The Effectivity of Centella Asiatica Extract in Experimental Colitis Model Induced by Dextran Sulfate Sodium in Rats
Öz
Background: Inflammatory bowel disease (IBD) is a group of
chronic and inflammatory conditions that are considered to be caused by environmental,
genetic, and immune factors. The treatment of IBD mainly involves combinations
of anti-inflammatory, immunosuppressive, and cytotoxic agents. However, due to serious
side effects of these agents, research is being performed to find new treatment
methods.
Methods:The 24 rats were divided into three groups. In control
group, the rats received drinking water and standard rat chow, in colitis
group, the rats received drinking water with DSS, and in CA+colitis group the
rats were administered 200 mg/kg/day CA and then received drinking water with
DSS. Histopathologic examination,
concentrations of myeloperoxidase (MPO), malondialdehyde (MDA), tumor necrosis factor
alpha (TNF-α), and interleukin-10 (IL-10), were determined.
Results:
The results indicated
that the TNF-α level was lower and the IL-10 was higher in the rats
administered with CA extract compared to the rats in the colitis group (p<0.05). The MPO and MDA levels were
significantly higher in the colitis group compared to other groups (p<0.05). Histopathologic examination
revealed less tissue damage in the rats administered with CA extract.
Conclusion: The CA extract exerts an immunoregulatory effect by
altering the levels of anti- and pro-inflammatory cytokines in experimental IBD
models. It also prevents tissue damage by inhibiting the formation of free
oxygen radicals. Depending on these effects, we consider that the CA extract
can be a useful agent in the treatment of IBD.
Anahtar Kelimeler
Inflammatory bowel disease Centella asiatica Dextran sulfate sodium Eksperimental colitis
Kaynakça
- 1. Podolsky DK. Inflammatory bowel disease. N Engl J Med. 2002;8:347(6):417-29.
- 2. Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature. 2007 Jul 26;448(7152):427-34.
- 3. Kuhbacher T, Fölsch UR. Practical guidelines for the treatment of inflammatory bowel disease. World J Gastroenterol. 2007:28;13(8):1149-55.
- 4. Roy DC, Barman SK, Shaik MM. Current updates on Centella asiatica: Phytochemistry, pharmacology and traditional uses. Medicinal Plant Research 2013, Vol.3, No.4, 20-36
- 5. Won JH, Shin JS, Park HJ, Jung HJ, Koh DJ, Jo BG et al. Anti-inflammatory effects of madecassic acid via the suppression of NF-kappaB pathway in LPS-induced RAW 264.7 macrophage cells. Planta Med. 2010;76(3):251-7.
- 6. Jayashree G, Kurup Muraleedhara G, Sudarslal S, Jacob VB. Anti-oxidant activity of Centella asiatica on lymphoma-bearing mice. Fitoterapia. 2003;74(5):431-4.
- 7. Sairam K, Rao CV, Goel RK. Effect of Centella asiatica Linn on physical and chemical factors induced gastric ulceration and secretion in rats. Indian J Exp Biol. 2001;39(2):137-42.
- 8. Punturee K, Wild CP, Kasinrerk W, Vinitketkumnuen U. Immunomodulatory activities of Centella asiatica and Rhinacanthus nasutus extracts. Asian Pac J Cancer Prev. 2005;6(3):396-400.
- 9. Sunilkumar, Parameshwaraiah S, Shivakumar HG. Evaluation of topical formulations of aqueous extract of Centella asiatica on open wounds in rats. Indian J Exp Biol. 1998;36(6):569-72.
- 10. Stucchi AF, Shofer S, Leeman S, Materne O, Beer E, McClung J et al. NK-1 antagonist reduces colonic inflammation and oxidative stress in dextran sulfate-induced colitis in rats. Am J Physiol Gastrointest Liver Physiol. 2000;279(6):G1298-306.
- 11. Lowry O, Rosenbrough N, Farr L. Protein measurement with the folin phenol reagent. J Biol Chem. 1951;193;265-275.
- 12. Draper HH, Hadley M. Methods.Enzymol. Malondialdehyde determination as index of lipid peroxidation.1990;186:421-31.
- 13. Malik TA. Inflammatory Bowel Disease: Historical Perspective, Epidemiology, and Risk Factors. Surg Clin North Am. 2015;95(6):1105-22.
- 14. Okayasu I, Hatakeyama S, Yamada M, Ohkusa T, Inagaki Y, Nakaya R. A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology. 1990;98(3):694-702.
- 15. Dieleman LA, Palmen MJ, Akol H, Bloemena E, Peña AS, Meuwissen SG et al. Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines. Clin Exp Immunol. 1998;114(3):385-91.
- 16. Chen LL, Wang XH, Cui Y, Lian GH, Zhang J, Ouyang CH et al. Therapeutic effects of four strains of probiotics on experimental colitis in mice. World J Gastroenterol. 2009;15(3):321-7.
- 17. Jungbeck M, Daller B, Federhofer J, Wege AK, Wimmer N, Männel DN et al. Neutralization of LIGHT ameliorates acute dextran sodium sulphate-induced intestinal inflammation. Immunology. 2009;128(3):451-8.
- 18. Cooper HS, Murthy SN, Shah RS, Sedergran DJ. Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest. 1993; 69(2):238-49.
- 19. Harries AD, Beeching NJ, Rogerson SJ, Nye FJ. The platelet count as a simple measure to distinguish inflammatory bowel disease from infective diarrhoea. J Infect. 1991;22(3):247-50.
- 20. Herías MV, Koninkx JF, Vos JG, Huis in't Veld JH, van Dijk JE. Probiotic effects of Lactobacillus casei on DSS-induced ulcerative colitis in mice. Int J Food Microbiol. 2005;103(2):143-55.
- 21. Stange EF, Travis SP, Vermeire S, Reinisch W, Geboes K, Barakauskiene A et al. European Crohn's and Colitis Organisation (ECCO). European evidence-based Consensus on the diagnosis and management of ulcerative colitis: Definitions and diagnosis. J Crohns Colitis. 2008;2(1):1-23.
- 22. Camuesco D, Comalada M, Rodríguez-Cabezas ME, Nieto A, Lorente MD, Concha A et al. The intestinal anti inflammatory effect of quercitrin is associated with an inhibition in iNOS expression. Br J Pharmacol. 2004;143(7):908-18.
- 23. Obermeier F, Kojouharoff G, Hans W, Schölmerich J, Gross V, Falk W. Interferon-gamma (IFN-gamma)- and tumour necrosis factor (TNF)-induced nitric oxide as toxic effector molecule in chronic dextran sulphate sodium (DSS)-induced colitis in mice. Clin Exp Immunol. 1999;116(2):238-45.
- 24. Rogler G, Andus T. Cytokines in inflammatory bowel disease. World J Surg. 1998;22(4):382-9.
- 25. Cui HH, Chen CL, Wang JD, Yang YJ, Cun Y, Wu JB et al. Effects of probiotic on intestinal mucosa of patients with ulcerative colitis. World J Gastroenterol. 2004;10(10):1521-5.
- 26. Mosmann TR Cytokine secretion patterns and cross-regulation of T cell subsets. Immunol Res. 1991;10(3-4):183-8.
- 27. Shukla A, Rasik AM, Jain GK, Shankar R, Kulshrestha DK, Dhawan BN. In vitro and in vivo wound healing activity of asiaticoside isolated from Centella asiatica. J Ethnopharmacol. 1999;65(1):1-11.
- 28. di Paola R, Esposito E, Mazzon E, Caminiti R, Toso RD, Pressi G et al. 3,5-Dicaffeoyl-4-malonylquinic acid reduced oxidative stress and inflammation in a experimental model of inflammatory bowel disease. Free Radic Res. 2010;44(1):74-89.
- 29. Guo W, Liu W, Jin B, Geng J, Li J, Ding H, et al. Asiatic acid ameliorates dextran sulfate sodium-induced murine experimental colitis via suppressing mitochondria-mediated NLRP3 inflammasome activation. Int Immunopharmacol. 2015;24(2):232-8.
- 30. Kühn R, Löhler J, Rennick D, Rajewsky K, Müller W. Interleukin-10-deficient mice develop chronic enterocolitis. Cell. 1993;75(2):263-74.
- 31. Kitahora T, Suzuki K, Asakura H, Yoshida T, Suematsu M, Watanabe M et al. Active oxygen species generated by monocytes and polymorphonuclear cells in Crohn's disease. Dig Dis Sci. 1988;33(8):951-5.
- 32. Mahida YR, Wu KC, Jewell DP. Respiratory burst activity of intestinal macrophages in normal and inflammatory bowel disease. Gut. 1989;30(10):1362-70.
- 33. Grisham MB, Granger DN. Neutrophil mediated mucosal injury. Role of reactive oxygen metabolites. Dig Dis Sci. 1988;33: 6-15.
- 34. Korenaga D, Takesue F, Kido K, Yasuda M, Inutsuka S, Honda M et al. Impaired antioxidant defense system of colonic tissue and cancer development in dextran sulfate sodium-induced colitis in mice. J Surg Res. 2002;102(2):144-9.
Öz
Giriş: İnflamatuvar barsak hastalıkları (İBD) çevresel, genetik, immun faktörlerin
sebep olduğu düşünülen bir grup kronik ve inflamatuvar durum olarak
tanımlanmaktadır. Tedavisinde basilica antiinflamatuvar, immünsupresif ve sitotoksik
ilaç kombinasyonları kullanılmaktadır. Fakat bu ajanların ciddi yan
etkilerinden dolayı yeni tedavi yöntemleri bulmak için araştırmalar
yapılmaktadır. Bu çalışmanın amacı dekstran sülfat sodium (DSS) indüklenmiş deneysel
kolit modelinde Centella Asiatica (CA) ekstresinin etkinliğini araştırmaktır.
Metod: Çalışmada 24 adet Wistar Albino rat üç eşit gruba ayrıldı. Kontrol
grubuna normal içme suyu ve standart rat yemi verildi. Kolit grubuna DSS’ li
içme suyu ve CA+kolit grubuna ise 200mg/kg/gün CA ekstresi ve DSS’ li içme suyu
verildi. Deney sonunda histopatolojik inceleme ve myeloperoksidaz (MPO), malonildialdehit
(MDO), tümor nekroz factör alfa (TNF-α) ve interlökin-10 (IL-10) düzeyleri
belirlendi.
Bulgular: TNF- α, MPO ve MDA düzeyleri kolit grubunda anlamlı düzeyde daha
yüksek bulundu. İL- 10 düzeyi ise CA+kolit grubunda daha yüksekti (p<0.05).
Histopatolojik incelemede CA+kolit grubunda
daha az doku hasarı saptandı.
Sonuç: CA ekstresi proinflamatuvar ve antiinflamatuvar sitokin düzeyini değiştirerek
immünregulatuvar bir etki göstermektedir. Ayrıca serbest oksijen radikalleri
oluşumunu önleyerek doku hasarını önlemektedir. Bu etkilerinden dolayı CA
ekstresinin IBD tedavisinde faydalı bir ajan olarak kullanılabileceğini
düşünmekteyiz.
Anahtar Kelimeler
İnflamatuvar barsak hastalıkları Centella Asiatika Dekstran sülfat sodium Deneysel kolit
Kaynakça
- 1. Podolsky DK. Inflammatory bowel disease. N Engl J Med. 2002;8:347(6):417-29.
- 2. Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature. 2007 Jul 26;448(7152):427-34.
- 3. Kuhbacher T, Fölsch UR. Practical guidelines for the treatment of inflammatory bowel disease. World J Gastroenterol. 2007:28;13(8):1149-55.
- 4. Roy DC, Barman SK, Shaik MM. Current updates on Centella asiatica: Phytochemistry, pharmacology and traditional uses. Medicinal Plant Research 2013, Vol.3, No.4, 20-36
- 5. Won JH, Shin JS, Park HJ, Jung HJ, Koh DJ, Jo BG et al. Anti-inflammatory effects of madecassic acid via the suppression of NF-kappaB pathway in LPS-induced RAW 264.7 macrophage cells. Planta Med. 2010;76(3):251-7.
- 6. Jayashree G, Kurup Muraleedhara G, Sudarslal S, Jacob VB. Anti-oxidant activity of Centella asiatica on lymphoma-bearing mice. Fitoterapia. 2003;74(5):431-4.
- 7. Sairam K, Rao CV, Goel RK. Effect of Centella asiatica Linn on physical and chemical factors induced gastric ulceration and secretion in rats. Indian J Exp Biol. 2001;39(2):137-42.
- 8. Punturee K, Wild CP, Kasinrerk W, Vinitketkumnuen U. Immunomodulatory activities of Centella asiatica and Rhinacanthus nasutus extracts. Asian Pac J Cancer Prev. 2005;6(3):396-400.
- 9. Sunilkumar, Parameshwaraiah S, Shivakumar HG. Evaluation of topical formulations of aqueous extract of Centella asiatica on open wounds in rats. Indian J Exp Biol. 1998;36(6):569-72.
- 10. Stucchi AF, Shofer S, Leeman S, Materne O, Beer E, McClung J et al. NK-1 antagonist reduces colonic inflammation and oxidative stress in dextran sulfate-induced colitis in rats. Am J Physiol Gastrointest Liver Physiol. 2000;279(6):G1298-306.
- 11. Lowry O, Rosenbrough N, Farr L. Protein measurement with the folin phenol reagent. J Biol Chem. 1951;193;265-275.
- 12. Draper HH, Hadley M. Methods.Enzymol. Malondialdehyde determination as index of lipid peroxidation.1990;186:421-31.
- 13. Malik TA. Inflammatory Bowel Disease: Historical Perspective, Epidemiology, and Risk Factors. Surg Clin North Am. 2015;95(6):1105-22.
- 14. Okayasu I, Hatakeyama S, Yamada M, Ohkusa T, Inagaki Y, Nakaya R. A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology. 1990;98(3):694-702.
- 15. Dieleman LA, Palmen MJ, Akol H, Bloemena E, Peña AS, Meuwissen SG et al. Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines. Clin Exp Immunol. 1998;114(3):385-91.
- 16. Chen LL, Wang XH, Cui Y, Lian GH, Zhang J, Ouyang CH et al. Therapeutic effects of four strains of probiotics on experimental colitis in mice. World J Gastroenterol. 2009;15(3):321-7.
- 17. Jungbeck M, Daller B, Federhofer J, Wege AK, Wimmer N, Männel DN et al. Neutralization of LIGHT ameliorates acute dextran sodium sulphate-induced intestinal inflammation. Immunology. 2009;128(3):451-8.
- 18. Cooper HS, Murthy SN, Shah RS, Sedergran DJ. Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest. 1993; 69(2):238-49.
- 19. Harries AD, Beeching NJ, Rogerson SJ, Nye FJ. The platelet count as a simple measure to distinguish inflammatory bowel disease from infective diarrhoea. J Infect. 1991;22(3):247-50.
- 20. Herías MV, Koninkx JF, Vos JG, Huis in't Veld JH, van Dijk JE. Probiotic effects of Lactobacillus casei on DSS-induced ulcerative colitis in mice. Int J Food Microbiol. 2005;103(2):143-55.
- 21. Stange EF, Travis SP, Vermeire S, Reinisch W, Geboes K, Barakauskiene A et al. European Crohn's and Colitis Organisation (ECCO). European evidence-based Consensus on the diagnosis and management of ulcerative colitis: Definitions and diagnosis. J Crohns Colitis. 2008;2(1):1-23.
- 22. Camuesco D, Comalada M, Rodríguez-Cabezas ME, Nieto A, Lorente MD, Concha A et al. The intestinal anti inflammatory effect of quercitrin is associated with an inhibition in iNOS expression. Br J Pharmacol. 2004;143(7):908-18.
- 23. Obermeier F, Kojouharoff G, Hans W, Schölmerich J, Gross V, Falk W. Interferon-gamma (IFN-gamma)- and tumour necrosis factor (TNF)-induced nitric oxide as toxic effector molecule in chronic dextran sulphate sodium (DSS)-induced colitis in mice. Clin Exp Immunol. 1999;116(2):238-45.
- 24. Rogler G, Andus T. Cytokines in inflammatory bowel disease. World J Surg. 1998;22(4):382-9.
- 25. Cui HH, Chen CL, Wang JD, Yang YJ, Cun Y, Wu JB et al. Effects of probiotic on intestinal mucosa of patients with ulcerative colitis. World J Gastroenterol. 2004;10(10):1521-5.
- 26. Mosmann TR Cytokine secretion patterns and cross-regulation of T cell subsets. Immunol Res. 1991;10(3-4):183-8.
- 27. Shukla A, Rasik AM, Jain GK, Shankar R, Kulshrestha DK, Dhawan BN. In vitro and in vivo wound healing activity of asiaticoside isolated from Centella asiatica. J Ethnopharmacol. 1999;65(1):1-11.
- 28. di Paola R, Esposito E, Mazzon E, Caminiti R, Toso RD, Pressi G et al. 3,5-Dicaffeoyl-4-malonylquinic acid reduced oxidative stress and inflammation in a experimental model of inflammatory bowel disease. Free Radic Res. 2010;44(1):74-89.
- 29. Guo W, Liu W, Jin B, Geng J, Li J, Ding H, et al. Asiatic acid ameliorates dextran sulfate sodium-induced murine experimental colitis via suppressing mitochondria-mediated NLRP3 inflammasome activation. Int Immunopharmacol. 2015;24(2):232-8.
- 30. Kühn R, Löhler J, Rennick D, Rajewsky K, Müller W. Interleukin-10-deficient mice develop chronic enterocolitis. Cell. 1993;75(2):263-74.
- 31. Kitahora T, Suzuki K, Asakura H, Yoshida T, Suematsu M, Watanabe M et al. Active oxygen species generated by monocytes and polymorphonuclear cells in Crohn's disease. Dig Dis Sci. 1988;33(8):951-5.
- 32. Mahida YR, Wu KC, Jewell DP. Respiratory burst activity of intestinal macrophages in normal and inflammatory bowel disease. Gut. 1989;30(10):1362-70.
- 33. Grisham MB, Granger DN. Neutrophil mediated mucosal injury. Role of reactive oxygen metabolites. Dig Dis Sci. 1988;33: 6-15.
- 34. Korenaga D, Takesue F, Kido K, Yasuda M, Inutsuka S, Honda M et al. Impaired antioxidant defense system of colonic tissue and cancer development in dextran sulfate sodium-induced colitis in mice. J Surg Res. 2002;102(2):144-9.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Klinik Tıp Bilimleri |
| Bölüm | Araştırma Makaleleri |
| Yazarlar | |
| Yayımlanma Tarihi | 1 Eylül 2017 |
| Gönderilme Tarihi | 11 Kasım 2016 |
| Yayımlandığı Sayı | Yıl 2017 Cilt: 24 Sayı: 3 |
Süleyman Demirel Üniversitesi Tıp Fakültesi Dergisi/Medical Journal of Süleyman Demirel University is licensed under Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International.