Abstract
Ulcerative colitis is a chronic inflammatory disorder of the intestinal mucosa and a prevalent gastrointestinal condition in developed countries. Peiminine, derived from the Fritillaria imperialis plant, exhibits remarkable anti-inflammatory and anti-cancer properties. This study aims to investigate the anti-inflammatory effects of peiminine in an experimental model of ulcerative colitis. Ulcerative colitis was induced intra-rectally in all groups, except the negative control, using 100 μl of 4% acetic acid. Peiminine treatment was initiated after ulcerative colitis induction and symptom manifestation. After the final injection, mice were sacrificed on day 15 for assessment. Various parameters were evaluated, including disease activity index, myeloperoxidase activity, nitric oxide levels, production and expression of IL-1, IL-6, TNF-α cytokines, and expression of IL-1β, IL-6, TNF-α, iNOS, and COX2 genes. Microscopic pathological evaluation was performed on colon tissue. Peiminine treatment resulted in reduced levels of NO, MPO, IL-1β, IL-6, and TNF-α. Furthermore, the expression of IL-1β, IL-6, TNF-α genes, iNOS, and COX2 genes was decreased in response to peiminine treatment in these mice. This study demonstrates the effectiveness of peiminine in alleviating inflammatory manifestations and mitigating intestinal tissue damage in an experimental model of ulcerative colitis, probably by anti-inflammatory procedure. Peiminine holds potential as a therapeutic adjunct for the management of ulcerative colitis.
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The data sets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
References
Chen G, Liu J, Jiang L et al (2018) Peiminine protects dopaminergic neurons from inflammation-induced cell death by inhibiting the ERK1/2 and NF-κB signalling pathways. Int J Mol Sci. https://doi.org/10.3390/ijms19030821
Chen P, Zhou D, Liu Y et al (2022) Peiminine inhibits myocardial injury and fibrosis after myocardial infarction in rats by regulating mitogen-activated protein kinase pathway. Korean J Physiol Pharmacol 26:87–94. https://doi.org/10.4196/kjpp.2022.26.2.87
Démaris A, Widigson ESK, Ilvemark JFKF et al (2022) Ulcerative colitis and acute severe ulcerative colitis patients are overlooked in infliximab population pharmacokinetic models: results from a comprehensive review. Pharmaceutics. https://doi.org/10.3390/pharmaceutics14102095
Du B, Cao L, Wang K et al (2020) Peiminine attenuates acute lung injury induced by LPS through inhibiting lipid rafts formation. Inflammation 43:1110–1119. https://doi.org/10.1007/s10753-020-01198-w
Elhag DA, Kumar M, Saadaoui M et al (2022) Inflammatory bowel disease treatments and predictive biomarkers of therapeutic response. Int J Mol Sci. https://doi.org/10.3390/ijms23136966
Gheibi S, Hashemi SR, Karimipour M et al (2018) Synergistic effects of hydro extract of jujube fruit in combination with Mesalazine (orally) and Asacol (intra-colonic) administration in ameliorating animal model of ulcerative colitis. J Coloproctol. 38:275–282. https://doi.org/10.1016/j.jcol.2018.05.008
Guo H, Ji F, Liu B et al (2013) Peiminine ameliorates bleomycin-induced acute lung injury in rats. Mol Med Rep 7:1103–1110. https://doi.org/10.3892/mmr.2013.1312
Hanauer SB (2006) Inflammatory bowel disease: epidemiology, pathogenesis, and therapeutic opportunities. Inflamm Bowel Dis 12(Suppl 1):S3-9. https://doi.org/10.1097/01.mib.0000195385.19268.68
Kangwan N, Pintha K, Khanaree C et al (2021) Anti-inflammatory effect of Perilla frutescens seed oil rich in omega-3 fatty acid on dextran sodium sulfate-induced colitis in mice. Res Pharm Sci 16:464–473. https://doi.org/10.4103/1735-5362.323913
Lee B, Kim E-Y, Kim J-H et al (2015) Antiallergic effects of peiminine through the regulation of inflammatory mediators in HMC-1 cells. Immunopharmacol Immunotoxicol 37:351–358. https://doi.org/10.3109/08923973.2015.1059441
Li J, Qin Y, Wang W et al (2021) Peiminine inhibits the progression of colorectal cancer through up-regulating miR-760 via declining the expression of long noncoding RNA LINC00659. Anticancer Drugs 32:148–156. https://doi.org/10.1097/CAD.0000000000000981
Lim J-M, Lee B, Min J-H et al (2018) Effect of peiminine on DNCB-induced atopic dermatitis by inhibiting inflammatory cytokine expression in vivo and in vitro. Int Immunopharmacol 56:135–142. https://doi.org/10.1016/j.intimp.2018.01.025
Luo Z, Zheng B, Jiang B et al (2019) Peiminine inhibits the IL-1β induced inflammatory response in mouse articular chondrocytes and ameliorates murine osteoarthritis. Food Funct 10:2198–2208. https://doi.org/10.1039/C9FO00307J
Lyu Q, Tou F, Su H et al (2015) The natural product peiminine represses colorectal carcinoma tumor growth by inducing autophagic cell death. Biochem Biophys Res Commun 462:38–45. https://doi.org/10.1016/j.bbrc.2015.04.102
Mashhadi M, Boojar A, Mashhadi Akbar Boojar F et al (2021) In vitro investigation of the anti-diabetic effects of imperialine on beta-TC6 pancreatic and C2C12 skeletal muscle cell lines. Data Brief. https://doi.org/10.1016/j.dib.2019.104828
Mashhouri S, Meysam Abtahi Froushani S, Asghar Tehrani A (2020) Non-adherent bone marrow-derived mesenchymal stem cells ameliorate clinical manifestations and inflammation in an experimental model of ulcerative colitis in rats. Iran J Med Sci. 45:341–351. https://doi.org/10.30476/ijms.2020.72514.0
Rashid I, Yaqoob U (2021) Traditional uses, phytochemistry and pharmacology of genus Fritillaria—a review. Bull Natl Res Cent 45:124. https://doi.org/10.1186/s42269-021-00577-z
Salmerón-Manzano E, Garrido-Cardenas JA, Manzano-Agugliaro F (2020) Worldwide research trends on medicinal plants. Int J Environ Res Public Health. https://doi.org/10.3390/ijerph17103376
Tang Q, Wang Y, Ma L et al (2018) Peiminine serves as an adriamycin chemosensitizer in gastric cancer by modulating the EGFR/FAK pathway. Oncol Rep 39:1299–1305. https://doi.org/10.3892/or.2018.6184
Tanideh N, Afaridi E, Mehrabani D et al (2014) The healing effect of berberis vulgaris in acetic acid-induced ulcerative colitis in rat. Middle-East J Sci Res 21:1288–1294. https://doi.org/10.5829/idosi.mejsr.2014.21.08.8598
Tehranipour M, Emamyian Zaman M, Vaezi GH, Nejad Shahrokh Abadi K (2018) The effect of aqueous extract of Cichorium intybus L. stem on the biochemical parameters of serum and urine in male rats with nephrolithiasis. Iran J Biol Sci 13:53–61
Yu L, Chen Y, Yuan S et al (2021) Peiminine induces G0/G1-phase arrest, apoptosis, and autophagy via the ROS/JNK signaling pathway in human osteosarcoma cells in vitro and in vivo. Front Pharmacol 12:770846. https://doi.org/10.3389/fphar.2021.770846
Zhao B, Shen C, Zheng Z et al (2018) Peiminine inhibits glioblastoma in vitro and in vivo through cell cycle arrest and autophagic flux blocking. Cell Physiol Biochem 51:1566–1583. https://doi.org/10.1159/000495646
Zheng Z, Xu L, Zhang S et al (2017) Peiminine inhibits colorectal cancer cell proliferation by inducing apoptosis and autophagy and modulating key metabolic pathways. Oncotarget 8:47619–47631. https://doi.org/10.18632/oncotarget.17411
Zhu M, Xu W, Jiang J et al (2021) Peiminine suppresses RANKL-induced osteoclastogenesis by inhibiting the NFATc1, ERK, and NF-κB signaling pathways. Front Endocrinol (lausanne) 12:736863. https://doi.org/10.3389/fendo.2021.736863
Acknowledgements
The current study is part of the Ph.D. thesis of Mrs. Maryam Ranjbar Bushehri. The article’s authors express gratitude to those who helped us in this research.
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MRB, NB, HEGG, GhKh, GhF: developed the theoretical formalism, performed the analytic calculations and performed the numerical simulations. authors contributed to the final version of the manuscript. HEGG: supervised the project.
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Ranjbar Bushehri, M., Babaei, N., Esmaeili Gouvarchin Ghaleh, H. et al. Anti-inflammatory activity of peiminine in acetic acid-induced ulcerative colitis model. Inflammopharmacol 32, 657–665 (2024). https://doi.org/10.1007/s10787-023-01360-4
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DOI: https://doi.org/10.1007/s10787-023-01360-4