Significant action of Tridax procumbens L. leaf extract on reducing the TNF-α and COX-2 gene expressions in induced inflammation site in Swiss albino mice

Abstract

The leaves of traditionally used herbal plant Tridax procumbens L. contain lots of phytochemicals having potency to reduce inflammation. In this study, the ethanol extract of the leaves of Tridax procumbens L. was analysed for the phytochemicals by GC–MS. The anti-inflammatory activity was then studied with the extract of 10, 50, and 100 mg/kg b.wt in carrageenan-induced mice model by measuring the inflammatory oedema and by analysing the histopathology. The mRNA expression levels of TNF-α and COX2 genes were studied in the inflammatory site to explore the molecular action by reverse transcription PCR and qPCR analyses. A significant (P ≤ 0.01) reduction in mice paw inflammation and a recovered histology were observed in treated groups when compared to control group in 24 h. The RT-PCR results showed a significant (P ≤ 0.01) decrease in the expression levels of TNF-α and COX2 in terms of band density in treated mice compared to control group. The qPCR RQ values also were decreased in treated groups with respect to increasing doses (RQ values of 18.985 ± 0.230, 12.140 ± 1.121, 6.718 ± 0.807 for TNF-α and 15.583 ± 1.043, 7.725 ± 1.013, 5.075 ± 0.615 for COX2, respectively for the three doses) in comparison with the control group (TNF-α 27.107 ± 2.254, COX2 20.626 ± 1.477). Tridax procumbens L. can be, thus, used for the development of a safe, natural, anti-inflammatory drug as it showed a strong inhibitory action on inflammation by acting at molecular level.

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References

  1. Bjarnason I, Hayllar J, MacPherson AJ, Russell AS (1993) Side effects of nonsteroidal anti-inflammatory drugs on the small and large intestine in humans. Gastroenterology 104(6):1832–1847

    CAS  PubMed  Article  Google Scholar 

  2. Bradley JR (2008) TNF-α mediated inflammatory disease. J Pathol 214:149–160

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  3. Choa J, Lu TC, Liao JW, Huang TH, Lee MS, Cheng HY, Ho LK, Kuo CL, Peng WH (2009) Analgesic and anti-inflammatory activities of ethanol root extract of Mahonia oiwakensis in mice. J Ethnopharmacol 125:297–303

    Article  Google Scholar 

  4. Cowan MM (1999) Plant products as anti-microbial agents. Clin Microbiol Rev 12:564–582

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  5. Eslami M, Sofiabadi M, Haghighian HK, Jamshidi S (2019) Investigating the effect of luteolin on interleukin-1 and tumor necrosis factor in inflammation induced by lipopolysaccharide in male rats. Jundishapur J Nat Pharm Prod 14(3):e58271

    CAS  Article  Google Scholar 

  6. Feldmann M, Maini RN (2001) Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned? Annu Rev Immunol 19:163–196

    CAS  PubMed  Article  Google Scholar 

  7. Gad SS (2018) Effect of ginger as anti-inflammatory agent on serum nitric oxide, tumor necrotic factor α (TNF-α) and interleukin 4 (IL-4) in albino rats with carrageenan induced paw edema. Virol Immunol J 2:1–15

    Google Scholar 

  8. Gamboa-Leon R, Vera-Ku M, Peraza-Sanchez SR, Ku-Chulim C, Horta-Baas A, Rosado-Vallado M (2014) Antileishmanial activity of a mixture of Tridax procumbens and Allium sativum in mice. Parasite 21:15

    PubMed  PubMed Central  Article  Google Scholar 

  9. Jachak SM, Gautam R, Selvam C, Madhan H, Srivastava A, Khan T (2011) Anti-inflammatory, cyclooxygenase inhibitory and antioxidant activities of standardized extracts of Tridax procumbens L. Fitoterapia 82:173–177

    PubMed  Article  Google Scholar 

  10. Lin L, Sun Y, Wang D, Zheng S, Zhang J, Zheng C (2016) Celastrol ameliorates ulcerative colitis-related colorectal cancer in mice via suppressing inflammatory responses and epithelial–mesenchymal transition. Front Pharmacol 6:320

    PubMed  PubMed Central  Google Scholar 

  11. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative pcr and the 2−△△CT method. Methods 25:402–408

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  12. Manjamalai A, Varghese SS, Haridas A, BerlinGrace VM (2012a) Antifungal, anti-inflammatory and GC–MS analysis for bioactive molecules of Tridax procumbens L. leaf. Asian J Pharm Clin Res 5:139–145

    CAS  Google Scholar 

  13. Manjamalai A, Varghese SS, Haridas A, BerlinGrace VM (2012b) Essential oil of Tridax procumbens L. induces apoptosis and suppresses angiogenesis and lung metastasis of the B16F-10 cell line in C57BL/6 mice. Asian Pac J Cancer Prev 13(11):5887–5895

    CAS  PubMed  Article  Google Scholar 

  14. Meric JB, Rottey S, Olaussen K, Soria JC, Khayat D, Rixe O, Spano JP (2006) Cyclooxygenase-2 as a target for anticancer drug development. Crit Rev Oncol Hematol 59(1):51–64

    PubMed  Article  Google Scholar 

  15. Morikawa K, Nonaka M, Narahara M, Torii I (2003) Inhibitory effect of quercetin on carrageenan-induced inflammation in rats. Life Sci 74(4):709–721

    CAS  PubMed  Article  Google Scholar 

  16. Nakamura A, Fujiwara S, Matsumoto I, Abe K (2009) Stress repression in restrained rats by (R)-(−)-linalool inhalation and gene expression profiling of their whole blood cells. J Agric Food Chem 57(12):5480–5485

    CAS  PubMed  Article  Google Scholar 

  17. Nantel F, Denis D, Gordon R, Northey A, Cirino M, Metters KM, Chan CC (1999) Distribution and regulation of cyclooxygenase-2 in carrageenan-induced inflammation. Br J Pharmacol 128(4):853–859

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  18. Nia R, Paper DH, Essien EE, Oladimeji OH, Iyadi KC, Franz G (2003) Investigation into in-vitro radical scavenging and in-vivo anti-inflammatory potential of Tridax procumbens. Niger J Physiol Sci 18(1–2):39–40

    Google Scholar 

  19. Noshahr ZS, Shahraki MR, Ahmadvand H, Nourabadi D, Nakhaei A (2015) Protective effects of Withania somnifera root on inflammatory markers and insulin resistance in fructose-fed rats. Rep Biochem Mol Biol 3:62–67

    Google Scholar 

  20. Osadebe PO, Okoye FBC (2003) Anti-inflammatory effects of crude methanolic extract and fractions of Alchornea cordifolia leaves. J Ethnopharmacol 89:19–24

    CAS  PubMed  Article  Google Scholar 

  21. Pathan A, Alshahrani A, Al-Marshad F (2015) Protective effect of Tridax procumbens Linn. potential in ulcerative colitis by using myeloperoxidase activity in AlbinoRats. Invent Rapid Ethnopharmacol 2015:1–5

    Google Scholar 

  22. Prabhu V, Nalini G, Chidambaranathan N, Sudarshan Kisan S (2011) Evaluation of anti-inflammatory and analgesic activity of Tridax procumbens Linn. against formalin, acetic acid and CFA induced pain models. Int J Pharm Pharm Sci 3(2):126–130

    Google Scholar 

  23. Restivo A, Brard L, Granai CO, Swamy N (2005) Antiproliferative effect of mimosine in ovarian cancer. J Clin Oncol 23:3200

    Article  Google Scholar 

  24. Sawant RS, Godghate AG (2013) Preliminary phytochemical analysis of leaves of Tridax procumbens Linn. Int J Sci Environ 2(3):388–394

    Google Scholar 

  25. Seibert K, Masferrer JL (1994) Role of inducible cyclooxygenase (COX2) in inflammation. Receptor 4(1):17–23

    CAS  PubMed  Google Scholar 

  26. Shri JNM (2003) Ginger: it’s role in xenobiotic metabolism. ICMR Bull 33(6):57–63

    Google Scholar 

  27. Smith TJ (2000) Squalene: potential chemopreventive agent. Expert Opin Investig Drugs 9(8):1841–1848

    CAS  PubMed  Article  Google Scholar 

  28. Steinmeyer J (2000) Pharmacological basis for the therapy of pain and inflammation with nonsteroidal anti-inflammatory drugs. Arthritis Res 2(5):379–385

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  29. Stepp JR (2004) The role of weeds as sources of pharmaceuticals. J Ethnopharmacol 92:163–166

    CAS  PubMed  Article  Google Scholar 

  30. Suluvoy JK, Grace VMB (2017) Phytochemical profile and free radical nitric oxide (NO) scavenging activity of Averrhoa bilimbi L. fruit extract. 3 Biotech 7(1):85

    PubMed  PubMed Central  Article  Google Scholar 

  31. Suseela L, Sarsvathy A, Brindha P (2002) Pharmacognostic studies on Tridax procumbens L. (Asteraceae). J Phytol Res 15(2):141–147

    Google Scholar 

  32. Takao K, Miyakawa T (2014) Genomic responses in mouse models greatly mimic human inflammatory diseases. Proc Natl Acad Sci USA 112(4):1167–1172

    PubMed  Article  Google Scholar 

  33. Udupa AL, Kulkarni DR, Udupa SL (1995) Effect of Tridax procumbens extraction in wound healing. Int J Pharmacogn 33(1):37–40

    Article  Google Scholar 

  34. Williams DA, Lernke TL (2002) Non-steroidal anti inflammatory drugs, Foyes principles of medicinal chemistry, 5th edn. Lippincott Williams, Philadelphia, pp 751–793

    Google Scholar 

  35. Yu Y, Shen Q, Lai Y, Park SY, Ou X, Lin D, Jin M, Zhang W (2018) Anti-inflammatory effects of curcumin in microglial cells. Front Pharmacol 9:386

    PubMed  PubMed Central  Article  Google Scholar 

  36. Zhang X, Dwivedi C (2010) Skin cancer chemoprevention by α-santalol. Front Biosci 3:777–787

    Google Scholar 

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Acknowledgement

The authors would like to thank the Department of Biotechnology, Karunya Institute of Technology and Sciences, Coimbatore, for funding this work in the form of seed money under the Short Term Research Grant (STRG). We also acknowledge the DST and DBT for partially supporting with chemicals required for gene expression studies.

Funding

This study was funded by Karunya Short Term Research Grant (REG/IQ/O/4264) and partially facilitated by Department of Science and Technology, SERB (SB/YS/LS-252/2013), and Department of Biotechnology, Government of India (DT/PR 14632/NNT/28/824/2015) funded projects.

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Correspondence to V. M. Berlin Grace.

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Berlin Grace, V.M., Viswanathan, S., David Wilson, D. et al. Significant action of Tridax procumbens L. leaf extract on reducing the TNF-α and COX-2 gene expressions in induced inflammation site in Swiss albino mice. Inflammopharmacol 28, 929–938 (2020). https://doi.org/10.1007/s10787-019-00634-0

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Keywords

  • Carrageenan
  • COX2
  • Phytochemicals
  • PCR
  • Tridax procumbens L.
  • Tnf-α