Costus root granules improve ulcerative colitis through regulation of TGF-β mediation of the PI3K/AKT signaling pathway

Wang,Xiaohong; Li,Dan; Zhang,Yong; Wu,Shuang; Tang,Fang

doi:10.3892/etm.2018.5946

Costus root granules improve ulcerative colitis through regulation of TGF-β mediation of the PI3K/AKT signaling pathway

Authors:
- Xiaohong Wang
- Dan Li
- Yong Zhang
- Shuang Wu
- Fang Tang
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Affiliations: Department of Traditional Chinese Medicine, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China, Tianjin Red Sun Kang Rentang Pharmaceutical Sales Co., Ltd., Tianjin 360045, P.R. China
Published online on: March 9, 2018 https://doi.org/10.3892/etm.2018.5946
Pages: 4477-4484

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Abstract

Ulcerative colitis is a chronic nonspecific inflammatory disease that occurs in the colon and rectum. Costus root is a type of traditional Chinese medicine that exhibits antibacterial properties and serves an inhibitory role in the regeneration of gut bacteria. However, the molecular mechanisms underlying Costus root‑mediated improvements in ulcerative colitis remain unclear. A complex formula of Costus root granules was created and investigated in the present study for its therapeutic effects in a rat model of ulcerative colitis. Ingredient dissolution into a traditional water decoction was used as a control. The potential mechanism mediated by Costus root granules was also analyzed in colonic epithelial cells isolated from the experimental rats. The results of the present study demonstrated that Costus root granule treatment inhibited inflammation in colonic tissue. Costus root granule treatment also suppressed the apoptosis of colonic epithelial cells isolated from the rat model of ulcerative colitis. Analyses of the underlying mechanisms of these effects indicated that the administration of Costus root granules increased transforming growth factor β expression, which activated the phosphoinositide 3‑kinase/RAC‑α serine/threonine‑protein kinase signaling pathway in colonic epithelial cells. Notably, the administration of Costus root granules improved stomachache, diarrhea and hematochezia in and increased the body weight of, the ulcerative colitis rats. In conclusion, these results indicate that Costus root granules markedly ameliorate inflammation of the colonic epithelium, decrease the apoptosis of colonic epithelial cells and improve colonic function, which suggests that Costus root granules are an efficient agent for the treatment of ulcerative colitis.

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1	Aung PP, Bowker B, Masterpol KS and Mahalingam M: Disseminated noninterstitial granulomatous dermatitis as a cutaneous manifestation of the preleukemic state in a patient with myelodysplasia and ulcerative colitis-apropos a case and review of the literature. Am J Dermatopathol. 36:e117–e120. 2014. View Article : Google Scholar : PubMed/NCBI
2	Mosli MH, Feagan BG, Sandborn WJ, D'haens G, Behling C, Kaplan K, Driman DK, Shackelton LM, Baker KA, Macdonald JK, et al: Histologic evaluation of ulcerative colitis: A systematic review of disease activity indices. Inflamm Bowel Dis. 20:564–575. 2014. View Article : Google Scholar : PubMed/NCBI
3	Morelli L, Palmeri M, Tartaglia D, Guadagni S, Di Candio G and Mosca F: Adenocarcinoma on j-pouch after proctocolectomy for ulcerative colitis-case report and review of literature. Int J Colorectal Dis. 29:1171–1173. 2014. View Article : Google Scholar : PubMed/NCBI
4	Mennigen R, Sewald W, Senninger N and Rijcken E: Morbidity of loop ileostomy closure after restorative proctocolectomy for ulcerative colitis and familial adenomatous polyposis: A systematic review. J Gastrointest Surg. 18:2192–2200. 2014. View Article : Google Scholar : PubMed/NCBI
5	Park HB, Park HC, Chung CY, Kim JS, Myung DS, Cho SB, Lee WS and Joo YE: Coexistence of solitary rectal ulcer syndrome and ulcerative colitis: A case report and literature review. Intest Res. 12:70–73. 2014. View Article : Google Scholar : PubMed/NCBI
6	Papaconstantinou I, Stefanopoulos A, Papailia A, Zeglinas C, Georgopoulos I and Michopoulos S: Isotretinoin and ulcerative colitis: A case report and review of the literature. World J Gastrointest Surg. 6:142–145. 2014. View Article : Google Scholar : PubMed/NCBI
7	Negoro A, Takano T, Tajiri H, Nezu R, Kawamura N and Brooks S: A role of colectomy in immune thrombocytopenic purpura associated with ulcerative colitis: A case report and a review of the literature. Int J Colorectal Dis. 29:1179–1180. 2014. View Article : Google Scholar : PubMed/NCBI
8	Castaño-Milla C, Chaparro M and Gisbert JP: Systematic review with meta-analysis: The declining risk of colorectal cancer in ulcerative colitis. Aliment Pharmacol Ther. 39:645–659. 2014. View Article : Google Scholar : PubMed/NCBI
9	Önal İK, Beyazit Y, Şener B, Savuk B, Etık Özer D, Sayilir A, Öztaş E, Torun S, Özın Özderın Y, Demırel Tunç B, et al: The value of fecal calprotectin as a marker of intestinal inflammation in patients with ulcerative colitis. Turk J Gastroenterol. 23:509–514. 2012. View Article : Google Scholar : PubMed/NCBI
10	Jena G and Trivedi PP: A review of the use of melatonin in ulcerative colitis: Experimental evidence and new approaches. Inflamm Bowel Dis. 20:553–563. 2014. View Article : Google Scholar : PubMed/NCBI
11	Okayasu I: Development of ulcerative colitis and its associated colorectal neoplasia as a model of the organ-specific chronic inflammation-carcinoma sequence. Pathol Int. 62:368–380. 2012. View Article : Google Scholar : PubMed/NCBI
12	Poulsen NA, Andersen V, Møller JC, Møller HS, Jessen F, Purup S and Larsen LB: Comparative analysis of inflamed and non-inflamed colon biopsies reveals strong proteomic inflammation profile in patients with ulcerative colitis. BMC Gastroenterol. 12:762012. View Article : Google Scholar : PubMed/NCBI
13	Shilpa K, Sangeetha KN, Muthusamy VS, Sujatha S and Lakshmi BS: Probing key targets in insulin signaling and adipogenesis using a methanolic extract of Costus pictus and its bioactive molecule, methyl tetracosanoate. Biotechnol Lett. 31:1837–1841. 2009. View Article : Google Scholar : PubMed/NCBI
14	Gireesh G, Thomas SK, Joseph B and Paulose CS: Antihyperglycemic and insulin secretory activity of Costus pictus leaf extract in streptozotocin induced diabetic rats and in in vitro pancreatic islet culture. J Ethnopharmacol. 123:470–474. 2009. View Article : Google Scholar : PubMed/NCBI
15	Quintans Júnior LJ, Santana MT, Melo MS, de Sousa DP, Santos IS, Siqueira RS, Lima TC, Silveira GO, Antoniolli AR, Ribeiro LA and Santos MR: Antinociceptive and anti-inflammatory effects of Costus spicatus in experimental animals. Pharm Biol. 48:1097–1102. 2010. View Article : Google Scholar : PubMed/NCBI
16	Binny K, Kumar SG and Dennis T: Anti-inflammatory and antipyretic properties of the rhizome of costus speciosus (koen.) sm. J Basic Clin Pharm. 1:177–181. 2010.PubMed/NCBI
17	Anyasor GN, Onajobi F, Osilesi O, Adebawo O and Oboutor EM: Anti-inflammatory and antioxidant activities of Costus afer Ker Gawl. Hexane leaf fraction in arthritic rat models. J Ethnopharmacol. 155:543–551. 2014. View Article : Google Scholar : PubMed/NCBI
18	Huang XL, Xu J, Zhang XH, Qiu BY, Peng L, Zhang M and Gan HT: PI3K/Akt signaling pathway is involved in the pathogenesis of ulcerative colitis. Inflamm Res. 60:727–734. 2011. View Article : Google Scholar : PubMed/NCBI
19	Mao JW, Tang HY, Tan XY and Wang YD: Effect of Etiasa on the expression of matrix metalloproteinase-2 and tumor necrosis factor-alpha in a rat model of ulcerative colitis. Mol Med Rep. 6:996–1000. 2012. View Article : Google Scholar : PubMed/NCBI
20	Davey G and Wu Z: Attitudes in China toward the use of animals in laboratory research. Altern Lab Anim. 35:313–316. 2007.PubMed/NCBI
21	Pedersen G, Saermark T, Giese B, Hansen A, Drag B and Brynskov J: A simple method to establish short-term cultures of normal human colonic epithelial cells from endoscopic biopsy specimens. Comparison of isolation methods, assessment of viability and metabolic activity. Scand J Gastroenterol. 35:772–780. 2000. View Article : Google Scholar : PubMed/NCBI
22	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
23	Almeida Mde A, Pizzini CV, Damasceno LS, Muniz Mde M, Almeida-Paes R, Peralta RH, Peralta JM, Oliveira Rde V, Vizzoni AG, de Andrade CL, et al: Validation of western blot for Histoplasma capsulatum antibody detection assay. BMC Infect Dis. 16:872016. View Article : Google Scholar : PubMed/NCBI
24	Christophorou D, Funakoshi N, Duny Y, Valats JC, Bismuth M, De Chambrun Pineton G, Daures JP and Blanc P: Systematic review with meta-analysis: Infliximab and immunosuppressant therapy vs. infliximab alone for active ulcerative colitis. Aliment Pharmacol Ther. 41:603–612. 2015. View Article : Google Scholar : PubMed/NCBI
25	Franco AI, Escobar L, Garcia XA, Van Domselaar M, Achecar LM, Luján DR and García MJ: Mesalazine-induced eosinophilic pneumonia in a patient with ulcerative colitis disease: A case report and literature review. Int J Colorectal Dis. 31:927–929. 2016. View Article : Google Scholar : PubMed/NCBI
26	Alobaid A, Torlakovic E and Kongkham P: Primary central nervous system immunomodulatory therapy-induced lymphoproliferative disorder in a patient with ulcerative colitis: A case report and review of the literature. World Neurosurg. 84:2074.e15–e19. 2015. View Article : Google Scholar
27	Takayama S and Iwasaki K: Systematic review of traditional Chinese medicine for geriatrics. Geriatr Gerontol Int. 17:679–688. 2017. View Article : Google Scholar : PubMed/NCBI
28	Sun GD, Li CY, Cui WP, Guo QY, Dong CQ, Zou HB, Liu SJ, Dong WP and Miao LN: Review of herbal traditional chinese medicine for the treatment of diabetic nephropathy. J Diabetes Res. 2016:57498572016. View Article : Google Scholar : PubMed/NCBI
29	Fan H, Liu F, Bligh SW, Shi S and Wang S: Structure of a homofructosan from Saussurea costus and anti-complementary activity of its sulfated derivatives. Carbohydr Polym. 105:152–160. 2014. View Article : Google Scholar : PubMed/NCBI
30	Hegde PK, Rao HA and Rao PN: A review on insulin plant (Costus igneus Nak). Pharmacogn Rev. 8:67–72. 2014. View Article : Google Scholar : PubMed/NCBI
31	Patil DT, Moss AC and Odze RD: Role of histologic inflammation in the natural history of ulcerative colitis. Gastrointest Endosc Clin N Am. 26:629–640. 2016. View Article : Google Scholar : PubMed/NCBI
32	Magnusson MK, Brynjólfsson SF, Dige A, Uronen-Hansson H, Börjesson LG, Bengtsson JL, Gudjonsson S, Öhman L, Agnholt J, Sjövall H, et al: Macrophage and dendritic cell subsets in IBD: ALDH+ cells are reduced in colon tissue of patients with ulcerative colitis regardless of inflammation. Mucosal Immunol. 9:171–182. 2016. View Article : Google Scholar : PubMed/NCBI
33	Cuković-Cavka S, Vucelić B, Urek MC, Brinar M and Turk N: The role of anti-TNF therapy in ulcerative colitis. Acta Med Croatica. 67:171–177. 2013.(In Croatian). PubMed/NCBI
34	Yamamoto-Furusho JK, Santiago-Hernández JJ, Pérez-Hernández N, Ramirez-Fuentes S, Fragoso JM and Vargas-Alarcón G: Interleukin 1 β (IL-1B) and IL-1 antagonist receptor (IL-1RN) gene polymorphisms are associated with the genetic susceptibility and steroid dependence in patients with ulcerative colitis. J Clin Gastroenterol. 45:531–535. 2011. View Article : Google Scholar : PubMed/NCBI
35	Lackeyram D, Young D, Kim CJ, Yang C, Archbold TL, Mine Y and Fan MZ: Interleukin-10 is differentially expressed in the small intestine and the colon experiencing chronic inflammation and ulcerative colitis induced by dextran sodium sulfate in young pigs. Physiol Res. 66:147–162. 2017.PubMed/NCBI
36	Bernardo D, Vallejo-Diez S, Mann ER, Al-Hassi HO, Martínez-Abad B, Montalvillo E, Tee CT, Murugananthan AU, Núñez H, Peake ST, et al: IL-6 promotes immune responses in human ulcerative colitis and induces a skin-homing phenotype in the dendritic cells and Tcells they stimulate. Eur J Immunol. 42:1337–1353. 2012. View Article : Google Scholar : PubMed/NCBI
37	Seidelin JB and Nielsen OH: Attenuated apoptosis response to Fas-ligand in active ulcerative colitis. Inflamm Bowel Dis. 14:1623–1629. 2008. View Article : Google Scholar : PubMed/NCBI
38	Xu X, Xu C, Saud SM, Lu X, Liu L, Fang L, Zhang X, Hu J and Li W: Effect of kuijie granule on the expression of TGF-β/Smads signaling pathway in patients with ulcerative colitis. Evid Based Complement Alternat Med. 2016:26018302016. View Article : Google Scholar : PubMed/NCBI