, J.; Kuneš, J. Obesity-related hypertension: possible pathophysiological mechanisms. J. Endocrinol. 2014, 223, R63–R78.
[5]	Raby, K.; Rocco, M.; Oparil, S.; Gilbert, O.N.; Upadhya, B. Heart failure primary prevention: what does SPRINT add: recent advances in hypertension. Hypertension. 2021, 77, 1804–1814.
[6]	Oliveira, V.; Kwitek, A.E.; Sigmund, C.D.; Morselli, L.L.; Grobe, J.L. Recent advances in hypertension: intersection of metabolic and blood pressure regulatory circuits in the central nervous system. Hypertension. 2021, 77, 1061–1068.
[7]	Zhao, Y.; Xia, L.; Zhou, X.; Fu, D.; Guo, Y.; Research development of Chinese and western medicine treatmentfor hypertension. Chin. Arch. Tradit. Add. Chin. Med. 2019, 37, 1673–7717.
[8]	Díez, J.; Butler, J. Growing heart failure burden of hypertensive heart disease: a call to action. Hypertension. 2023, 80, 13–21.
[9]	Zhang, J.H.; Qiu, J.N.; Wang, L.; Zhang, S.; Cheng, F.F.; Liu, B.; Jiang, Y.Y. Research progress on chemical constituents and pharmacological effects of Prunella vulgaris. Chin. Tradit. Herbal Drugs. 2018, 49, 3431–3440.
[10]	Mir, R.H.; Bhat, M.F.; Sawhney, G.; Kumar, P.; Andrabi, N.I.; Shaikh, M.; Mohi-Ud-Din, R.; Masoodi, M.H. Prunella vulgarisL: critical pharmacological, expositorytraditional uses and extensive phytochemistry: a review. Curr. Drug Discov. Technol. 2022, 19, e140122191102.
[11]	Pan, J.Y.; Wang, H.Y.; Chen, Y.H. Prunella vulgarisL.–A review of its ethnopharmacology, phytochemistry, quality control and pharmacological effects. Front. Pharmacol. 2022, 13, 903171.
[12]	Rasool, R.; Ganai, B.A. Prunella vulgarisL.: a literature review on its therapeutic potentials. Pharmacologia. 2013, 4, 441–448.
[13]	Chen, Y.H.; Zhu, Z.B.; Guo, Q.S.; Zhang, L.X.; Zhang, X.M. Variation in concentrations of major bioactive compounds in Prunella vulgarisL. related to plant parts and phenologicalstages. Biol. Res. 2012, 45, 171–175.
[14]	Feng, L.; Jia, X.B.; Shi, F.; Chen, Y. Identification of two polysaccharides from Prunella vulgarisL. and evaluation on their anti-lung adenocarcinoma activity. Molecules. 2010, 15, 5093–5103.
[15]	Zheng, X.Q.; Song, L.X.; Han, Z.Z.; Yang, Y.B.; Zhang, Y.; Gu, L.H.; Yang, L.; Chou, G.X.; Wang, Z.T. Pentacyclic triterpenoids from spikes of Prunella vulgarisL. with thyroid tumour cell cytostatic bioactivities. Nat. Prod. Res. 2023, 37, 1518–1526.
[16]	Özbek, O.; Saglam, B.; Usta, N.C.; Budak, Y. GC–MS analysis and anti–microbial activity of Prunella vulgarisL. extracts. J. Indian Chem. Soc. 2022, 99, 100460.
[17]	Zhang, H.; Long, T.; Lou, Y.C.; Ma, L.; Liu, M.M.; Wang, Z.W.; Zhu, Y. Antihypertensive effect of the extract from compound prunella vulgaris l.in spontaneous hypertension rats. China Pharm. 2016, 19, 828–832.
[18]	Sun, N.; Yang, H.H.; Zhou, M.; Hou, Y.Y.; Wu, X.R.; Li, W.Q.; Liu, H.; Zheng, L.J.; Sun, J.G.; Jin, L.X.; Ma, S.; Shu, P.H. A review of chemical constituents from Ajuga nipponensis and their anti-inflammatory activities analysis. Biochem. Syst. Ecol. 2022, 105, 104531.
[19]	Sun, N.; Yang, H.H.; Zhou, M.; Hou, Y.Y.; Wu, X.R.; Li, W.Q.; Zhang, Y.F.; Sun, J.G.; Xiong, X.; Huang, J.H.; Shu, P.H. Isolation and evaluation of antioxidants from Arisaema heterophyllum tubers. Phytochem. Lett. 2023, 53, 106–110.
[20]	Zhang, R.Z.; Zhu, X.; Bai, H.; Ning, K. Network pharmacology databases for traditional Chinese medicine: review and assessment. Front. Pharmacol. 2019, 10, 123.
[21]	Li, W.W.; Yuan, G.Q.; Pan, Y.X.; Wang, C.; Chen, H.X. Network pharmacology studies on the bioactive compounds and action mechanisms of natural products for the treatment of diabetes mellitus: a review. Front. Pharmacol. 2017, 8, 74.
[22]	Safran, M.; Dalah, I.; Alexander, J.; Rosen, N.; Iny Stein, T.; Shmoish, M.; Nativ, N.; Bahir, I.; Doniger, T.; Krug, H.; Sirota-Madi, A.; Olender, T.; Golan, Y.; Stelzer, G.; Harel, A.; Lancet, D. GeneCards Version 3: the human gene integrator. Database. 2010, 2010, baq020.
[23]	Rappaport, N.; Fishilevich, S.; Nudel, R.; Twik, M.; Belinky, F.; Plaschkes, I.; Stein, T.I.; Cohen, D.; Oz-Levi, D.; Safran, M.; Lancet, D. Rational confederation of genes and diseases: NGS interpretation via GeneCards, MalaCards and VarElect. Biomed. Eng. Online. 2017, 16, 72.
[24]	Franceschini, A.; Szklarczyk, D.; Frankild, S.; Kuhn, M.; Simonovic, M.; Roth, A.; Lin, J.Y.; Minguez, P.; Bork, P.; von Mering, C.; Jensen, L.J. STRING v9.1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res. 2013, 41, D808–D815.
[25]	Balogh, O.M.; Benczik, B.; Horváth, A.; Pétervári, M.; Csermely, P.; Ferdinandy, P.; Ágg, B. Efficient link prediction in the protein-protein interaction network using topological information in a generative adversarial network machine learning model. BMC Bioinformatics. 2022, 23, 78.
[26]	Li, G.S.; Li, M.; Wang, J.X.; Li, Y.H.; Pan, Y. United neighborhood closeness centrality and orthology for predicting essential proteins. IEEE/ACM Trans. Comput. Biol. Bioinform. 2020, 17, 1451–1458.
[27]	Burley, S.K.; Berman, H.M.; Kleywegt, G.J.; Markley, J.L.; Nakamura, H.; Velankar, S. Protein data bank (PDB): the single global macromolecular structure archive. Methods Mol. Biol. 2017, 1607, 627–641.
[28]	Zhang, T.; Jiang, M.; Chen, L.; Niu, B.; Cai, Y.D. Prediction of gene phenotypes based on GO and KEGG pathway enrichment scores. Biomed Res. Int. 2013, 2013, 870795.
[29]	Kanehisa, M.; Sato, Y. KEGG Mapper for inferring cellular functions from protein sequences. Protein Sci. 2020, 29, 28–35.
[30]	Xiong, G.L.; Wu, Z.X.; Yi, J.C.; Fu, L.; Yang, Z.J.; Hsieh, C.; Yin, M.Z.; Zeng, X.X.; Wu, C.K.; Lu, A.P.; Chen, X.; Hou, T.J.; Cao, D.S. ADMETlab 2.0: an integrated online platform for accurate and comprehensive predictions of ADMET properties. Nucleic Acids Res. 2021, 49, W5–W14.
[31]	Watson, R.R.; Schönlau, F. Nutraceutical and antioxidant effects of a delphinidin-rich maqui berry extract Delphinol^®:a review. Minerva Cardioangiol. 2015, 63, 1–12.
[32]	Chen, Y.M.; Ge, Z.W.; Huang, S.X.; Zhou, L.; Zhai, C.L.; Chen, Y.H.; Hu, Q.Y.; Cao, W.; Weng, Y.T.; Li, Y.Y. Delphinidin attenuates pathological cardiac hypertrophy via the AMPK/NOX/MAPK signaling pathway. Aging. 2020, 12, 5362–5383.

Exploring the antihypertensive mechanism of Prunella vulgaris through integrated network pharmacology analysis

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