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BMC Complementary Medicine and Therapies

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Open Access 01-12-2024 | Clostridioides Difficile | Research

The anti-inflammatory and anti-apoptotic effects of Achillea millefolium L. extracts on Clostridioides difficile ribotype 001 in human intestinal epithelial cells

Authors: Hamideh Raeisi, Masoumeh Azimirad, Samaneh Asadi-Sanam, Hamid Asadzadeh Aghdaei, Abbas Yadegar, Mohammad Reza Zali

Published in: BMC Complementary Medicine and Therapies | Issue 1/2024

Abstract

Background

Clostridioides difficile infection (CDI) is one of the most common health care-acquired infections. The dramatic increase in antimicrobial resistance of C. difficile isolates has led to growing demand to seek new alternative medicines against CDI. Achillea millefolium L. extracts exhibit strong biological activity to be considered as potential therapeutic agents. In this work, the inhibitory effects of A. millefolium, its decoction (DEC) and ethanol (ETOH) extracts, were investigated on the growth of C. difficile RT001 and its toxigenic cell-free supernatant (Tox-S) induced inflammation and apoptosis.

Methods

Phytochemical analysis of extracts was performed by HPLC and GC analysis. The antimicrobial properties of extracts were evaluated against C. difficile RT001. Cell viability and cytotoxicity of Caco-2 and Vero cells treated with various concentrations of extracts and Tox-S were examined by MTT assay and microscopy, respectively. Anti-inflammatory and anti-apoptotic effects of extracts were assessed in Tox-S stimulated Caco-2 cells by RT-qPCR.

Results

Analysis of the phytochemical profile of extracts revealed that the main component identified in both extracts was chlorogenic acid. Both extracts displayed significant antimicrobial activity against C. difficile RT001. Moreover, both extracts at concentration 50 µg/mL had no significant effect on cell viability compared to untreated cells. Pre-treatment of cells with extracts (50 µg/mL) significantly reduced the percentage of Vero cells rounding induced by Tox-S. Also, both pre-treatment and co-treatment of Tox-S stimulated Caco-2 cells with extracts significantly downregulated the gene expression level of IL-8, IL-1β, TNF-α, TGF-β, iNOS, Bax, caspase-9 and caspase-3 and upregulated the expression level of Bcl-2.

Conclusion

The results of the present study for the first time demonstrate the antimicrobial activity and protective effects of A. millefolium extracts on inflammatory response and apoptosis induced by Tox-S from C. difficile RT001 clinical strain in vitro. Further research is needed to evaluate the potential application of A. millefolium extracts as supplementary medicine for CDI prevention and treatment in clinical setting.

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Farooq PD, Urrunaga NH, Tang DM, von Rosenvinge EC. Pseudomembranous colitis. Dis Mon. 2015;61(5):181–206. https://doi.org/10.1016/j.disamonth.2015.01.006.CrossRefPubMedPubMedCentral

SmitsW K, Lyras D, Lacy DB, Wilcox MH, Kuijper EJ. Clostridium difficile infection. Nat Rev Dis Primers. 2016;2(1):16020. https://doi.org/10.1038/nrdp.2016.20.CrossRef

Lessa FC, Winston LG, McDonald LC. Burden of Clostridium difficile infection in the United States. N Engl J Med. 2015;372(24):2369–70. https://doi.org/10.1056/NEJMc1505190.CrossRefPubMed

Kelly CR, Fischer M, Allegretti JR, LaPlante K, Stewart DB, Limketkai BN, Stollman NH. ACG clinical guidelines: prevention, diagnosis, and treatment of Clostridioides difficile infections. Am J Gastroenterol. 2021;116(6):1124–47. https://doi.org/10.14309/ajg.0000000000001278.CrossRefPubMed

Mullish BH, Williams HR. Clostridium difficile infection and antibiotic-associated diarrhoea. Clin Med. 2018;18(3):237–41. https://doi.org/10.7861/clinmedicine.18-3-237.CrossRef

Chen S, Sun C, Wang H, Wang J. The role of rho gtpases in toxicity of Clostridium difficile toxins. Toxins. 2015;7(12):5254–67. https://doi.org/10.3390/toxins7124874.CrossRefPubMedPubMedCentral

Saavedra PHV, Huang L, Ghazavi F, Kourula S, Vanden Berghe T, Takahashi N, Vandenabeele P, Lamkanfi M. Apoptosis of intestinal epithelial cells restricts Clostridium difficile infection in a model of pseudomembranous colitis. Nat Commun. 2018;9(1):4846. https://doi.org/10.1038/s41467-018-07386-5.CrossRefPubMedPubMedCentral

Shen A. Clostridium difficile toxins: mediators of inflammation. J Innate Immun. 2012;4(2):149–58. https://doi.org/10.1159/000332946.CrossRefPubMedPubMedCentral

Nelson RL, Suda KJ, Evans CT. Antibiotic treatment for Clostridium difficile-associated diarrhoea in adults. Cochrane Database Syst Rev. 2017;3(3):CD004610–0. https://doi.org/10.1002/14651858.CD004610.pub5.CrossRefPubMed

10.

Louie TJ, Miller MA, Mullane KM, Weiss K, Lentnek A, Golan Y, Gorbach S, Sears P, Shue YK. Fidaxomicin versus Vancomycin for Clostridium difficile infection. N Engl J Med. 2011;364(5):422–31. https://doi.org/10.1056/NEJMoa0910812.CrossRefPubMed

11.

D’Agostino RB, Collins SH, Pencina KM, Kean Y, Gorbach S. Risk estimation for recurrent clostridium difficile infection based on clinical factors. Clin Infect Dis. 2014;58(10):1386–93. https://doi.org/10.1093/cid/ciu107.CrossRefPubMed

12.

Mullane K. Fidaxomicin in Clostridium difficile infection: latest evidence and clinical guidance. Ther Adv Chronic Dis. 2014;5(2):69–84. https://doi.org/10.1177/2040622313511285.CrossRefPubMedPubMedCentral

13.

Stranges PM, Hutton DW, Collins CD. Cost-effectiveness analysis evaluating fidaxomicin versus oral Vancomycin for the treatment of Clostridium difficile infection in the United States. Value Health. 2013;16(2):297–304. https://doi.org/10.1016/j.jval.2012.11.004.CrossRefPubMed

14.

Azimirad M, Yadegar A, Gholami F, Shahrokh S, Asadzadeh Aghdaei H, Ianiro G, Suzuki H, Cammarota G, Zali MR. Treatment of recurrent Clostridioides difficile infection using fecal microbiota transplantation in Iranian patients with underlying inflammatory bowel disease. J Inflamm Res. 2020;13:563–70. https://doi.org/10.2147/JIR.S265520.CrossRefPubMedPubMedCentral

15.

Raeisi H, Azimirad M, Nabavi-Rad A, Asadzadeh Aghdaei H, Yadegar A, Zali MR. Application of recombinant antibodies for treatment of Clostridioides difficile infection: current status and future perspective [Review]. Front Immunol. 2022;13. https://doi.org/10.3389/fimmu.2022.972930.

16.

Lee J, Choi HS, Lee J, Park J, Kim SB, Shin MS, Lee S, Hwang GS, Koo BA, KangKS. Preparation of herbal formulation for inflammatory bowel disease based on in vitro screening and in vivo evaluation in a mouse model of experimental colitis. Molecules. 2019;24(3). https://doi.org/10.3390/molecules24030464.

17.

Kalaiselvan S, Rasool MK. Triphala herbal extract suppresses inflammatory responses in LPS-stimulated RAW 264.7 macrophages and adjuvant-induced arthritic rats via inhibition of NF-κB pathway. J Immunotoxicol. 2016;13(4):509–25. https://doi.org/10.3109/1547691x.2015.1136010.CrossRefPubMed

18.

Villalva M, Jaime L, Villanueva-Bermejo D, Lara B, Fornari T, Reglero G, Santoyo S. Supercritical anti-solvent fractionation for improving antioxidant and anti-inflammatory activities of an Achillea millefolium L. extract. Food Res Int. 2019;115:128–34. https://doi.org/10.1016/j.foodres.2018.08.027.CrossRefPubMed

19.

Wang L, Du H, Chen P. Chlorogenic acid inhibits the proliferation of human lung cancer A549 cell lines by targeting annexin A2 in vitro and in vivo. Biomed Pharmacother. 2020;131:110673. https://doi.org/10.1016/j.biopha.2020.110673.CrossRefPubMed

20.

Ke F, Yadav PK, Ju LZ. Herbal medicine in the treatment of ulcerative colitis. Saudi. J Gastroenterol. 2012;18(1):3–10. https://doi.org/10.4103/1319-3767.91726.CrossRef

21.

Witaicenis A, Seito LN, da Silveira Chagas A, de Almeida LD, Luchini AC, Rodrigues-Orsi P, Cestari SH, Di Stasi LC. Antioxidant and intestinal anti-inflammatory effects of plant-derived coumarin derivatives. Phytomedicine. 2014;21(3):240–6. https://doi.org/10.1016/j.phymed.2013.09.001.CrossRefPubMed

22.

Zhang LC, Wang Y, Tong LC, Sun S, Liu WY, Zhang S, Wang RM, Wang ZB, Li L. Berberine alleviates dextran sodium sulfate-induced colitis by improving intestinal barrier function and reducing inflammation and oxidative stress. Exp Ther Med. 2017;13(6):3374–82. https://doi.org/10.3892/etm.2017.4402.CrossRefPubMedPubMedCentral

23.

Naz R, Ayub H, Nawaz S, Islam ZU, Yasmin T, Bano A, Wakeel A, Zia S, Roberts TH. Antimicrobial activity, toxicity and anti-inflammatory potential of methanolic extracts of four ethnomedicinal plant species from Punjab, Pakistan. BMC Complement Altern Med. 2017;17(1):302. https://doi.org/10.1186/s12906-017-1815-z.CrossRefPubMedPubMedCentral

24.

Ivanović M, Grujić D, Cerar J, Islamčević Razboršek M, Topalić-Trivunović L, Savić A, Kočar D, Kolar M. Extraction of bioactive metabolites from Achillea millefolium L. with choline chloride based natural deep eutectic solvents: a study of the antioxidant and antimicrobial activity. Antioxidants. 2022;11(4). https://doi.org/10.3390/antiox11040724.

25.

Strzępek-Gomółka M, Gaweł-Bęben K, Kukula-Koch W. Achillea Species as sources of active phytochemicals for dermatological and cosmetic applications. Oxid Med Cell Longev. 2021. https://doi.org/10.1155/2021/6643827.CrossRefPubMedPubMedCentral

26.

Saeidnia S, Gohari A, Mokhber-Dezfuli N, Kiuchi F. A review on phytochemistry and medicinal properties of the genus Achillea. Daru. 2011;19(3):173–186.PubMedPubMedCentral

27.

Bitwell C, Indra SS, Luke C, Kakoma MK. A review of modern and conventional extraction techniques and their applications for extracting phytochemicals from plants. Sci Afr. 2023;19:e01585. https://doi.org/10.1016/j.sciaf.2023.e01585.CrossRef

28.

Candan F, Unlu M, Tepe B, Daferera D, Polissiou M, Sökmen A, Akpulat HA. Antioxidant and antimicrobial activity of the essential oil and methanol extracts of Achillea millefolium subsp. millefolium Afan. (Asteraceae). J Ethnopharmacol. 2003;87(2):215–20. https://doi.org/10.1016/S0378-8741(03)00149-1.CrossRefPubMed

29.

El-Kalamouni C, Venskutonis PR, Zebib B, Merah O, Raynaud C, Talou T. Antioxidant and antimicrobial activities of the essential oil of Achillea millefolium L. grown in France. Medicines. 2017;4(2). https://doi.org/10.3390/medicines4020030.

30.

Potrich FB, Allemand A, da Silva LM, dos Santos AC, Baggio CH, Freitas CS, Mendes DAGB, Andre E, De Paula Werner MF, Marques MCA. Antiulcerogenic activity of hydroalcoholic extract of Achillea millefolium L.: involvement of the antioxidant system. J Ethnopharmacol. 2010;130(1):85–92. https://doi.org/10.1016/j.jep.2010.04.014.CrossRefPubMed

31.

Csupor B, Hajdu Z, Zupko I, Réthy B, Falkay G, Forgo P, Hohmann J. Antiproliferative effect of flavonoids and sesquiterpenoids from achillea millefolium s.l. on cultured human tumour cell lines. Phytother Res. 2009;23:672–6. https://doi.org/10.1002/ptr.2697.CrossRef

32.

Lin LT, Liu LT, Chiang LC, Lin CC. In vitro anti-hepatoma activity of fifteen natural medicines from Canada. Phytother Res. 2002;16(5):440–4. https://doi.org/10.1002/ptr.937.CrossRefPubMed

33.

Li Y, Zhang ML, Cong B, Wang SM, Dong M, Sauriol F, Huo CH, Shi QW, Gu YC, Kiyota H. Achillinin a, a cytotoxic guaianolide from the flower of Yarrow, Achillea millefolium. Biosci Biotechno Biochem. 2011;75(8):1554–6. https://doi.org/10.1271/bbb.110234.CrossRef

34.

Azimirad M, Krutova M, Yadegar A, Shahrokh S, Olfatifar M, Aghdaei HA, Fawley WN, Wilcox MH, Zali MR. Clostridioides difficile ribotypes 001 and 126 were predominant in Tehran healthcare settings from 2004 to 2018: a 14-year-long cross-sectional study. Emerg Microbes Infect. 2020;9(1):1432–43. https://doi.org/10.1080/22221751.2020.1780949.CrossRefPubMedPubMedCentral

35.

Azimirad M, Krutova M, Balaii H, Kodori M, Shahrokh S, Azizi O, Yadegar A, Aghdaei HA, Zali MR. Coexistence of Clostridioides difficile and Staphylococcus aureus in gut of Iranian outpatients with underlying inflammatory bowel disease. Anaerobe. 2020;61:102113. https://doi.org/10.1016/j.anaerobe.2019.102113.CrossRefPubMed

36.

Azimirad M, Noori M, Azimirad F, Gholami F, Naseri K, Yadegar A, Asadzadeh Aghdaei H, Zali MR. Curcumin and capsaicin regulate apoptosis and alleviate intestinal inflammation induced by Clostridioides difficile in vitro. Ann Clin Microbiol Antimicrob. 2022;21(1):41. https://doi.org/10.1186/s12941-022-00533-3.CrossRefPubMedPubMedCentral

37.

Li S, Shi L, Yang Z, Feng H. Cytotoxicity of Clostridium difficile toxin B does not require cysteine protease-mediated autocleavage and release of the glucosyltransferase domain into the host cell cytosol. Pathog Dis. 2013;67(1):11–8. https://doi.org/10.1111/2049-632X.12016.CrossRefPubMed

38.

Pike CM, Theriot CM. Mechanisms of colonization resistance against Clostridioides difficile. J Infect Dis. 2021;223(12 Suppl 2):194–s200. https://doi.org/10.1093/infdis/jiaa408.CrossRef

39.

Baghani A, Mesdaghinia A, Kuijper EJ, Aliramezani A, Talebi M, Douraghi M. High prevalence of Clostridiodes diffiicle PCR ribotypes 001 and 126 in Iran. Sci Rep. 2020;10(1):4658. https://doi.org/10.1038/s41598-020-61604-z.CrossRefPubMedPubMedCentral

40.

Grigore A, Colceru-Mihul S, Bazdoaca C, Yuksel R, Ionita C, Glava L. Antimicrobial activity of an Achillea millefolium L. Proc. 2020;57:34. https://doi.org/10.3390/proceedings2020057034.CrossRef

41.

Zhang QW, Lin LG, Ye WC. Techniques for extraction and isolation of natural products: a comprehensive review. Chin Med. 2018;13:20–0. https://doi.org/10.1186/s13020-018-0177-x.CrossRefPubMedPubMedCentral

42.

Karaalp C, Yurtman AN, Karabay Yavasoglu NU. Evaluation of antimicrobial properties of Achillea L. flower head extracts. Pharm Biol. 2009;47(1):86–91. https://doi.org/10.1080/13880200802448682.CrossRef

43.

Turkmenoglu FP, Agar OT, Akaydin G, Hayran M, Demirci B. Characterization of volatile compounds of eleven Achillea species from Turkey and biological activities of essential oil and methanol extract of a. hamzaoglui arabacı & budak. Molecules. 2015;20(6):11432–58. https://doi.org/10.3390/molecules200611432.CrossRefPubMedPubMedCentral

44.

Swamy MK, Akhtar MS, Sinniah UR. Antimicrobial properties of plant essential oils against human pathogens and their mode of action: an updated review. Evid.-based Complement. Altern Med. 201;3012462. https://doi.org/10.1155/2016/3012462.

45.

Raut JS, Karuppayil SM. A status review on the medicinal properties of essential oils. Ind Crops Prod. 2014;62:250–64. https://doi.org/10.1016/j.indcrop.2014.05.055.CrossRef

46.

Plaskova A, Mlcek J. New insights of the application of water or ethanol-water plant extract rich in active compounds in food. Front Nutr. 2023;28(10):1118761. https://doi.org/10.3389/fnut.2023.1118761.CrossRef

47.

Kępa M, Miklasińska-Majdanik M, Wojtyczka RD, Idzik D, Korzeniowski K, Smoleń-Dzirba J, Wąsik TJ. Antimicrobial potential of caffeic acid against Staphylococcus aureus clinical strains. Biomed Res Int. 2018;7413504. https://doi.org/10.1155/2018/7413504.

48.

Chen K, Peng C, Chi F, Yu C, Yang Q, Li Z. Antibacterial and antibiofilm activities of chlorogenic acid against Yersinia enterocolitica. Front Microbiol. 2022;13. https://doi.org/10.3389/fmicb.2022.885092.

49.

Wu Y, Liang S, Zhang M, Wang Z, Wang Z, Ren X. The Effect of Chlorogenic Acid on Bacillus subtilis based on Metabolomics. Molecules. 2020;25(18). https://doi.org/10.3390/molecules25184038.

50.

Huang X, Lao Y, Pan Y, Chen Y, Zhao H, Gong L, Xie N, Mo CH. Synergistic antimicrobial effectiveness of plant essential oil and its application in seafood preservation: a review. Molecules. 2021;26(2). https://doi.org/10.3390/molecules26020307.

51.

Burk D, Cichacz Z, Daskalova S. Aqueous extract of Achillea millefolium L. (Asteraceae) inflorescences suppresses lipopolysaccharide-induced inflammatory responses in RAW 264.7 murine macrophages. J Med Plant Res. 2010;4:225–34.

52.

Giorgi A, Bombelli R, Luini A, Speranza G, Cosentino M, Lecchini S, Cocucci M. Antioxidant and cytoprotective properties of infusions from leaves and inflorescences of Achillea collina Becker ex Rchb. Phytother Res. 2009;23(4):540–5. https://doi.org/10.1002/ptr.2679.CrossRefPubMed

53.

Cavalcanti AM, Baggio CH, Freitas CS, Rieck L, de Sousa RS, Da Silva-Santos JE, Mesia-Vela S, Marques MCA. Safety and antiulcer efficacy studies of Achillea millefolium L. after chronic treatment in Wistar rats. J Ethnopharmacol. 2006;107(2):277–84. https://doi.org/10.1016/j.jep.2006.03.011.CrossRefPubMed

54.

Zeng A, Liang X, Zhu S, Liu C, Wang S, Zhang Q, Zhao J, Song L. Chlorogenic acid induces apoptosis, inhibits metastasis and improves antitumor immunity in breast cancer via the NF–κB signaling pathway. Oncol Rep. 2021;45(2):717–27. https://doi.org/10.3892/or.2020.7891.CrossRefPubMed

55.

Abotaleb M, Liskova A, Kubatka P, Büsselberg D. Therapeutic potential of plant phenolic acids in the treatment of cancer. Biomolecules. 2020;10(2). https://doi.org/10.3390/biom10020221.

56.

Nottrott S, Schoentaube J, Genth H, Just I, Gerhard R. Clostridium difficile toxin A-induced apoptosis is p53-independent but depends on glucosylation of rho GTPases. Apoptosis. 2007;12(8):1443–53. https://doi.org/10.1007/s10495-007-0074-8.CrossRefPubMed

57.

Zhang Y, Li Y, Li H, Chen W, Liu W. Clostridium difficile toxin B recombinant protein inhibits tumor growth and induces apoptosis through inhibiting Bcl-2 expression, triggering inflammatory responses and activating C-erbB-2 and Cox-2 expression in breast cancer mouse model. Biomed Pharmacother. 2018;101:391–8. https://doi.org/10.1016/j.biopha.2018.02.045.CrossRefPubMed

58.

Mooyottu S, Kollanoor-Johny A, Flock G, Bouillaut L, Upadhyay A, Sonenshein AL, Venkitanarayanan K. Carvacrol and trans-cinnamaldehyde reduce Clostridium difficile toxin production and cytotoxicity in vitro. Int J Mol Sci. 2014;15(3):4415–30. https://doi.org/10.3390/ijms15034415.CrossRefPubMedPubMedCentral

59.

Shimamura Y, Aoki N, Sugiyama Y, Tanaka T, Murata M, Masuda S. Plant-derived polyphenols interact with staphylococcal enterotoxin a and inhibit toxin activity. PLoS ONE. 2016;11(6):e0157082. https://doi.org/10.1371/journal.pone.0157082.CrossRefPubMedPubMedCentral

60.

Li Y, Xu S, Xu Q, Chen Y. Clostridium difficile toxin B induces colonic inflammation through the TRIM46/DUSP1/MAPKs and NF-κB signalling pathway. Artif Cells Nanomed Biotechnol. 2020;48(1):452–62. https://doi.org/10.1080/21691401.2019.1709856.CrossRefPubMed

61.

Xue VW, Chung JY, Córdoba CAG, Cheung AH, Kang W, Lam EW, Leung KT, To KF, Lan HY, Tang PM. Transforming growth factor-β: a multifunctional regulator of cancer immunity. Cancers. 2020;12(11). https://doi.org/10.3390/cancers12113099.

62.

Tinoco-Veras CM, Santos AAQA, Stipursky J, Meloni M, Araujo APB, Foschetti DA, López-Ureña D, Quesada-Gómez C, Leitão RFC, Gomes FCA. Transforming growth factor β1/SMAD signaling pathway activation protects the intestinal epithelium from Clostridium difficile Toxin A-induced damage. Infect Immun. 2017;85(10):e00430–00417. https://doi.org/10.1128/IAI.00430-17.CrossRefPubMedPubMedCentral

63.

Freysdottir J, Logadottir OT, Omarsdottir SS, Vikingsson A, Hardardottir I. A polysaccharide fraction from Achillea millefolium increases cytokine secretion and reduces activation of akt, ERK and NF-κB in THP-1 monocytes. Carbohydr Polym. 2016;143:131–8. https://doi.org/10.1016/j.carbpol.2016.02.017.CrossRefPubMed

64.

Chou S-T, Peng H-Y, Hsu J-C, Lin C-C, Shih Y. Achillea millefolium L. essential oil inhibits LPS-induced oxidative stress and nitric oxide production in RAW 264.7 macrophages. Int J Mol Sci. 2013;14(7):12978–93. https://doi.org/10.3390/ijms140712978.CrossRefPubMedPubMedCentral

65.

Muniyappa R, Xu R, Ram JL, Sowers JR. Inhibition of rho protein stimulates iNOS expression in rat vascular smooth muscle cells. Am J Physiol Heart Circ Physiol. 2000;278(6):H1762–1768. https://doi.org/10.1152/ajpheart.2000.278.6.H1762.CrossRefPubMed

66.

Natarajan K, Abraham P, Kota R, Isaac. NF-κB-iNOS-COX2-TNF α inflammatory signaling pathway plays an important role in methotrexate induced small intestinal injury in rats. Food Chem Toxicol. 2018;118:766–83. https://doi.org/10.1016/j.fct.2018.06.040.CrossRefPubMed

67.

Woo ER, Lee JY, Cho IJ, Kim SG, Kang KW. Amentoflavone inhibits the induction of nitric oxide synthase by inhibiting NF-kappaB activation in macrophages. Pharmacol Res. 2005;51(6):539–46. https://doi.org/10.1016/j.phrs.2005.02.002.CrossRefPubMed

68.

Sarkar D, Saha P, Gamre S, Bhattacharjee S, Hariharan C, Ganguly S, Sen R, Mandal G, Chattopadhyay S, Majumdar S. Anti-inflammatory effect of allylpyrocatechol in LPS-induced macrophages is mediated by suppression of iNOS and COX-2 via the NF-κB pathway. Int Immunopharmacol. 2008;8(9):1264–71. https://doi.org/10.1016/j.intimp.2008.05.003.CrossRefPubMed

69.

Iyer AKV, Rojanasakul Y, Azad N. Nitrosothiol signaling and protein nitrosation in cell death. Nitric Oxide Biol Chem. 2014;42:9–18. https://doi.org/10.1016/j.niox.2014.07.002.CrossRef

70.

Warren CFA, Wong-Brown MW, Bowden NA. BCL-2 family isoforms in apoptosis and cancer. Cell Death Dis. 2019;10(3):177. https://doi.org/10.1038/s41419-019-1407-6.CrossRefPubMedPubMedCentral

71.

Cullen SP, Martin SJ. Caspase activation pathways: some recent progress. Cell Death Differ. 2009;16(7):935–8. https://doi.org/10.1038/cdd.2009.59.CrossRefPubMed

72.

Zhu J, Yang Y, Wu J. Bcl-2 cleavages at two adjacent sites by different caspases promote cisplatin-induced apoptosis. Cell Res. 2007;17(5):441–8. https://doi.org/10.1038/cr.2007.36.CrossRefPubMed

73.

Semwal DK, Kumar A, Aswal S, Chauhan A, Semwal RB. Protective and therapeutic effects of natural products against diabetes mellitus via regenerating pancreatic β-cells and restoring their dysfunction. Phytother Res. 2021;35(3):1218–29. https://doi.org/10.1002/ptr.6885.CrossRefPubMed

74.

Ok S, Kang JS, Kim KM. Cultivated wild ginseng extracts upregulate the anti-apoptosis systems in cells and mice induced by bisphenol A. Mol Cell Toxicol. 2017;13(1):73–82. https://doi.org/10.1007/s13273-017-0008-7.CrossRef

75.

Baharara J, Namvar F, Ramezani T, Mousavi M, Mohamad R. Silver nanoparticles biosynthesized using Achillea biebersteinii flower extract: apoptosis induction in MCF-7 cells via caspase activation and regulation of bax and bcl-2 gene expression. Molecules. 2015;20(2). https://doi.org/10.3390/molecules20022693.

76.

Bali EB, Açık L, Elçi P, Sarper M, Avcu F, Vural M. In vitro anti-oxidant, cytotoxic and pro-apoptotic effects of Achillea Teretifolia Willd extracts on human prostate cancer cell lines. Pharmacogn Mag. 2015;11(Suppl 2):308–S315. https://doi.org/10.4103/0973-1296.166060.CrossRef

77.

Okkay U, Ferah Okkay I, Aydin IC, Bayram C, Ertugrul MS, Gezer A, Hacimuftuoglu A. Effects of Achillea millefolium on cisplatin induced ocular toxicity: an experimental study. Cutan Ocul Toxicol. 2021;40(3):214–20. https://doi.org/10.1080/15569527.2021.1919137.CrossRefPubMed

78.

Ali SI, Gopalakrishnan B, Venkatesalu V. Pharmacognosy, phytochemistry and pharmacological properties of Achillea millefolium L.: a review. Phytother Res. 2017;31(8):1140–61. https://doi.org/10.1002/ptr.5840.CrossRefPubMed

79.

Baretta IP, Felizardo RA, Bimbato VF, Santos MGJd, Kassuya CAL, Gasparotto Junior A, da Silva CR, de Oliveira SM, Ferreira J, Andreatini R. Anxiolytic-like effects of acute and chronic treatment with Achillea millefolium L. extract. J Ethnopharmacol. 2012;140(1):46–54. https://doi.org/10.1016/j.jep.2011.11.047.CrossRefPubMed

Title: The anti-inflammatory and anti-apoptotic effects of Achillea millefolium L. extracts on Clostridioides difficile ribotype 001 in human intestinal epithelial cells
Authors: Hamideh Raeisi
Masoumeh Azimirad
Samaneh Asadi-Sanam
Hamid Asadzadeh Aghdaei
Abbas Yadegar
Mohammad Reza Zali
Publication date: 01-12-2024
Publisher: BioMed Central
Keyword: Clostridioides Difficile
Published in: BMC Complementary Medicine and Therapies / Issue 1/2024
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-024-04335-2

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The anti-inflammatory and anti-apoptotic effects of Achillea millefolium L. extracts on Clostridioides difficile ribotype 001 in human intestinal epithelial cells

Abstract

Background

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Results

Conclusion

Keynote webinar | Spotlight on medication adherence

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Abstract

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Retraction Note: Gastroprotective effect of desmosdumotin C isolated from Mitrella kentii against ethanol-induced gastric mucosal hemorrhage in rats: possible involvement of glutathione, heat-shock protein-70, sulfhydryl compounds, nitric oxide, and anti-Helicobacter pylori activity

A systematic review and meta-analysis on sodium tanshinone IIA sulfonate injection for the adjunctive therapy of pulmonary heart disease

Ethnobotanical survey on herbal remedies for the management of type 2 diabetes in the Casablanca-Settat region, Morocco

Oxidative stress promotes cytotoxicity in human cancer cell lines exposed to Escallonia spp. extracts

Effect of aromatherapy with peppermint essential oil on the gag reflex: a randomized, placebo-controlled, single-blind, crossover study

Punicalagin, a pomegranate polyphenol sensitizes the activity of antibiotics against three MDR pathogens of the Enterobacteriaceae