Coptisine attenuates post‑infectious IBS via Nrf2‑dependent inhibition of the NLPR3 inflammasome

Xiong,Ying; Wei,Hong; Chen,Chong; Jiao,Lu; Zhang,Juan; Tan,Yonggang; Zeng,Li

doi:10.3892/mmr.2022.12879

Coptisine attenuates post‑infectious IBS via Nrf2‑dependent inhibition of the NLPR3 inflammasome

Authors:
- Ying Xiong
- Hong Wei
- Chong Chen
- Lu Jiao
- Juan Zhang
- Yonggang Tan
- Li Zeng
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Affiliations: Department of Gastroenterology, Shenzhen Longhua District Central Hospital, Shenzhen, Guangdong 518110, P.R. China, Department of Gastroenterology, The First Affiliated Hospital of Shenzhen University, The Second People's Hospital of Shenzhen, Shenzhen, Guangdong 518035, P.R. China
Published online on: October 21, 2022 https://doi.org/10.3892/mmr.2022.12879
Article Number: 362

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Abstract

Inhibition of the activation of the NLR family pyrin domain‑containing 3 (NLRP3) inflammasome has previously been reported to confer protection against post‑infectious irritable bowel syndrome (PI‑IBS). Coptisine, the second most abundant isoquinoline alkaloid in Coptis chinensis, can inhibit NLRP3 inflammasome activation; however, whether coptisine exhibits protective effects against PI‑IBS remains unclear. In the present study, coptisine significantly reduced gastrointestinal motility and abdominal withdrawal reflex scores in a PI‑IBS rat model that was induced using intragastric administration of Trichinella spiralis larvae. Coptisine treatment significantly decreased the protein levels of oxidative stress markers, 4‑hydroxynonenal, protein carbonyl and 8‑hydroxy‑2'deoxyguanosine, and proinflammatory cytokines, TNF‑α, IL‑1β and IL‑18 in the colon of PI‑IBS rats. Moreover, coptisine treatment significantly increased nuclear factor erythroid 2‑related factor 2 (Nrf2) nuclear translocation and heme oxygenase‑1 protein expression levels, while significantly downregulating the protein expression levels of NLRP3, apoptosis‑associated speck‑like protein containing a CARD and caspase‑1 in the colons of PI‑IBS rats. It is important to note that the anti‑inflammatory effects of coptisine were blocked by the Nrf2 inhibitor ML385. In summary, the present study indicated that coptisine potentially attenuated PI‑IBS in rats via Nrf2‑dependent inhibition of the NLPR3 inflammasome.

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1	Aziz I and Simrén M: The overlap between irritable bowel syndrome and organic gastrointestinal diseases. Lancet Gastroenterol Hepatol. 6:139–148. 2021. View Article : Google Scholar : PubMed/NCBI
2	Bao CH, Wang CY, Li GN, Yan YL, Wang D, Jin XM, Wu LY, Liu HR, Wang XM, Shi Z and Wu HG: Effect of mild moxibustion on intestinal microbiota and NLRP6 inflammasome signaling in rats with post-inflammatory irritable bowel syndrome. World J Gastroenterol. 25:4696–4714. 2019. View Article : Google Scholar : PubMed/NCBI
3	Black CJ and Ford AC: Global burden of irritable bowel syndrome: Trends, predictions and risk factors. Nat Rev Gastroenterol Hepatol. 17:473–486. 2020. View Article : Google Scholar : PubMed/NCBI
4	Klem F, Wadhwa A, Prokop LJ, Sundt WJ, Farrugia G, Camilleri M, Singh S and Grover M: Prevalence, risk factors, and outcomes of irritable bowel syndrome after infectious enteritis: A systematic review and meta-analysis. Gastroenterology. 152:1042–1054.e1. 2017. View Article : Google Scholar : PubMed/NCBI
5	Tian Z, Zhuang X, Luo M, Yin W and Xiong L: The propionic acid and butyric acid in serum but not in feces are increased in patients with diarrhea-predominant irritable bowel syndrome. BMC Gastroenterol. 20:732020. View Article : Google Scholar : PubMed/NCBI
6	Yu ZC, Cen YX, Wu BH, Wei C, Xiong F, Li DF, Liu TT, Luo MH, Guo LL, Li YX, et al: Berberine prevents stress-induced gut inflammation and visceral hypersensitivity and reduces intestinal motility in rats. World J Gastroenterol. 25:3956–3971. 2019. View Article : Google Scholar : PubMed/NCBI
7	Scuderi SA, Casili G, Lanza M, Filippone A, Paterniti I, Esposito E and Campolo M: Modulation of NLRP3 inflammasome attenuated inflammatory response associated to diarrhea-predominant irritable bowel syndrome. Biomedicines. 8:5192020. View Article : Google Scholar : PubMed/NCBI
8	Zeng L, Li K, Wei H, Hu J, Jiao L, Yu S and Xiong Y: A Novel EphA2 inhibitor exerts beneficial effects in PI–IBS in vivo and in vitro models via Nrf2 and NF-κB signaling pathways. Front Pharmacol. 9:2722018. View Article : Google Scholar : PubMed/NCBI
9	Gu QY, Zhang J and Feng YC: Role of NLRP3 inflammasome in Bifidobacterium longum-regulated visceral hypersensitivity of postinfectious irritable bowel syndrome. Artif Cells Nanomed Biotechnol. 44:1933–1937. 2016. View Article : Google Scholar : PubMed/NCBI
10	Liao L, Schneider KM, Galvez EJC, Frissen M, Marschall HU, Su H, Hatting M, Wahlström A, Haybaeck J, Puchas P, et al: Intestinal dysbiosis augments liver disease progression via NLRP3 in a murine model of primary sclerosing cholangitis. Gut. 68:1477–1492. 2019. View Article : Google Scholar : PubMed/NCBI
11	He Y, Hara H and Núñez G: Mechanism and regulation of NLRP3 inflammasome activation. Trends Biochem Sci. 41:1012–1021. 2016. View Article : Google Scholar : PubMed/NCBI
12	Hennig P, Garstkiewicz M, Grossi S, Di Filippo M, French LE and Beer HD: The Crosstalk between Nrf2 and Inflammasomes. Int J Mol Sci. 19:5622018. View Article : Google Scholar : PubMed/NCBI
13	Arioz BI, Tastan B, Tarakcioglu E, Tufekci KU, Olcum M, Ersoy N, Bagriyanik A, Genc K and Genc S: Melatonin attenuates LPS-Induced acute depressive-like behaviors and microglial NLRP3 Inflammasome activation through the SIRT1/Nrf2 pathway. Front Immunol. 10:15112019. View Article : Google Scholar : PubMed/NCBI
14	Yang Y, Vong CT, Zeng S, Gao C, Chen Z, Fu C, Wang S, Zou L, Wang A and Wang Y: Tracking evidences of Coptis chinensis for the treatment of inflammatory bowel disease from pharmacological, pharmacokinetic to clinical studies. J Ethnopharmacol. 268:1135732021. View Article : Google Scholar : PubMed/NCBI
15	Song D, Hao J and Fan D: Biological properties and clinical applications of berberine. Front Med. 14:564–582. 2020. View Article : Google Scholar : PubMed/NCBI
16	Wu J, Luo Y, Deng D, Su S, Li S, Xiang L, Hu Y, Wang P and Meng X: Coptisine from Coptis chinensis exerts diverse beneficial properties: A concise review. J Cell Mol Med. 23:7946–7960. 2019. View Article : Google Scholar : PubMed/NCBI
17	Wu J, Luo Y, Jiang Q, Li S, Huang W, Xiang L, Liu D, Hu Y, Wang P, Lu X, et al: Coptisine from Coptis chinensis blocks NLRP3 inflammasome activation by inhibiting caspase-1. Pharmacol Res. 147:1043482019. View Article : Google Scholar : PubMed/NCBI
18	Adriani A, Ribaldone DG, Astegiano M, Durazzo M, Saracco GM and Pellicano R: Irritable bowel syndrome: The clinical approach. Panminerva Med. 60:213–222. 2018. View Article : Google Scholar : PubMed/NCBI
19	Ghoshal UC and Gwee KA: Post-infectious IBS, tropical sprue and small intestinal bacterial overgrowth: The missing link. Nat Rev Gastroenterol Hepatol. 14:435–441. 2017. View Article : Google Scholar : PubMed/NCBI
20	Xiong Y, Li KX, Wei H, Jiao L, Yu SY and Zeng L: Eph/ephrin signalling serves a bidirectional role in lipopolysaccharide-induced intestinal injury. Mol Med Rep. 18:2171–2181. 2018.PubMed/NCBI
21	Forman HJ and Zhang H: Targeting oxidative stress in disease: Promise and limitations of antioxidant therapy. Nat Rev Drug Discov. 20:689–709. 2021. View Article : Google Scholar : PubMed/NCBI
22	Puentes-Pardo JD, Moreno-SanJuan S, Carazo Á and León J: Heme Oxygenase-1 in gastrointestinal tract health and disease. Antioxidants (Basel). 9:12142020. View Article : Google Scholar : PubMed/NCBI
23	Feng M, Kong SZ, Wang ZX, He K, Zou ZY, Hu YR, Ma H, Li XG and Ye XL: The protective effect of coptisine on experimental atherosclerosis ApoE^−/− mice is mediated by MAPK/NF-κB-dependent pathway. Biomed Pharmacother. 93:721–729. 2017. View Article : Google Scholar : PubMed/NCBI
24	Hu YR, Ma H, Zou ZY, He K, Xiao YB, Wang Y, Feng M, Ye XL and Li XG: Activation of Akt and JNK/Nrf2/NQO1 pathway contributes to the protective effect of coptisine against AAPH-induced oxidative stress. Biomed Pharmacother. 85:313–322. 2017. View Article : Google Scholar : PubMed/NCBI
25	He K, Ye X, Wu H, Wang Y, Zou Z, Ning N, Hu Y, Chen B, Fang X and Li X: The safety and anti-hypercholesterolemic effect of coptisine in Syrian golden hamsters. Lipids. 50:185–194. 2015. View Article : Google Scholar : PubMed/NCBI
26	Mangan MSJ, Olhava EJ, Roush WR, Seidel HM, Glick GD and Latz E: Targeting the NLRP3 inflammasome in inflammatory diseases. Nat Rev Drug Discov. 17:588–606. 2018. View Article : Google Scholar : PubMed/NCBI