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Original Research

Open Access

Gentianine facilitates proliferation and inhibits inflammation and oxidative stress in caerulein-triggered acute pancreatitis cell model

  • Debiao Pan1
  • Hailin Ye1
  • Jun Wang1
  • Jiaodan Mao2,*,

1Department of Hepatic-biliary-pancreatic-Surgery, Lishui People’s Hospital, 323000 Lishui, Zhejiang, China

2Department of Oncology, Lishui People’s Hospital, 323000 Lishui, Zhejiang, China

DOI: 10.22514/sv.2024.059 Vol.20,Issue 5,May 2024 pp.77-84

Submitted: 19 February 2024 Accepted: 08 April 2024

Published: 08 May 2024

*Corresponding Author(s): Jiaodan Mao E-mail: maojiaodan4020601@163.com

Abstract

Acute pancreatitis (AP) is a life-threatening inflammatory condition of the pancreas. Gentianine (GTN), derived from Gentiana scabra, has been demonstrated to suppress inflammation in various diseases. Nonetheless, the specific effects and related pathways through which GTN influences AP progression remain unclear. Herein, we aimed to elucidate the regulatory effects of GTN on AP. Our results confirmed that the reduction in cell proliferation induced by caerulein could be reversed after GTN treatment (25 µM, 50 µM and 100 µM). Moreover, while caerulein treatment increased cell apoptosis, subsequent GTN treatment reduced this effect, as well as the inflammation provoked by caerulein. Furthermore, activation of the Toll-like receptor 4 (TLR4)/nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) pathway induced by caerulein was counteracted by GTN administration. In summary, this research revealed for the first time that GTN promotes cell proliferation and reduces inflammation and oxidative stress in AR42J cells in a caerulein-induced AP cell model, suggesting that GTN holds promise as an effective therapeutic agent for AP.


Keywords

Gentianine; Acute pancreatitis; Inflammation; Caerulein


Cite and Share

Debiao Pan,Hailin Ye,Jun Wang,Jiaodan Mao. Gentianine facilitates proliferation and inhibits inflammation and oxidative stress in caerulein-triggered acute pancreatitis cell model. Signa Vitae. 2024. 20(5);77-84.

References

[1] Mederos MA, Reber HA, Girgis MD. Acute pancreatitis: a review.. JAMA. 2021; 325: 382–390.

[2] Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, et al. Classification of acute pancreatitis—2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013; 62: 102–111.

[3] Zhu C, Yang W, Li D, Song Y, Chen S, Wang Q, et al. Calycosin attenuates severe acute pancreatitis-associated acute lung injury by curtailing high mobility group box 1-induced inflammation. World Journal of Gastroenterology. 2021; 27: 7669–7686.

[4] Zhen J, Chen W, Liu Y, Zang X. Baicalin protects against acute pancreatitis involving JNK signaling pathway via regulating miR-15a. The American Journal of Chinese Medicine. 2021; 49: 147–161.

[5] Han F, Ding Z, Shi X, Zhu Q, Shen Q, Xu X, et al. Irisin inhibits neutrophil extracellular traps formation and protects against acute pancreatitis in mice. Redox Biology. 2023; 64: 102787.

[6] Kwak W, Kim J, Ryu K, Cho Y, Jeon S, Moon C. Effects of gentianine on the production of pro-inflammatory cytokines in male sprague-dawley rats treated with lipopolysaccharide (LPS). Biological and Pharmaceutical Bulletin. 2005; 28: 750–753.

[7] Li Y, Lv L, Li S, Qian H. Gentianine alleviates dextran sulfate sodium-induced ulcerative colitis via inhibition of TLR4/NLRP3-mediated pyroptosis. International Immunopharmacology. 2024; 126: 111214.

[8] Wenjin C, Jianwei W. Protective effect of gentianine, a compound from Du Huo Ji Sheng Tang, against freund’s complete adjuvant-induced arthritis in rats. Inflammation. 2017; 40: 1401–1408.

[9] Wang N, Liu Y, Jia C, Gao C, Zheng T, Wu M, et al. Machine learning enables discovery of Gentianine targeting TLR4/NF-κB pathway to repair ischemic stroke injury. Pharmacological Research. 2021; 173: 105913.

[10] Zhang K, Zhang X. MiR-146b-3p protects against AR42J cell injury in cerulein-induced acute pancreatitis model through targeting Anxa2. Open Life Sciences. 2021; 16: 255–265.

[11] Zhu Y, Liu S, Wang F. MicroRNA MiR-27a-5p alleviates the cerulein-induced cell apoptosis and inflammatory injury of AR42J cells by targeting Traf3 in acute pancreatitis. Inflammation. 2020; 43: 1988–1998.

[12] Zhou Z, Chen Y, Dong W, An R, Liang K, Wang X. Da Cheng Qi decoction alleviates cerulein-stimulated AR42J pancreatic acinar cell injury via the JAK2/STAT3 signaling pathway. Evidence-Based Complementary and Alternative Medicine. 2021; 2021: 6657036.

[13] Limi S, Ojakian G, Raffaniello R. Rab3D regulates amylase levels, not agonist-induced amylase release, in AR42J cells. Cellular and Molecular Biology Letters. 2012; 17: 258–273.

[14] Raffaniello R, Fedorova D, Ip D, Rafiq S. Hsp90 co-localizes with Rab-GDI-1 and regulates agonist-induced amylase release in AR42J cells. Cellular Physiology and Biochemistry. 2009; 24: 369–378.

[15] Ikeda Y, Fukuoka S. Phosphatidic acid production, required for cholecystokinin octapeptide-stimulated amylase secretion from pancreatic acinar AR42J cells, is regulated by a wortmannin-sensitive process. Biochemical and Biophysical Research Communications. 2003; 306: 943–947.

[16] Kylänpää M. Inflammation and immunosuppression in severe acute pancreatitis. World Journal of Gastroenterology. 2010; 16: 2867–2872.

[17] Habtezion A. Inflammation in acute and chronic pancreatitis. Current Opinion in Gastroenterology. 2015; 31: 395–399.

[18] Wu H, Chen H, Zhou R. Phospholipase D2 targeted by miR‐5132‐5p alleviates cerulein‐induced acute pancreatitis via the Nrf2/NFκB pathway. Immunity, Inflammation and Disease. 2023; 11: e831.

[19] Wang X, Qian J, Meng Y, Wang P, Cheng R, Zhou G, et al. Salidroside alleviates severe acute pancreatitis-triggered pancreatic injury and inflammation by regulating miR-217-5p/YAF2 axis. International Immunopharmacology. 2022; 111: 109123.

[20] Yuan J, Chheda C, Piplani H, Geng M, Tan G, Thakur R, et al. Pancreas-specific deletion of protein kinase D attenuates inflammation, necrosis, and severity of acute pancreatitis. Molecular Basis of Disease. 2021; 1867: 165987.

[21] Dixit A, Cheema H, George J, Iyer S, Dudeja V, Dawra R, et al. Extracellular release of ATP promotes systemic inflammation during acute pancreatitis. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2019; 317: G463–G475.

[22] Fawzy HA, Mohammed AA, Fawzy HM, Fikry EM. Reorienting of pramipexole as a promising therapy for acute pancreatitis in a rat model by suppressing TLR4\NF-κB p65\NLRP3 inflammasome signaling. Canadian Journal of Physiology and Pharmacology. 2022; 100: 542–552.

[23] Li H, Xie J, Guo X, Yang G, Cai B, Liu J, et al. Bifidobacterium spp. and their metabolite lactate protect against acute pancreatitis via inhibition of pancreatic and systemic inflammatory responses. Gut Microbes. 2022; 14: 2127456.

[24] Wen Y, Han C, Liu T, Wang R, Cai W, Yang J, et al. Chaiqin chengqi decoction alleviates severity of acute pancreatitis via inhibition of TLR4 and NLRP3 inflammasome: identification of bioactive ingredients via pharmacological sub-network analysis and experimental validation. Phytomedicine. 2020; 79: 153328.

[25] Jia L, Chen H, Yang J, Fang X, Niu W, Zhang M, et al. Combinatory antibiotic treatment protects against experimental acute pancreatitis by suppressing gut bacterial translocation to pancreas and inhibiting NLRP3 inflammasome pathway. Innate Immunity. 2020; 26: 48–61.


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