Skip to main content
Top
Published in: BMC Complementary Medicine and Therapies 1/2017

Open Access 01-12-2017 | Research article

Sini-san improves duodenal tight junction integrity in a rat model of functional dyspepsia

Authors: Xiongfei Chang, Luqing Zhao, Jiajia Wang, Xiaofang Lu, Shengsheng Zhang

Published in: BMC Complementary Medicine and Therapies | Issue 1/2017

Login to get access

Abstract

Background

Recent reports have demonstrated that impaired barrier function and local microinflammation in the duodenal mucosa contribute to the pathogeneses of functional dyspepsia (FD). Thus, restoring normal barrier integrity becomes a potential therapeutic strategy in the treatment of FD. Sini-San (SNS) is a traditional Chinese prescription that exhibits therapeutic effects in FD, but the underlying mechanisms remain not well understood.

Methods

FD rats were established by tail clamping method and the therapeutic effect of SNS was evaluated by measuring the visceral sensitivity and gastric compliance. Transepithelial electrical resistance (TEER) that reveals epithelial barrier integrity was measured by Ussing chamber. The expression of tight junction (TJ) proteins, occludin and claudin-1, in the duodenum was determined by Western blot and immunofluorescence. The amount of tumor necrosis factor alpha (TNF-α) and interferon gamma (INF-γ) in duodenal mucosa was detected by enzyme-linked immune sorbent assay (ELISA). The mRNA level of transient receptor potential vanilloid type 1 (TRPV1) was measured by quantitative real time-polymerase chain reaction (qPCR).

Results

SNS could improve gastric compliance and attenuate visceral hypersensitivity (VH) in FD rats. TEER was decreased in FD rats, but treatment with SNS restored normal level of TEER and the expression of occludin and claudin-1 in FD rats. In addition, SNS administration ameliorated FD-associated increase in the production of TNF-α, IFN-γ and the expression of TRPV1.

Conclusions

The therapeutic effect of SNS on FD is at least partially through improvement of TJ integrity and attenuation of FD-associated low-grade inflammation in the duodenum. Our findings highlight the molecular basis of SNS-based treatment of FD in human patients.
Appendix
Available only for authorised users
Literature
1.
go back to reference Mahadeva S, Goh KL. Epidemiology of functional dyspepsia: a global perspective. World J Gastroentero. 2006;12(17):2661–6.CrossRef Mahadeva S, Goh KL. Epidemiology of functional dyspepsia: a global perspective. World J Gastroentero. 2006;12(17):2661–6.CrossRef
2.
go back to reference Vanheel H, Vicario M, Vanuytsel T, Van Oudenhove L, Martinez C, Keita AV, et al. Impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia. Gut. 2014;63(2):262–71.CrossRefPubMed Vanheel H, Vicario M, Vanuytsel T, Van Oudenhove L, Martinez C, Keita AV, et al. Impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia. Gut. 2014;63(2):262–71.CrossRefPubMed
3.
go back to reference Stanghellini V, Chan FK, Hasler WL, Malagelada JR, Suzuki H, Tack J, et al. Gastroduodenal Disorders. Gastroenterology. 2016;150(6):1380–92.CrossRefPubMed Stanghellini V, Chan FK, Hasler WL, Malagelada JR, Suzuki H, Tack J, et al. Gastroduodenal Disorders. Gastroenterology. 2016;150(6):1380–92.CrossRefPubMed
4.
go back to reference Miner-Williams WM, Moughan PJ. Intestinal barrier dysfunction: implications for chronic inflammatory conditions of the bowel. Nutr Res Rev. 2016;29(1):40–59.CrossRefPubMed Miner-Williams WM, Moughan PJ. Intestinal barrier dysfunction: implications for chronic inflammatory conditions of the bowel. Nutr Res Rev. 2016;29(1):40–59.CrossRefPubMed
5.
go back to reference Jin ZH, Duan JH, Zhao HC. Clinical study on colonic transmission time and the effect of sini powder on it in functional constipation patients. Chin J Integr Trad West Med. 2006;26(10):896–8. Jin ZH, Duan JH, Zhao HC. Clinical study on colonic transmission time and the effect of sini powder on it in functional constipation patients. Chin J Integr Trad West Med. 2006;26(10):896–8.
6.
go back to reference Chen L. In the treatment of functional dyspepsia with Si-ni-san depression random parallel control study. J Pract Tradit Chin Intern Med. 2014;28(2):50–1. Chen L. In the treatment of functional dyspepsia with Si-ni-san depression random parallel control study. J Pract Tradit Chin Intern Med. 2014;28(2):50–1.
7.
go back to reference Wang X-M, Wang C-D. Clinical observation of Si-ni-san decoction treated 180 cases patients with functional dyspepsia. Modern Digestion Intervention. 2007;12(4):251–2. Wang X-M, Wang C-D. Clinical observation of Si-ni-san decoction treated 180 cases patients with functional dyspepsia. Modern Digestion Intervention. 2007;12(4):251–2.
8.
go back to reference FU Kemo MY. Protection effect of Jiaweisini decoction on function of liver and intestinal mucosa of cirrhosis patients. China Moden Doctor. 2014;52(10):105–7. FU Kemo MY. Protection effect of Jiaweisini decoction on function of liver and intestinal mucosa of cirrhosis patients. China Moden Doctor. 2014;52(10):105–7.
9.
go back to reference Hu L-N, Fang X-Y, Liu H-L, Gao Z, Wu X-F, Sun Y, et al. Protective effects of 18β-glycyrrhetinic acid on LPS-induced injury in intestinal epithelial cells. Chin J Nat Med. 2014;11(1):24–9.CrossRef Hu L-N, Fang X-Y, Liu H-L, Gao Z, Wu X-F, Sun Y, et al. Protective effects of 18β-glycyrrhetinic acid on LPS-induced injury in intestinal epithelial cells. Chin J Nat Med. 2014;11(1):24–9.CrossRef
10.
go back to reference Wen J, Qiao Y, Yang J, Liu X, Song Y, Liu Z, et al. UPLC-MS/MS determination of paeoniflorin, naringin, naringenin and glycyrrhetinic acid in rat plasma and its application to a pharmacokinetic study after oral administration of Si-Ni-san decoction. J Pharmaceut Bio Med. 2012;66:271–7.CrossRef Wen J, Qiao Y, Yang J, Liu X, Song Y, Liu Z, et al. UPLC-MS/MS determination of paeoniflorin, naringin, naringenin and glycyrrhetinic acid in rat plasma and its application to a pharmacokinetic study after oral administration of Si-Ni-san decoction. J Pharmaceut Bio Med. 2012;66:271–7.CrossRef
11.
go back to reference Sun Y, Dong Y, Jiang HJ, Cai TT, Chen L, Zhou X, et al. Dissection of the role of paeoniflorin in the traditional Chinese medicinal formula Si-Ni-san against contact dermatitis in mice. Life Sci. 2009;84(11):337–44.CrossRefPubMed Sun Y, Dong Y, Jiang HJ, Cai TT, Chen L, Zhou X, et al. Dissection of the role of paeoniflorin in the traditional Chinese medicinal formula Si-Ni-san against contact dermatitis in mice. Life Sci. 2009;84(11):337–44.CrossRefPubMed
12.
go back to reference Zhang L, Dong Y, Sun Y, Chen T, Xu Q. Role of four major components in the effect of Si-Ni-san, a traditional Chinese prescription, against contact sensitivity in mice. J Pharm Pharmacol. 2006;58(9):1257–64.CrossRefPubMed Zhang L, Dong Y, Sun Y, Chen T, Xu Q. Role of four major components in the effect of Si-Ni-san, a traditional Chinese prescription, against contact sensitivity in mice. J Pharm Pharmacol. 2006;58(9):1257–64.CrossRefPubMed
13.
go back to reference Wei W, Li X, Hao J, Zhang R, Guo J, Zong Y, et al. Proteomic analysis of functional dyspepsia in stressed rats treated with traditional Chinese medicine "Wei Kangning". J Gastroen hepatol. 2011;26(9):1425–33. Wei W, Li X, Hao J, Zhang R, Guo J, Zong Y, et al. Proteomic analysis of functional dyspepsia in stressed rats treated with traditional Chinese medicine "Wei Kangning". J Gastroen hepatol. 2011;26(9):1425–33.
14.
go back to reference Uchida M, Kobayashi O, Iwamoto C. Effects of L-tryptophan on gastric emptying evaluated by breath test in relation to gastric accommodation evaluated by Barostat in rats. J Pharmacol Sci. 2015;127(2):229–31.CrossRefPubMed Uchida M, Kobayashi O, Iwamoto C. Effects of L-tryptophan on gastric emptying evaluated by breath test in relation to gastric accommodation evaluated by Barostat in rats. J Pharmacol Sci. 2015;127(2):229–31.CrossRefPubMed
15.
go back to reference Liu J, Li F, Tang XD, Ma J, Ma X, Ge DY, et al. XiangshaLiujunzi decoction alleviates the symptoms of functional dyspepsia by regulating brain-gut axis and production of neuropeptides. BMC Complem Altern M. 2015;15:387.CrossRef Liu J, Li F, Tang XD, Ma J, Ma X, Ge DY, et al. XiangshaLiujunzi decoction alleviates the symptoms of functional dyspepsia by regulating brain-gut axis and production of neuropeptides. BMC Complem Altern M. 2015;15:387.CrossRef
16.
go back to reference Bratten J, Jones MP. Prolonged recording of duodenal acid exposure in patients with functional dyspepsia and controls using a radiotelemetry pH monitoring system. J Clin Gastroenterol. 2009;43(6):527–33.CrossRefPubMed Bratten J, Jones MP. Prolonged recording of duodenal acid exposure in patients with functional dyspepsia and controls using a radiotelemetry pH monitoring system. J Clin Gastroenterol. 2009;43(6):527–33.CrossRefPubMed
17.
go back to reference Feinle C, Meier O, Otto B, D'Amato M, Fried M. Role of duodenal lipid and cholecystokinin a receptors in the pathophysiology of functional dyspepsia. Gut. 2001;48(3):347–55.CrossRefPubMedPubMedCentral Feinle C, Meier O, Otto B, D'Amato M, Fried M. Role of duodenal lipid and cholecystokinin a receptors in the pathophysiology of functional dyspepsia. Gut. 2001;48(3):347–55.CrossRefPubMedPubMedCentral
18.
go back to reference Schwartz MP, Samsom M, Smout AJ. Chemospecific alterations in duodenal perception and motor response in functional dyspepsia. Am J Gastroentero. 2001;96(9):2596–602.CrossRef Schwartz MP, Samsom M, Smout AJ. Chemospecific alterations in duodenal perception and motor response in functional dyspepsia. Am J Gastroentero. 2001;96(9):2596–602.CrossRef
19.
go back to reference Van Itallie CM, Anderson JM. Architecture of tight junctions and principles of molecular composition. Semin Cell Dev Biol. 2014;36:157–65.CrossRefPubMed Van Itallie CM, Anderson JM. Architecture of tight junctions and principles of molecular composition. Semin Cell Dev Biol. 2014;36:157–65.CrossRefPubMed
20.
go back to reference Walker MM, Talley NJ. The role of duodenal inflammation in functional dyspepsia. J Clin Gastroenterol. 2017;51(1):12–8.CrossRefPubMed Walker MM, Talley NJ. The role of duodenal inflammation in functional dyspepsia. J Clin Gastroenterol. 2017;51(1):12–8.CrossRefPubMed
21.
go back to reference Du L, Shen J, Kim JJ, Yu Y, Ma L, Dai N. Increased duodenal eosinophil degranulation in patients with functional dyspepsia: a prospective study. Sci Rep-UK. 2016;6:34305.CrossRef Du L, Shen J, Kim JJ, Yu Y, Ma L, Dai N. Increased duodenal eosinophil degranulation in patients with functional dyspepsia: a prospective study. Sci Rep-UK. 2016;6:34305.CrossRef
22.
go back to reference Schmitz H, Barmeyer C, Fromm M, Runkel N, Foss HD, Bentzel CJ, et al. Altered tight junction structure contributes to the impaired epithelial barrier function in ulcerative colitis. Gastroenterology. 1999;116(2):301–9.CrossRefPubMed Schmitz H, Barmeyer C, Fromm M, Runkel N, Foss HD, Bentzel CJ, et al. Altered tight junction structure contributes to the impaired epithelial barrier function in ulcerative colitis. Gastroenterology. 1999;116(2):301–9.CrossRefPubMed
23.
go back to reference Wilcz-Villega EM, McClean S, O'Sullivan MA. Mast cell tryptase reduces junctional adhesion molecule-a (JAM-A) expression in intestinal epithelial cells: implications for the mechanisms of barrier dysfunction in irritable bowel syndrome. Am J Gastroenterol. 2013;108(7):1140–51.CrossRefPubMed Wilcz-Villega EM, McClean S, O'Sullivan MA. Mast cell tryptase reduces junctional adhesion molecule-a (JAM-A) expression in intestinal epithelial cells: implications for the mechanisms of barrier dysfunction in irritable bowel syndrome. Am J Gastroenterol. 2013;108(7):1140–51.CrossRefPubMed
24.
go back to reference Tanaka F, Tominaga K, Fujikawa Y, Nagami Y, Kamata N, Yamagami H, et al. Concentration of glial cell line-derived neurotrophic factor positively correlates with symptoms in functional dyspepsia. Digest Dis Sci. 2016;61(12):3478–85.CrossRefPubMed Tanaka F, Tominaga K, Fujikawa Y, Nagami Y, Kamata N, Yamagami H, et al. Concentration of glial cell line-derived neurotrophic factor positively correlates with symptoms in functional dyspepsia. Digest Dis Sci. 2016;61(12):3478–85.CrossRefPubMed
26.
go back to reference Furuse M, Hirase T, Itoh M, Nagafuchi A, Yonemura S, Tsukita S, et al. Occludin: a novel integral membrane protein localizing at tight junctions. J Cell Biol. 1993;123:1777–88.CrossRefPubMed Furuse M, Hirase T, Itoh M, Nagafuchi A, Yonemura S, Tsukita S, et al. Occludin: a novel integral membrane protein localizing at tight junctions. J Cell Biol. 1993;123:1777–88.CrossRefPubMed
27.
go back to reference Feldman GJ, Mullin JM, Ryan MP. Occludin: structure, function and regulation. Adv Drug Deliver Rev. 2005;57(6):883–917.CrossRef Feldman GJ, Mullin JM, Ryan MP. Occludin: structure, function and regulation. Adv Drug Deliver Rev. 2005;57(6):883–917.CrossRef
28.
go back to reference Lee HS, Kim DK, Kim YB, Lee KJ. Effect of acute stress on immune cell counts and the expression of tight junction proteins in the duodenal mucosa of rats. Gut live. 2013;7(2):190–6.CrossRef Lee HS, Kim DK, Kim YB, Lee KJ. Effect of acute stress on immune cell counts and the expression of tight junction proteins in the duodenal mucosa of rats. Gut live. 2013;7(2):190–6.CrossRef
29.
go back to reference Vanuytsel T, van Wanrooy S, Vanheel H, Vanormelingen C, Verschueren S, Houben E, et al. Psychological stress and corticotropin-releasing hormone increase intestinal permeability in humans by a mast cell-dependent mechanism. Gut. 2014;63(8):1293–9.CrossRefPubMed Vanuytsel T, van Wanrooy S, Vanheel H, Vanormelingen C, Verschueren S, Houben E, et al. Psychological stress and corticotropin-releasing hormone increase intestinal permeability in humans by a mast cell-dependent mechanism. Gut. 2014;63(8):1293–9.CrossRefPubMed
30.
go back to reference Lin HJ, Kao ST, Siao YM, Yeh CC. The Chinese medicine Sini-san inhibits HBx-induced migration and invasiveness of human hepatocellular carcinoma cells. BMC Complem Altern M. 2015;15:348.CrossRef Lin HJ, Kao ST, Siao YM, Yeh CC. The Chinese medicine Sini-san inhibits HBx-induced migration and invasiveness of human hepatocellular carcinoma cells. BMC Complem Altern M. 2015;15:348.CrossRef
31.
go back to reference Yang F, Zhao K, Zhang X, Zhang J, Xu B. ATP induces disruption of tight junction proteins via IL-1 Beta-dependent MMP-9 activation of human blood-brain barrier in vitro. Neural Plast. 2016;8928530 Yang F, Zhao K, Zhang X, Zhang J, Xu B. ATP induces disruption of tight junction proteins via IL-1 Beta-dependent MMP-9 activation of human blood-brain barrier in vitro. Neural Plast. 2016;8928530
32.
go back to reference Talley NJ, Walker MM, Aro P, Ronkainen J, Storskrubb T, Hindley LA, et al. Non-ulcer dyspepsia and duodenal eosinophilia: an adult endoscopic population-based case-control study. Clin Gastroenterol H. 2007;5(10):1175–83.CrossRef Talley NJ, Walker MM, Aro P, Ronkainen J, Storskrubb T, Hindley LA, et al. Non-ulcer dyspepsia and duodenal eosinophilia: an adult endoscopic population-based case-control study. Clin Gastroenterol H. 2007;5(10):1175–83.CrossRef
33.
go back to reference Tang Y, Liao Y, Kawaguchi-Sakita N, Raut V, Fakhrejahani E, Qian N, et al. Sinisan, a traditional Chinese medicine, attenuates experimental chronic pancreatitis induced by trinitrobenzene sulfonic acid in rats. J Hepato-Bil-Pan Sci. 2011;18(4):551–8. Tang Y, Liao Y, Kawaguchi-Sakita N, Raut V, Fakhrejahani E, Qian N, et al. Sinisan, a traditional Chinese medicine, attenuates experimental chronic pancreatitis induced by trinitrobenzene sulfonic acid in rats. J Hepato-Bil-Pan Sci. 2011;18(4):551–8.
34.
go back to reference Farzaei MH, Bahramsoltani R, Abdollahi M, Rahimi R. The role of visceral hypersensitivity in irritable bowel syndrome: pharmacological targets and novel treatments. J Neurogastroenterol Motil. 2016;22(4):558–74.CrossRefPubMedPubMedCentral Farzaei MH, Bahramsoltani R, Abdollahi M, Rahimi R. The role of visceral hypersensitivity in irritable bowel syndrome: pharmacological targets and novel treatments. J Neurogastroenterol Motil. 2016;22(4):558–74.CrossRefPubMedPubMedCentral
35.
go back to reference Ma W, Quirion R. Inflammatory mediators modulating the transient receptor potential vanilloid 1 receptor: therapeutic targets to treat inflammatory and neuropathic pain. Expert Opin Ther Tar. 2007;11(3):307–20.CrossRef Ma W, Quirion R. Inflammatory mediators modulating the transient receptor potential vanilloid 1 receptor: therapeutic targets to treat inflammatory and neuropathic pain. Expert Opin Ther Tar. 2007;11(3):307–20.CrossRef
36.
go back to reference Yoshida A, Furube E, Mannari T, Takayama Y, Kittaka H, Tominaga M, et al. TRPV1 is crucial for proinflammatory STAT3 signaling and thermoregulation-associated pathways in the brain during inflammation. SCI REP-UK. 2016;6:26088.CrossRef Yoshida A, Furube E, Mannari T, Takayama Y, Kittaka H, Tominaga M, et al. TRPV1 is crucial for proinflammatory STAT3 signaling and thermoregulation-associated pathways in the brain during inflammation. SCI REP-UK. 2016;6:26088.CrossRef
Metadata
Title
Sini-san improves duodenal tight junction integrity in a rat model of functional dyspepsia
Authors
Xiongfei Chang
Luqing Zhao
Jiajia Wang
Xiaofang Lu
Shengsheng Zhang
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2017
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-017-1938-2

Other articles of this Issue 1/2017

BMC Complementary Medicine and Therapies 1/2017 Go to the issue