A Network Pharmacology-based Study on the Anti-aging Properties of Traditional Chinese Medicine Sisheng Bulao Elixir
- Authors: Xing C.1, Zeng Z.1, Shan Y.2, Guo W.3, Shah R.2, Wang L.2, Wang Y.4, Du H.1
-
Affiliations:
- Daxing Research Institute, University of Science and Technology Beijing
- School of Chemistry and Biological Engineering, University of Science and Technology Beijing
- Department of Obstetrics and Gynecology, Peking University Third Hospital
- H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi
- Issue: Vol 27, No 12 (2024)
- Pages: 1840-1849
- Section: Chemistry
- URL: https://rjeid.com/1386-2073/article/view/644009
- DOI: https://doi.org/10.2174/0113862073276253231114063813
- ID: 644009
Cite item
Full Text
Abstract
Background::Traditional Chinese Medicine (TCM) has a rich history of use in preventing senescence for millennia in China. Nonetheless, a systematic method to study the antiaging properties and the underlying molecular mechanism of TCM remains absent.
Objective::The objective of this study is to decipher the anti-aging targets and mechanisms of Sisheng Bulao Elixir (SBE) using a systematic approach based on a novel aging database and network pharmacology.
Methods::Bioactive compounds and target proteins in SBE were identified via the Traditional Chinese Medicine System Pharmacology (TCMSP) database. Aging-related proteins were uncovered through alignment with the Ageing Alta database. A compound-target (CT) protein network analysis highlighted key flavonoids targeting aging. Core aging-related proteins were extracted through protein-protein interaction (PPI) network analysis. Molecular docking validated binding activities between core compounds and aging-related proteins. The antioxidant activity of SBE was confirmed using an in vitro senescent cells model.
Results::A total of 39 active compounds were extracted from a pool of 639 compounds in SBE. Through a matching process with the Aging Alta, 88 target proteins associated with the aging process were identified. Impressively, 80 out of these 88 proteins were found to be targeted by flavonoids. Subsequently, an analysis using CT methodology highlighted 11 top bioactive flavonoids. Notably, core aging-related proteins, including AKT1, MAPK3, TP53, VEGFA, IL6, and HSP90AA1, emerged through the PPI network analysis. Moreover, three flavonoids, namely quercetin, kaempferol, and luteolin, exhibited interactions with over 100 aging-related proteins. Molecular docking studies were conducted on these flavonoids with their shared three target proteins, namely AKT1, HSP90AA1, and IL6, to assess their binding activities. Finally, the antioxidant properties of SBE were validated using an in vitro model of senescent cells.
Conclusion::This study offers novel insights into SBE's anti-aging attributes, providing evidence of its molecular mechanisms. It enhances our understanding of traditional remedies in anti-aging research.
About the authors
Cencan Xing
Daxing Research Institute, University of Science and Technology Beijing
Email: info@benthamscience.net
Zehua Zeng
Daxing Research Institute, University of Science and Technology Beijing
Email: info@benthamscience.net
Yubang Shan
School of Chemistry and Biological Engineering, University of Science and Technology Beijing
Email: info@benthamscience.net
Wenhuan Guo
Department of Obstetrics and Gynecology, Peking University Third Hospital
Email: info@benthamscience.net
Roshan Shah
School of Chemistry and Biological Engineering, University of Science and Technology Beijing
Email: info@benthamscience.net
Luna Wang
School of Chemistry and Biological Engineering, University of Science and Technology Beijing
Email: info@benthamscience.net
Yan Wang
H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi
Author for correspondence.
Email: info@benthamscience.net
Hongwu Du
Daxing Research Institute, University of Science and Technology Beijing
Author for correspondence.
Email: info@benthamscience.net
References
- Vergilio, M.M.; Vasques, L.I.; Leonardi, G.R. Characterization of skin aging through high-frequency ultrasound imaging as a technique for evaluating the effectiveness of anti-aging products and procedures: A review. Int. Soci. Skin Imag., 2021, 27, 966-973.
- Harman, D. The free radical theory of aging. Antioxid. Redox Signal., 2003, 5(5), 557-561. doi: 10.1089/152308603770310202 PMID: 14580310
- Hossain, I.; Park, S.; Husna, A.; Kim, Y.; Kim, H.; Kim, T.H. PIM-PI-1 and Poly(ethylene glycol)/Poly(propylene glycol)-based mechanically robust copolyimide membranes with high CO 2-selectivity and an anti-aging property: A joint experimentalcomputational exploration. ACS Appl. Mater. Interfaces, 2021, 13(42), 49890-49906. doi: 10.1021/acsami.1c14034 PMID: 34643079
- Campisi, J.; Kim, S.; Lim, C.S.; Rubio, M. Cellular senescence, cancer and aging: the telomere connection. Exp. Gerontol., 2001, 36(10), 1619-1637. doi: 10.1016/S0531-5565(01)00160-7 PMID: 11672984
- Lin, C.L.; Wang, C.C.; Chang, S.C.; Inbaraj, B.S.; Chen, B.H. Antioxidative activity of polysaccharide fractions isolated from Lycium barbarum Linnaeus. Int. J. Biol. Macromol., 2009, 45(2), 146-151. doi: 10.1016/j.ijbiomac.2009.04.014 PMID: 19409411
- Chang, R.C.C.; So, K.F. Use of anti-aging herbal medicine, Lycium barbarum, against aging-associated diseases. What do we know so far? Cell. Mol. Neurobiol., 2008, 28(5), 643-652. doi: 10.1007/s10571-007-9181-x PMID: 17710531
- Yuan, L.G.; Deng, H.B.; Chen, L.H.; Li, D.D.; He, Q.Y. Reversal of apoptotic resistance by Lycium barbarum glycopeptide 3 in aged T cells. Biomed. Environ. Sci., 2008, 21(3), 212-217. doi: 10.1016/S0895-3988(08)60031-8 PMID: 18714818
- Gao, Y.; Wei, Y.; Wang, Y.; Gao, F.; Chen, Z. Lycium Barbarum: A traditional chinese herb and a promising anti-aging agent. Aging Dis., 2017, 8(6), 778-791. doi: 10.14336/AD.2017.0725 PMID: 29344416
- Zavarin, E.; Mirov, N.T.; Snajberk, K. Turpentine chemistry and taxonomy of three pines of Southeastern Asia. Phytochemistry, 1966, 5(1), 91-96. doi: 10.1016/S0031-9422(00)85085-2
- Ríos, J.L. Chemical constituents and pharmacological properties of Poria cocos. Planta Med., 2011, 77(7), 681-691. doi: 10.1055/s-0030-1270823 PMID: 21347995
- Yuan, H.; Jiang, S.; Liu, Y.; Daniyal, M.; Jian, Y.; Peng, C.; Shen, J.; Liu, S.; Wang, W. The flower head of Chrysanthemum morifolium Ramat. (Juhua): A paradigm of flowers serving as Chinese dietary herbal medicine. J. Ethnopharmacol., 2020, 261, 113043. doi: 10.1016/j.jep.2020.113043 PMID: 32593689
- Yan, L.; Wang, J.; He, X.; Jin, Y.; Chen, P.; Bai, Y.; Li, P.; Su, W. Platycladus orientalis seed extract as a potential triple reuptake MAO inhibitor rescue depression phenotype through restoring monoamine neurotransmitters. J. Ethnopharmacol., 2022, 295, 115302. doi: 10.1016/j.jep.2022.115302 PMID: 35489661
- Li, X.; He, Y.; Zeng, P.; Liu, Y.; Zhang, M.; Hao, C.; Wang, H.; Lv, Z.; Zhang, L. Molecular basis for Poria cocos mushroom polysaccharide used as an antitumour drug in China. J. Cell. Mol. Med., 2019, 23(1), 4-20. doi: 10.1111/jcmm.13564 PMID: 30444050
- Shen, C.Y.; Jiang, J.G.; Yang, L.; Wang, D.W.; Zhu, W. Anti‐ageing active ingredients from herbs and nutraceuticals used in traditional Chinese medicine: pharmacological mechanisms and implications for drug discovery. Br. J. Pharmacol., 2017, 174(11), 1395-1425. doi: 10.1111/bph.13631 PMID: 27659301
- Fang, C.L.; Paul, C.R.; Day, C.H.; Chang, R.L.; Kuo, C.H.; Ho, T.J.; Hsieh, D.J.Y.; Viswanadha, V.P.; Kuo, W.W.; Huang, C.Y. Poria cocos (Fuling) targets TGFβ/Smad7 associated collagen accumulation and enhances Nrf2‐antioxidant mechanism to exert anti‐skin aging effects in human dermal fibroblasts. Environ. Toxicol., 2021, 36(5), 729-736. doi: 10.1002/tox.23075 PMID: 33336893
- Hopkins, A.L. Network pharmacology: The next paradigm in drug discovery. Nat. Chem. Biol., 2008, 4(11), 682-690. doi: 10.1038/nchembio.118 PMID: 18936753
- Hopkins, A.L. Network pharmacology. Nat. Biotechnol., 2007, 25(10), 1110-1111. doi: 10.1038/nbt1007-1110 PMID: 17921993
- Luo, T.; Lu, Y.; Yan, S.; Xiao, X.; Rong, X.; Guo, J. Network pharmacology in research of chinese medicine formula: Methodology, application and prospective. Chin. J. Integr. Med., 2020, 26(1), 72-80. doi: 10.1007/s11655-019-3064-0 PMID: 30941682
- Li, S.; Fan, T-P.; Jia, W.; Lu, A.; Zhang, W. Network pharmacology in traditional chinese medicine. Evid. Based Complement. Alternat. Med., 2014, 2014, 138460. PMID: 24707305
- Li, S.; Zhang, B. Traditional Chinese medicine network pharmacology: Theory, methodology and application. Chin. J. Nat. Med., 2013, 11(2), 110-120. doi: 10.1016/S1875-5364(13)60037-0 PMID: 23787177
- Zhang, R.; Zhu, X.; Bai, H.; Ning, K. Network pharmacology databases for traditional chinese medicine: Review and assessment. Front. Pharmacol., 2019, 10, 123. doi: 10.3389/fphar.2019.00123 PMID: 30846939
- Zhou, Z.; Chen, B.; Chen, S.; Lin, M.; Chen, Y.; Jin, S.; Chen, W.; Zhang, Y. Applications of network pharmacology in traditional chinese medicine research. Evid. Based Complement. Alternat. Med., 2020, 2020, 1-7. doi: 10.1155/2020/1646905 PMID: 32148533
- Liu, G-H.; Bao, Y.; Qu, J.; Zhang, W.; Zhang, T.; Kang, W.; Yang, F.; Ji, Q.; Jiang, X.; Ma, Y.; Ma, S.; Liu, Z.; Chen, S.; Wang, S.; Sun, S.; Geng, L.; Yan, K.; Yan, P.; Fan, Y.; Song, M.; Ren, J.; Wang, Q.; Yang, S.; Yang, Y.; Xiong, M.; Liang, C.; Li, L-Z.; Cao, T.; Hu, J.; Yang, P.; Ping, J.; Hu, H.; Zheng, Y.; Sun, G.; Li, J.; Liu, L.; Zou, Z.; Ding, Y.; Li, M.; Liu, D.; Wang, M.; Ji, Q.; Sun, X.; Wang, C.; Bi, S.; Shan, H.; Zhuo, X. Aging Atlas: A multi-omics database for aging biology. Nucleic Acids Res., 2021, 49(D1), D825-D830. doi: 10.1093/nar/gkaa894 PMID: 33119753
- Ru, J.; Li, P.; Wang, J.; Zhou, W.; Li, B.; Huang, C.; Li, P.; Guo, Z.; Tao, W.; Yang, Y.; Xu, X.; Li, Y.; Wang, Y.; Yang, L. TCMSP: A database of systems pharmacology for drug discovery from herbal medicines. J. Cheminform., 2014, 6(1), 13. doi: 10.1186/1758-2946-6-13 PMID: 24735618
- Fang, S.; Dong, L.; Liu, L.; Guo, J.; Zhao, L.; Zhang, J.; Bu, D.; Liu, X.; Huo, P.; Cao, W.; Dong, Q.; Wu, J.; Zeng, X.; Wu, Y.; Zhao, Y. HERB: A high-throughput experiment-and reference-guided database of traditional Chinese medicine. Nucleic Acids Res., 2021, 49(D1), D1197-D1206. doi: 10.1093/nar/gkaa1063 PMID: 33264402
- Yu, G.; Wang, L.G.; Han, Y.; He, Q.Y. clusterProfiler: An R package for comparing biological themes among gene clusters. OMICS, 2012, 16(5), 284-287. doi: 10.1089/omi.2011.0118 PMID: 22455463
- Smoot, M.E.; Ono, K.; Ruscheinski, J.; Wang, P.L.; Ideker, T. Cytoscape 2.8: New features for data integration and network visualization. Bioinformatics, 2011, 27(3), 431-432. doi: 10.1093/bioinformatics/btq675 PMID: 21149340
- Seeliger, D.; de Groot, B.L. Ligand docking and binding site analysis with PyMOL and Autodock/Vina. J. Comput. Aided Mol. Des., 2010, 24(5), 417-422. doi: 10.1007/s10822-010-9352-6 PMID: 20401516
- Studio, D. Discovery Studio; Accelrys, 2008. 2.1
- Trott, O.; Olson, A.J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem., 2010, 31(2), 455-461. PMID: 19499576
- Szklarczyk, D.; Gable, A.L.; Nastou, K.C.; Lyon, D.; Kirsch, R.; Pyysalo, S.; Doncheva, N.T.; Legeay, M.; Fang, T.; Bork, P.; Jensen, L.J.; von Mering, C. The STRING database in 2021: Customizable proteinprotein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res., 2021, 49(D1), D605-D612. doi: 10.1093/nar/gkaa1074 PMID: 33237311
- Zhou, D.; Borsa, M.; Simon, A.K. Hallmarks and detection techniques of cellular senescence and cellular ageing in immune cells. Aging Cell, 2021, 20(2), e13316. doi: 10.1111/acel.13316 PMID: 33524238
- Kris-Etherton, P.M.; Harris, W.S.; Appel, L.J. Omega-3 fatty acids and cardiovascular disease: new recommendations from the American Heart Association. Arterioscler. Thromb. Vasc. Biol., 2003, 23(2), 151-152. doi: 10.1161/01.ATV.0000057393.97337.AE PMID: 12588750
- Lim, H.; Kwon, Y.S.; Kim, D.; Lee, J.; Kim, H.P. Flavonoids from Scutellaria baicalensis inhibit senescence-associated secretory phenotype production by interrupting IκBζ/C/EBPβ pathway: Inhibition of age-related inflammation. Phytomedicine, 2020, 76, 153255. doi: 10.1016/j.phymed.2020.153255 PMID: 32554301
- Yang, Y.-C.; Lin, H.-Y.; Su, K.-Y.; Chen, C.-H.; Yu, Y.-L.; Lin, C.-C.; Yu, S.-L.; Yan, H.-Y.; Su, K.-J.; Chen, Y.-L.S. Rutin, a flavonoid that is a main component of saussurea involucrata, attenuates the senescence effect in D-Galactose aging mouse model. Evidence-Based Complementary and Alternative Medicine, 2012, 2012
- Nakajima, A.; Aoyama, Y.; Nguyen, T.T.L.; Shin, E.J.; Kim, H.C.; Yamada, S.; Nakai, T.; Nagai, T.; Yokosuka, A.; Mimaki, Y.; Ohizumi, Y.; Yamada, K. Nobiletin, a citrus flavonoid, ameliorates cognitive impairment, oxidative burden, and hyperphosphorylation of tau in senescence-accelerated mouse. Behav. Brain Res., 2013, 250, 351-360. doi: 10.1016/j.bbr.2013.05.025 PMID: 23714077
- Sun, C.; Wang, X.; Zheng, G.; Fan, S.; Lu, J.; Zhang, Z.; Wu, D.; Shan, Q.; Hu, B.; Zheng, Y. Protective effect of different flavonoids against endothelial senescence via NLRP3 inflammasome. J. Funct. Foods, 2016, 26, 598-609. doi: 10.1016/j.jff.2016.08.031
- Miyauchi, H.; Minamino, T.; Tateno, K.; Kunieda, T.; Toko, H.; Komuro, I. Akt negatively regulates the in vitro lifespan of human endothelial cells via a p53/p21-dependent pathway. EMBO J., 2004, 23(1), 212-220. doi: 10.1038/sj.emboj.7600045 PMID: 14713953
- Xing, C.; Liu, X.F.; Zhang, C.F.; Yang, L. Hsp90-associated DNA replication checkpoint protein and proteasome-subunit components are involved in the age-related macular degeneration. Chin. Med. J., 2021, 134(19), 2322-2332. doi: 10.1097/CM9.0000000000001773 PMID: 34629418
- De Benedetti, F.; Alonzi, T.; Moretta, A.; Lazzaro, D.; Costa, P.; Poli, V.; Martini, A.; Ciliberto, G.; Fattori, E. Interleukin 6 causes growth impairment in transgenic mice through a decrease in insulin-like growth factor-I. A model for stunted growth in children with chronic inflammation. J. Clin. Invest., 1997, 99(4), 643-650. doi: 10.1172/JCI119207 PMID: 9045866
- Kim, H.J.; Jung, K.J.; Yu, B.P.; Cho, C.G.; Chung, H.Y. Influence of aging and calorie restriction on MAPKs activity in rat kidney. Exp. Gerontol., 2002, 37(8-9), 1041-1053. doi: 10.1016/S0531-5565(02)00082-7 PMID: 12213555
- van Heemst, D.; Mooijaart, S.P.; Beekman, M.; Schreuder, J.; de Craen, A.J.M.; Brandt, B.W.; Eline Slagboom, P.; Westendorp, R.G.J. Variation in the human TP53 gene affects old age survival and cancer mortality. Exp. Gerontol., 2005, 40(1-2), 11-15. doi: 10.1016/j.exger.2004.10.001 PMID: 15732191
- Murphy, J.F.; Fitzgerald, D.J. Vascular endothelial cell growth factor (VEGF) induces cyclooxygenase (COX)‐dependent proliferation of endothelial cells (EC) via the VEGF‐2 receptor. FASEB J., 2001, 15(9), 1667-1669. doi: 10.1096/fj.00-0757fje PMID: 11427521
- Burton, M.D.; Rytych, J.L.; Amin, R.; Johnson, R.W. Dietary luteolin reduces proinflammatory microglia in the brain of senescent mice. Rejuvenation Res., 2016, 19(4), 286-292. doi: 10.1089/rej.2015.1708 PMID: 26918466
- Domaszewska-Szostek, A.; Puzianowska-Kuźnicka, M.; Kuryłowicz, A. Flavonoids in skin senescence prevention and treatment. Int. J. Mol. Sci., 2021, 22(13), 6814. doi: 10.3390/ijms22136814 PMID: 34201952
- Jiang, Y.H.; Jiang, L.Y.; Wang, Y.C.; Ma, D.F.; Li, X. Quercetin attenuates atherosclerosis via modulating oxidized LDL-induced endothelial cellular senescence. Front. Pharmacol., 2020, 11, 512. doi: 10.3389/fphar.2020.00512 PMID: 32410992
Supplementary files
