Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

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

Research Article

The Anti-hyperuricemia and Anti-inflammatory Effects of Atractylodes Macrocephala in Hyperuricemia and Gouty Arthritis Rat Models

Author(s): Xvwu Qian, Ying Jiang, Yiyuan Luo* and Yuchen Jiang

Volume 26, Issue 5, 2023

Published on: 04 August, 2022

Page: [950 - 964] Pages: 15

DOI: 10.2174/1386207325666220603101540

Price: $65

Abstract

Aims: Atractylodes macrocephala is a traditional Chinese medicine with a variety of pharmacological activities. This study aimed to evaluate its anti-hyperuricemia and antiinflammatory effects on gout, and to preliminarily explore its mechanism.

Methods: The hyperuricemia rat model was established by intraperitoneal injection of oteracil potassium and intragastric gavage of yeast powder solution. And the acute gouty arthritis (GA) model was established by injecting monosodium urate (MSU) suspension. In the study of the antihyperuricemia effect of Atractylodes macrocephala, the healthy male Sprague-Dawley rats were randomly divided into the blank group, hyperuricemia group allopurinol group as well as low, moderate and high dose groups of Atractylodes macrocephala decoction (N=8 rats in each group). Serum, liver and kidney tissue samples were collected from each group. Serum uric acid (UA), adenosine deaminase (ADA) and xanthine oxidase (XOD) levels in each group were detected by enzyme-linked immunosorbent assay (ELISA). Protein levels of ADA and XOD in liver tissues were detected by Western blot, and renal histological changes were observed by Hematoxylin-eosin (H&E) and Masson staining. In order to investigate the anti-inflammatory effect of Atractylodes macrocephala, the healthy male Sprague-Dawley rats were randomly divided into the blank group, GA group, colchicine group, high, moderate and low dose groups of Atractylodes macrocephala decoction (N=8 rats in each group), and serum and synovial tissue of each group were collected. Then the level of serum interleukin (IL)-1β and tumor necrosis factor (TNF)-α was observed by ELISA, and the histological changes of synovial tissue were observed by H&E staining. Besides, the expression of adenosine monophosphate- activated protein kinase (AMPK) /silent information regulator (SIRT) 1/ nuclear factor kappa B (NF-κB) protein in synovial tissue was observed by Western blot and immunohistochemistry. The markers of M1 and M2 macrophages, inducible nitric oxide synthase (iNOS) and arginase-1 (ARG1) were observed by Western blot and immunofluorescence.

Results: Atractylodes macrocephala could reduce the production of UA by inhibiting the level of ADA and XOD, and could improve renal injury and fibrosis. In addition, Atractylodes macrophages could reduce the levels of IL-1β and TNF-α, activate AMPK/SIRT1 signaling pathway, and inhibit the activation of NF-κB and the polarization of macrophages to a pro-inflammatory phenotype.

Conclusion: Atractylodes macrocephala shows good anti-hyperuricemic and anti-inflammatory effects, and its anti-inflammation pharmacological activity may be related to the inhibition of M1 macrophage polarization and NF-κB activation through activating AMPK/SIRT1.

Keywords: Atractylodes macrocephala, Hyperuricemia, Gouty arthritis, AMPK, SIRT1, NF-κB, Macrophage polarization.

Graphical Abstract

[1]
Zhu, Y.; Pandya, B.J.; Choi, H.K. Comorbidities of gout and hyperuricemia in the US general population: NHANES 2007-2008. Am. J. Med., 2012, 125(7), 679-687.e1.
[http://dx.doi.org/10.1016/j.amjmed.2011.09.033] [PMID: 22626509]
[2]
Abhishek, A.; Roddy, E.; Doherty, M. Gout - a guide for the general and acute physicians. Clin. Med. (Lond.), 2017, 17(1), 54-59.
[http://dx.doi.org/10.7861/clinmedicine.17-1-54] [PMID: 28148582]
[3]
Khanna, P.P.; Shiozawa, A.; Walker, V.; Bancroft, T.; Essoi, B.; Akhras, K.S.; Khanna, D. Health-related quality of life and treatment satisfaction in patients with gout: Results from a cross-sectional study in a managed care setting. Patient Prefer. Adherence, 2015, 9, 971-981.
[PMID: 26185426]
[4]
Desai, J.; Steiger, S.; Anders, H.J. Molecular pathophysiology of gout. Trends Mol. Med., 2017, 23(8), 756-768.
[http://dx.doi.org/10.1016/j.molmed.2017.06.005] [PMID: 28732688]
[5]
Ragab, G.; Elshahaly, M.; Bardin, T. Gout: An old disease in new perspective - A review. J. Adv. Res., 2017, 8(5), 495-511.
[http://dx.doi.org/10.1016/j.jare.2017.04.008] [PMID: 28748116]
[6]
Schlesinger, N. Difficult-to-treat gouty arthritis: A disease warranting better management. Drugs, 2011, 71(11), 1413-1439.
[http://dx.doi.org/10.2165/11592290-000000000-00000] [PMID: 21812506]
[7]
Dalbeth, N.; Choi, H.K.; Terkeltaub, R. Review: Gout: A roadmap to approaches for improving global outcomes. Arthritis Rheumatol., 2017, 69(1), 22-34.
[http://dx.doi.org/10.1002/art.39799] [PMID: 27389665]
[8]
Stamp, L.K.; Day, R.O.; Yun, J. Allopurinol hypersensitivity: Investigating the cause and minimizing the risk. Nat. Rev. Rheumatol., 2016, 12(4), 235-242.
[http://dx.doi.org/10.1038/nrrheum.2015.132] [PMID: 26416594]
[9]
FitzGerald, J.D.; Dalbeth, N.; Mikuls, T.; Brignardello-Petersen, R.; Guyatt, G.; Abeles, A.M.; Gelber, A.C.; Harrold, L.R.; Khanna, D.; King, C.; Levy, G.; Libbey, C.; Mount, D.; Pillinger, M.H.; Rosenthal, A.; Singh, J.A.; Sims, J.E.; Smith, B.J.; Wenger, N.S.; Bae, S.S.; Danve, A.; Khanna, P.P.; Kim, S.C.; Lenert, A.; Poon, S.; Qasim, A.; Sehra, S.T.; Sharma, T.S.K.; Toprover, M.; Turgunbaev, M.; Zeng, L.; Zhang, M.A.; Turner, A.S.; Neogi, T. 2020 American college of rheumatology guideline for the management of gout. Arthritis Care Res. (Hoboken), 2020, 72(6), 744-760.
[http://dx.doi.org/10.1002/acr.24180] [PMID: 32391934]
[10]
Finkelstein, Y.; Aks, S.E.; Hutson, J.R.; Juurlink, D.N.; Nguyen, P.; Dubnov-Raz, G.; Pollak, U.; Koren, G.; Bentur, Y. Colchicine poisoning: The dark side of an ancient drug. Clin. Toxicol. (Phila.), 2010, 48(5), 407-414.
[http://dx.doi.org/10.3109/15563650.2010.495348] [PMID: 20586571]
[11]
Xiao, N.; Chen, H.; He, S.Y.; Xue, C.X.; Sui, H.; Chen, J.; Qu, J.L.; Liang, L.N.; Zhang, L. Evaluating the efficacy and adverse effects of clearing heat and removing dampness method of traditional Chinese medicine by comparison with western medicine in patients with gout. Evid. Based Complement. Alternat. Med., 2018, 2018, 8591349.
[http://dx.doi.org/10.1155/2018/8591349] [PMID: 30538765]
[12]
Chi, X.; Zhang, H.; Zhang, S.; Ma, K. Chinese herbal medicine for gout: A review of the clinical evidence and pharmacological mechanisms. Chin. Med., 2020, 15(1), 17.
[http://dx.doi.org/10.1186/s13020-020-0297-y] [PMID: 32082411]
[13]
Liang, G.; Nie, Y.; Chang, Y.; Zeng, S.; Liang, C.; Zheng, X.; Xiao, D.; Zhan, S.; Zheng, Q. Protective effects of Rhizoma smilacis glabrae extracts on potassium oxonate- and monosodium urate-induced hyperuricemia and gout in mice. Phytomedicine, 2019, 59, 152772.
[http://dx.doi.org/10.1016/j.phymed.2018.11.032] [PMID: 31005813]
[14]
Zheng, F.; Chen, L.; Gao, J.; Niu, F.; Duan, X.; Yin, L.; Tian, W. Identification of autotoxic compounds from Atractylodes macrocephala Koidz and preliminary investigations of their influences on immune system. J. Plant Physiol., 2018, 230, 33-39.
[http://dx.doi.org/10.1016/j.jplph.2018.08.006] [PMID: 30144693]
[15]
Liu, Y.; Zhang, B.; Cai, Q. Study on the pharmacodynamics and metabolomics of five medicinal species in Atractylodes DC. on rats with rheumatoid arthritis. Biomed. Pharmacother., 2020, 131, 110554.
[http://dx.doi.org/10.1016/j.biopha.2020.110554] [PMID: 32890964]
[16]
Wang, Y.; Lin, Z.; Zhang, B.; Jiang, Z.; Guo, F.; Yang, T. Cichorium intybus L. Extract suppresses experimental gout by inhibiting the NF-κB and NLRP3 signaling pathways. Int. J. Mol. Sci., 2019, 20(19), 20.
[http://dx.doi.org/10.3390/ijms20194921]
[17]
Kong, P.; Yu, Y.; Wang, L.; Dou, Y.Q.; Zhang, X.H.; Cui, Y.; Wang, H.Y.; Yong, Y.T.; Liu, Y.B.; Hu, H.J.; Cui, W.; Sun, S.G.; Li, B.H.; Zhang, F.; Han, M. circ-Sirt1 controls NF-κB activation via sequence-specific interaction and enhancement of SIRT1 expression by binding to miR-132/212 in vascular smooth muscle cells. Nucleic Acids Res., 2019, 47(7), 3580-3593.
[http://dx.doi.org/10.1093/nar/gkz141] [PMID: 30820544]
[18]
Yang, Q.B.; He, Y.L.; Zhong, X.W.; Xie, W.G.; Zhou, J.G. Resveratrol ameliorates gouty inflammation via upregulation of sirtuin 1 to promote autophagy in gout patients. Inflammopharmacology, 2019, 27(1), 47-56.
[http://dx.doi.org/10.1007/s10787-018-00555-4] [PMID: 30600470]
[19]
Terkeltaub, R. What makes gouty inflammation so variable? BMC Med., 2017, 15(1), 158.
[http://dx.doi.org/10.1186/s12916-017-0922-5] [PMID: 28818081]
[20]
Pu, Z.; Liu, Y.; Li, C.; Xu, M.; Xie, H.; Zhao, J. Using network pharmacology for systematic understanding of geniposide in ameliorating inflammatory responses in colitis through suppression of NLRP3 inflammasome in macrophage by AMPK/Sirt1 dependent signaling. Am. J. Chin. Med., 2020, 48, 1693.
[21]
Tu, Y.; Fang, Q.J.; Sun, W.; Liu, B.H.; Liu, Y.L.; Wu, W.; Yee, H.Y.; Yuan, C.C.; Wang, M.Z.; Wan, Z.Y.; Tang, R.M.; Wan, Y.G.; Tang, H.T. Total flavones of abelmoschus manihot remodels gut microbiota and inhibits microinflammation in chronic renal failure progression by targeting autophagy-mediated macrophage polarization. Front. Pharmacol., 2020, 11, 566611.
[http://dx.doi.org/10.3389/fphar.2020.566611] [PMID: 33101025]
[22]
Liao, W.T.; You, H.L.; Li, C.; Chang, J.G.; Chang, S.J.; Chen, C.J. Cyclic GMP-dependent protein kinase II is necessary for macrophage M1 polarization and phagocytosis via toll-like receptor 2. J. Mol. Med. (Berl.), 2015, 93(5), 523-533.
[http://dx.doi.org/10.1007/s00109-014-1236-0] [PMID: 25475742]
[23]
Liu, L.; Zhu, X.; Zhao, T.; Yu, Y.; Xue, Y.; Zou, H. Sirt1 ameliorates monosodium urate crystal-induced inflammation by altering macrophage polarization via the PI3K/Akt/STAT6 pathway. Rheumatology (Oxford), 2019, 58(9), 1674-1683.
[http://dx.doi.org/10.1093/rheumatology/kez165] [PMID: 31106362]
[24]
Chen, L.; Lan, Z. Polydatin attenuates potassium oxonate-induced hyperuricemia and kidney inflammation by inhibiting NF-κB/NLRP3 inflammasome activation via the AMPK/SIRT1 pathway. Food Funct., 2017, 8(5), 1785-1792.
[http://dx.doi.org/10.1039/C6FO01561A] [PMID: 28428988]
[25]
Chao, C.L.; Huang, H.C.; Lin, H.C.; Chang, T.C.; Chang, W.L. sesquiterpenes from baizhu stimulate glucose uptake by activating AMPK and PI3K. Am. J. Chin. Med., 2016, 44(5), 963-979.
[http://dx.doi.org/10.1142/S0192415X16500531] [PMID: 27430917]
[26]
Hou, S.X.; Zhu, W.J.; Pang, M.Q.; Jeffry, J.; Zhou, L.L. Protective effect of iridoid glycosides from Paederia scandens (LOUR.) MERRILL (Rubiaceae) on uric acid nephropathy rats induced by yeast and potassium oxonate. Food Chem. Toxicol., 2014, 64, 57-64.
[http://dx.doi.org/10.1016/j.fct.2013.11.022] [PMID: 24287205]
[27]
Eräranta, A.; Kurra, V.; Tahvanainen, A.M.; Vehmas, T.I.; Kööbi, P.; Lakkisto, P.; Tikkanen, I.; Niemelä, O.J.; Mustonen, J.T.; Pörsti, I.H. Oxonic acid-induced hyperuricemia elevates plasma aldosterone in experimental renal insufficiency. J. Hypertens., 2008, 26(8), 1661-1668.
[http://dx.doi.org/10.1097/HJH.0b013e328303205d] [PMID: 18622246]
[28]
Chen, G.L.; Wei, W.; Xu, S.Y. Effect and mechanism of total saponin of Dioscorea on animal experimental hyperuricemia. Am. J. Chin. Med., 2006, 34(1), 77-85.
[http://dx.doi.org/10.1142/S0192415X06003655] [PMID: 16437741]
[29]
Wu, J.; Li, J.; Li, W.; Sun, B.; Xie, J.; Cheng, W.; Zhang, Q. Achyranthis bidentatae radix enhanced articular distribution and anti-inflammatory effect of berberine in Sanmiao Wan using an acute gouty arthritis rat model. J. Ethnopharmacol., 2018, 221, 100-108.
[http://dx.doi.org/10.1016/j.jep.2018.04.025] [PMID: 29679725]
[30]
Zhang, K.H.; Wang, M.Q.; Wei, L.L.; Feng, C.J.; Zhang, Y.S.; Teng, J.B. Investigation of the effects and mechanisms of Dendrobium loddigesii Rolfe Extract on the treatment of Gout. Evid. Based Complement. Alternat. Med., 2020, 2020, 4367347.
[http://dx.doi.org/10.1155/2020/4367347] [PMID: 33062010]
[31]
Chen, J.W.; Zhou, Y.; Xue, Z.Y.; Li, C.; Guo, J.; Zhou, L.Y.; Jiang, J.M. Effect of jianpihuashi decoction on rats with hyperuricemia. Zhong Yao Cai, 2013, 36(9), 1486-1489.
[PMID: 24620698]
[32]
Johnson, P.; Loganathan, C.; Iruthayaraj, A.; Poomani, K.; Thayumanavan, P. S-allyl cysteine as potent anti-gout drug: Insight into the xanthine oxidase inhibition and anti-inflammatory activity. Biochimie, 2018, 154, 1-9.
[http://dx.doi.org/10.1016/j.biochi.2018.07.015] [PMID: 30059711]
[33]
Lee, Y.M.; Shon, E.J.; Kim, O.S.; Kim, D.S. Effects of Mollugo pentaphylla extract on monosodium urate crystal-induced gouty arthritis in mice. BMC Complement. Altern. Med., 2017, 17(1), 447.
[http://dx.doi.org/10.1186/s12906-017-1955-1] [PMID: 28874151]
[34]
Liu, Y.; Duan, C.; Chen, H.; Wang, C.; Liu, X.; Qiu, M.; Tang, H.; Zhang, F.; Zhou, X.; Yang, J. Inhibition of COX-2/mPGES-1 and 5-LOX in macrophages by leonurine ameliorates monosodium urate crystal-induced inflammation. Toxicol. Appl. Pharmacol., 2018, 351, 1-11.
[http://dx.doi.org/10.1016/j.taap.2018.05.010] [PMID: 29763636]
[35]
Wu, Z.C.; Xue, Q.; Zhao, Z.L.; Zhou, P.J.; Zhou, Q.; Zhang, Z.; Deng, J.P.; Yang, K.; Fan, H.; Wang, Y.F.; Wang, Z.P. Suppressive effect of huzhentongfeng on experimental gouty arthritis: An in vivo and in vitro study. Evid. Based Complement. Alternat. Med., 2019, 2019, 2969364.
[http://dx.doi.org/10.1155/2019/2969364] [PMID: 31871475]
[36]
Committee, C.P. Pharmacopoeia of the People’s Republic of China; China Medical Science Press, , 2015.
[37]
Shan, J.J.; Tian, G.Y. Studies on physico-chemical properties and hypoglycemic activity of complex polysaccharide AMP-B from Atractylodes macrocephala Koidz. Yao Xue Xue Bao, 2003, 38(6), 438-441.
[PMID: 14513804]
[38]
Zhu, B.; Zhang, Q.L.; Hua, J.W.; Cheng, W.L.; Qin, L.P. The traditional uses, phytochemistry, and pharmacology of Atractylodes macrocephala Koidz.: A review. J. Ethnopharmacol., 2018, 226, 143-167.
[http://dx.doi.org/10.1016/j.jep.2018.08.023] [PMID: 30130541]
[39]
Wang, C.; Duan, H.; He, L. Inhibitory effect of atractylenolide I on angiogenesis in chronic inflammation in vivo and in vitro. Eur. J. Pharmacol., 2009, 612(1-3), 143-152.
[http://dx.doi.org/10.1016/j.ejphar.2009.04.001] [PMID: 19356732]
[40]
Gu, S.; Li, L.; Huang, H.; Wang, B.; Zhang, T. Antitumor, antiviral, and anti-inflammatory efficacy of essential oils from Atractylodes macrocephala Koidz. Produced with different processing methods. Molecules, 2019, 24(16), 24.
[http://dx.doi.org/10.3390/molecules24162956] [PMID: 31443182]
[41]
Bailly, C. Atractylenolides, essential components of Atractylodes-based traditional herbal medicines: Antioxidant, anti-inflammatory and anticancer properties. Eur. J. Pharmacol., 2021, 891, 173735.
[http://dx.doi.org/10.1016/j.ejphar.2020.173735] [PMID: 33220271]
[42]
Alghamdi, Y.S.; Soliman, M.M.; Nassan, M.A. Impact of Lesinurad and allopurinol on experimental Hyperuricemia in mice: Biochemical, molecular and Immunohistochemical study. BMC Pharmacol. Toxicol., 2020, 21(1), 10.
[http://dx.doi.org/10.1186/s40360-020-0386-7] [PMID: 32041665]
[43]
Amaral, F.A.; Bastos, L.F.; Oliveira, T.H.; Dias, A.C.; Oliveira, V.L.; Tavares, L.D.; Costa, V.V.; Galvão, I.; Soriani, F.M.; Szymkowski, D.E.; Ryffel, B.; Souza, D.G.; Teixeira, M.M. Transmembrane TNF-α is sufficient for articular inflammation and hypernociception in a mouse model of gout. Eur. J. Immunol., 2016, 46, 204.
[44]
Salminen, A.; Kaarniranta, K. AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network. Ageing Res. Rev., 2012, 11(2), 230-241.
[http://dx.doi.org/10.1016/j.arr.2011.12.005] [PMID: 22186033]
[45]
Wang, Y.; Viollet, B.; Terkeltaub, R.; Liu-Bryan, R. AMP-activated protein kinase suppresses urate crystal-induced inflammation and transduces colchicine effects in macrophages. Ann. Rheum. Dis., 2016, 75(1), 286-294.
[http://dx.doi.org/10.1136/annrheumdis-2014-206074] [PMID: 25362043]
[46]
Chang, H.C.; Guarente, L. SIRT1 and other sirtuins in metabolism. Trends Endocrinol. Metab., 2014, 25(3), 138-145.
[http://dx.doi.org/10.1016/j.tem.2013.12.001] [PMID: 24388149]
[47]
Fulco, M.; Cen, Y.; Zhao, P.; Hoffman, E.P.; McBurney, M.W.; Sauve, A.A.; Sartorelli, V. Glucose restriction inhibits skeletal myoblast differentiation by activating SIRT1 through AMPK-mediated regulation of Nampt. Dev. Cell, 2008, 14(5), 661-673.
[http://dx.doi.org/10.1016/j.devcel.2008.02.004] [PMID: 18477450]
[48]
Busch, F.; Mobasheri, A.; Shayan, P.; Stahlmann, R.; Shakibaei, M. Sirt-1 is required for the inhibition of apoptosis and inflammatory responses in human tenocytes. J. Biol. Chem., 2012, 287(31), 25770-25781.
[http://dx.doi.org/10.1074/jbc.M112.355420] [PMID: 22689577]
[49]
Tian, Y.; Ma, J.; Wang, W.; Zhang, L.; Xu, J.; Wang, K.; Li, D. Resveratrol supplement inhibited the NF-κB inflammation pathway through activating AMPKα-SIRT1 pathway in mice with fatty liver. Mol. Cell. Biochem., 2016, 422(1-2), 75-84.
[http://dx.doi.org/10.1007/s11010-016-2807-x] [PMID: 27613163]
[50]
Wang, Y. Tripterine ameliorates monosodium urate crystal-induced gouty arthritis by altering macrophage polarization via the miR-449a/NLRP3 axis. Inflamm. Res., 2021, 70(3), 323-341.
[http://dx.doi.org/10.1007/s00011-021-01439-0] [PMID: 33559709]
[51]
Funes, S.C.; Rios, M.; Escobar-Vera, J.; Kalergis, A.M. Implications of macrophage polarization in autoimmunity. Immunology, 2018, 154(2), 186-195.
[http://dx.doi.org/10.1111/imm.12910] [PMID: 29455468]
[52]
Mei, J.; Zhou, F.; Qiao, H.; Li, H.; Tang, T. Nerve modulation therapy in gouty arthritis: Targeting increased sFRP2 expression in dorsal root ganglion regulates macrophage polarization and alleviates endothelial damage. Theranostics, 2019, 9(13), 3707-3722.
[http://dx.doi.org/10.7150/thno.33908] [PMID: 31281508]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy