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Combinatorial Chemistry & High Throughput Screening


ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

Virtual Screening of Potential Anti-fatigue Mechanism of Polygonati Rhizoma Based on Network Pharmacology

Author(s): Ze-Feng Wang, Ye-Qing Hu, Qi-Guo Wu* and Rui Zhang

Volume 22, Issue 9, 2019

Page: [612 - 624] Pages: 13

DOI: 10.2174/1386207322666191106110615

Price: $65


Background and Objective: A large number of people are facing the danger of fatigue due to the fast-paced lifestyle. Fatigue is common in some diseases, such as cancer. The mechanism of fatigue is not definite. Traditional Chinese medicine is often used for fatigue, but the potential mechanism of Polygonati Rhizoma (PR) is still not clear. This study attempts to explore the potential anti-fatigue mechanism of Polygonati Rhizoma through virtual screening based on network pharmacology.

Methods: The candidate compounds of PR and the known targets of fatigue are obtained from multiple professional databases. PharmMapper Server is designed to identify potential targets for the candidate compounds. We developed a Herbal medicine-Compound-Disease-Target network and analyzed the interactions. Protein-protein interaction network is developed through the Cytoscape software and analyzed by topological methods. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment are carried out by DAVID Database. Finally, we develop Compound-Target-Pathway network to illustrate the anti-fatigue mechanism of PR.

Results: This approach identified 12 active compounds and 156 candidate targets of PR. The top 10 annotation terms for GO and KEGG were obtained by enrichment analysis with 35 key targets. The interaction between E2F1 and PI3K-AKT plays a vital role in the anti-fatigue effect of PR due to this study.

Conclusion: This study demonstrates that PR has multi-component, multi-target and multipathway effects.

Keywords: Fatigue, network pharmacology, E2F1, PI3K-AKT, KEGG, polygonati rhizoma (PR).

Jiao, J.; Jia, X.; Liu, P.; Zhang, Q.; Liu, F.; Ma, C.; Xi, P.; Liang, Z. Species identification of polygonati rhizoma in China by both morphological and molecular marker methods. C. R. Biol., 2018, 341(2), 102-110.
[] [PMID: 29428511]
Jiao, J.; Huang, W.; Bai, Z.; Liu, F.; Ma, C.; Liang, Z. DNA barcoding for the efficient and accurate identification of medicinal polygonati rhizoma in China. PLoS One, 2018, 13(7)e0201015
[] [PMID: 30021015]
Zhao, P.; Zhao, C.; Li, X.; Gao, Q.; Huang, L.; Xiao, P.; Gao, W. The genus Polygonatum: A review of ethnopharmacology, phytochemistry and pharmacology. J. Ethnopharmacol., 2018, 214, 274-291.
[] [PMID: 29246502]
Kato, A.; Miura, T. Hypoglycemic activity of polygonati rhizoma in normal and diabetic mice. Biol. Pharm. Bull., 1993, 16(11), 1118-1120.
[] [PMID: 8312868]
Yang, X.X.; Wei, J.D.; Mu, J.K.; Liu, X.; Dong, J.C.; Zeng, L.X.; Gu, W.; Li, J.P.; Yu, J. Integrated metabolomic profiling for analysis of antilipidemic effects of Polygonatum kingianum extract on dyslipidemia in rats. World J. Gastroenterol., 2018, 24(48), 5505-5524.
[] [PMID: 30622379]
Zhang, H.; Cai, X.T.; Tian, Q.H.; Xiao, L.X.; Zeng, Z.; Cai, X.T.; Yan, J.Z.; Li, Q.Y. Microwave-assisted degradation of polysaccharide from Polygonatum sibiricum and antioxidant activity. J. Food Sci., 2019, 84(4), 754-761.
[] [PMID: 30908644]
Long, T.; Liu, Z.; Shang, J.; Zhou, X.; Yu, S.; Tian, H.; Bao, Y. Polygonatum sibiricum polysaccharides play anti-cancer effect through TLR4-MAPK/NF-κB signaling pathways. Int. J. Biol. Macromol., 2018, 111, 813-821.
[] [PMID: 29343453]
Jo, K.; Kim, H.; Choi, H.S.; Lee, S.S.; Bang, M.H.; Suh, H.J. Isolation of a sleep-promoting compound from Polygonatum sibiricum rhizome. Food Sci. Biotechnol., 2018, 27(6), 1833-1842.
[] [PMID: 30483448]
Yelithao, K.; Surayot, U.; Park, W.; Lee, S.; Lee, D.H.; You, S. Effect of sulfation and partial hydrolysis of polysaccharides from Polygonatum sibiricum on immune-enhancement. Nat. Prod. Res., 2019, 33(16), 2359-2362.
[PMID: 29451015]
Zhao, H.; Wang, Q.L.; Hou, S.B.; Chen, G. Chemical constituents from the rhizomes of Polygonatum sibiricum Red. and anti-inflammatory activity in RAW264.7 macrophage cells. Nat. Prod. Res., 2019, 33(16), 2359-2362.
[] [PMID: 29451015]
Cui, X.; Wang, S.; Cao, H.; Guo, H.; Li, Y.; Xu, F.; Zheng, M.; Xi, X.; Han, C.A. Review: The bioactivities and pharmacological applications of Polygonatum sibiricum polysaccharides. Molecules, 2018, 23(5), 1170.
[] [PMID: 29757991]
Wang, X.; Qu, Y.; Zhang, Y.; Li, S.; Sun, Y.; Chen, Z.; Teng, L.; Wang, D. Antifatigue potential activity of sarcodon imbricatus in acute excise-treated and chronic fatigue syndrome in mice via regulation of Nrf2-mediated oxidative stress. Oxid. Med. Cell. Longev., 2018, 20189140896
[] [PMID: 30050662]
Tharakan, B.; Dhanasekaran, M.; Manyam, B.V. Antioxidant and DNA protecting properties of anti-fatigue herb Trichopus zeylanicus. Phytother. Res., 2005, 19(8), 669-673.
[] [PMID: 16177968]
Ahlberg, K.; Ekman, T.; Gaston-Johansson, F.; Mock, V. Assessment and management of cancer-related fatigue in adults. Lancet, 2003, 362(9384), 640-650.
[] [PMID: 12944066]
Collins, J.J.; Devine, T.D.; Dick, G.S.; Johnson, E.A.; Kilham, H.A.; Pinkerton, C.R.; Stevens, M.M.; Thaler, H.T.; Portenoy, R.K. The measurement of symptoms in young children with cancer: The validation of the memorial symptom assessment scale in children aged 7-12. J. Pain Symptom Manage., 2002, 23(1), 10-16.
[] [PMID: 11779663]
Wagner, L.I.; Cella, D. Fatigue and cancer: Causes, prevalence and treatment approaches. Br. J. Cancer, 2004, 91(5), 822-828.
[] [PMID: 15238987]
Zengariniab, E.; Ruggieroa, C. Mario UlisesPérez-Zepedac; Hoogendijk EO; Vellas B; Mecocci P; Cesari M. Fatigue: Relevance and implications in the aging population. Exp. Gerontol., 2015, 70, 78-83.
Avlund, K. Fatigue in older adults: an early indicator of the aging process? Aging Clin. Exp. Res., 2010, 22(2), 100-115.
[] [PMID: 20440097]
Beyer, I.; Njemini, R.; Bautmans, I.; Demanet, C.; Bergmann, P.; Mets, T. Inflammation-related muscle weakness and fatigue in geriatric patients. Exp. Gerontol., 2012, 47(1), 52-59.
[] [PMID: 22032874]
Gonzales, J.U.; Wiberg, M.; Defferari, E.; Proctor, D.N. Arterial stiffness is higher in older adults with increased perceived fatigue and fatigability during walking. Exp. Gerontol., 2015, 61, 92-97.
[] [PMID: 25482474]
Wang, Y.Y.; Li, X.X.; Liu, J.P.; Luo, H.; Ma, L.X.; Alraek, T. Traditional Chinese medicine for chronic fatigue syndrome: a systematic review of randomized clinical trials. Complement. Ther. Med., 2014, 22(4), 826-833.
[] [PMID: 25146086]
Chen, R.; Moriya, J.; Yamakawa, J.; Takahashi, T.; Kanda, T. Traditional Chinese medicine for chronic fatigue syndrome. Evid. Based Complement. Alternat. Med., 2010, 7(1), 3-10.
[] [PMID: 18955323]
Harvey, A.L. Natural products in drug discovery. Drug Discov. Today, 2008, 13(19-20), 894-901.
[] [PMID: 18691670]
Barabási, A.L.; Gulbahce, N.; Loscalzo, J. Network medicine: A network-based approach to human disease. Nat. Rev. Genet., 2011, 12(1), 56-68.
[] [PMID: 21164525]
Li, S.; Zhang, B. Traditional Chinese medicine network pharmacology: theory, methodology and application. Chin. J. Nat. Med., 2013, 11(2), 110-120.
[] [PMID: 23787177]
Zhao, J.; Yang, J.; Tian, S.S.; Zhang, W.D. A survey of web resources and tools for the study of TCM network pharmacology. Quant. Biol., 2019, 7(1), 17-29.
Chen, G.M.; Huang, C.Y.; Liu, Y.Y.; Chen, T.; Huang, R.; Liang, M.; Zhang, J.; Xu, H. A network pharmacology approach to uncover the potential mechanism of Yinchensini decoction. Evid. Based Complement. Alternat. Med., 2018, 2018, 1-14.
Liu, X.; Ouyang, S.; Yu, B.; Liu, Y.; Huang, K.; Gong, J.; Zheng, S.; Li, Z.; Li, H.; Jiang, H. PharmMapper server: A web server for potential drug target identification using pharmacophore mapping approach. Nucleic Acids Res.,, 2010, 38(Web Server issue), W609-14.
[] [PMID: 20430828]
Franz, M.; Lopes, C.T.; Huck, G.; Dong, Y.; Sumer, O.; Bader, G.D. Cytoscape.js: A graph theory library for visualisation and analysis. Bioinformatics, 2016, 32(2), 309-311.
[PMID: 26415722]
Piñero, J.; Bravo, À.; Queralt-Rosinach, N.; Gutiérrez-Sacristán, A.; Deu-Pons, J.; Centeno, E.; García-García, J.; Sanz, F.; Furlong, L.I. DisGeNET: A comprehensive platform integrating information on human disease-associated genes and variants. Nucleic Acids Res., 2017, 45(D1), D833-D839.
[] [PMID: 27924018]
Kuwahara, H.; Horie, T.; Ishikawa, S.; Tsuda, C.; Kawakami, S.; Noda, Y.; Kaneko, T.; Tahara, S.; Tachibana, T.; Okabe, M.; Melki, J.; Takano, R.; Toda, T.; Morikawa, D.; Nojiri, H.; Kurosawa, H.; Shirasawa, T.; Shimizu, T. Oxidative stress in skeletal muscle causes severe disturbance of exercise activity without muscle atrophy. Free Radic. Biol. Med., 2010, 48(9), 1252-1262.
[] [PMID: 20156551]
Rosenfeldt, F.; Wilson, M.; Lee, G.; Kure, C.; Ou, R.; Braun, L.; de Haan, J. Oxidative stress in surgery in an ageing population: Pathophysiology and therapy. Exp. Gerontol., 2013, 48(1), 45-54.
[] [PMID: 22465624]
Shanware, N.P.; Bray, K.; Abraham, R.T. The PI3K, metabolic, and autophagy networks: Interactive partners in cellular health and disease. Annu. Rev. Pharmacol. Toxicol., 2013, 53(1), 89-106.
[] [PMID: 23294306]
Hu, S.; Wu, Y.; Zhao, B.; Hu, H.; Zhu, B.; Sun, Z.; Li, P.; Du, S. Panax notoginseng saponins protect cerebral microvascular endothelial cells against oxygen-glucose deprivation/reperfusion-induced barrier dysfunction via activation of PI3K/Akt/Nrf2 antioxidant signaling pathway. Molecules, 2018, 23(11), 2781.
[] [PMID: 30373188]
Zhuang, C.L.; Mao, X.Y.; Liu, S.; Chen, W.Z.; Huang, D.D.; Zhang, C.J.; Chen, B.C.; Shen, X.; Yu, Z. Ginsenoside Rb1 improves postoperative fatigue syndrome by reducing skeletal muscle oxidative stress through activation of the PI3K/Akt/Nrf2 pathway in aged rats. Eur. J. Pharmacol., 2014, 740, 480-487.
[] [PMID: 24975098]
Zeng, B.; Liu, L.; Liao, X.; Zhang, C.; Ruan, H. Thyroid hormone protects cardiomyocytes from H2O2-induced oxidative stress via the PI3K-AKT signaling pathway. Exp. Cell Res., 2019, 380(2), 205-215.
[] [PMID: 31059699]
Wang, Y.; Kong, Q.J.; Sun, J.C.; Xu, X.M.; Yang, Y.; Liu, N.; Shi, J.G. Protective effect of epigenetic silencing of CyclinD1 against spinal cord injury using bone marrow-derived mesenchymal stem cells in rats. J. Cell. Physiol., 2018, 233(7), 5361-5369.
[] [PMID: 29215736]
Iyer, N.G.; Ozdag, H.; Caldas, C. p300/CBP and cancer. Oncogene, 2004, 23(24), 4225-4231.
[] [PMID: 15156177]
Chan, H.M.; La Thangue, N.B. p300/CBP proteins: HATs for transcriptional bridges and scaffolds. J. Cell Sci., 2001, 114(Pt 13), 2363-2373.
[PMID: 11559745]
Gayther, S.A.; Batley, S.J.; Linger, L.; Bannister, A.; Thorpe, K.; Chin, S.F.; Daigo, Y.; Russell, P.; Wilson, A.; Sowter, H.M.; Delhanty, J.D.; Ponder, B.A.; Kouzarides, T.; Caldas, C. Mutations truncating the EP300 acetylase in human cancers. Nat. Genet., 2000, 24(3), 300-303.
[] [PMID: 10700188]
Bower, J.E.; Lamkin, D.M. Inflammation and cancer-related fatigue: mechanisms, contributing factors, and treatment implications. Brain Behav. Immun., 2013, 30(Suppl.), S48-S57.
[] [PMID: 22776268]
Byar, K.L.; Berger, A.M.; Bakken, S.L.; Cetak, M.A. Impact of adjuvant breast cancer chemotherapy on fatigue, other symptoms, and quality of life. Oncol. Nurs. Forum, 2006, 33(1), E18-E26.
[] [PMID: 16470230]
Blaney, J.; Lowe-Strong, A.; Rankin, J.; Campbell, A.; Allen, J.; Gracey, J. The cancer rehabilitation journey: barriers to and facilitators of exercise among patients with cancer-related fatigue. Phys. Ther., 2010, 90(8), 1135-1147.
[] [PMID: 20558566]
Saligan, L.N.; Olson, K.; Filler, K.; Larkin, D.; Cramp, F.; Yennurajalingam, S.; Escalante, C.P.; del Giglio, A.; Kober, K.M.; Kamath, J.; Palesh, O.; Mustian, K. Erratum to: The biology of cancer-related fatigue: A review of the literature. Support. Care Cancer, 2015, 23(9), 2853.
[] [PMID: 26081598]
Zhu, G.; Zhang, B.; Jiang, F.; Zhao, L.; Liu, F. ShenQi FuZheng Injection ameliorates fatigue-like behavior in mouse models of cancer-related fatigue. Biomed. Pharmacother., 2019, 111, 1376-1382.
[] [PMID: 30841452]
Banchereau, J.; Steinman, R.M. Dendritic cells and the control of immunity. Nature, 1998, 392(6673), 245-252.
[] [PMID: 9521319]
Fang, F.; Wang, Y.; Li, R.; Zhao, Y.; Guo, Y.; Jiang, M.; Sun, J.; Ma, Y.; Ren, Z.; Tian, Z.; Wei, F.; Yang, D.; Xiao, W. Transcription factor E2F1 suppresses dendritic cell maturation. J. Immunol., 2010, 184(11), 6084-6091.
[] [PMID: 20421650]
Chen, Y.L.; Uen, Y.H.; Li, C.F.; Horng, K.C.; Chen, L.R.; Wu, W.R.; Tseng, H.Y.; Huang, H.Y.; Wu, L.C.; Shiue, Y.L. The E2F transcription factor 1 transactives stathmin 1 in hepatocellular carcinoma. Ann. Surg. Oncol., 2013, 20(12), 4041-4054.
[] [PMID: 22911364]
Chaussepied, M.; Ginsberg, D. Transcriptional regulation of AKT activation by E2F. Mol. Cell, 2004, 16(5), 831-837.
[] [PMID: 15574337]
Hsiao, C.P.; Wang, D.; Kaushal, A.; Saligan, L. Mitochondria-related gene expression changes are associated with fatigue in patients with nonmetastatic prostate cancer receiving external beam radiation therapy. Cancer Nurs., 2013, 36(3), 189-197.
[] [PMID: 23047795]
DeGregori, J.; Johnson, D.G. Distinct and overlapping roles for E2F family members in transcription, proliferation and apoptosis. Curr. Mol. Med., 2006, 6(7), 739-748.
[PMID: 17100600]
Puigserver, P.; Wu, Z.; Park, C.W.; Graves, R.; Wright, M.; Spiegelman, B.M. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell, 1998, 92(6), 829-839.
[] [PMID: 9529258]
Blanchet, E.; Annicotte, J.S.; Pradelli, L.A.; Hugon, G.; Matecki, S.; Mornet, D.; Rivier, F.; Fajas, L. E2F transcription factor-1 deficiency reduces pathophysiology in the mouse model of Duchenne muscular dystrophy through increased muscle oxidative metabolism. Hum. Mol. Genet., 2012, 21(17), 3910-3917.
[] [PMID: 22678059]
Blanchet, E.; Annicotte, J.S.; Lagarrigue, S.; Aguilar, V.; Clapé, C.; Chavey, C.; Fritz, V.; Casas, F.; Apparailly, F.; Auwerx, J.; Fajas, L. E2F transcription factor-1 regulates oxidative metabolism. Nat. Cell Biol., 2011, 13(9), 1146-1152.
[] [PMID: 21841792]
Salvi, N.; Guellich, A.; Michelet, P.; Demoule, A.; Le Guen, M.; Renou, L.; Bonne, G.; Riou, B.; Langeron, O.; Coirault, C. Upregulation of PPARbeta/delta is associated with structural and functional changes in the type I diabetes rat diaphragm. PLoS One, 2010, 5(7)e11494
[] [PMID: 20628611]
Mouisel, E.; Relizani, K.; Mille-Hamard, L.; Denis, R.; Hourdé, C.; Agbulut, O.; Patel, K.; Arandel, L.; Morales-Gonzalez, S.; Vignaud, A.; Garcia, L.; Ferry, A.; Luquet, S.; Billat, V.; Ventura-Clapier, R.; Schuelke, M.; Amthor, H. Myostatin is a key mediator between energy metabolism and endurance capacity of skeletal muscle. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2014, 307(4), R444-R454.
[] [PMID: 24965795]
Wagner, K.D.; Wagner, N. Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) acts as regulator of metabolism linked to multiple cellular functions. Pharmacol. Ther., 2010, 125(3), 423-435.
[] [PMID: 20026355]
Feige, J.N.; Gelman, L.; Michalik, L.; Desvergne, B.; Wahli, W. From molecular action to physiological outputs: peroxisome proliferator-activated receptors are nuclear receptors at the crossroads of key cellular functions. Prog. Lipid Res., 2006, 45(2), 120-159.
[] [PMID: 16476485]
Kumar, R.; Negi, P.S.; Singh, B.; Ilavazhagan, G.; Bhargava, K.; Sethy, N.K. Cordyceps sinensis promotes exercise endurance capacity of rats by activating skeletal muscle metabolic regulators. J. Ethnopharmacol., 2011, 136(1), 260-266.
[] [PMID: 21549819]
Fajas, L.; Landsberg, R.L.; Huss-Garcia, Y.; Sardet, C.; Lees, J.A.; Auwerx, J. E2Fs regulate adipocyte differentiation. Dev. Cell, 2002, 3(1), 39-49.
[] [PMID: 12110166]
Himbert, C.; Ose, J.; Lin, T.; Warby, C.A.; Gigic, B.; Steindorf, K.; Schrotz-King, P.; Abbenhardt-Martin, C.; Zielske, L.; Boehm, J.; Ulrich, C.M. Inflammation- and angiogenesis-related biomarkers are correlated with cancer-related fatigue in colorectal cancer patients: Results from the ColoCare Study. Eur. J. Cancer Care (Engl.), 2019, 28(4)e13055
[] [PMID: 31016796]
Pereira, B.I.; Devine, O.P.; Vukmanovic-Stejic, M.; Chambers, E.S.; Subramanian, P.; Patel, N.; Virasami, A.; Sebire, N.J.; Kinsler, V.; Valdovinos, A.; LeSaux, C.J.; Passos, J.F.; Antoniou, A.; Rustin, M.H.A.; Campisi, J.; Akbar, A.N. Senescent cells evade immune clearance via HLA-E-mediated NK and CD8+ T cell inhibition. Nat. Commun., 2019, 10(1), 2387.
[] [PMID: 31160572]

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