Beneficial effects of the traditional medicine Igongsan and its constituent ergosterol on dextran sulfate sodium-induced colitis in mice

Kim,Su‑Jin; Shin,Hyun‑Ji; Lee,Geun‑Hyuk; Kim,Dae‑Seung; Kim,Hye‑Lin; Park,Jinbong; Jung,Yunu; Youn,Dong‑Hyun; Kang,Jongwook; Hong,Seung‑Heon; Um,Jae‑Young

doi:10.3892/mmr.2015.3824

Beneficial effects of the traditional medicine Igongsan and its constituent ergosterol on dextran sulfate sodium-induced colitis in mice

Authors:
- Su‑Jin Kim
- Hyun‑Ji Shin
- Geun‑Hyuk Lee
- Dae‑Seung Kim
- Hye‑Lin Kim
- Jinbong Park
- Yunu Jung
- Dong‑Hyun Youn
- Jongwook Kang
- Seung‑Heon Hong
- Jae‑Young Um
View Affiliations

Affiliations: Department of Cosmeceutical Science, Daegu Hanny University, Yugok‑dong, Kyungsan 712‑715, Republic of Korea, Department of Oriental Pharmacy, College of Pharmacy, Wonkwang Oriental Medicines Research Institute, Iksan, Jeonbuk 570‑749, Republic of Korea, Department of Pharmacology, College of Korean Medicine, Institute of Korean Medicine, Kyung Hee University, Dongdaemun‑Gu, Seoul 130‑701, Republic of Korea
Published online on: May 22, 2015 https://doi.org/10.3892/mmr.2015.3824
Pages: 3549-3556

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Ulcerative colitis (UC) is a type of inflammatory bowel disease and is considered a chronic gastrointestinal disorder. Igongsan (IGS) is a Korean herbal medicine, which has been used to treat digestive disorders. However, the ameliorative effect and molecular mechanisms of IGS in intestinal inflammation have not yet been studied in detail. The present study aimed to investigate the protective effects of IGS and its constituent, ergosterol, in a mouse model of dextran sulfate sodium (DSS)‑induced colitis. Colitis was induced in mice by supplementing their drinking water with 5% (w/v) DSS for 7 days. The effects of IGS were then determined on DSS‑induced clinical signs of colitis, including weight loss, colon shortening, diarrhea and obscure/gross bleeding. In addition, the effects of IGS were determined on the expression levels of inflammation‑associated genes in the colon tissue of DSS‑treated mice. The results of the present study demonstrated that mice treated with DSS exhibited marked clinical symptoms, including weight loss and reduced colon length. Treatment with IGS attenuated these symptoms and also suppressed the expression levels of tumor necrosis factor‑α and interleukin‑6, as well as the expression of cyclooxygenase‑2 in the colon tissue of DSS‑treated mice. IGS also reduced the activation of the transcription factor nuclear factor‑κB p65 in the colon tissue of DSS‑treated mice. In addition, ergosterol was shown to attenuate the DSS‑induced clinical symptoms of colitis in mice. In conclusion, the present study provided experimental evidence that IGS may be a useful therapeutic drug for patients with UC.

View Figures

View References

1	Hyams JS: Inflammatory bowel disease. Pediatr Rev. 21:291–295. 2000. View Article : Google Scholar : PubMed/NCBI
2	Danese S, Sans M and Fiocchi C: Inflammatory bowel disease: The role of environmental factors. Autoimmun Rev. 3:394–400. 2004. View Article : Google Scholar : PubMed/NCBI
3	Hendrickson BA, Gokhale R and Cho JH: Clinical aspects and pathophysiology of inflammatory bowel disease. Clin Microbiol Rev. 15:79–94. 2002. View Article : Google Scholar : PubMed/NCBI
4	Lichtenstein GR and Rutgeerts P: Importance of mucosal healing in ulcerative colitis. Inflamm Bowel Dis. 16:338–346. 2010. View Article : Google Scholar
5	Ullman T, Croog V, Harpaz N, Sachar D and Itzkowitz S: Progression of flat low-grade dysplasia to advanced neoplasia in patients with ulcerative colitis. Gastroenterology. 125:1311–1319. 2003. View Article : Google Scholar : PubMed/NCBI
6	Eaden JA, Abrams KR and Mayberry JF: The risk of colorectal cancer in ulcerative colitis: A meta-analysis. Gut. 48:526–535. 2001. View Article : Google Scholar : PubMed/NCBI
7	Domènech E: Inflammatory bowel disease: Current therapeutic options. Digestion. 73(Suppl 1): 67–76. 2006. View Article : Google Scholar : PubMed/NCBI
8	Buchman AL: Side effects of corticosteroid therapy. J Clin Gastroenterol. 33:289–294. 2001. View Article : Google Scholar : PubMed/NCBI
9	Farrell RJ and Kelleher D: Glucocorticoid resistance in inflammatory bowel disease. J Endocrinol. 178:339–346. 2003. View Article : Google Scholar : PubMed/NCBI
10	Li Y, de Haar C, Chen M, et al: Disease-related expression of the IL6/STAT3/SOCS3 signalling pathway in ulcerative colitis and ulcerative colitis-related carcinogenesis. Gut. 59:227–235. 2010. View Article : Google Scholar
11	Papadakis KA and Targan SR: Role of cytokines in the pathogenesis of inflammatory bowel disease. Annu Rev Med. 51:289–298. 2000. View Article : Google Scholar : PubMed/NCBI
12	Ogata H and Hibi T: Cytokine and anti-cytokine therapies for inflammatory bowel disease. Curr Pharm Des. 9:1107–1113. 2003. View Article : Google Scholar : PubMed/NCBI
13	Mueller C: Tumour necrosis factor in mouse models of chronic intestinal inflammation. Immunology. 105:1–8. 2002. View Article : Google Scholar : PubMed/NCBI
14	Vane JR, Bakhle YS and Botting RM: Cyclooxygenases 1 and 2. Annu Rev Pharmacol Toxicol. 38:97–120. 1998. View Article : Google Scholar : PubMed/NCBI
15	Roberts PJ, Morgan K, Miller R, Hunter JO and Middleton SJ: Neuronal COX-2 expression in human myenteric plexus in active inflammatory bowel disease. Gut. 48:468–472. 2001. View Article : Google Scholar : PubMed/NCBI
16	Agoff SN, Brentnall TA, Crispin DA, et al: The role of cyclooxygenase 2 in ulcerative colitis-associated neoplasia. Am J Pathol. 157:737–745. 2000. View Article : Google Scholar : PubMed/NCBI
17	Bantel H, Berg C, Vieth M, Stolte M, Kruis W and Schulze-Osthoff K: Mesalazine inhibits activation of transcription factor NF-kappaB in inflamed mucosa of patients with ulcerative colitis. Am J Gastroenterol. 95:3452–3457. 2000.
18	Andresen L, Jørgensen VL, Perner A, Hansen A, Eugen-Olsen J and Rask-Madsen J: Activation of nuclear factor kappaB in colonic mucosa from patients with collagenous and ulcerative colitis. Gut. 54:503–509. 2005. View Article : Google Scholar : PubMed/NCBI
19	Ma TY, Iwamoto GK, Hoa NT, et al: TNF-alpha-induced increase in intestinal epithelial tight junction permeability requires NF-kappa B activation. Am J Physiol Gastrointest Liver Physiol. 286:G367–G376. 2004. View Article : Google Scholar : PubMed/NCBI
20	Atreya I, Atreya R and Neurath MF: NF-kappaB in inflammatory bowel disease. J Intern Med. 263:591–596. 2008. View Article : Google Scholar : PubMed/NCBI
21	Jobin C and Sartor RB: The I kappa B/NF-kappa B system: A key determinant of mucosalinflammation and protection. Am J Physiol Cell Physiol. 278:C451–462. 2000.PubMed/NCBI
22	Kim SJ, Shin HJ, Lee BJ, et al: The antiinflammatory mechanism of Igongsan in mouse peritoneal macrophages via suppression of NF-κB/Caspase-1 activation. Phytother Res. 28:736–744. 2014. View Article : Google Scholar
23	Kim SJ, Kim YG, Kim DS, et al: Oldenlandia diffusa ameliorates dextran sulphate sodium-induced colitis through inhibition of NF-κB activation. Am J Chin Med. 39:957–969. 2011. View Article : Google Scholar
24	Murthy SN, Cooper HS, Shim H, Shah RS, Ibrahim SA and Sedergran DJ: Treatment of dextran sulfate sodium-induced murine colitis by intracolonic cyclosporin. Dig Dis Sci. 38:1722–1734. 1993. View Article : Google Scholar : PubMed/NCBI
25	Cooper HS, Murthy SN, Shah RS and Sedergran DJ: Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest. 69:238–249. 1993.PubMed/NCBI
26	Porter SN, Howarth GS and Butler RN: An orally administered growth factor extract derived from bovine whey suppresses breath ethane in colitic rats. Scand J Gastroenterol. 33:967–974. 1998. View Article : Google Scholar : PubMed/NCBI
27	Kim MS, Lim WK, Cha JG, et al: The activation of PI 3-K and PKC zeta in PMA-induced differentiation of HL-60 cells. Cancer Lett. 171:79–85. 2001. View Article : Google Scholar : PubMed/NCBI
28	Okayasu I, Hatakeyama S, Yamada M, Ohkusa T, Inagaki Y and Nakaya R: A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice. Gastroenterology. 98:694–702. 1990.PubMed/NCBI
29	Fiocchi C: Inflammatory bowel disease: Evolutionary concepts in biology, epidemiology, mechanisms and therapy. Curr Opin Gastroenterol. 29:347–349. 2013. View Article : Google Scholar : PubMed/NCBI
30	Ardizzone S and Bianchi Porro G: Biologic therapy for inflammatory bowel disease. Drugs. 65:2253–2286. 2005. View Article : Google Scholar : PubMed/NCBI
31	Rufo PA and Bousvaros A: Current therapy of inflammatory bowel disease in children. Paediatr Drugs. 8:279–302. 2006. View Article : Google Scholar : PubMed/NCBI
32	Sato K, Ohkura S, Kitahara Y, et al: Involvement of CPI-17 downregulation in the dysmotility of the colon from dextran sodium sulphate-induced experimental colitis in a mouse model. Neurogastroenterol Motil. 19:504–514. 2007. View Article : Google Scholar : PubMed/NCBI
33	Sandborn WJ and Targan SR: Biologic therapy of inflammatory bowel disease. Gastroenterology. 122:1592–1608. 2002. View Article : Google Scholar : PubMed/NCBI
34	Ishiguro K, Ando T, Maeda O, et al: Paeonol attenuates TNBS-induced colitis by inhibiting NF-kappaB and STAT1 transactivation. Toxicol Appl Pharmacol. 217:35–42. 2006. View Article : Google Scholar : PubMed/NCBI
35	Kim SJ, Kim KW, Kim DS, et al: The protective effect of Cassia obtusifolia on DSS-induced colitis. Am J Chin Med. 39:565–577. 2011. View Article : Google Scholar : PubMed/NCBI
36	Raddatz D, Bockemühl M and Ramadori G: Quantitative measurement of cytokine mRNA in inflammatory bowel disease: Relation to clinical and endoscopic activity and outcome. Eur J Gastroenterol Hepatol. 17:547–557. 2005. View Article : Google Scholar : PubMed/NCBI
37	Zheng P, Niu FL, Liu WZ, Shi Y and Lu LG: Anti-inflammatory mechanism of oxymatrine in dextran sulfate sodium-induced colitis of rats. World J Gastroenterol. 11:4912–4915. 2005.PubMed/NCBI
38	Beubler E, Schuligoi R, Chopra AK, Ribardo DA and Peskar BA: Cholera toxin induces prostaglandin synthesis via post-transcriptional activation of cyclooxygenase-2 in the rat jejunum. J Pharmacol Exp Ther. 297:940–945. 2001.PubMed/NCBI
39	Tak PP and Firestein GS: NF-kappaB: A key role in inflammatory diseases. J Clin Invest. 107:7–11. 2001. View Article : Google Scholar : PubMed/NCBI
40	Bak YK, Lampe JW and Sung MK: Effects of dietary supplementation of glucosamine sulfate on intestinal inflammation in a mouse model of experimental colitis. J Gastroenterol Hepatol. 29:957–963. 2014. View Article : Google Scholar
41	Song YA, Park YL, Kim KY, et al: Black tea extract prevents lipo-polysaccharide-induced NF-κB signaling and attenuates dextran sulfate sodium-induced experimental colitis. BMC Complement Altern Med. 11:912011. View Article : Google Scholar
42	Joh EH, Lee IA, Jung IH and Kim DH: Ginsenoside Rb1 and its metabolite compound K inhibit IRAK-1 activation - the key step of inflammation. Biochem Pharmacol. 82:278–286. 2011. View Article : Google Scholar : PubMed/NCBI
43	Yang XL, Guo TK, Wang YH, et al: Ginsenoside Rd attenuates the inflammatory response via modulating p38 and JNK signaling pathways in rats with TNBS-induced relapsing colitis. Int Immunopharmacol. 12:408–414. 2012. View Article : Google Scholar : PubMed/NCBI
44	Lee IA, Hyam SR, Jang SE, Han MJ and Kim DH: Ginsenoside Re ameliorates inflammation by inhibiting the binding of lipopoly-saccharide to TLR4 on macrophages. J Agric Food Chem. 60:9595–9602. 2012. View Article : Google Scholar : PubMed/NCBI
45	Xu L, Yang ZL, Li P and Zhou YQ: Modulating effect of Hesperidin on experimental murine colitis induced by dextran sulfate sodium. Phytomedicine. 16:989–995. 2009. View Article : Google Scholar : PubMed/NCBI
46	Liu Y, Xiang J, Liu M, Wang S, Lee RJ and Ding H: Protective effects of glycyrrhizic acid by rectal treatment on a TNBS-induced rat colitis model. J Pharm Pharmacol. 63:439–446. 2011. View Article : Google Scholar : PubMed/NCBI
47	Kageyama-Yahara N, Wang P, Wang X, et al: The inhibitory effect of ergosterol, a bioactive constituent of a traditional Japanese herbal medicine saireito on the activity of mucosal-type mast cells. Biol Pharm Bull. 33:142–145. 2010. View Article : Google Scholar : PubMed/NCBI