Natural phytochemicals as P2X7 receptor inhibitors for the treatment of inflammation-related diseases
Main Article Content
Keywords
autoimmune diseases, baicalin, dihydrotanshinone, molecular docking, P2X7 receptor, phytochemicals
Abstract
P2X7 receptor (P2X7R) inhibition is critical for reducing the overactivation of its downstream signaling pathway in autoimmune diseases. Phytochemicals are a source of medicinal compounds for various diseases and contribute to the development of effective and safe P2X7R-targeted drugs. This review is aimed at identifying and screening novel safe, effective, and economically feasible inhibitors of P2X7R from phytochemicals extracted from food and plants. The results of the docking study revealed that the VINA scores of dihydrotanshinone, baicalin, berberine, genistin, dioscin, resveratrol, apigenin, cannabidiol, esculin, and luteolin were lower than or equal to that of A740003 (P2X7R inhibitor). The VINA scores of dihydrotanshinone and baicalin were lower than or equal to JNJ47965567 (P2X7R inhibitor). Dihydrotanshinone and baicalin can be used as lead compounds for P2X7R inhibition. These active ingredients will contribute to the discovery of lead compounds and the development of innovative P2X7R agents for the treatment of autoimmune diseases.
References
Ahn, Y., Seo, J., Lee, E.J., Kim, J.Y., Park, M.Y., Hwang, S., Almurayshid, A., Lim, B.J., Yu, J.W. and Oh, S.H., 2020. ATP-P2X7-induced inflammasome activation contributes to melanocyte death and CD8+ T-cell trafficking to the skin in Vitiligo. The Journal of Investigative Dermatology. 140(9): 1794–1804. 10.1016/j.jid.2019.12.035
Alakurtti, S., Mäkelä, T., Koskimies, S. and Yli-Kauhaluoma, J., 2006. Pharmacological properties of the ubiquitous natural product betulin. European Journal of Pharmaceutical Sciences. 29(1): 1–13. 10.1016/j.ejps.2006.04.006
Allegri, L., Domenis, R., Navarra, M., Celano, M., Russo, D., Capriglione, F., Damante, G. and Baldan F., 2021. Dihydrotanshinone exerts antitumor effects and improves the effects of cisplatin in anaplastic thyroid cancer cells. Oncology Reports. 46(3): 204. 10.3892/or.2021.8155
Atalay, S., Jarocka-Karpowicz, I. and Skrzydlewska, E., 2019., Antioxidative and anti-inflammatory properties of cannabidiol. Antioxidants (Basel). 9(1): 21. 10.3390/antiox9010021
Aziz, N., Kim, M.Y. and Cho, J.Y., 2018. Anti-inflammatory effects of luteolin: a review of in vitro, in vivo, and in silico studies. Journal of Ethnopharmacology. 225: 342–358. 10.1016/j.jep.2018.05.019
Babaei, F., Mirzababaei, M. and Nassiri-Asl, M., 2018. Quercetin in food: possible mechanisms of its effect on memory. Journal of Food Science. 83(9): 2280–2287. 10.1111/1750-3841.14317
Bai, J., Zhang, Y., Tang, C., Hou, Y., Ai, X., Chen, X., Zhang, Y., Wang, X. and Meng, X., 2021. Gallic acid: pharmacological activities and molecular mechanisms involved in inflammation--related diseases. Biomedicine Pharmacotherapy. 133: 110985. 10.1016/j.biopha.2020.110985
Burstein, S., 2015. Cannabidiol (CBD) and its analogs: a review of their effects on inflammation. Bioorganic Medicinal Chemistry. 23(7): 1377–1385. 10.1016/j.bmc.2015.01.059
Campagno, K.E., Lu, W., Jassim, A.H., Albalawi, F., Cenaj, A., Tso, H.Y., Clark, S.P., Sripinun, P., Gómez, N.M. and Mitchell, C.H., 2021. Rapid morphologic changes to microglial cells and upregulation of mixed microglial activation state markers induced by P2X7 receptor stimulation and increased intraocular pressure. Journal of Neuroinflammation. 18(1): 217. 10.1186/s12974-021-02251-7
Chai, Y., Cai, Y., Fu, Y., Wang, Y., Zhang, Y., Zhang, X., Zhu, L., Miao, M. and Yan, T., 2022. Salidroside ameliorates depression by suppressing NLRP3-mediated pyroptosis via P2X7/NF-κB/NLRP3 signaling pathway. Frontiers in Pharmacology. 13: 812362. 10.3389/fphar.2022.812362
Chang, X., He, H., Zhu, L., Gao, J., Wei, T., Ma, Z. and Yan, T., 2015. Protective effect of apigenin on Freund's complete adjuvant--induced arthritis in rats via inhibiting P2X7/NF-κB pathway. Chemico-Biological Interactions. 236: 41–46. 10.1016/j.cbi.2015.04.021
Chen, X., Yu, J., Zhong, B., Lu, J., Lu, J.J., Li, S. and Lu, Y., 2019. Pharmacological activities of dihydrotanshinone I, a-natural product from Salvia miltiorrhiza Bunge. Pharmacological Research. 145: 104254. 10.1016/j.phrs.2019.104254
Cheng, L., Chen, Q., Pi, R. and Chen, J., 2021. A research update on the therapeutic potential of rhein and its derivatives. European Journal of Pharmacology. 899: 173908. 10.1016/j.ejphar.2021.173908
Choi, Y.R., Shim, J. and Kim, M.J., 2020. Genistin: a novel potent anti-adipogenic and anti-lipogenic agent. Molecules. 25(9): 2042. 10.3390/molecules25092042
Cicero, A.F. and Baggioni, A., 2016. Berberine and its role in chronic disease. Advances in Experimental Medicine and Biology. 928: 27–45. 10.1007/978-3-319-41334-1_2
Deng, Y., Zhao, X.T., Zhou, M.T., Xue, X.Y., Liao, L., Wang, J. and Li, Y.X., 2022. Phillygenin mitigates LPS/ATP-induced L02 cell inflammation by regulation of P2X7R/NF-κB/NLRP3 inflammasome signaling pathway. Chinese Journal Expermental Traditional Medicine Formulae. 10.13422/j.cnki.syfjx.20220808
Di Virgilio, F., Dal Ben, D., Sarti, A.C., Giuliani, A.L. and Falzoni, S., 2017. The P2X7 receptor in infection and inflammation. Immunity. 47(1): 15–31. 10.1016/j.immuni.2017.06.020
Ding, X., Lu, D. and Fan, J., 2021. A natural product phillygenin suppresses osteosarcoma growth and metastasis by regulating the SHP-1/JAK2/STAT3 signaling. Bioscience, Biotechnology, and Biochemistry. 85(2): 307–314. 10.1093/bbb/zbaa007
Dong, X., Fu, J., Yin, X., Cao, S., Li, X., Lin, L.; Huyiligeqi; Ni, J., 2016. Emodin: a review of its pharmacology, toxicity and pharmacokinetics. Phytotherapy Research. 30(8): 1207–1218. 10.1002/ptr.5631
Dou, J.Y., Jiang, Y.C., Hu, Z.H., Yao, K.C., Yuan, M.H., Bao, X.X., Zhou, M.J., Liu, Y., Li, Z.X., Lian, L.H., Nan, J.X. and Wu, Y.L., 2022. Betulin targets lipin1/2-meidated P2X7 receptor as a therapeutic approach to attenuate lipid accumulation and metaflammation. Biomolecules Therapeutics. 30(3): 246–256. 10.4062/biomolther.2021.136
Faria, R.X., de Jesus Hiller, N., Salles, J.P., Resende, J.A.L.C., Diogo, R.T., von Ranke, N.L., Bello, M.L., Rodrigues, C.R., Castro, H.C. and de Luna Martins, D., 2019. Arylboronic acids inhibit P2X7 receptor function and the acute inflammatory response. Journal of Bioenergetics and Biomembranes. 51(4): 277–290. 10.1007/s10863-019-09802-x
Fresta, C.G., Caruso, G., Fidilio, A., Platania, C.B.M., Musso, N., Caraci, F., Drago, F. and Bucolo, C., 2020. Dihydrotanshinone, a natural diterpenoid, preserves blood-retinal barrier integrity via P2X7 receptor. International Journal of Molecular Sciences. 21(23): 9305. 10.3390/ijms21239305
Ge, H., Sun, M., Wei, X., Zhang, M., Tu, H., Hao, Y., Chen, R., Ye, M. and Gao, Y., 2020. Protective effects of dihydromyricetin on primary hippocampal astrocytes from cytotoxicity induced by comorbid diabetic neuropathic pain and depression. Purinergic Signalling. 16(4): 585–599. 10.1007/s11302-020-09752-9
Ginwala, R., Bhavsar, R., Chigbu, D.I., Jain, P. and Khan, Z.K., 2019. Potential role of flavonoids in treating chronic inflammatory diseases with a special focus on the anti-inflammatory activity of apigenin. Antioxidants (Basel). 8(2): 35. 10.3390/antiox8020035
Gu, M., Zheng, A.B., Jin, J., Cui, Y., Zhang, N., Che, Z.P., Wang, Y., Zhan, J. and Tu, W.J., 2016. Cardioprotective effects of genistin in rat myocardial ischemia-reperfusion injury studies by regulation of P2X7/NF-κB pathway. Evidence-Based Complementary and Alternative Medicine. 2016: 5381290. 10.1155/2016/5381290
Guan, S., Shen, Y., Ge, H., Xiong, W., He, L., Liu, L., Yin, C., Wei, X. and Gao, Y., 2019. Dihydromyricetin alleviates diabetic neuropathic pain and depression comorbidity symptoms by inhibiting P2X7 receptor. Frontiers in Psychiatry. 10: 770. 10.3389/fpsyt.2019.00770
Haanes, K.A., Schwab, A. and Novak, I., 2012. The P2X7 receptor supports both life and death in fibrogenic pancreatic stellate cells. PLoS One. 7(12): e51164. 10.1371/journal.pone.0051164
Hao, H., Cao, L., Jiang, C., Che, Y., Zhang, S., Takahashi, S., Wang, G. and Gonzalez, FJ., 2017. Farnesoid X receptor regulation of the NLRP3 inflammasome underlies cholestasis-associated sepsis. Cell Metabolism. 25(4): 856–867. 10.1016/j.cmet.2017.03.007
He, F. and Yao, G., 2021. Ginsenoside Rg1 as a potential regulator of hematopoietic stem/progenitor cells. Stem Cells International. 2021: 4633270. 10.1155/2021/4633270
He, X., Zhang, Y., Xu, Y., Xie, L., Yu, Z. and Zheng, J., 2021. Function of the P2X7 receptor in hematopoiesis and leukemogenesis. Experimental Hematology. 104: 40–47. 10.1016/j.exphem.2021.10.001
Hou, L., Jiang, F., Huang, B., Zheng, W., Jiang, Y., Cai, G., Liu, D., Hu, C.Y. and Wang, C., 2021. Dihydromyricetin ameliorates inflammation-induced insulin resistance via phospholipase C-CaMKK-AMPK signal pathway. Oxidative Medicine and Cellular Longevity. 2021: 8542809. 10.21203/rs.3.rs-184435/v1
Hu, F., Xing, F., Zhu, G., Xu, G., Li, C., Qu, J., Lee, I. and Pan, L., 2015. Rhein antagonizes P2X7 receptor in rat peritoneal macrophages. Scientific Reports. 5: 14012. 10.1038/srep14012
Huang, T., Liu, Y. and Zhang, C., 2019. Pharmacokinetics and bioavailability enhancement of baicalin: a review. European Journal of Drug Metabolism and Pharmacokinetics. 44(2): 159–168. 10.1007/s13318-018-0509-3
Huang, Z., Xie, N., Illes, P., Di Virgilio, F., Ulrich, H., Semyanov, A., Verkhratsky, A., Sperlagh, B., Yu, S.G., Huang, C. and Tang, Y., 2021. From purines to purinergic signalling: molecular functions and human diseases. Signal Transduction and Targeted Therapy. 6(1): 162. 10.1038/s41392-021-00553-z
Illes, P., Müller, C.E., Jacobson, K.A., Grutter, T., Nicke, A., Fountain, S.J., Kennedy, C., Schmalzing, G., Jarvis, M.F., Stojilkovic, S.S., King, B.F. and Di Virgilio, F., 2021. Update of P2X receptor properties and their pharmacology: IUPHAR Review 30. British Journal of Pharmacology. 178(3): 489–514. 10.1111/bph.15299
Islam, A., Islam, M.S., Uddin, M.N., Hasan, M.M.I. and Akanda, M.R., 2020. The potential health benefits of the isoflavone glycoside genistin. Archives of Pharmacal Research. 43(4): 395–408. 10.1007/s12272-020-01233-2
Karasawa, A. and Kawate, T., 2016. Structural basis for subtype--specific inhibition of the P2X7 receptor. Elife. 5: e22153. 10.7554/eLife.22153
Kashyap, P., Shikha, D., Thakur, M. and Aneja, A., 2022. Functionality of apigenin as a potent antioxidant with emphasis on bioavailability, metabolism, action mechanism and in vitro and in vivo studies: a review. Journal of Food Biochemistry. 46(4): e13950. 10.1111/jfbc.13950
Kotha, R.R. and Luthria, DL., 2019. Curcumin: biological, pharmaceutical, nutraceutical, and analytical aspects. Molecules. 24(16): 2930. 10.3390/molecules24162930
Li, G.M., Chen, J.R., Zhang, H.Q., Cao, X.Y., Sun, C., Peng, F., Yin, Y.P., Lin, Z., Yu, L., Chen, Y., Tang, Y.L., Xie, X.F. and Peng, C., 2021. Update on pharmacological activities, security, and pharmacokinetics of rhein. Evidence-Based Complementary and Alternative Medicine. 2021: 4582412. 10.1155/2021/4582412
Liu, C., Ma, H., Slitt, A.L. and Seeram, N.P., 2020a. Inhibitory effect of cannabidiol on the activation of NLRP3 inflammasome is associated with its modulation of the P2X7 receptor in human monocytes. Journal of Natural Products. 83(6): 2025–2029. 10.1021/acs.jnatprod.0c00138
Liu, J., Yong, H., Liu, Y. and Bai, R., 2020b. Recent advances in the preparation, structural characteristics, biological properties and applications of gallic acid grafted polysaccharides. International Journal of Biological Macromolecules. 156: 1539–1555. 10.1016/j.ijbiomac.2019.11.202
Liu, Y., Grimm, M., Dai, W.T., Hou, M.C., Xiao, Z.X. and Cao, Y., 2020c. CB-Dock: a web server for cavity detection-guided protein--ligand blind docking. Acta Pharmacologica Sinica. 41: 138–144. 10.1038/s41401-019-0228-6
Liu, Z., Pan, H., Zhang, Y., Zheng, Z., Xiao, W., Hong, X., Chen, F., Peng, X., Pei, Y., Rong, J., He, J., Zou, L., Wang, J., Zhong, J., Han, X. and Cao, Y., 2022. Ginsenoside-Rg1 attenuates sepsis--induced cardiac dysfunction by modulating mitochondrial damage via the P2X7 receptor-mediated Akt/GSK-3β signaling pathway. Journal of Biochemical and Molecular Toxicology. 36(1): e22885. 10.1002/jbt.22885
Lu, L., Huang, J., Xue, X., Wang, T., Huang, Z. and Li, J., 2021a. Berberine regulated miR150-5p to inhibit P2X7 receptor, EMMPRIN and MMP-9 expression in oxLDL induced macrophages. Frontiers in Pharmacology. 12: 639558. 10.3389/fphar.2021.639558
Lu, Z., Yao, Y., Wang, J. and Peng, J.Y., 2021b. Dioscin ameliorates diabetes cognitive dysfunction via adjusting P2X7R/NLRP3-signal. International Immunopharmacology. 101: 108314. 10.1016/j.intimp.2021.108314
Nevoral, J., Zalmanova, T., Hoskova, K., Stiavnicka, M., Hosek, P., Petelak, A. and Petr, J., 2018. Involvement of K+ATP and Ca2+ channels in hydrogen sulfide-suppressed ageing of porcine oocytes. Biological Research. 51(1): 38. 10.1186/s40659-018-0187-2
Parsons, C., Jahanafroozi, M. and Kathariou, S., 2019. Requirement of lmo1930, a gene in the menaquinone biosynthesis operon, for esculin hydrolysis and lithium chloride tolerance in Listeria monocytogenes. Microorganisms. 7(11): 539. 10.3390/microorganisms7110539
Patel, R.V., Mistry, B.M., Shinde, S.K., Syed, R., Singh, V. and Shin, H.S., 2018. Therapeutic potential of quercetin as a cardiovascular agent. European Journal of Medicinal Chemistry. 155: 889–904. 10.1016/j.ejmech.2018.06.053
Pelegrin, P., 2021. P2X7 receptor and the NLRP3 inflammasome: partners in crime. Biochemical Pharmacology. 187: 114385. 10.1016/j.bcp.2020.114385
Prateeksha., Yusuf, M.A., Singh, B.N., Sudheer, S., Kharwar, R.N., Siddiqui, S., Abdel-Azeem, A.M., Fernandes Fraceto, L., Dashora, K. and Gupta, V.K., 2019. Chrysophanol: a natural anthraquinone with multifaceted biotherapeutic potential. Biomolecules. 9(2): 68. 10.3390/biom9020068
Roman, S., Cusdin, F.S., Fonfria, E., Goodwin, J.A., Reeves, J., Lappin, S.C., Chambers, L., Walter, D.S., Clay, W.C. and Michel, A.D., 2009. Cloning and pharmacological characterization of the dog P2X7 receptor. British Journal of Pharmacology. 158(6): 1513–1526. 10.1111/j.1476-5381.2009.00425.x
Semwal, R.B., Semwal, D.K., Combrinck, S. and Viljoen, A., 2021. Emodin—a natural anthraquinone derivative with diverse pharmacological activities. Phytochemistry. 190: 112854. 10.1016/j.phytochem.2021.112854
Serralha, R.S., Rodrigues, I.F., Bertolini, A., Lima, D.Y., Nascimento, M., Mouro, M.G., Punaro, G.R., Visoná, I., Rodrigues, A.M. and Higa, E.M.S., 2020. Esculin reduces P2X7 and reverses mitochondrial dysfunction in the renal cortex of diabetic rats. Life Sciences. 254: 117787. 10.1016/j.lfs.2020.117787
Sharma, B.R. and Kanneganti, T.D., 2021. NLRP3 inflammasome in cancer and metabolic diseases. Nature Immunology 22(5): 550–559. 10.1038/s41590-021-00886-5
Shen, C.Y., Jiang, J.G., Yang, L., Wang, D.W. and Zhu, W., 2017. Anti-ageing active ingredients from herbs and nutraceuticals used in traditional Chinese medicine: pharmacological mechanisms and implications for drug discovery. British Journal of Pharmacology. 174(11): 1395–1425. 10.1111/bph.13631
Shi, X.X., Zheng, K.C., Shan, P.R., Zhang, L., Wu, S.J. and Huang, Z.Q., 2021. Elevated circulating level of P2X7 receptor is related to severity of coronary artery stenosis and prognosis of acute myocardial infarction. Cardiology Journal. 28(3): 453–459. 10.5603/CJ.a2020.0074
Skaper, S.D., Debetto, P. and Giusti, P., 2010. The P2X7 purinergic receptor: from physiology to neurological disorders. FASEB Journal. 24(2): 337–345. 10.1096/fj.09-138883
Song, Y., Wang, X., Qin, S., Zhou, S., Li, J. and Gao, Y., 2018. Esculin ameliorates cognitive impairment in experimental diabetic nephropathy and induces anti-oxidative stress and anti-inflammatory effects via the MAPK pathway. Molecular Medicine Reports. 17(5): 7395–7402. 10.3892/mmr.2018.8727
Sun, S., Tuo, Q., Li, D., Wang, X., Li, X., Zhang, Y., Zhao, G. and Lin, F., 2020. Antioxidant effects of salidroside in the cardiovascular system. Evidence-Based Complementary and Alternative Medicine. 2020: 9568647. 10.1155/2020/9568647
Taheri, Y., Sharifi-Rad, J., Antika, G., Yılmaz, Y.B., Tumer, T.B., Abuhamdah, S., Chandra, S., Saklani, S., Kılıç, C.S., Sestito, S., Daştan, S.D., Kumar, M., Alshehri, M.M., Rapposelli, S., Cruz-Martins, N. and Cho, W.C., 2021. Paving luteolin therapeutic potentialities and agro-food-pharma applications: emphasis on in vivo pharmacological effects and bioavailability traits. Oxidative Medicine and Cellular Longevity. 2021: 1987588. 10.1155/2021/1987588
Tang, D., Chen, K., Huang, L. and Li, J., 2017. Pharmacokinetic properties and drug interactions of apigenin, a natural flavone. Expert Opinion on Drug Metabolism Toxicology. 13(3): 323–330. 10.1080/17425255.2017.1251903
Tao, X., Yin, L., Xu, L. and Peng, J., 2018. Dioscin: a diverse acting natural compound with therapeutic potential in metabolic diseases, cancer, inflammation and infections. Pharmacological Research. 137: 259–269. 10.1016/j.phrs.2018.09.022
Tew, X.N., Xin Lau, N.J., Chellappan, D.K., Madheswaran, T., Zeeshan, F., Tambuwala, M.M., Aljabali, A.A., Balusamy, S.R., Perumalsamy, H., Gupta, G., Oliver, B.G., Hsu, A., Wark, P., Reddy, K., Wadhwa, R., Hansbro, P.M. and Dua, K., 2020. Immunological axis of berberine in managing inflammation underlying chronic respiratory inflammatory diseases. Chemico-Biological Interactions. 317: 108947. 10.1016/j.cbi.2020.108947
Thawkar, B.S. and Kaur, G., 2019. Inhibitors of NF-κB and P2X7/NLRP3/Caspase 1 pathway in microglia: novel therapeutic opportunities in neuroinflammation induced early-stage Alzheimer’s disease. Journal of Neuroimmunology. 326: 62–74. 10.1016/j.jneuroim.2018.11.010
Tuli, H.S., Sak, K., Gupta, D.S., Kaur, G., Aggarwal, D., Chaturvedi Parashar, N., Choudhary, R., Yerer, M.B., Kaur, J., Kumar, M., Garg, V.K. and Sethi, G., 2021. Anti-inflammatory and anticancer properties of birch bark-derived betulin: recent developments. Plants (Basel). 10(12): 2663. 10.3390/plants10122663
Vivoli, E., Cappon, A., Milani, S., Piombanti, B., Provenzano, A., Novo, E., Masi, A., Navari, N., Narducci, R., Mannaioni, G., Moneti G., Oliveira, C.P., Parola, M. and Marra, F., 2016. NLRP3 inflammasome as a target of berberine in experimental murine liver injury: interference with P2X7 signalling. Clinical Science (London). 130(20): 1793–1806. 10.1042/CS20160400
Wang, D., Wang, H., Gao, H., Zhang, H., Zhang, H., Wang, Q. and Sun, Z., 2020a. P2X7 receptor mediates NLRP3 inflammasome activation in depression and diabetes. Cell Bioscience. 10: 28. 10.1186/s13578-020-00388-1
Wang, Z., Ren, W., Zhao, F., Han, Y., Liu, C. and Jia, K., 2020b. Curcumin amends Ca2+ dysregulation in microglia by suppressing the activation of P2X7 receptor. Molecular and Cellular Biochemistry. 465(1–2): 65–73. 10.1007/s11010-019-03668-8
Xin, L., Gao, J., Lin, H., Qu, Y., Shang, C., Wang, Y., Lu, Y. and Cui, X., 2020. Regulatory mechanisms of baicalin in cardiovascular diseases: a review. Frontiers in Pharmacology. 11: 583200. 10.3389/fphar.2020.583200
Xin, Q., Yuan, R., Shi, W., Zhu, Z., Wang, Y. and Cong, W., 2019. A review for the anti-inflammatory effects of paeoniflorin in inflammatory disorders. Life Sciences. 237: 116925. 10.1016/j.lfs.2019.116925
Xu, H., Xiong, C., He, L., Wu, B., Peng, L., Cheng, Y., Jiang, F., Tan, L., Tang, L., Tu, Y., Yang, Y., Liu, C., Gao, Y., Li, G., Zhang, C., Liu, S., Xu, C., Wu, H., Li, G. and Liang, S., 2015. Trans-resveratrol attenuates high fatty acid-induced P2X7 receptor expression and IL-6 release in PC12 cells: possible role of P38 MAPK pathway. Inflammation. 38(1): 327–337. 10.1007/s10753-014-0036-6
Xu, Z., Chen, Z.M., Wu, X., Zhang, L., Cao, Y. and Zhou, P., 2020. Distinct molecular mechanisms underlying potassium efflux for NLRP3 inflammasome activation. Frontiers in Immunology. 11: 609441. 10.3389/fimmu.2020.609441
Yang, L., Ren, S., Xu, F., Ma, Z., Liu, X. and Wang, L., 2019. Recent advances in the pharmacological activities of dioscin. BioMed Research International. 2019: 5763602. 10.1155/2019/5763602
Yang, R., Li, Z., Zou, Y., Yang, J., Li, L., Xu, X., Schmalzing, G., Nie, H., Li, G., Liu, S., Liang, S. and Xu, C., 2021. Gallic acid alleviates neuropathic pain behaviors in rats by inhibiting P2X7 receptor-mediated NF-κB/STAT3 signaling pathway. Frontiers in Pharmacology. 12: 680139. 10.3389/fphar.2021.680139
Ye, T., Li, X., Zhou, P., Ye, S., Gao, H., Hua, R., Ma, J., Wang, Y. and Cai, B., 2020. Chrysophanol improves memory ability of-d-galactose and Aβ25-35 treated rat correlating with inhibiting tau hyperphosphorylation and the CaM-CaMKIV signal pathway in hippocampus. 3 Biotech 10(3): 111. 10.1007/s13205-020-2103-z
Yu, D., Tang, Z., Li, B., Yu, J., Li, W., Liu, Z. and Tian, C., 2021. Resveratrol against cardiac fibrosis: research progress in-experimental animal models. Molecules. 26(22): 6860. 10.3390/molecules26226860
Yu, J., Chen, Y., Li, M., Gao, Q., Peng, Y., Gong, Q., Zhang, Z. and Wu, X., 2015. Paeoniflorin down-regulates ATP-induced inflammatory cytokine production and P2X7R expression on peripheral blood mononuclear cells from patients with primary Sjögren’s syndrome. International Immunopharmacology. 28(1): 115–120. 10.1016/j.intimp.2015.05.023
Zhang, J., Chen, Y., Luo, H., Sun, L., Xu, M., Yu, J., Zhou, Q., Meng, G. and Yang, S., 2018. Recent update on the pharmacological effects and mechanisms of dihydromyricetin. Frontiers in Pharmacology. 9: 1204. 10.3389/fphar.2018.01204
Zhang, K., Liu, J., You, X., Kong, P., Song, Y., Cao, L., Yang, S., Wang, W., Fu, Q. and Ma, Z., 2016. P2X7 as a new target for chrysophanol to treat lipopolysaccharide-induced depression in mice. Neuroscience Letters. 613: 60–65. 10.1016/j.neulet.2015.12.043
Zhang, L.X., Li, C.X., Kakar, M.U., Khan, M.S., Wu, P.F., Amir, R.M., Dai, D.F., Naveed, M., Li, Q.Y., Saeed, M., Shen, J.Q., Rajput, S.A. and Li, J.H., 2021a. Resveratrol (RV): a pharmacological review and call for further research. Biomedicine Pharmacotherapy. 143: 112164. 10.1016/j.biopha.2021.112164
Zhang, W.Y., Guo, Y.J., Han, W.X., Yang, M.Q., Wen, L.P., Wang, K.Y. and Jiang, P., 2019. Curcumin relieves depressive-like behaviors via inhibition of the NLRP3 inflammasome and kynurenine pathway in rats suffering from chronic unpredictable mild stress. International Immunopharmacology. 67: 138–144. 10.1016/j.intimp.2018.12.012
Zhang, Z.H., Yang, H.X., Jin, Q., Wu, Y.L., Cui, Z.Y., Shang, Y., Liu, J., Zhan, Z.Y., Lian, L.H. and Nan, J.X., 2021b. Luteolin attenuates hepatic injury in septic mice by regulating P2X7R-based HMGB1 release. Food Function. 12(21): 10714–10727. 10.1039/D1FO01746B
Zhao, C.C., Wu, X.Y., Yi, H., Chen, R. and Fan, G., 2021a. The therapeutic effects and mechanisms of salidroside on cardiovascular and metabolic diseases: an updated review. Chemistry Biodiversity. 18(7): e2100033. 10.1002/cbdv.202100033
Zhao, X., Gong, L., Wang, C., Liu, M., Hu, N., Dai, X., Peng, C. and Li, Y., 2021b. Quercetin mitigates ethanol-induced hepatic steatosis in zebrafish via P2X7R-mediated PI3K/ Keap1/Nrf2 signaling pathway. Journal of Ethnopharmacology. 268: 113569. 10.1016/j.jep.2020.113569
Zhao, Y., Chen, X., Lyu, S., Ding, Z., Wu, Y., Gao, Y. and Du, J., 2021c. Identification of novel P2X7R antagonists by using structure--based virtual screening and cell-based assays. Chemical Biology Drug Design. 98(1): 192–205. 10.1111/cbdd.13867
Zhou, M., Tang, Y., Liao, L., Liu, M., Deng, Y., Zhao, X. and Li, Y., 2021. Phillygenin inhibited LPS-induced RAW 264.7 cell inflammation by NF-κB pathway. European Journal of Pharmacology. 899: 174043. 10.1016/j.ejphar.2021.174043
Zhou, Y.X., Gong, X.H. and Zhang, H., Peng, C., 2020. A review on the pharmacokinetics of paeoniflorin and its anti-inflammatory and immunomodulatory effects. Biomedicine Pharmacotherapy. 130: 110505. 10.1016/j.biopha.2020.110505
Zhu, F., Du, B. and Xu, B., 2018. Anti-inflammatory effects of phytochemicals from fruits, vegetables, and food legumes: a review. Critical Reviews in Food Science and Nutrition. 58(8): 1260–1270. 10.1080/10408398.2016.1251390
Zhu, S., Wang, Y., Wang, X., Li, J. and Hu, F., 2014. Emodin inhibits ATP-induced IL-1β secretion, ROS production and-phagocytosis attenuation in rat peritoneal macrophages via antagonizing P2X7 receptor. Pharmaceutical Biology. 52(1): 51–67. 10.3109/13880209.2013.810648