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The Hydro-alcoholic Extract of Achillea wilhelmsii C. Koch Ameliorates Acetic Acid-induced Ulcerative Colitis through TLR-4

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Abstract

Achillea wilhelmsii contains several anti-inflammatory and antioxidant phytochemicals, proposing protecting effect on inflammatory responses in autoimmune diseases such as inflammatory bowel diseases. However, its protective and anti-inflammatory activities against Ulcerative Colitis are unknown. This study intended to verify whether A. wilhelmsii is able to improve colitis via mediating inflammatory cytokines. Colitis was induced by intrarectal administration of acetic acid 4% in rats, except in sham group. Animals were treated with the hydro-alcoholic extract of A. wilhelmsii at concentrations of 50, 100, 200 mg/kg for 48 h. The other groups included the control (only treated with acetic acid), sham group (normal saline), and a standard group (Dexamethasone). Microscopic and histopathologic examinations were conducted in inflamed colonic tissue. Both macroscopic and microscopic examinations of colitis tissue were carried out. Tissue concentrations of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were assessed by Eliza kits, while myeloperoxidase (MPO) was measured spectrophotometrically. mRNA expression of toll-like receptor (TLR)-4 was assessed in Real time-PCR. A. wilhelmsii ameliorated macroscopic and microscopic symptoms of induced colitis. The extract also downregulated pro-inflammatory mediators including IL-6, TNF-α, and MPO in the colon tissue. Substantial decline was recorded in mucosal TLR-4 expression, signifying considerable reduction of IL-6, and TNF-α production. This is the first report indicating that A. wilhelmsii abrogates experimental colitis through its anti-inflammatory activity, which in particular might be correlated with downregulation of TLR-4 expression.

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References

  1. Sandborn WJ, Su C, Sands BE, D’Haens GR, Vermeire S, Schreiber S, Danese S, Feagan BG, Reinisch W, Niezychowski W (2017) Tofacitinib as induction and maintenance therapy for ulcerative colitis. N Engl J Med 376(18):1723–1736

    Article  CAS  PubMed  Google Scholar 

  2. Loftus EV, Colombel J-F, Feagan BG, Vermeire S, Sandborn WJ, Sands BE, Danese S, D’Haens GR, Kaser A, Panaccione R (2017) Long-term efficacy of vedolizumab for ulcerative colitis. J Crohns Colitis 11(4):400–411

    PubMed  Google Scholar 

  3. Park JH, Peyrin-Biroulet L, Eisenhut M, Shin JI (2017) IBD immunopathogenesis: a comprehensive review of inflammatory molecules. Autoimmun Rev 16(4):416–426. https://doi.org/10.1016/j.autrev.2017.02.013

    Article  CAS  PubMed  Google Scholar 

  4. Cui L, Feng L, Zhang ZH, Jia XB (2014) The anti-inflammation effect of baicalin on experimental colitis through inhibiting TLR4/NF-κB pathway activation. Int Immunopharmacol 23(1):294–303

    Article  CAS  PubMed  Google Scholar 

  5. Nitzan O, Elias M, Peretz A, Saliba W (2016) Role of antibiotics for treatment of inflammatory bowel disease. World J Gastroenterol 22(3):1078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Saeidnia S, Gohari A, Mokhber-Dezfuli N, Kiuchi F (2011) A review on phytochemistry and medicinal properties of the genus Achillea. DARU J Pharm Sci 19(3):173

    CAS  Google Scholar 

  7. Khazneh E, Hřibová P, Hošek J, Suchý P, Kollár P, Pražanová G, Muselík J, Hanaková Z, Václavík J, Miłek M (2016) The chemical composition of Achillea wilhelmsii C. Koch and its desirable effects on hyperglycemia, inflammatory mediators and hypercholesterolemia as risk factors for cardiometabolic disease. Molecules 21(4):404

    Article  PubMed  PubMed Central  Google Scholar 

  8. Lori-Gooini Z, Rabiei Z, Farhadi B, Bijad E, Azomon E, Rafieian-Kopaei M (2018) Investigation of chemical compounds and effects of Achilea wilhelmsii L essential oil on antioxidant and malondialdehyde levels of serum and brains of reserpined mice. Iran J Physiol Pharmacol 2(3):176–166

    Google Scholar 

  9. Saeidinia S, Gouhari A, Yasa N, Shafiei A (2005) Composition of the volatile oil of Achillea conferta DC. from Iran. Daru J Pharm Sci 13:34–36

    Google Scholar 

  10. Fathi H, LashtooAghaee B, Ebrahimzadeh M (2011) Antioxidant activity and phenolic contents of Achillea wilhelmsii. Pharmacologyonline 2:942–949

    Google Scholar 

  11. Fakhraei N, Abdolghaffari AH, Delfan B, Abbasi A, Rahimi N, Khansari A, Rahimian R, Dehpour AR (2014) Protective effect of hydroalcoholic olive leaf extract on experimental model of colitis in rat: involvement of nitrergic and opioidergic systems. Phytother Res 28(9):1367–1373

    Article  CAS  PubMed  Google Scholar 

  12. Antonioli L, Fornai M, Colucci R, Ghisu N, Da Settimo F, Natale G, Kastsiuchenka O, Duranti E, Virdis A, Vassalle C (2007) Inhibition of adenosine deaminase attenuates inflammation in experimental colitis. J Pharmacol Exp Ther 322(2):435–442

    Article  CAS  PubMed  Google Scholar 

  13. Dadkhah A, Fatemi F, Ababzadeh S, Roshanaei K, Alipour M, Tabrizi BS (2014) Potential preventive role of Iranian Achillea wilhelmsii C. Koch essential oils in acetaminophen-induced hepatotoxicity. Bot Stud 55(1):37. https://doi.org/10.1186/1999-3110-55-37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Morris GP, Beck PL, Herridge MS, Depew WT, Szewczuk MR, Wallace JL (1989) Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterol 96(2):795–803

    Article  CAS  Google Scholar 

  15. Stumhofer JS, Laurence A, Wilson EH, Huang E, Tato CM, Johnson LM, Villarino AV, Huang Q, Yoshimura A, Sehy D (2006) Interleukin 27 negatively regulates the development of interleukin 17–producing T helper cells during chronic inflammation of the central nervous system. Nat Immunol 7(9):937–945

    Article  CAS  PubMed  Google Scholar 

  16. Farzaei MH, Ghasemi-Niri SF, Abdolghafari AH, Baeeri M, Khanavi M, Navaei-Nigjeh M, Abdollahi M, Rahimi R (2015) Biochemical and histopathological evidence on the beneficial effects of Tragopogon graminifolius in TNBS-induced colitis. Pharm Biol 53(3):429–436

    Article  PubMed  Google Scholar 

  17. Krawisz J, Sharon P, Stenson W (1984) Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity: assessment of inflammation in rat and hamster models. Gastroenterol 87(6):1344–1350

    Article  CAS  Google Scholar 

  18. Momtaz S, Baeeri M, Rahimifard M, Haghi-Aminjan H, Hassani S, Abdollahi M (2019) Manipulation of molecular pathways and senescence hallmarks by natural compounds in fibroblast cells. J Cell Biochem 120(4):6209–6222

    Article  CAS  PubMed  Google Scholar 

  19. Neurath MF (2014) Cytokines in inflammatory bowel disease. Nat Rev Immunol 14(5):329–342

    Article  CAS  PubMed  Google Scholar 

  20. Farzaei MH, El-Senduny FF, Momtaz S, Parvizi F, Iranpanah A, Tewari D, Naseri R, Abdolghaffari AH, Rezaei N (2018) An update on dietary consideration in inflammatory bowel disease: anthocyanins and more. Expert Rev Gastroenterol Hepatol 12(10):1007–1024

    Article  CAS  PubMed  Google Scholar 

  21. Farzaei MH, Bahramsoltani R, Abdolghaffari AH, Sodagari HR, Esfahani SA, Rezaei N (2016) A mechanistic review on plant-derived natural compounds as dietary supplements for prevention of inflammatory bowel disease. Expert Rev Gastroenterol Hepatol 10(6):745–758

    Article  CAS  PubMed  Google Scholar 

  22. Larussa T, Imeneo M, Luzza F (2017) Potential role of nutraceutical compounds in inflammatory bowel disease. World J Gastroenterol 23(14):2483–2492. https://doi.org/10.3748/wjg.v23.i14.2483

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Triantafillidis JK, Triantafyllidi A, Vagianos C, Papalois A (2016) Favorable results from the use of herbal and plant products in inflammatory bowel disease: evidence from experimental animal studies. Ann Gastroenterol 29(3):268–281. https://doi.org/10.20524/aog.2016.0059

    Article  PubMed  PubMed Central  Google Scholar 

  24. Salaritabar A, Darvishi B, Hadjiakhoondi F, Manayi A, Sureda A, Nabavi SF, Fitzpatrick LR, Nabavi SM, Bishayee A (2017) Therapeutic potential of flavonoids in inflammatory bowel disease: a comprehensive review. World J Gastroenterol 23(28):5097

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Mueller D, Triebel S, Rudakovski O, Richling E (2013) Influence of triterpenoids present in apple peel on inflammatory gene expression associated with inflammatory bowel disease (IBD). Food Chem 139(1):339–346. https://doi.org/10.1016/j.foodchem.2013.01.101

    Article  CAS  PubMed  Google Scholar 

  26. Santino A, Scarano A, De Santis S, De Benedictis M, Giovinazzo G, Chieppa M (2017) Gut microbiota modulation and anti-inflammatory properties of dietary polyphenols in IBD: new and consolidated perspectives. Curr Pharm Des 23(16):2344–2351

    Article  CAS  PubMed  Google Scholar 

  27. Abdel-Rahman RF, Alqasoumi SI, El-Desoky AH, Soliman GA, Paré PW, Hegazy MEF (2015) Evaluation of the anti-inflammatory, analgesic and anti-ulcerogenic potentials of Achillea fragrantissima (Forssk.). S Afr J Bot 98:122–127. https://doi.org/10.1016/j.sajb.2015.02.009

    Article  Google Scholar 

  28. Benedek B, Kopp B, Melzig MF (2007) Achillea millefolium L. sl–Is the anti-inflammatory activity mediated by protease inhibition? J Ethnopharmacol 113(2):312–317

    Article  PubMed  Google Scholar 

  29. Cavalcanti AM, Baggio CH, Freitas CS, Rieck L, de Sousa RS, Da Silva-Santos JE, Mesia-Vela S, Marques MCA (2006) Safety and antiulcer efficacy studies of Achillea millefolium L. after chronic treatment in Wistar rats. J Ethnopharmacol 107(2):277–284. https://doi.org/10.1016/j.jep.2006.03.011

    Article  PubMed  Google Scholar 

  30. Amiri M, Navabi J, Shokoohinia Y, Heydarpour F, Bahrami G, Behbood L, Derakhshandeh P, Momtaz S, Farzaei MH (2019) Efficacy and safety of a standardized extract from Achillea wilhelmsii C. Koch in patients with ulcerative colitis: A randomized double blind placebo-controlled clinical trial. Complement Ther Med 45:262–268

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, Iran

    Saeideh Momtaz & Amir Hossein Abdolghaffari

  2. Department of Toxicology and Pharmacology, School of Pharmacy, and Toxicology and Diseases Group, Pharmaceutical Sciences Research Center (PSRC), The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, 1417614411, Iran

    Saeideh Momtaz, Mahban Rahimifard, Maryam Baeeri, Mohammad Abdollahi & Amir Hossein Abdolghaffari

  3. Gastrointestinal Pharmacology Interest Group (GPIG), Universal Scientific Education and Research Network (USERN), Tehran, Iran

    Saeideh Momtaz & Amir Hossein Abdolghaffari

  4. Department of Toxicology & Pharmacology, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, No. 99, Yakhchal, Gholhak, Shariati St, P.O. Box: 19419-33111, Tehran, Iran

    Mohammad Amir Azimian, Pardis Gharazi, Mustafa Dehnamaki, Zahra Rezaei & Amir Hossein Abdolghaffari

  5. Department of Pathology, Imam Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Ali Reza Abdollahi

  6. Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Mohammad Hosein Farzaei

  7. Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran

    Mohammad Hosein Farzaei

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  1. Saeideh Momtaz
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Contributions

MA, AHA, and MHF gave the idea and supervised the whole study. SM, MAA, PGH, MD, and ZR drafted the manuscript and did the literature search and screening. SM, MR, and MB participated in data interpretation. AA participated in pathological analysis and drafting of some parts of the manuscript. SM and AHA performed the final editing. All authors read and approved the final version.

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Correspondence to Mohammad Hosein Farzaei or Amir Hossein Abdolghaffari.

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Significance statement: Colitis is a common inflammatory bowel disease. Treatment of colitis rats with Achillea wilhelmsii improved macroscopic and microscopic lesion indices in colitis colon and suppressed inflammatory mediators levels in rat colitis tissue. A. wilhelmsii can be a complementary option in clinical trials for treatment of IBD.

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Momtaz, S., Azimian, M.A., Gharazi, P. et al. The Hydro-alcoholic Extract of Achillea wilhelmsii C. Koch Ameliorates Acetic Acid-induced Ulcerative Colitis through TLR-4. Proc. Natl. Acad. Sci., India, Sect. B Biol. Sci. 93, 127–135 (2023). https://doi.org/10.1007/s40011-022-01404-9

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