Effects of berberine on a rat model of chronic stress and depression via gastrointestinal tract pathology and gastrointestinal flora profile assays

Zhu,Xiaohui; Sun,Yangdong; Zhang,Chenggang; Liu,Haifeng

doi:10.3892/mmr.2017.6353

Effects of berberine on a rat model of chronic stress and depression via gastrointestinal tract pathology and gastrointestinal flora profile assays

Authors:
- Xiaohui Zhu
- Yangdong Sun
- Chenggang Zhang
- Haifeng Liu
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Affiliations: Department of Gastroenterology, General Hospital of the Chinese People's Armed Police Forces, Beijing 100039, P.R. China, Department of Biological Engineering, College of Pharmacy, Jilin University, Jinan, Shandong 130021, P.R. China, Beijing Institute of Radiation Medicine, State Key Laboratory of Proteomics, Cognitive and Mental Health Research Center of PLA, Beijing 100850, P.R. China
Published online on: March 22, 2017 https://doi.org/10.3892/mmr.2017.6353
Pages: 3161-3171

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Abstract

Chronic stress and depression are challenging conditions to treat, owing to their complexity and lack of clinically available and effective therapeutic agents. The aim of the present study was to investigate the mechanism by which berberine acts, by examining alterations to gastrointestinal tract histopathology and flora profile in a rat model, following the induction of stress. Research associating gastrointestinal flora and depression has increased, thus, the present study hypothesized that stress induces depression and changes in the gastrointestinal system. The chronic mild stress rat model was previously established based on a set of 10 chronic unpredictable stress methods. In the present study, the measurements of body weight, behavior, gastrointestinal tract histopathology and gastrointestinal flora profile were collected in order to elucidate understanding of chronic stress and depression in this region. In the present study, induced stress and the resulting depression was demonstrated to significantly decrease the body weight and sucrose preference of rats, as well as significantly increasing traverse time, vertical movement time, grooming time and motionless time in an open‑field test. Following modeling and subsequent treatment with low or high doses of berberine, the measurements were significantly different when compared with unstressed rats. Berberine appears to reverse the physical damage brought about by stress within the gastric mucosa and intestinal microvilli of the stomach, ileum, cecum and colon. Using enterobacterial repetitive intergenic consensus sequence‑based polymerase chain reaction analysis, several distinctive bands disappeared following modeling; however, novel distinctive bands appeared in response to the graded berberine treatment. In conclusion, the present study identified that high concentrations of berberine markedly protects rats from various symptoms of chronic stress and depression, with the potential of facilitating treatment within clinical practice.

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1	Technow JR, Hazel NA, Abela JR and Hankin BL: Stress sensitivity interacts with depression history to predict depressive symptoms among youth: Prospective changes following first depression onset. J Abnorm Child Psychol. 43:489–501. 2015. View Article : Google Scholar : PubMed/NCBI
2	Mayberry LS, Egede LE, Wagner JA and Osborn CY: Stress, depression and medication nonadherence in diabetes: Test of the exacerbating and buffering effects of family support. J Behav Med. 38:363–371. 2015. View Article : Google Scholar : PubMed/NCBI
3	Fan LB, Blumenthal JA, Watkins LL and Sherwood A: Work and home stress: Associations with anxiety and depression symptoms. Occup Med (Lond). 65:110–116. 2015. View Article : Google Scholar : PubMed/NCBI
4	Wang X, Cai L, Qian J and Peng J: Social support moderates stress effects on depression. Int J Ment Health Syst. 8:412014. View Article : Google Scholar : PubMed/NCBI
5	Reynaud E, Guedj E, Trousselard M, El Khoury-Malhame M, Zendjidjian X, Fakra E, Souville M, Nazarian B, Blin O, Canini F and Khalfa S: Acute stress disorder modifies cerebral activity of amygdala and prefrontal cortex. Cogn Neurosci. 6:39–43. 2015. View Article : Google Scholar : PubMed/NCBI
6	Pulopulos MM, Hidalgo V, Almela M, Puig-Perez S, Villada C and Salvador A: Acute stress and working memory in older people. Stress. 18:178–187. 2015. View Article : Google Scholar : PubMed/NCBI
7	Nilsson D, Nordenstam C, Green S, Wetterhall A, Lundin T and Svedin CG: Acute stress among adolescents and female rape victims measured by ASC-Kids: A pilot study. Nord J Psychiatry. 69:539–545. 2015. View Article : Google Scholar : PubMed/NCBI
8	Gonzalez M, Melamed G and Dillon C: Acute stress disorder in the emergency, its relationship with trigger factors from a gender perspective. Vertex. 25:172–178. 2014.(In Spanish). PubMed/NCBI
9	Razzoli M, McCallum J, Gurney A, Engeland WC and Bartolomucci A: Chronic stress aggravates glucose intolerance in leptin receptor-deficient (db/db) mice. Genes Nutr. 10:4582015. View Article : Google Scholar : PubMed/NCBI
10	Radenbach C, Reiter AM, Engert V, Sjoerds Z, Villringer A, Heinze HJ, Deserno L and Schlagenhauf F: The interaction of acute and chronic stress impairs model-based behavioral control. Psychoneuroendocrinology. 53:268–280. 2015. View Article : Google Scholar : PubMed/NCBI
11	Hoffman AN, Parga A, Paode PR, Watterson LR, Nikulina EM, Hammer RP Jr and Conrad CD: Chronic stress enhanced fear memories are associated with increased amygdala zif268 mRNA expression and are resistant to reconsolidation. Neurobiol Learn Mem. 120:61–68. 2015. View Article : Google Scholar : PubMed/NCBI
12	Breuer K, Göldner FM, Jager B, Werfel T and Schmid-Ott G: Chronic stress experience and burnout syndrome have appreciable influence on health-related quality of life in patients with psoriasis. J Eur Acad Dermatol Venereol. 29:1898–1904. 2015. View Article : Google Scholar : PubMed/NCBI
13	Gutknecht L, Popp S, Waider J, Sommerlandt FM, Göppner C, Post A, Reif A, van den Hove D, Strekalova T, Schmitt A, et al: Interaction of brain 5-HT synthesis deficiency, chronic stress and sex differentially impact emotional behavior in Tph2 knockout mice. Psychopharmacology (Berl). 232:2429–2441. 2015. View Article : Google Scholar : PubMed/NCBI
14	Elfving B, Jakobsen JL, Madsen JC, Wegener G and Muller HK: Chronic restraint stress increases the protein expression of VEGF and its receptor VEGFR-2 in the prefrontal cortex. Synapse. 190–194:692015.
15	Duncan J, Wang N, Zhang X, Johnson S, Harris S, Zheng B, Zhang Q, Rajkowska G, Miguel-Hidalgo JJ, Sittman D, et al: Chronic social stress and ethanol increase expression of KLF11, a cell death mediator, in rat brain. Neurotox Res. 28:18–31. 2015. View Article : Google Scholar : PubMed/NCBI
16	Zhao J, Jung YH, Jang CG, Chun KH, Kwon SW and Lee J: Metabolomic identification of biochemical changes induced by fluoxetine and imipramine in a chronic mild stress mouse model of depression. Sci Rep. 5:88902015. View Article : Google Scholar : PubMed/NCBI
17	Xing H, Zhang K, Zhang R, Zhang Y, Gu L, Shi H, Bi K and Chen X: Determination of depression biomarkers in rat plasma by liquid chromatography-mass spectrometry for the study of the antidepressant effect of Zhi-Zi-Hou-Po decoction on rat model of chronic unpredictable mild stress. J Chromatogr B Analyt Technol Biomed Life Sci. 988:135–142. 2015. View Article : Google Scholar : PubMed/NCBI
18	Thompson AK, Fourman S, Packard AE, Egan AE, Ryan KK and Ulrich-Lai YM: Metabolic consequences of chronic intermittent mild stress exposure. Physiol Behav. 150:24–30. 2015. View Article : Google Scholar : PubMed/NCBI
19	Yu M, Zhang X, Lu F and Fang L: Depression and risk for diabetes: A meta-analysis. Can J Diabetes. 39:266–272. 2015. View Article : Google Scholar : PubMed/NCBI
20	Smith HR: Depression in cancer patients: Pathogenesis, implications and treatment (Review). Oncol Lett. 9:1509–1514. 2015.PubMed/NCBI
21	Fagelman KM, Methratta S, Cilley RE, Wilson MZ and Hollenbeak CS: The depression index: An objective measure of the severity of pectus excavatum based on vertebral diameter, a morphometric correlate to patient size. J Pediatr Surg. 50:1130–1133. 2015. View Article : Google Scholar : PubMed/NCBI
22	Tchuenbou J, Hamy A, Papapietro V, Sagan C, Paineau J and Le Bodic L: Gastrointestinal mucormycosis: A rare cause of digestive system hemorrhage. Gastroenterol Clin Biol. 23:794–795. 1999.(In French). PubMed/NCBI
23	Infant nutrition: Metabolism and the digestive system. Proceedings, international symposium in infant nutrition and the development of the gastrointestinal tract. Niagara falls, Ontario, June 21–25, 1982. J Pediatr Gastroenterol Nutr. 2:(Suppl 1). S1–S342. 1983.
24	Gastrointestinal hormones and pathology of the digestive system. Adv Exp Med Biol. 106:1–326. 1978.
25	Results in gastroenterology 1978. Immune system and the gastrointestinal tract; classification and therapy of intestinal neoplasms. 33rd meeting of the German society for digestive and metabolic diseases, Hamburg, 28–30 September 1978. Z Gastroenterol Verh. 1–115. 1978.(In German).
26	Cossel L: Functional disorders of the gastrointestinal system; a contribution to the chronic digestive disorders of the duodenum and to the acute stomach dilatation. Zentralbl Chir. 80:273–289. 1955.(In German). PubMed/NCBI
27	Ge L, Zhu MM, Yang JY, Wang F, Zhang R, Zhang JH, Shen J, Tian HF and Wu CF: Differential proteomic analysis of the anti-depressive effects of oleamide in a rat chronic mild stress model of depression. Pharmacol Biochem Behav. 131:77–86. 2015. View Article : Google Scholar : PubMed/NCBI
28	Adak A, Maity C, Ghosh K and Mondal KC: Alteration of predominant gastrointestinal flora and oxidative damage of large intestine under simulated hypobaric hypoxia. Z Gastroenterol. 52:180–186. 2014. View Article : Google Scholar : PubMed/NCBI
29	Wiwanitkit V: Antibiotic and gastrointestinal tract flora. Vet Microbiol. 148:4522011. View Article : Google Scholar : PubMed/NCBI
30	Shimizu K, Ogura H, Asahara T, Nomoto K, Morotomi M, Nakahori Y, Osuka A, Yamano S, Goto M, Matsushima A, et al: Gastrointestinal dysmotility is associated with altered gut flora and septic mortality in patients with severe systemic inflammatory response syndrome: A preliminary study. Neurogastroenterol Motil. 23:330–335, e157. 2011. View Article : Google Scholar : PubMed/NCBI
31	Björkstén B: Impact of gastrointestinal flora on systemic diseases. J Pediatr Gastroenterol Nutr. 46:(Suppl 1). E12–E13. 2008. View Article : Google Scholar
32	Shanahan F: Gut flora in gastrointestinal disease. Eur J Surg Suppl. 47–52. 2002.PubMed/NCBI
33	Marteau P: Role of the intestinal flora in gastrointestinal diseases. Lancet. 356:(Suppl). s282000. View Article : Google Scholar : PubMed/NCBI
34	Adams JB, Johansen LJ, Powell LD, Quig D and Rubin RA: Gastrointestinal flora and gastrointestinal status in children with autism-comparisons to typical children and correlation with autism severity. BMC Gastroenterol. 11:222011. View Article : Google Scholar : PubMed/NCBI
35	in't Huis Veld JH: Gastrointestinal flora and health in man and animal. Tijdschr Diergeneeskd. 116:232–239. 1991.(In Dutch). PubMed/NCBI
36	Sharples GJ and Lloyd RG: A novel repeated DNA sequence located in the intergenic regions of bacterial chromosomes. Nucleic Acids Res. 18:6503–6508. 1990. View Article : Google Scholar : PubMed/NCBI
37	Ture M, Altinok I and Capkin E: Comparison of pulsed-field gel electrophoresis and enterobacterial repetitive intergenic consensus PCR and biochemical tests to characterize Lactococcus garvieae. J Fish Dis. 38:37–47. 2015. View Article : Google Scholar : PubMed/NCBI
38	Fendri I, Ben Hassena A, Grosset N, Barkallah M, Khannous L, Chuat V, Gautier M and Gdoura R: Genetic diversity of food-isolated Salmonella strains through Pulsed Field Gel Electrophoresis (PFGE) and Enterobacterial Repetitive Intergenic Consensus (ERIC-PCR). PLoS One. 8:e813152013. View Article : Google Scholar : PubMed/NCBI
39	Adzitey F: Genetic diversity of Escherichia coli isolated from ducks and the environment using enterobacterial repetitive intergenic consensus. Pak J Biol Sci. 16:1173–1178. 2013. View Article : Google Scholar : PubMed/NCBI
40	Hulton CS, Higgins CF and Sharp PM: ERIC sequences: A novel family of repetitive elements in the genomes of Escherichia coli, Salmonella typhimurium and other enterobacteria. Mol Microbiol. 5:825–834. 1991. View Article : Google Scholar : PubMed/NCBI
41	Versalovic J, Koeuth T and Lupski JR: Distribution of repetitive DNA sequences in eubacteria and application to fingerprinting of bacterial genomes. Nucleic Acids Res. 19:6823–6831. 1991. View Article : Google Scholar : PubMed/NCBI
42	Zhang Q, Cai L, Zhong G and Luo W: Simultaneous determination of jatrorrhizine, palmatine, berberine, and obacunone in Phellodendri Amurensis Cortex by RP-HPLC. Zhongguo Zhong Yao Za Zhi. 35:2061–2064. 2010.(In Chinese). PubMed/NCBI
43	Berberine. Altern Med Rev. 5:175–177. 2000.PubMed/NCBI
44	Yu HH, Kim KJ, Cha JD, Kim HK, Lee YE, Choi NY and You YO: Antimicrobial activity of berberine alone and in combination with ampicillin or oxacillin against methicillin-resistant Staphylococcus aureus. J Med Food. 8:454–461. 2005. View Article : Google Scholar : PubMed/NCBI
45	Kuo CL, Chi CW and Liu TY: The anti-inflammatory potential of berberine in vitro and in vivo. Cancer Lett. 203:127–137. 2004. View Article : Google Scholar : PubMed/NCBI
46	Gu Y, Zhang Y, Shi X, Li X, Hong J, Chen J, Gu W, Lu X, Xu G and Ning G: Effect of traditional Chinese medicine berberine on type 2 diabetes based on comprehensive metabonomics. Talanta. 81:766–772. 2010. View Article : Google Scholar : PubMed/NCBI
47	Kulkarni SK and Dhir A: Sigma-1 receptors in major depression and anxiety. Expert Rev Neurother. 9:1021–1034. 2009. View Article : Google Scholar : PubMed/NCBI
48	Kulkarni SK and Dhir A: Current investigational drugs for major depression. Expert Opin Investig Drugs. 18:767–788. 2009. View Article : Google Scholar : PubMed/NCBI
49	Kulkarni SK and Dhir A: On the mechanism of antidepressant-like action of berberine chloride. Eur J Pharmacol. 589:163–172. 2008. View Article : Google Scholar : PubMed/NCBI
50	Kulkarni SK and Dhir A: Berberine: A plant alkaloid with therapeutic potential for central nervous system disorders. Phytother Res. 24:317–324. 2010. View Article : Google Scholar : PubMed/NCBI