Identifying the Anti-inflammatory Effects of Astragalus Polysaccharides in Anti-N-Methyl-D-Aspartate Receptor Encephalitis: Network Pharmacology and Experimental Validation
- Авторы: Lu Y.1, Wu Y.1, Sun L.1, Yang S.1, Kuang H.1, Li R.1, Meng Y.1, Wu Y.1
-
Учреждения:
- Department of Neurology, First Affiliated Hospital of Guangxi Medical University
- Выпуск: Том 27, № 7 (2024)
- Страницы: 1022-1032
- Раздел: Chemistry
- URL: https://kazanmedjournal.ru/1386-2073/article/view/644929
- DOI: https://doi.org/10.2174/1386207326666230816162113
- ID: 644929
Цитировать
Полный текст
Аннотация
Background:Astragalus polysaccharides (APS), a group of bioactive compounds obtained from the natural source Astragalus membranaceus (AM), exhibits numerous pharmacological actions in the central nervous system, such as anti-inflammatory, antioxidant, and immunomodulatory properties. Despite the remarkable benefits, the effectiveness of APS in treating anti- N-methyl-D-aspartate receptor (NMDAR) encephalitis and the corresponding mechanism have yet to be fully understood. As such, this study aims to investigate the impact of APS on anti-NMDAR encephalitis and explore the potential molecular network mechanism.
Methods:The impact of APS intervention on mice with anti-NMDAR encephalitis was assessed, and the possible molecular network mechanism was investigated utilizing network pharmacology and bioinformatics techniques such as Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG),proteinprotein interaction (PPI) network, and molecular docking. Enzymelinked immunosorbent assay (ELISA) was applied to detect the expression of core target proteins.
Results:APS significantly ameliorated cognitive impairment and reduced susceptibility to PTZinduced seizures in mice with anti-NMDAR encephalitis, confirming the beneficial effect of APS on anti-NMDAR encephalitis. Seventeen intersecting genes were identified between APS and anti- NMDAR encephalitis. GO and KEGG analyses revealed the characteristics of the intersecting gene networks. STRING interaction in the PPI network was applied to find crucial molecules. The results of molecular docking suggested that APS may regulate interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) as potential targets in anti-NMDAR encephalitis. Furthermore, the levels of IL-1β, IL-6, and TNF-α detected by ELISA in anti-NMDAR encephalitis mice were significantly downregulated in response to the administration of APS.
Conclusion:The findings of this study demonstrate the significant role of APS in the treatment of anti-NMDAR encephalitis, as it effectively suppresses inflammatory cytokines. These results suggest that APS has the potential to be considered as a viable herbal medication for the treatment of anti-NMDAR encephalitis.
Об авторах
Yuling Lu
Department of Neurology, First Affiliated Hospital of Guangxi Medical University
Email: info@benthamscience.net
Ying Wu
Department of Neurology, First Affiliated Hospital of Guangxi Medical University
Email: info@benthamscience.net
Lanfeng Sun
Department of Neurology, First Affiliated Hospital of Guangxi Medical University
Email: info@benthamscience.net
Shengyu Yang
Department of Neurology, First Affiliated Hospital of Guangxi Medical University
Email: info@benthamscience.net
Huimin Kuang
Department of Neurology, First Affiliated Hospital of Guangxi Medical University
Email: info@benthamscience.net
Rida Li
Department of Neurology, First Affiliated Hospital of Guangxi Medical University
Email: info@benthamscience.net
Youshi Meng
Department of Neurology, First Affiliated Hospital of Guangxi Medical University
Email: info@benthamscience.net
Yuan Wu
Department of Neurology, First Affiliated Hospital of Guangxi Medical University
Автор, ответственный за переписку.
Email: info@benthamscience.net
Список литературы
- Dalmau, J.; Lancaster, E.; Martinez-Hernandez, E.; Rosenfeld, M.R.; Balice-Gordon, R. Clinical experience and laboratory investigations in patients with anti-NMDAR encephalitis. Lancet Neurol., 2011, 10(1), 63-74. doi: 10.1016/S1474-4422(10)70253-2 PMID: 21163445
- Dalmau, J.; Graus, F. Antibody-mediated encephalitis. N. Engl. J. Med., 2018, 378(9), 840-851. doi: 10.1056/NEJMra1708712 PMID: 29490181
- Camdessanché, J.P.; Streichenberger, N.; Cavillon, G.; Rogemond, V.; Jousserand, G.; Honnorat, J.; Convers, P.; Antoine, J.C. Brain immunohistopathological study in a patient with anti-NMDAR encephalitis. Eur. J. Neurol., 2011, 18(6), 929-931. doi: 10.1111/j.1468-1331.2010.03180.x PMID: 20722705
- Taraschenko, O.; Fox, H.S.; Zekeridou, A.; Pittock, S.J.; Eldridge, E.; Farukhuddin, F.; Al-Saleem, F.; Devi Kattala, C.; Dessain, S.K.; Casale, G.; Willcockson, G.; Dingledine, R. Seizures and memory impairment induced by patient‐derived anti‐N‐methyl‐D‐aspartate receptor antibodies in mice are attenuated by anakinra, an interleukin‐1 receptor antagonist. Epilepsia, 2021, 62(3), 671-682. doi: 10.1111/epi.16838 PMID: 33596332
- Abboud, H.; Probasco, J.C.; Irani, S.; Ances, B.; Benavides, D.R.; Bradshaw, M.; Christo, P.P.; Dale, R.C.; Fernandez-Fournier, M.; Flanagan, E.P.; Gadoth, A.; George, P.; Grebenciucova, E.; Jammoul, A.; Lee, S.T.; Li, Y.; Matiello, M.; Morse, A.M.; Rae-Grant, A.; Rojas, G.; Rossman, I.; Schmitt, S.; Venkatesan, A.; Vernino, S.; Pittock, S.J.; Titulaer, M.J. Autoimmune encephalitis: Proposed best practice recommendations for diagnosis and acute management. J. Neurol. Neurosurg. Psychiatry, 2021, 92(7), 757-768. doi: 10.1136/jnnp-2020-325300 PMID: 33649022
- Graus, F.; Titulaer, M.J.; Balu, R.; Benseler, S.; Bien, C.G.; Cellucci, T.; Cortese, I.; Dale, R.C.; Gelfand, J.M.; Geschwind, M.; Glaser, C.A.; Honnorat, J.; Höftberger, R.; Iizuka, T.; Irani, S.R.; Lancaster, E.; Leypoldt, F.; Prüss, H.; Rae-Grant, A.; Reindl, M.; Rosenfeld, M.R.; Rostásy, K.; Saiz, A.; Venkatesan, A.; Vincent, A.; Wandinger, K.P.; Waters, P.; Dalmau, J. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol., 2016, 15(4), 391-404. doi: 10.1016/S1474-4422(15)00401-9 PMID: 26906964
- Hacohen, Y.; Wright, S.; Waters, P.; Agrawal, S.; Carr, L.; Cross, H.; De Sousa, C.; DeVile, C.; Fallon, P.; Gupta, R.; Hedderly, T.; Hughes, E.; Kerr, T.; Lascelles, K.; Lin, J.P.; Philip, S.; Pohl, K.; Prabahkar, P.; Smith, M.; Williams, R.; Clarke, A.; Hemingway, C.; Wassmer, E.; Vincent, A.; Lim, M.J. Paediatric autoimmune encephalopathies: clinical features, laboratory investigations and outcomes in patients with or without antibodies to known central nervous system autoantigens. J. Neurol. Neurosurg. Psychiatry, 2013, 84(7), 748-755. doi: 10.1136/jnnp-2012-303807 PMID: 23175854
- Huang, Q.; Xie, Y.; Hu, Z.; Tang, X. Anti-N-methyl-D-aspartate receptor encephalitis: A review of pathogenic mechanisms, treatment, prognosis. Brain Res., 2020, 1727, 146549. doi: 10.1016/j.brainres.2019.146549 PMID: 31726044
- Wang, D.Y.; Salem, J.E.; Cohen, J.V.; Chandra, S.; Menzer, C.; Ye, F.; Zhao, S.; Das, S.; Beckermann, K.E.; Ha, L.; Rathmell, W.K.; Ancell, K.K.; Balko, J.M.; Bowman, C.; Davis, E.J.; Chism, D.D.; Horn, L.; Long, G.V.; Carlino, M.S.; Lebrun-Vignes, B.; Eroglu, Z.; Hassel, J.C.; Menzies, A.M.; Sosman, J.A.; Sullivan, R.J.; Moslehi, J.J.; Johnson, D.B. Fatal toxic effects associated with immune checkpoint inhibitors. JAMA Oncol., 2018, 4(12), 1721-1728. doi: 10.1001/jamaoncol.2018.3923 PMID: 30242316
- Morris, E.C.; Neelapu, S.S.; Giavridis, T.; Sadelain, M. Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy. Nat. Rev. Immunol., 2022, 22(2), 85-96. doi: 10.1038/s41577-021-00547-6 PMID: 34002066
- Zheng, Y.; Ren, W.; Zhang, L.; Zhang, Y.; Liu, D.; Liu, Y. A review of the pharmacological action of astragalus polysaccharide. Front. Pharmacol., 2020, 11, 349. doi: 10.3389/fphar.2020.00349 PMID: 32265719
- Jia, X.; Xie, L.; Liu, Y.; Liu, T.; Yang, P.; Hu, J.; Peng, Z.; Luo, K.; Du, M.; Chen, C. Astragalus polysaccharide (APS) exerts protective effect against acute ischemic stroke (AIS) through enhancing M2 micoglia polarization by regulating adenosine triphosphate (ATP)/purinergic receptor (P2X7R) axis. Bioengineered, 2022, 13(2), 4468-4480. doi: 10.1080/21655979.2021.1980176 PMID: 35166175
- Liu, X.; Ma, J.; Ding, G.; Gong, Q.; Wang, Y.; Yu, H.; Cheng, X. Microglia polarization from m1 toward m2 phenotype is promoted by Astragalus Polysaccharides mediated through inhibition of mir-155 in experimental autoimmune encephalomyelitis. Oxid. Med. Cell. Longev., 2021, 2021, 1-15. doi: 10.1155/2021/5753452 PMID: 34976303
- Byun, J.I.; Lee, S.T.; Moon, J.; Jung, K.H.; Sunwoo, J.S.; Lim, J.A.; Kim, T.J.; Shin, Y.W.; Lee, K.J.; Jun, J.S.; Lee, H.S.; Lee, W.J.; Kim, Y.S.; Kim, S.; Jeon, D.; Park, K.I.; Jung, K.Y.; Kim, M.; Chu, K.; Lee, S.K. Distinct intrathecal interleukin-17/interleukin-6 activation in anti-N-methyl-d-aspartate receptor encephalitis. J. Neuroimmunol., 2016, 297, 141-147. doi: 10.1016/j.jneuroim.2016.05.023 PMID: 27397087
- Nogales, C.; Mamdouh, Z.M.; List, M.; Kiel, C.; Casas, A.I.; Schmidt, H.H.H.W. Network pharmacology: Curing causal mechanisms instead of treating symptoms. Trends Pharmacol. Sci., 2022, 43(2), 136-150. doi: 10.1016/j.tips.2021.11.004 PMID: 34895945
- Liu, M.; Li, Z.; Ouyang, Y.; Chen, M.; Guo, X.; Mazhar, M.; Kang, J.; Zhou, H.; Wu, Q.; Yang, S. Material basis and integrative pharmacology of danshen decoction in the treatment of cardiovascular diseases. Phytomedicine, 2023, 108, 154503. doi: 10.1016/j.phymed.2022.154503 PMID: 36332387
- Liu, C.; Li, H.; Wang, K.; Zhuang, J.; Chu, F.; Gao, C.; Liu, L.; Feng, F.; Zhou, C.; Zhang, W.; Sun, C. Identifying the antiproliferative effect of Astragalus polysaccharides on breast cancer: Coupling network pharmacology with targetable screening from the cancer genome atlas. Front. Oncol., 2019, 9, 368. doi: 10.3389/fonc.2019.00368 PMID: 31157164
- Zhao, Z.H.; Xu, M.; Fu, C.; Huang, Y.; Wang, T.H.; Zuo, Z.F.; Liu, X.Z. A mechanistic exploratory study on the therapeutic efficacy of astragaloside iv against diabetic retinopathy revealed by network pharmacology. Front. Pharmacol., 2022, 13, 903485. doi: 10.3389/fphar.2022.903485 PMID: 35814228
- Li, M.; Zheng, Y.; Deng, S.; Yu, T.; Ma, Y.; Ge, J.; Li, J.; Li, X.; Ma, L. Potential therapeutic effects and applications of Eucommiae Folium in secondary hypertension. J. Pharm. Anal., 2022, 12(5), 711-718. doi: 10.1016/j.jpha.2021.10.004 PMID: 36320603
- Jiao, W.; Mi, S.; Sang, Y.; Jin, Q.; Chitrakar, B.; Wang, X.; Wang, S. Integrated network pharmacology and cellular assay for the investigation of an anti-obesity effect of 6-shogaol. Food Chem., 2022, 374, 131755. doi: 10.1016/j.foodchem.2021.131755 PMID: 34883426
- Xia, J.; Hu, J.N.; Wang, Z.; Cai, E.B.; Ren, S.; Wang, Y.P.; Lei, X.J.; Li, W. Based on network pharmacology and molecular docking to explore the protective effect of Epimedii Folium extract on cisplatin-induced intestinal injury in mice. Front. Pharmacol., 2022, 13, 1040504. doi: 10.3389/fphar.2022.1040504 PMID: 36313368
- Wagnon, I.; Hélie, P.; Bardou, I.; Regnauld, C.; Lesec, L.; Leprince, J.; Naveau, M.; Delaunay, B.; Toutirais, O.; Lemauff, B.; Etard, O.; Vivien, D.; Agin, V.; Macrez, R.; Maubert, E.; Docagne, F. Autoimmune encephalitis mediated by B-cell response against N-methyl-d-aspartate receptor. Brain, 2020, 143(10), 2957-2972. doi: 10.1093/brain/awaa250 PMID: 32893288
- Dang, R.; Wang, M.; Li, X.; Wang, H.; Liu, L.; Wu, Q.; Zhao, J.; Ji, P.; Zhong, L.; Licinio, J.; Xie, P. Edaravone ameliorates depressive and anxiety-like behaviors via Sirt1/Nrf2/HO-1/Gpx4 pathway. J. Neuroinflammation, 2022, 19(1), 41. doi: 10.1186/s12974-022-02400-6 PMID: 35130906
- Lüttjohann, A.; Fabene, P.F.; van Luijtelaar, G. A revised Racines scale for PTZ-induced seizures in rats. Physiol. Behav., 2009, 98(5), 579-586. doi: 10.1016/j.physbeh.2009.09.005 PMID: 19772866
- Titulaer, M.J.; McCracken, L.; Gabilondo, I.; Armangué, T.; Glaser, C.; Iizuka, T.; Honig, L.S.; Benseler, S.M.; Kawachi, I.; Martinez-Hernandez, E.; Aguilar, E.; Gresa-Arribas, N.; Ryan-Florance, N.; Torrents, A.; Saiz, A.; Rosenfeld, M.R.; Balice-Gordon, R.; Graus, F.; Dalmau, J. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: An observational cohort study. Lancet Neurol., 2013, 12(2), 157-165. doi: 10.1016/S1474-4422(12)70310-1 PMID: 23290630
- Dong, Q.; Li, Z.; Zhang, Q.; Hu, Y.; Liang, H.; Xiong, L. Astragalus mongholicus bunge (Fabaceae): Bioactive compounds and potential therapeutic mechanisms against alzheimers disease. Front. Pharmacol., 2022, 13, 924429. doi: 10.3389/fphar.2022.924429 PMID: 35837291
- Huang, Y.C.; Tsay, H.J.; Lu, M.K.; Lin, C.H.; Yeh, C.W.; Liu, H.K.; Shiao, Y.J. Astragalus membranaceus-polysaccharides ameliorates obesity, hepatic steatosis, neuroinflammation and cognition impairment without affecting amyloid deposition in metabolically stressed APPswe/PS1dE9 mice. Int. J. Mol. Sci., 2017, 18(12), 2746. doi: 10.3390/ijms18122746 PMID: 29258283
- Aldarmaa, J.; Liu, Z.; Long, J.; Mo, X.; Ma, J.; Liu, J. Anti-convulsant effect and mechanism of Astragalus mongholicus extract in vitro and in vivo: Protection against oxidative damage and mitochondrial dysfunction. Neurochem. Res., 2010, 35(1), 33-41. doi: 10.1007/s11064-009-0027-4 PMID: 19578991
- Yang, J.; Jia, Z.; Xiao, Z.; Zhao, J.; Lu, Y.; Chu, L.; Shao, H.; Pei, L.; Zhang, S.; Chen, Y. Baicalin rescues cognitive dysfunction, mitigates neurodegeneration, and exerts anti-epileptic effects through activating TLR4/MYD88/Caspase-3 pathway in rats. Drug Des. Devel. Ther., 2021, 15, 3163-3180. doi: 10.2147/DDDT.S314076 PMID: 34321866
- Jalsrai, A.; Grecksch, G.; Becker, A. Evaluation of the effects of astragalus mongholicus bunge saponin extract on central nervous system functions. J. Ethnopharmacol., 2010, 131(3), 544-549. doi: 10.1016/j.jep.2010.07.031 PMID: 20655376
- Qin, X.; Hua, J.; Lin, S.; Zheng, H.; Wang, J.; Li, W.; Ke, J.; Cai, H. Astragalus polysaccharide alleviates cognitive impairment and β-amyloid accumulation in APP/PS1 mice via Nrf2 pathway. Biochem. Biophys. Res. Commun., 2020, 531(3), 431-437. doi: 10.1016/j.bbrc.2020.07.122 PMID: 32800555
- Liu, Y.; Liu, W.; Li, J.; Tang, S.; Wang, M.; Huang, W.; Yao, W.; Gao, X. A polysaccharide extracted from astragalus membranaceus residue improves cognitive dysfunction by altering gut microbiota in diabetic mice. Carbohydr. Polym., 2019, 205, 500-512. doi: 10.1016/j.carbpol.2018.10.041 PMID: 30446134
- Liu, J.; Liu, L.; Kang, W.; Peng, G.; Yu, D.; Ma, Q.; Li, Y.; Zhao, Y.; Li, L.; Dai, F.; Wang, J. Cytokines/Chemokines: Potential biomarkers for non-paraneoplastic anti-n-methyl-d-aspartate receptor encephalitis. Front. Neurol., 2020, 11, 582296. doi: 10.3389/fneur.2020.582296 PMID: 33408682
- Peng, Y.; Liu, B.; Pei, S.; Zheng, D.; Wang, Z.; Ji, T.; Pan, S.; Shen, H.Y.; Wang, H. Higher CSF Levels of NLRP3 inflammasome is associated with poor prognosis of anti-n-methyl-d-aspartate receptor encephalitis. Front. Immunol., 2019, 10, 905. doi: 10.3389/fimmu.2019.00905 PMID: 31214158
- Wang, D.; Wu, Y.; Pan, Y.; Wang, S.; Liu, G.; Gao, Y. Multi-proteomic analysis revealed distinct protein profiles in cerebrospinal fluid of patients between anti-nmdar encephalitis norse and cryptogenic norse. Mol. Neurobiol., 2022, 60(1), 98-115. PMID: 36224320
- Li, Q.; Chen, J.; Yin, M.; Zhao, J.; Lu, F.; Wang, Z.; Yu, X.; Wang, S.; Zheng, D.; Wang, H. High level of soluble cd146 in cerebrospinal fluid might be a biomarker of severity of anti-n-methyl-d-aspartate receptor encephalitis. Front. Immunol., 2021, 12, 680424. doi: 10.3389/fimmu.2021.680424 PMID: 34220828
- Li, J.; Gu, Y.; An, H.; Zhou, Z.; Zheng, D.; Wang, Z.; Wen, Z.; Shen, H.Y.; Wang, Q.; Wang, H. Cerebrospinal fluid light and heavy neurofilament level increased in anti‐ N ‐methyl‐ D ‐aspartate receptor encephalitis. Brain Behav., 2019, 9(8), e01354. doi: 10.1002/brb3.1354 PMID: 31313506
- Lee, W.J.; Lee, S.T.; Moon, J.; Sunwoo, J.S.; Byun, J.I.; Lim, J.A.; Kim, T.J.; Shin, Y.W.; Lee, K.J.; Jun, J.S.; Lee, H.S.; Kim, S.; Park, K.I.; Jung, K.H.; Jung, K.Y.; Kim, M.; Lee, S.K.; Chu, K. Tocilizumab in autoimmune encephalitis refractory to rituximab: An institutional cohort study. Neurotherapeutics, 2016, 13(4), 824-832. doi: 10.1007/s13311-016-0442-6 PMID: 27215218
- Jiao, C.; Liang, H.; Liu, L.; Li, S.; Chen, J.; Xie, Y. Transcriptomic analysis of the anti-inflammatory effect of Cordyceps militaris extract on acute gouty arthritis. Front. Pharmacol., 2022, 13, 1035101. doi: 10.3389/fphar.2022.1035101 PMID: 36313318
- Cao, Z.; Liu, Y.; Zhang, Z.; Yang, P.; Li, Z.; Song, M.; Qi, X.; Han, Z.; Pang, J.; Li, B.; Zhang, X.; Dai, H.; Wang, J.; Wang, C. Pirfenidone ameliorates silica-induced lung inflammation and fibrosis in mice by inhibiting the secretion of interleukin-17A. Acta Pharmacol. Sin., 2022, 43(4), 908-918. doi: 10.1038/s41401-021-00706-4 PMID: 34316030
- Liu, N.; Liu, C.; Yang, Y.; Ma, G.; Wei, G.; Liu, S.; Kong, L.; Du, G. Xiao-Xu-Ming decoction prevented hemorrhagic transformation induced by acute hyperglycemia through inhibiting AGE-RAGE-mediated neuroinflammation. Pharmacol. Res., 2021, 169, 105650. doi: 10.1016/j.phrs.2021.105650 PMID: 33964468
- Tong, M.; Kayani, T.; Jones, D.M.; Salmon, J.E.; Whirledge, S.; Chamley, L.W.; Abrahams, V.M. Antiphospholipid Antibodies Increase Endometrial Stromal Cell Decidualization, Senescence, and Inflammation via toll‐like receptor 4, reactive oxygen species, and p38 MAPK signaling. Arthritis Rheumatol., 2022, 74(6), 1001-1012. doi: 10.1002/art.42068 PMID: 35044724
Дополнительные файлы
