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Open Access

Puerariae Radix protects against ulcerative colitis in mice by inhibiting NLRP3 inflammasome activation

Yu Gaa,b,1, Yuanyuan Weia,b,1, Qingyu Zhaoa,b, Yimeng Fana,b, Yannan Zhanga,b, Zhifang Zhangc, Sijia Haoc, Lixia Wangd, Zhifen Wange, Jinlong Hane, Shuang Wue, Zhihui Haoa,b( )
Innovation Centre of Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100086, China
National Center of Technology Innovation for Medicinal Function of Food, National Food and Strategic Reserves Administration, Beijing 100193, China
Inner Mongolia Medical University, Hohhot 010059, China
China Agricultural University Yantai Institute, Yantai 264670, China
Shandong Academy of Agricultural Sciences, Jinan 250100, China

1 Equal contribution.

Peer review under responsibility of Tsinghua University Press.

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Abstract

Ulcerative colitis (UC) is a common infl ammatory disease of the gastrointestinal tract. Traditional Chinese medicine (TCM) has long been used in Asia as a treatment for UC and Puerariae Radix (PR) is a reliable anti-diarrheal therapy. The aims of this study were to investigate the protective effect of PR using the dextran sulfate sodium salt (DSS)-induced UC model in mice and identify molecular mechanisms of PR action. The chemical constituents of PR via ultra-performance liquid chromatography/tandem mass spectrometry and identifi ed potential PR and UC targets using a network pharmacology (NP) approach were obtained to guide mouse experiments. A total of 180 peaks were identifi ed from PR including 48 flavonoids, 46 organic acids, 14 amino acids, 8 phenols, 8 carbohydrates, 7 alkaloids, 6 coumarins and 43 other constituents. NP results showed that caspase-1 was the most dysregulated of the core genes associated with UC. A PR dose of 0.136 mg/g administered to DSS treated mice reversed weight loss and decreased colon lengths found in UC mice. PR also alleviated intestinal mucosal shedding, infl ammatory cell infi ltration and mucin loss. PR treatment suppressed upregulation of NOD-like receptor protein 3 (NLRP3), cysteinyl aspartate-specific proteases-1 (caspase-1), apoptosis-associated speck-like (ASC) and gasdermin D (GSDMD) at both the protein and mRNA expression levels. The addition of a small molecule dual-specifi city phosphatase inhibitor NSC 95397 inhibited the positive effects of PR. These results indicated that PR exerts a protective effect on DSS-induced colitis by inhibiting NLRP3 infl ammasome activation in mice.

Keywords

Puerariae RadixUlcerative colitisMolecular mechanismsPyroptosisNOD-like receptor protein 3 inflammasome

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References

[1]

G. Wang, B. Xu, F. Shi, et al., Protective effect of methane-rich saline on acetic acid-induced ulcerative colitis via blocking the TLR4/NF-κB/MAPK pathway and promoting IL-10/JAK1/STAT3-mediated anti-inflammatory response, Oxid. Med. Cell Longev. 28 (2019) 7850324. https://doi.org/10.1155/2019/7850324.
Crossref Google Scholar
[2]

P.A. Ruiz, B. Morón, H.M. Becker, et al., Titanium dioxide nanoparticles exacerbate DSS-induced colitis: role of the NLRP3 inflammasome, Gut 66 (2017) 1216-1224. https://doi.org/10.1136/gutjnl-2015-310297.
Crossref Google Scholar
[3]

Z. Deng, J. Ni, X. Wu, et al., GPA peptide inhibits NLRP3 inflammasome activation to ameliorate colitis through AMPK pathway, Aging (Albany NY) 12 (2020) 18522-18544. https://doi.org/10.18632/aging.103825.
Crossref Google Scholar
[4]

S. Chen, S. Zuo, J. Zhu, et al., Decreased expression of cystathionine β-synthase exacerbates intestinal barrier injury in ulcerative colitis, J. Crohns. Colitis. 13 (2019) 1067-1080. https://doi.org/10.1093/ecco-jcc/jjz027.
Crossref Google Scholar
[5]

P. Munkholm, Review article: the incidence and prevalence of colorectal cancer in inflammatory bowel disease, Aliment. Pharmacol. Ther. 18 (2003) 1-5. https://doi.org/10.1046/j.1365-2036.18.s2.2.x.
Crossref Google Scholar
[6]

M.Y. Li, H.J. Luo, X. Wu, et al. Anti-inflammatory effects of huangqin decoction on dextran sulfate sodium-induced ulcerative colitis in mice through regulation of the gut microbiota and suppression of the Ras-PI3K-Akt-HIF-1α and NF-κB pathways, Front. Pharmacol. 10 (2020) 1552. https://doi.org/10.3389/fphar.2019.01552.
Crossref Google Scholar
[7]

R. Ungaro, S. Mehandru, P.B. Allen, et al., Ulcerative colitis, Lancet 389 (2017) 1756-1770. https://doi.org/10.1016/S0140-6736(16)32126-2.
Crossref Google Scholar
[8]

H.N. Iskandar, T. Dhere, F.A. Farraye, Ulcerative colitis: update on medical management, Curr. Gastroenterol. Rep. 17 (2015) 44. https://doi.org/10.1007/s11894-015-0466-9.
Crossref Google Scholar
[9]

Z. Deng, J. Ni, X. Wu, et al., GPA peptide inhibits NLRP3 inflammasome activation to ameliorate colitis through AMPK pathway, Aging (Albany NY) 12 (2020) 18522-18544. https://doi.org/10.18632/aging.103825.
Crossref Google Scholar
[10]

P. Kunovszki, K. Judit Szántó, J. Gimesi-Országh, et al., Epidemiological data and utilization patterns of anti-TNF alpha therapy in the Hungarian ulcerative colitis population between 2012-2016, Expert. Opin. Biol. Ther. 20 (2020) 443-449. https://doi.org/10.1080/14712598.2020.1718097.
Crossref Google Scholar
[11]

E.K. Karjalainen, L. Renkonen-Sinisalo, H.K. Mustonen, et al., Restorative proctocolectomy in ulcerative colitis: effect of preoperative immunomodulatory therapy on postoperative complications and pouch failure, Scand. J.Surg. 110 (2021) 51-58. https://doi.org/10.1177/1457496919900409.
Crossref Google Scholar
[12]

F. Jie, S. Xiao, Y. Qiao, et al., Kuijieling decoction suppresses NLRP3-mediated pyroptosis to alleviate inflammation and experimental colitis in vivo and in vitro, J. Ethnopharmacol. 264 (2021) 113243. https://doi.org/10.1016/j.jep.2020.113243.
Crossref Google Scholar
[13]

L. Chao, Z. Li, J. Zhou, et al., Shen-Ling-Bai-Zhu-San improves dextran sodium sulfate-induced colitis by inhibiting caspase-1/caspase-11-mediated pyroptosis, Front. Pharmacol. 11 (2020) 814. https://doi.org/10.3389/fphar.2020.00814.
Crossref Google Scholar
[14]

X.J. Gao, B. Tang, H.H. Liang, et al., The protective effect of nigeglanine on dextran sulfate sodium-induced experimental colitis in mice and Caco-2 cells, J. Cell Physiol. 234 (2019) 23398-23408. https://doi.org/10.1002/jcp.28909.
Crossref Google Scholar
[15]

L.R. Zhao, R.L. Xing, P.M. Wang, et al., NLRP1 and NLRP3 inflammasomes mediate LPS/ATP-induced pyroptosis in knee osteoarthritis, Mol. Med. Rep. 17 (2018) 5463-5469. https://doi.org/10.3892/mmr.2018.8520.
Crossref Google Scholar
[16]

W. Zhao, L. Ma, C. Cai, et al. Caffeine inhibits NLRP3 inflammasome activation by suppressing MAPK/NF-κB and A2aR signaling in LPS-induced THP-1 macrophages, Int. J. Biol. Sci. 15 (2019) 1571-1581. https://doi.org/10.7150/ijbs.34211.
Crossref Google Scholar
[17]

C. Marchetti, B. Swartzwelter, F. Gamboni, et al., OLT1177, a β-sulfonyl nitrile compound, safe in humans, inhibits the NLRP3 inflammasome and reverses the metabolic cost of inflammation, Proc. Natl. Acad. Sci. U.S.A. 115 (2018) E1530-E1539. https://doi.org/10.1073/pnas.1716095115.
Crossref Google Scholar
[18]

B. Leng, Y. Zhang, X. Liu, et al., Astragaloside Ⅳ suppresses high glucose-induced NLRP3 inflammasome activation by inhibiting TLR4/NF-κB and CaSR, Mediators Inflamm. (2019) 1082497. https://doi.org/10.1155/2019/1082497.
Crossref Google Scholar
[19]

A.A. Fouad, A.M. Abdel-Aziz, A.A.H. Hamouda, Diacerein downregulates NLRP3/caspase-1/IL-1β and IL-6/STAT3 pathways of inflammation and apoptosis in a rat model of cadmium testicular toxicity, Biol. Trace Elem. Res. 195 (2020) 499-505. https://doi.org/10.1007/s12011-019-01865-6.
Crossref Google Scholar
[20]

R. Zhou, X. Yang, X. Li, et al., Recombinant CC16 inhibits NLRP3/caspase-1-induced pyroptosis through p38 MAPK and ERK signaling pathways in the brain of a neonatal rat model with sepsis, J. Neuroinflammation 16 (2019) 239. https://doi.org/10.1186/s12974-019-1651-9.
Crossref Google Scholar
[21]

P.C. Liao, L.K. Chao, J.C. Chou, et al., Lipopolysaccharide/adenosine triphosphate-mediated signal transduction in the regulation of NLRP3 protein expression and caspase-1-mediated interleukin-1β secretion, Inflamm. Res. 62 (2013) 89-96. https://doi.org/10.1007/s00011-012-0555-2.
Crossref Google Scholar
[22]

N.K. Dubey, B.Y. Peng, C.M. Lin, et al., NSC 95397 suppresses proliferation and induces apoptosis in colon cancer cells through MKP-1 and the ERK1/2 pathway, Int. J. Mol. Sci. 19 (2018) 1625. https://doi.org/10.3390/ijms19061625.
Crossref Google Scholar
[23]

Z. Zhang, T.N. Lam, Z. Zuo, Radix Puerariae: an overview of its chemistry, pharmacology, pharmacokinetics, and clinical use, J. Clin. Pharmacol. 53 (2013) 787-811. https://doi.org/10.1002/jcph.96.
Crossref Google Scholar
[24]

R. Li, Y. Chen, M. Shi, et al., Gegen Qinlian decoction alleviates experimental colitis via suppressing TLR4/NF-κB signaling and enhancing antioxidant effect, Phytomedicine 23 (2016) 1012-1120. https://doi.org/10.1016/j.phymed.2016.06.010.
Crossref Google Scholar
[25]

Y.D. Jeon, J.H. Lee, Y.M. Lee, et al., Puerarin inhibits inflammation and oxidative stress in dextran sulfate sodium-induced colitis mice model, Biomed. Pharmacother. 124 (2020) 109847. https://doi.org/10.1016/j.biopha.2020.
Crossref Google Scholar
[26]

Y. Choi, S. Bose, N.R. Shin, et al., Lactate-fortified Puerariae Radix fermented by bifidobacterium breve improved diet-induced metabolic dysregulation via alteration of gut microbial communities, Nutrients 12 (2020) 276. https://doi.org/10.3390/nu12020276.
Crossref Google Scholar
[27]

Y. Sook Kim, I. Soo Lee, J. Sook Kim, Protective effects of Puerariae Radix extract and its single compounds on methylglyoxal-induced apoptosis in human retinal pigment epithelial cells, J. Ethnopharmacol. 152 (2014) 594-598. https://doi.org/10.1016/j.jep.2014.01.008.
Crossref Google Scholar
[28]

Y.Y. Wei, Y.M. Fan, Y. Ga, et al., Shaoyao decoction attenuates DSS-induced ulcerative colitis, macrophage and NLRP3 inflammasome activation through the MKP1/NF-κB pathway, Phytomedicine 92 (2021) 153743. https://doi.org/10.1016/j.phymed.2021.153743.
Crossref Google Scholar
[29]

L. Du, C. Ha, Epidemiology and pathogenesis of ulcerative colitis, Gastroenterol. Clin. North Am. 49 (2020) 643-654. https://doi.org/10.1016/j.gtc.2020.07.005.
Crossref Google Scholar
[30]

Z. Zhou, W. He, H. Tian, et al. Thyme (Thymus vulgaris L.) polyphenols ameliorate DSS-induced ulcerative colitis of mice by mitigating intestinal barrier damage, regulating gut microbiota, and suppressing TLR4/NF-κB-NLRP3 inflammasome pathways, Food Funct. 3 (2023). https://doi.org/10.1039/d2fo02523j.
Crossref Google Scholar
[31]

Z.S. Hong, J. Xie, X.F. Wang, et al., Moringa oleifera Lam. peptide remodels intestinal mucosal barrier by inhibiting JAK-STAT activation and modulating gut microbiota in colitis, Front Immunol. 13 (2022) 924178. https://doi.org/10.3389/fimmu.2022.924178.
Crossref Google Scholar
[32]

Q. Chen, S. Xiao, Z. Li, et al., Chemical and metabolic profiling of Si-Ni decoction analogous formulae by high performance liquid chromatography-mass spectrometry, Sci. Rep. 5 (2015) 11638. https://doi.org/10.1038/srep11638.
Crossref Google Scholar
[33]

D. Cai, Y. Zhao, F. Yu, Puerarin ameliorates acute lung injury by modulating NLRP3 inflammasome-induced pyroptosis, Cell Death Discov. 18 (2022) 368. https://doi.org/10.1038/s41420-022-01137-8.
Crossref Google Scholar
[34]

Y.D. Jeon, J.H. Lee, Y.M. Lee, et al., Puerarin inhibits inflammation and oxidative stress in dextran sulfate sodium-induced colitis mice model, Biomed. Pharmacother. 124 (2020) 109847. https://doi.org/10.1016/j.biopha.2020.109847.
Crossref Google Scholar
[35]

B. Zhang, X. Wei, M. Ding, et al., Daidzein protects Caco-2 cells against lipopolysaccharide-induced intestinal epithelial barrier injury by suppressing PI3K/AKT and P38 pathways, Molecules 27 (2022) 8928. https://doi.org/10.3390/molecules27248928.
Crossref Google Scholar
[36]

T. Xia, M. Liu, Q. Zhao, et al., PRMT5 regulates cell pyroptosis by silencing CASP1 in multiple myeloma, Cell Death Dis. 22 (2021) 1099. https://doi.org/10.1038/s41419-021-04125-5.
Crossref Google Scholar
[37]

L. Sun, W. Ma, W. Gao, et al., Propofol directly induces caspase-1-dependent macrophage pyroptosis through the NLRP3-ASC inflammasome, Cell Death Dis. 10 (2019) 542. https://doi.org/10.1038/s41419-019-1761-4.
Crossref Google Scholar
[38]

Y. Chen, B. Yang, R.P. Ross, et al., Orally administered CLA ameliorates DSS-induced colitis in mice via intestinal barrier improvement, oxidative stress reduction, and inflammatory cytokine and gut microbiota modulation, J. Agric. Food Chem. 67 (2019) 13282-13298. https://doi.org/10.1021/acs.jafc.9b05744.
Crossref Google Scholar
[39]

J. Zhang, F. Liang, Z. Chen, et al. Vitexin protects against dextran sodium sulfate-induced colitis in mice and its potential mechanisms, J. Agric. Food Chem. 70 (2022) 12041-12054. https://doi.org/10.1021/acs.jafc.2c05177.
Crossref Google Scholar
[40]

F. Wang, Q. Liang, Y. Ma, et al. Silica nanoparticles induce pyroptosis and cardiac hypertrophy via ROS/NLRP3/Caspase-1 pathway, Free Radic. Biol. Med. 182 (2022) 171-181. https://doi.org/10.1016/j.freeradbiomed.2022.02.027.
Crossref Google Scholar
[41]

F. Hoss, J.F. Rodriguez-Alcazar, E. Latz, Assembly and regulation of ASC specks, Cell Mol. Life Sci. 74 (2017) 1211-1229. https://doi.org/10.1007/s00018-016-2396-6.
Crossref Google Scholar
[42]

X. Ye, G. Song, S. Huang, et al., Caspase-1: a promising target for preserving blood-brain barrier integrity in acute stroke, Front. Mol. Neurosci. 18 (2022) 856372. https://doi.org/10.3389/fnmol.2022.856372.
Crossref Google Scholar
[43]

C.L. Evavold, J. Ruan, Y. Tan, et al., The pore-forming protein gasdermin d regulates interleukin-1 secretion from living macrophages, Immunity 16 (2018) 35-44. https://doi.org/10.1016/j.immuni.2017.11.013.
Crossref Google Scholar
[44]

X. Lin, Z. Yi, J. Diao, et al. ShaoYao decoction ameliorates colitis-associated colorectal cancer by downregulating proinflammatory cytokines and promoting epithelial-mesenchymal transition, J. Transl. Med. 12 (2014) 105. https://doi.org/10.1186/1479-5876-12-105.
Crossref Google Scholar
[45]

Y. Yang, N. Hu, X.J. Gao, et al., Dextran sulfate sodium-induced colitis and ginseng intervention altered oral pharmacokinetics of cyclosporine A in rats, J. Ethnopharmacol. 265 (2021) 113251. https://doi.org/10.1016/j.jep.2020.113251.
Crossref Google Scholar
[46]

Chinese Pharmacopoeia Commission, Pharmacopoeia of the People’s Republic of China. China Medical Science and Technology Press, 347 (2020) 333.
Google Scholar
[47]

C.F. Guazelli, V. Fattori, B.B. Colombo, et al., Quercetin-loaded microcapsules ameliorate experimental colitis in mice by anti-inflammatory and antioxidant mechanisms, J. Nat. Prod. 76 (2013) 200-208. https://doi.org/10.1021/np300670w.
Crossref Google Scholar
Food Science and Human Wellness
Volume 13 Issue 4,
July 2024
Pages 2266-2276
DOI: 10.26599/FSHW.2022.9250189
Cite this article:
Ga Y, Wei Y, Zhao Q, et al. Puerariae Radix protects against ulcerative colitis in mice by inhibiting NLRP3 inflammasome activation. Food Science and Human Wellness, 2024, 13(4): 2266-2276. https://doi.org/10.26599/FSHW.2022.9250189

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Received: 06 January 2023
Revised: 26 January 2023
Accepted: 19 February 2023
Published: 20 May 2024
© 2024 Beijing Academy of Food Sciences. Publishing services by Tsinghua University Press.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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