Berberine Administration in Treatment of Colitis: A Review

Milad       Ashrafizadeh; Masoud       Najafi; Reza       Mohammadinejad; Tahereh       Farkhondeh; Saeed       Samarghandian
Abstract

Berberine (Brb) is one of the well-known naturally occurring compounds exclusively found in Berberis vulgaris and other members of this family, such as Berberis aristata, Berberis aroatica, and Berberis aquifolium. This plant-derived natural compound has a variety of therapeutic impacts, including anti-oxidant, anti-inflammatory, anti-diabetic, and anti-tumor. Multiple studies have demonstrated that Brb has great anti-inflammatory activity and is capable of reducing the levels of proinflammatory cytokines, while it enhances the concentrations of anti-inflammatory cytokines, making it suitable for the treatment of inflammatory disorders. Colitis is an inflammatory bowel disease with chronic nature. Several factors are involved in the development of colitis and it appears that inflammation and oxidative stress are the most important ones. With respect to the anti-inflammatory and antioxidant effects of Brb, its administration seems to be beneficial in the treatment of colitis. In the present review, the protective effects of Brb in colitis treatment and its impact on molecular pathways are discussed.
Keywords: Antioxidant, anti-inflammatory, berberine, colitis, inflammatory bowel disease, Berberis aquifolium.
Graphical Abstract

[1] 
Hatamipour M, Ramezani M, Tabassi SAS, Johnston TP, Sahebkar A. Demethoxycurcumin: A naturally occurring curcumin analogue for treating non-cancerous diseases. J Cell Physiol  2019; 234(11): 19320-30.
[http://dx.doi.org/10.1002/jcp.28626] [PMID:  31344992] 
[2] 
Hatamipour M, Ramezani M, Tabassi SAS, Johnston TP, Ramezani M, Sahebkar A. Demethoxycurcumin: A naturally occurring curcumin analogue with antitumor properties. J Cell Physiol  2018; 233(12): 9247-60.
[http://dx.doi.org/10.1002/jcp.27029] [PMID:  30076727] 
[3] 
Bagheri H, Ghasemi F, Barreto GE, Rafiee R, Sathyapalan T, Sahebkar A. Effects of curcumin on mitochondria in neurodegenerative diseases BioFactors. (Oxford, England) 2019.
[4] 
Shah SC, Colombel J-F, Sands BE, Narula N. Mucosal healing is associated with improved long-term outcomes of patients with ulcerative colitis: a systematic review and meta-analysis. Clinical Gastroenterology and hepatology  2016; 14(9): 1245-55.e8.
[http://dx.doi.org/10.1016/j.cgh.2016.01.015] 
[5] 
Ghasemi F, Shafiee M, Banikazemi Z, et al. Curcumin inhibits NFkB and Wnt/β-catenin pathways in cervical cancer cells. Pathol Res Pract  2019; 215(10)152556
[http://dx.doi.org/10.1016/j.prp.2019.152556] [PMID:  31358480] 
[6] 
Gorabi AM, Hajighasemi S, Kiaie N, et al. Anti-fibrotic effects of curcumin and some of its analogues in the heart. Heart Fail Rev  2019; 1-13.
[http://dx.doi.org/10.1007/s10741-019-09854-6] [PMID:  31512150] 
[7] 
Korani S, Korani M, Sathyapalan T, Sahebkar A. Therapeutic effects of Crocin in autoimmune diseases: A review BioFactors. (Oxford, England) 2019.
[http://dx.doi.org/10.1002/biof.1557] 
[8] 
Bibak B, Shakeri F, Barreto GE, Keshavarzi Z, Sathyapalan T, Sahebkar A. A review of the pharmacological and therapeutic effects of auraptene BioFactors. (Oxford, England) 2019.
[http://dx.doi.org/10.1002/biof.1550] 
[9] 
Imenshahidi M, Hosseinzadeh H. Berberine and barberry (Berberis vulgaris): A clinical review. Phytother Res  2019; 33(3): 504-23.
[http://dx.doi.org/10.1002/ptr.6252] [PMID:  30637820] 
[10] 
Imenshahidi M, Hosseinzadeh H. Berberis vulgaris and berberine: an update review. Phytother Res  2016; 30(11): 1745-64.
[http://dx.doi.org/10.1002/ptr.5693] [PMID:  27528198] 
[11] 
Imenshahidi M, Qaredashi R, Hashemzaei M, Hosseinzadeh H. Inhibitory effect of berberis vulgaris aqueous extract on acquisition and reinstatement effects of morphine in conditioned place preferences (CPP) in mice. Jundishapur J Nat Pharm Prod  2014; 9(3)e16145
[http://dx.doi.org/10.17795/jjnpp-16145] [PMID:  25237645] 
[12] 
Imanshahidi M, Hosseinzadeh H. Pharmacological and therapeutic effects of Berberis vulgaris and its active constituent, berberine. Phytother Res  2008; 22(8): 999-1012.
[http://dx.doi.org/10.1002/ptr.2399] [PMID:  18618524] 
[13] 
Mirhadi E, Rezaee M, Malaekeh-Nikouei B. Nano strategies for berberine delivery, a natural alkaloid of Berberis. Biomed Pharmacother  2018; 104: 465-73.
[http://dx.doi.org/10.1016/j.biopha.2018.05.067] [PMID:  29793179] 
[14] 
Shinji S, Nakamura S, Nihashi Y, Umezawa K, Takaya T. Berberine and palmatine inhibit the growth of human rhabdomyosarcoma cells. Biosci Biotechnol Biochem  2019; 1-13.
[PMID:  31462179] 
[15] 
Guo P, Cai C, Wu X, et al. An insight into the molecular mechanism of berberine towards multiple cancer types through systems pharmacology. Front Pharmacol  2019; 10: 857.
[http://dx.doi.org/10.3389/fphar.2019.00857] [PMID:  31447670] 
[16] 
Zhang W, Xu JH, Yu T, Chen QK.  Effects of berberine and metformin on intestinal inflammation and gut microbiome composition in db/db mice Biomedicine pharmacotherapy = Biomedecine pharmacotherapie 2019.
[17] 
Wang Y, Yan A, Li S, Liu B, Li H, Yan Y. Efficacy and safety of berberine in the treatment of type 2 diabetes with insulin resistance: Protocol for a systematic review. Medicine (Baltimore)  2019; 98(35)e16947
[http://dx.doi.org/10.1097/MD.0000000000016947] [PMID:  31464934] 
[18] 
Han CY, Sun TT, Xv GP, Wang SS, Gu JG, Liu CY. Berberine ameliorates CCl4-induced liver injury in rats through regulation of the Nrf2-Keap1-ARE and p53 signaling pathways. Mol Med Rep  2019; 20(4): 3095-102.
[http://dx.doi.org/10.3892/mmr.2019.10551] [PMID:  31432116] 
[19] 
You X, Cao X, Lin Y. Berberine enhances the radiosensitivity of hepatoma cells by Nrf2 pathway. Front Biosci  2019; 24: 1190-202.
[http://dx.doi.org/10.2741/4775] [PMID:  31136975] 
[20] 
Wang W, Zha G, Zou JJ, Wang X, Li CN, Wu XJ. Berberine attenuates cigarette smoke extract-induced airway inflammation in mice: Involvement of TGF-beta1/Smads Signaling Pathway Current medical science 2019; 39(5): 748-53.
[21] 
El-Zeftawy M, Ghareeb D, ElBealy ER, et al. Berberine chloride ameliorated PI3K/Akt-p/SIRT-1/PTEN signaling pathway in insulin resistance syndrome induced in rats. J Food Biochem  2019; 43(12)e13049
[http://dx.doi.org/10.1111/jfbc.13049] [PMID:  31512260] 
[22] 
Zeng Z, Pan Y, Wu W, et al. Myocardial hypertrophy is improved with berberine treatment via long non-coding RNA MIAT mediated autophagy. J Pharm Pharmacol  2019; 71(12): 1822-31.
[http://dx.doi.org/10.1111/jphp.13170] [PMID:  31612504] 
[23] 
Wang C, Wang Y, Ma SR, et al. Berberine inhibits adipocyte differentiation, proliferation and adiposity through down-regulating galectin-3. Sci Rep  2019; 9(1): 13415.
[http://dx.doi.org/10.1038/s41598-019-50103-5] [PMID:  31527742] 
[24] 
Liu P, Li Y, Qi X, et al. Protein kinase C is involved in the neuroprotective effect of berberine against intrastriatal injection of quinolinic acid-induced biochemical alteration in mice. J Cell Mol Med  2019; 23(9): 6343-54.
[http://dx.doi.org/10.1111/jcmm.14522] [PMID:  31318159] 
[25] 
Yuan NN, Cai CZ, Wu MY, Su HX, Li M, Lu JH. Neuroprotective effects of berberine in animal models of Alzheimer’s disease: a systematic review of pre-clinical studies. BMC Complement Altern Med  2019; 19(1): 109.
[http://dx.doi.org/10.1186/s12906-019-2510-z] [PMID:  31122236] 
[26] 
de Oliveira JS, Abdalla FH, Dornelles GL, et al. Neuroprotective effects of berberine on recognition memory impairment, oxidative stress, and damage to the purinergic system in rats submitted to intracerebroventricular injection of streptozotocin. Psychopharmacology (Berl)  2019; 236(2): 641-55.
[http://dx.doi.org/10.1007/s00213-018-5090-6] [PMID:  30377748] 
[27] 
Huang SX, Qiu G, Cheng FR, et al. Berberine Protects Secondary Injury in Mice with Traumatic Brain Injury Through Anti-oxidative and Anti-inflammatory Modulation. Neurochem Res  2018; 43(9): 1814-25.
[http://dx.doi.org/10.1007/s11064-018-2597-5] [PMID:  30027364] 
[28] 
Cai Z, Wang C, He W, Chen Y. Berberine Alleviates Amyloid-Beta Pathology in the Brain of APP/PS1 Transgenic Mice via Inhibiting β/γ-Secretases Activity and Enhancing α-Secretases. Curr Alzheimer Res  2018; 15(11): 1045-52.
[http://dx.doi.org/10.2174/1567205015666180702105740] [PMID:  29962345] 
[29] 
Feng X, Sureda A, Jafari S, et al. Berberine in Cardiovascular and Metabolic Diseases: From Mechanisms to Therapeutics. Theranostics  2019; 9(7): 1923-51.
[http://dx.doi.org/10.7150/thno.30787] [PMID:  31037148] 
[30] 
Wang K, Feng X, Chai L, Cao S, Qiu F. The metabolism of berberine and its contribution to the pharmacological effects. Drug Metab Rev  2017; 49(2): 139-57.
[http://dx.doi.org/10.1080/03602532.2017.1306544] [PMID:  28290706] 
[31] 
Jin Y, Khadka DB, Cho W-J. Pharmacological effects of berberine and its derivatives: a patent update. Expert Opin Ther Pat  2016; 26(2): 229-43.
[http://dx.doi.org/10.1517/13543776.2016.1118060] [PMID:  26610159] 
[32] 
Lin X, Zhang N. Berberine: Pathways to protect neurons. Phytother Res  2018; 32(8): 1501-10.
[http://dx.doi.org/10.1002/ptr.6107] [PMID:  29732634] 
[33] 
Zhang F, Jia Y, Zheng X, et al. Janus nanocarrier-based co-delivery of doxorubicin and berberine weakens chemotherapy-exacerbated hepatocellular carcinoma recurrence. Acta Biomater  2019; 100: 352-64.
[http://dx.doi.org/10.1016/j.actbio.2019.09.034] [PMID:  31563690] 
[34] 
Khan I, Joshi G, Nakhate KT. Ajazuddin, Kumar R, Gupta U. Nano-co-delivery of berberine and anticancer drug using plga nanoparticles: exploration of better anticancer activity and in vivo kinetics. Pharm Res  2019; 36(10): 149.
[http://dx.doi.org/10.1007/s11095-019-2677-5] [PMID:  31420752] 
[35] 
Camilleri M, Lasch K, Zhou W. Irritable bowel syndrome: methods, mechanisms, and pathophysiology. The confluence of increased permeability, inflammation, and pain in irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol  2012; 303(7): G775-85.
[http://dx.doi.org/10.1152/ajpgi.00155.2012] [PMID:  22837345] 
[36] 
Öhman L, Simrén M. Pathogenesis of IBS: role of inflammation, immunity and neuroimmune interactions. Nat Rev Gastroenterol Hepatol  2010; 7(3): 163-73.
[http://dx.doi.org/10.1038/nrgastro.2010.4] [PMID:  20101257] 
[37] 
Langhorst J, Choi K-E. The role of human defensins in gastrointestinal diseases. Expert Rev Clin Immunol  2011; 7(6): 779-87.
[http://dx.doi.org/10.1586/eci.11.62] [PMID:  22014019] 
[38] 
Bradesi S, McRoberts JA, Anton PA, Mayer EA. Inflammatory bowel disease and irritable bowel syndrome: separate or unified? Curr Opin Gastroenterol  2003; 19(4): 336-42.
[http://dx.doi.org/10.1097/00001574-200307000-00003] [PMID:  15703574] 
[39] 
Spiller RC. Neuropathology of IBS? Gastroenterology  2002; 123(6): 2144-7.
[http://dx.doi.org/10.1053/gast.2002.37287] [PMID:  12454870] 
[40] 
Hartung JE, Eskew O, Wong T, et al. Nuclear factor-kappa B regulates pain and COMT expression in a rodent model of inflammation. Brain Behav Immun  2015; 50: 196-202.
[http://dx.doi.org/10.1016/j.bbi.2015.07.014] [PMID:  26187567] 
[41] 
Yu Z-C, Cen Y-X, Wu B-H, et al. Berberine prevents stress induced gut inflammation and visceral hypersensitivity and reduces intestinal motility in rats. World J Gastroenterol  2019; 25(29): 3956-71.
[http://dx.doi.org/10.3748/wjg.v25.i29.3956] [PMID:  31413530] 
[42] 
Kantono M, Guo B. Inflammasomes and cancer: the dynamic role of the inflammasome in tumor development. Front Immunol  2017; 8: 1132.
[http://dx.doi.org/10.3389/fimmu.2017.01132] [PMID:  28955343] 
[43] 
He Y, Hara H, Núñez G. Mechanism and regulation of NLRP3 inflammasome activation. Trends Biochem Sci  2016; 41(12): 1012-21.
[http://dx.doi.org/10.1016/j.tibs.2016.09.002] [PMID:  27669650] 
[44] 
Antonucci L, Fagman JB, Kim JY, et al. Basal autophagy maintains pancreatic acinar cell homeostasis and protein synthesis and prevents ER stress. Proc Natl Acad Sci USA  2015; 112(45): E6166-74.
[http://dx.doi.org/10.1073/pnas.1519384112] [PMID:  26512112] 
[45] 
Yao M, Fan X, Yuan B, et al. Berberine inhibits NLRP3 Inflammasome pathway in human triple-negative breast cancer MDA-MB-231 cell. BMC Complement Altern Med  2019; 19(1): 216.
[http://dx.doi.org/10.1186/s12906-019-2615-4] [PMID:  31412862] 
[46] 
Liu M, Gao L, Zhang N. Berberine reduces neuroglia activation and inflammation in streptozotocin-induced diabetic mice. Int J Immunopathol Pharmacol 2019.332058738419866379
[http://dx.doi.org/10.1177/2058738419866379] [PMID:  31337260] 
[47] 
Luo Y, Tian G, Zhuang Z, et al. Berberine prevents non-alcoholic steatohepatitis-derived hepatocellular carcinoma by inhibiting inflammation and angiogenesis in mice. Am J Transl Res  2019; 11(5): 2668-82.
[PMID:  31217846] 
[48] 
Zhao C, Wang Y, Yuan X, et al. Berberine inhibits lipopolysaccharide-induced expression of inflammatory cytokines by suppressing TLR4-mediated NF-ĸB and MAPK signaling pathways in rumen epithelial cells of Holstein calves. J Dairy Res  2019; 86(2): 171-6.
[http://dx.doi.org/10.1017/S0022029919000323] [PMID:  31142385] 
[49] 
Dong J, Zuo Z, Yan W, Liu W, Zheng Q, Liu X. Berberine ameliorates diabetic neuropathic pain in a rat model: involvement of oxidative stress, inflammation, and μ-opioid receptors. Naunyn Schmiedebergs Arch Pharmacol  2019; 392(9): 1141-9.
[http://dx.doi.org/10.1007/s00210-019-01659-6] [PMID:  31079200] 
[50] 
Metzger CE, Narayanan SA, Elizondo JP, et al. DSS-induced colitis produces inflammation-induced bone loss while irisin treatment mitigates the inflammatory state in both gut and bone. Sci Rep  2019; 9(1): 15144.
[http://dx.doi.org/10.1038/s41598-019-51550-w] [PMID:  31641205] 
[51] 
Guo C, Wu K, Liang X, Liang Y, Li R. Infliximab clinically treating ulcerative colitis: A systematic review and meta-analysis. Pharmacol Res 2019.148104455
[http://dx.doi.org/10.1016/j.phrs.2019.104455] [PMID:  31562896] 
[52] 
Ren M-T, Gu M-L, Zhou X-X, et al. Sirtuin 1 alleviates endoplasmic reticulum stress-mediated apoptosis of intestinal epithelial cells in ulcerative colitis. World J Gastroenterol  2019; 25(38): 5800-13.
[http://dx.doi.org/10.3748/wjg.v25.i38.5800] [PMID:  31636473] 
[53] 
Johnson CM, Linzay CD, Dassopoulos T. Maneuvering clinical pathways for ulcerative colitis. Curr Gastroenterol Rep  2019; 21(10): 52.
[http://dx.doi.org/10.1007/s11894-019-0716-3] [PMID:  31486929] 
[54] 
Colombel J-F, Mahadevan U. Inflammatory bowel disease 2017: innovations and changing paradigms. Gastroenterology  2017; 152(2): 309-12.
[http://dx.doi.org/10.1053/j.gastro.2016.12.004] [PMID:  27960091] 
[55] 
Low D, Nguyen DD, Mizoguchi E. Animal models of ulcerative colitis and their application in drug research. Drug Des Devel Ther  2013; 7: 1341-57.
[PMID:  24250223] 
[56] 
Cosnes J, Gower–Rousseau C, Seksik P, Cortot A. Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology  2011; 140(6): 1785-94.
[http://dx.doi.org/10.1053/j.gastro.2011.01.055] 
[57] 
Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature  2007; 448(7152): 427-34.
[http://dx.doi.org/10.1038/nature06005] [PMID:  17653185] 
[58] 
Sorrentino D. Microbial dysbiosis in spouses of ulcerative colitis patients: Any clues to disease pathogenesis? World J Gastroenterol  2017; 23(37): 6747-9.
[http://dx.doi.org/10.3748/wjg.v23.i37.6747] [PMID:  29085220] 
[59] 
McGuckin MA, Eri R, Simms LA, Florin TH, Radford-Smith G. Intestinal barrier dysfunction in inflammatory bowel diseases. Inflamm Bowel Dis  2009; 15(1): 100-13.
[http://dx.doi.org/10.1002/ibd.20539] [PMID:  18623167] 
[60] 
Chen ML, Sundrud MS. Cytokine networks and T-cell subsets in inflammatory bowel diseases. Inflamm Bowel Dis  2016; 22(5): 1157-67.
[http://dx.doi.org/10.1097/MIB.0000000000000714] [PMID:  26863267] 
[61] 
Rutgeerts P, Sandborn WJ, Feagan BG, et al. Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med  2005; 353(23): 2462-76.
[http://dx.doi.org/10.1056/NEJMoa050516] [PMID:  16339095] 
[62] 
Moghaddam NSA, Oskouie MN, Butler AE, Petit PX, Barreto GE, Sahebkar A. Hormetic effects of curcumin: What is the evidence? J Cell Physiol  2019; 234(7): 10060-71.
[http://dx.doi.org/10.1002/jcp.27880] [PMID:  30515809] 
[63] 
Motaharinia J, Panahi Y, Barreto GE, Beiraghdar F, Sahebkar A. Efficacy of curcumin on prevention of drug‐induced nephrotoxicity: A review of animal studies BioFactors. (Oxford, England) 2019.
[http://dx.doi.org/10.1002/biof.1538] 
[64] 
Bahrami A, Fereidouni M, Pirro M, Bianconi V, Sahebkar A. Modulation of regulatory T cells by natural products in cancer. Cancer Lett  2019; 459: 72-85.
[http://dx.doi.org/10.1016/j.canlet.2019.06.001] [PMID:  31176742] 
[65] 
Gong Z, Zhao S, Zhou J, et al. Curcumin alleviates DSS-induced colitis via inhibiting NLRP3 inflammsome activation and IL-1β production. Mol Immunol  2018; 104: 11-9.
[http://dx.doi.org/10.1016/j.molimm.2018.09.004] [PMID:  30396035] 
[66] 
Yue W, Liu Y, Li X, Lv L, Huang J, Liu J. Curcumin ameliorates dextran sulfate sodium-induced colitis in mice via regulation of autophagy and intestinal immunity The Turkish journal of gastroenterology: the official journal of Turkish Society of Gastroenterology  2019; 30(3): 290-8.
[http://dx.doi.org/10.5152/tjg.2019.18342] 
[67] 
Zhang L, Xue H, Zhao G, et al. Curcumin and resveratrol suppress dextran sulfate sodium-induced colitis in mice. Mol Med Rep  2019; 19(4): 3053-60.
[http://dx.doi.org/10.3892/mmr.2019.9974] [PMID:  30816479] 
[68] 
Fan Y, Zhang Z, Yao C, et al. Amurensin H, a Derivative From Resveratrol, Ameliorates Lipopolysaccharide/Cigarette Smoke-Induced Airway Inflammation by Blocking the Syk/NF-κB Pathway. Front Pharmacol  2019; 10: 1157.
[http://dx.doi.org/10.3389/fphar.2019.01157] [PMID:  31636566] 
[69] 
Jiang T, Gu J, Chen W, Chang Q. Resveratrol inhibits high glucose-induced inflammatory “metabolic memory” in human retinal vascular endothelial cells through SIRT1-dependent signaling. Can J Physiol Pharmacol  2019; 97(12): 1141-51.
[http://dx.doi.org/10.1139/cjpp-2019-0201] [PMID:  31638409] 
[70] 
Mayangsari Y, Suzuki T. Resveratrol Ameliorates Intestinal Barrier Defects and Inflammation in Colitic Mice and Intestinal Cells. J Agric Food Chem  2018; 66(48): 12666-74.
[http://dx.doi.org/10.1021/acs.jafc.8b04138] [PMID:  30426751] 
[71] 
Alrafas HR, Busbee PB, Nagarkatti M, Nagarkatti PS. Resveratrol modulates the gut microbiota to prevent murine colitis development through induction of Tregs and suppression of Th17 cells. J Leukoc Biol  2019; 106(2): 467-80.
[http://dx.doi.org/10.1002/JLB.3A1218-476RR] [PMID:  30897248] 
[72] 
Hong Z, Piao M. Effect of quercetin monoglycosides on oxidative stress and gut microbiota diversity in mice with dextran sodium sulphate-induced colitis. BioMed Res Int 2018.20188343052
[http://dx.doi.org/10.1155/2018/8343052] [PMID:  30539022] 
[73] 
Li YH, Sun W, Zhou BJ, et al. iTRAQ-based pharmacoproteomics reveals potential targets of berberine, a promising therapy for ulcerative colitis. Eur J Pharmacol  2019; 850: 167-79.
[http://dx.doi.org/10.1016/j.ejphar.2019.02.021] [PMID:  30771347] 
[74] 
Podolsky DK. Inflammatory bowel disease (2). N Engl J Med  1991; 325(14): 1008-16.
[http://dx.doi.org/10.1056/NEJM199110033251406] [PMID:  1886623] 
[75] 
Totsuka T, Kanai T, Nemoto Y, et al. Immunosenescent colitogenic CD4(+) T cells convert to regulatory cells and suppress colitis. Eur J Immunol  2008; 38(5): 1275-86.
[http://dx.doi.org/10.1002/eji.200737914] [PMID:  18412161] 
[76] 
Takahara M, Takaki A, Hiraoka S, Adachi T, Shimomura Y, Matsushita H, et al. Berberine improved experimental chronic colitis by regulating interferon-γ-and IL-17A-producing lamina propria CD4+ T cells through AMPK activation. Sci Rep  2019; 9(1): 1-13.
[http://dx.doi.org/10.1038/s41598-019-48331-w] [PMID:  30626917] 
[77] 
Li Q, Qu X, Pang X, et al. Berberine Protects Mice Against Dextran Sulfate Sodium-Induced Colitis by Activating mTORC1 Pathway. Front Pharmacol  2019; 10: 786.
[http://dx.doi.org/10.3389/fphar.2019.00786] [PMID:  31354497] 
[78] 
Heras-Sandoval D, Pérez-Rojas JM, Pedraza-Chaverri J. Novel compounds for the modulation of mTOR and autophagy to treat neurodegenerative diseases. Cell Signal 2020.65109442
[http://dx.doi.org/10.1016/j.cellsig.2019.109442] [PMID:  31639492] 
[79] 
Chapman NM, Chi H. mTOR signaling, Tregs and immune modulation. Immunotherapy  2014; 6(12): 1295-311.
[http://dx.doi.org/10.2217/imt.14.84] [PMID:  25524385] 
[80] 
Brandt M, Grazioso TP, Fawal M-A, Tummala KS, Torres-Ruiz R, Rodriguez-Perales S, et al. mTORC1 inactivation promotes colitis induced colorectal cancer but protects from APC loss-dependent tumorigenesis. Cell metabolism  2018; 27(1): 118-35.
[81] 
Csibi A, Fendt S-M, Li C, et al. The mTORC1 pathway stimulates glutamine metabolism and cell proliferation by repressing SIRT4. Cell  2013; 153(4): 840-54.
[http://dx.doi.org/10.1016/j.cell.2013.04.023] [PMID:  23663782] 
[82] 
Tan HWS, Sim AYL, Long YC. Glutamine metabolism regulates autophagy-dependent mTORC1 reactivation during amino acid starvation. Nat Commun  2017; 8(1): 338.
[http://dx.doi.org/10.1038/s41467-017-00369-y] [PMID:  28835610] 
[83] 
Csibi A, Lee G, Yoon S-O, et al. The mTORC1/S6K1 pathway regulates glutamine metabolism through the eIF4B-dependent control of c-Myc translation. Curr Biol  2014; 24(19): 2274-80.
[http://dx.doi.org/10.1016/j.cub.2014.08.007] [PMID:  25220053] 
[84] 
Hoque SS, Poxton IR, Ghosh S. Gut bacteria and ulcerative colitis—A broken tolerance. Gastroenterology  2000; 118(4): A807.
[http://dx.doi.org/10.1016/S0016-5085(00)85369-X] 
[85] 
Shen J, Zuo Z-X, Mao A-P. Effect of probiotics on inducing remission and maintaining therapy in ulcerative colitis, Crohn’s disease, and pouchitis: meta-analysis of randomized controlled trials. Inflamm Bowel Dis  2014; 20(1): 21-35.
[http://dx.doi.org/10.1097/01.MIB.0000437495.30052.be] [PMID:  24280877] 
[86] 
Cui H-H, Chen C-L, Wang J-D, et al. Effects of probiotic on intestinal mucosa of patients with ulcerative colitis. World J Gastroenterol  2004; 10(10): 1521-5.
[http://dx.doi.org/10.3748/wjg.v10.i10.1521] [PMID:  15133865] 
[87] 
Zhao H-M, Huang X-Y, Zuo Z-Q, et al. Probiotics increase T regulatory cells and reduce severity of experimental colitis in mice. World J Gastroenterol  2013; 19(5): 742-9.
[http://dx.doi.org/10.3748/wjg.v19.i5.742] [PMID:  23430765] 
[88] 
Cui H, Cai Y, Wang L, et al. Berberine regulates Treg/Th17 balance to treat ulcerative colitis through modulating the gut microbiota in the colon. Front Pharmacol  2018; 9: 571.
[http://dx.doi.org/10.3389/fphar.2018.00571] [PMID:  29904348] 
[89] 
Zhu D, Yu Y, Wang W, et al. Long noncoding RNA PART1 promotes progression of non-small cell lung cancer cells via JAKSTAT signaling pathway. Cancer Med  2019; 8(13): 6064-81.
[http://dx.doi.org/10.1002/cam4.2494] [PMID:  31436388] 
[90] 
Wang J, Li X, Ren P, et al. Anticancer activity of globularifolin against human adenoid cystic carcinoma cells is due to ROS mediated apoptotic cell death and modulation of the JAK/STAT signalling pathway. J BUON  2019; 24(3): 1276-82.
[PMID:  31424690] 
[91] 
Liu C, Arnold R, Henriques G, Djabali K. Inhibition of JAK-STAT Signaling with Baricitinib Reduces Inflammation and Improves Cellular Homeostasis in Progeria Cells. Cells  2019; 8(10)E1276
[http://dx.doi.org/10.3390/cells8101276] [PMID:  31635416] 
[92] 
Kamel EO, Hassanein EHM, Ahmed MA, Ali FEM. Perindopril ameliorates hepatic IR injury via regulation of NF-kappaBp65/ TLR-4, JAK1/STAT-3, Nrf-2 and PI3K/Akt/mTOR signaling pathways Anatomical record (Hoboken, NJ : 2007). 2019.
[93] 
Zhu L, Gu P, Shen H. Protective effects of berberine hydrochloride on DSS-induced ulcerative colitis in rats. Int Immunopharmacol  2019; 68: 242-51.
[http://dx.doi.org/10.1016/j.intimp.2018.12.036] [PMID:  30743078] 
[94] 
Zhang L-C, Wang Y, Tong L-C, et al. Berberine alleviates dextran sodium sulfate-induced colitis by improving intestinal barrier function and reducing inflammation and oxidative stress. Exp Ther Med  2017; 13(6): 3374-82.
[http://dx.doi.org/10.3892/etm.2017.4402] [PMID:  28587416] 
[95] 
Li M, Yu H, Pan H, et al. Nrf2 suppression delays diabetic wound healing through sustained oxidative stress and inflammation. Front Pharmacol  2019; 10: 1099.
[http://dx.doi.org/10.3389/fphar.2019.01099] [PMID:  31616304] 
[96] 
Duan XD, Jiang WD, Wu P, et al. Soybean β-conglycinin caused intestinal inflammation and oxidative damage in association with NF-κB, TOR and Nrf2 in juvenile grass carp (Ctenopharyngodon idella): varying among different intestinal segments. Fish Shellfish Immunol  2019; 95: 105-16.
[http://dx.doi.org/10.1016/j.fsi.2019.10.021] [PMID:  31610288] 
[97] 
Liang Y, Fan C, Yan X, et al. Berberine ameliorates lipopolysaccharide-induced acute lung injury via the PERK-mediated Nrf2/HO-1 signaling axis. Phytother Res  2019; 33(1): 130-48.
[http://dx.doi.org/10.1002/ptr.6206] [PMID:  30346043] 
[98] 
Hassanein EHM, Shalkami AS, Khalaf MM, Mohamed WR, Hemeida RAM. The impact of Keap1/Nrf2, P38MAPK/NF-κB and Bax/Bcl2/caspase-3 signaling pathways in the protective effects of berberine against methotrexate-induced nephrotoxicity. Biomed Pharmacother  2019; 109: 47-56.
[http://dx.doi.org/10.1016/j.biopha.2018.10.088] [PMID:  30396091] 
[99] 
Khor TO, Huang M-T, Kwon KH, Chan JY, Reddy BS, Kong A-N. Nrf2-deficient mice have an increased susceptibility to dextran sulfate sodium-induced colitis. Cancer Res  2006; 66(24): 11580-4.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-3562] [PMID:  17178849] 
[100] 
Wang X, Campos CR, Peart JC, et al. Nrf2 upregulates ATP binding cassette transporter expression and activity at the blood-brain and blood-spinal cord barriers. J Neurosci  2014; 34(25): 8585-93.
[http://dx.doi.org/10.1523/JNEUROSCI.2935-13.2014] [PMID:  24948812] 
[101] 
Jing W, Safarpour Y, Zhang T, et al. Berberine upregulates Pglycoprotein in human Caco-2 cells and in an experimental model of colitis in the rat via activation of Nrf2-dependent mechanisms. J Pharmacol Exp Ther  2018; 366(2): 332-40.
[http://dx.doi.org/10.1124/jpet.118.249615] [PMID:  29891588] 
[102] 
Basso D, Zambon C-F, Plebani M. Inflammatory bowel diseases: from pathogenesis to laboratory testing. Clin Chem Lab Med  2014; 52(4): 471-81.
[http://dx.doi.org/10.1515/cclm-2013-0588] [PMID:  24108210] 
[103] 
Mahida YR. The key role of macrophages in the immunopathogenesis of inflammatory bowel disease. Inflamm Bowel Dis  2000; 6(1): 21-33.
[http://dx.doi.org/10.1097/00054725-200002000-00004] [PMID:  10701146] 
[104] 
Liu Y, Liu X, Hua W, et al. Berberine inhibits macrophage M1 polarization via AKT1/SOCS1/NF-κB signaling pathway to protect against DSS-induced colitis. Int Immunopharmacol  2018; 57: 121-31.
[http://dx.doi.org/10.1016/j.intimp.2018.01.049] [PMID:  29482156] 
[105] 
Jess T, Gamborg M, Matzen P, Munkholm P, Sørensen TI. Increased risk of intestinal cancer in Crohn’s disease: a meta-analysis of population-based cohort studies. Am J Gastroenterol  2005; 100(12): 2724-9.
[http://dx.doi.org/10.1111/j.1572-0241.2005.00287.x] [PMID:  16393226] 
[106] 
Gillen CD, Andrews HA, Prior P, Allan RN. Crohn’s disease and colorectal cancer. Gut  1994; 35(5): 651-5.
[http://dx.doi.org/10.1136/gut.35.5.651] [PMID:  8200559] 
[107] 
Gillen CD, Walmsley RS, Prior P, Andrews HA, Allan RN. Ulcerative colitis and Crohn’s disease: a comparison of the colorectal cancer risk in extensive colitis. Gut  1994; 35(11): 1590-2.
[http://dx.doi.org/10.1136/gut.35.11.1590] [PMID:  7828978] 
[108] 
Terzić J, Grivennikov S, Karin E, Karin M. Inflammation and colon cancer Gastroenterology  2010 ;138(6):2101-14 2010; 138(6): 2101-14..
[http://dx.doi.org/10.1053/j.gastro.2010.01.058] 
[109] 
Karin M, Greten FR. NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol  2005; 5(10): 749-59.
[http://dx.doi.org/10.1038/nri1703] [PMID:  16175180] 
[110] 
Li D, Zhang Y, Liu K, et al. Berberine inhibits colitis-associated tumorigenesis via suppressing inflammatory responses and the consequent EGFR signaling-involved tumor cell growth. Lab Invest  2017; 97(11): 1343-53.
[http://dx.doi.org/10.1038/labinvest.2017.71] [PMID:  28759012] 
[111] 
Li YH, Xiao HT, Hu DD, et al. Berberine ameliorates chronic relapsing dextran sulfate sodium-induced colitis in C57BL/6 mice by suppressing Th17 responses. Pharmacol Res  2016; 110: 227-39.
[http://dx.doi.org/10.1016/j.phrs.2016.02.010] [PMID:  26969793] 
[112] 
Cottone M, Renna S, Modesto I, Orlando A. Is 5-ASA still the treatment of choice for ulcerative colitis? Curr Drug Targets  2011; 12(10): 1396-405.
[http://dx.doi.org/10.2174/138945011796818126] [PMID:  21466493] 
[113] 
Zhao L-N, Li J-Y, Yu T, Chen G-C, Yuan Y-H, Chen Q-K. 5-Aminosalicylates reduce the risk of colorectal neoplasia in patients with ulcerative colitis: an updated meta-analysis. PLoS One  2014; 9(4)e94208
[http://dx.doi.org/10.1371/journal.pone.0094208] [PMID:  24710620] 
[114] 
Bantel H, Berg C, Vieth M, Stolte M, Kruis W, Schulze-Osthoff K. Mesalazine inhibits activation of transcription factor NF-kappaB in inflamed mucosa of patients with ulcerative colitis. Am J Gastroenterol  2000; 95(12): 3452-7.
[http://dx.doi.org/10.1111/j.1572-0241.2000.03360.x] [PMID:  11151876] 
[115] 
Sharon P, Ligumsky M, Rachmilewitz D, Zor U. Role of prostaglandins in ulcerative colitis. Enhanced production during active disease and inhibition by sulfasalazine. Gastroenterology  1978; 75(4): 638-40.
[http://dx.doi.org/10.1016/S0016-5085(19)31672-5] [PMID:  30669] 
[116] 
Li YH, Zhang M, Xiao HT, et al. Addition of berberine to 5-aminosalicylic acid for treatment of dextran sulfate sodium-induced chronic colitis in C57BL/6 mice. PLoS One  2015; 10(12)e0144101
[http://dx.doi.org/10.1371/journal.pone.0144101] [PMID:  26642326] 
[117] 
Kawano M, Takagi R, Kaneko A, Matsushita S. Berberine is a dopamine D1- and D2-like receptor antagonist and ameliorates experimentally induced colitis by suppressing innate and adaptive immune responses. J Neuroimmunol  2015; 289: 43-55.
[http://dx.doi.org/10.1016/j.jneuroim.2015.10.001] [PMID:  26616870] 
[118] 
Li C, Xi Y, Li S, et al. Berberine ameliorates TNBS induced colitis by inhibiting inflammatory responses and Th1/Th17 differentiation. Mol Immunol  2015; 67(2 Pt B): 444-54.
[http://dx.doi.org/10.1016/j.molimm.2015.07.013] [PMID:  26224047] 
[119] 
Hong T, Yang Z, Lv C-F, Zhang Y. Suppressive effect of berberine on experimental dextran sulfate sodium-induced colitis. Immunopharmacol Immunotoxicol  2012; 34(3): 391-7.
[http://dx.doi.org/10.3109/08923973.2011.609887] [PMID:  22564173] 
[120] 
Yan F, Wang L, Shi Y, et al. Berberine promotes recovery of colitis and inhibits inflammatory responses in colonic macrophages and epithelial cells in DSS-treated mice. Am J Physiol Gastrointest Liver Physiol  2012; 302(5): G504-14.
[http://dx.doi.org/10.1152/ajpgi.00312.2011] [PMID:  22173918] 
[121] 
Minaiyan M, Ghannadi A, Mahzouni P, Jaffari-Shirazi E. Comparative study of Berberis vulgaris fruit extract and berberine chloride effects on acetic acid-induced colitis in rats. Iranian journal of pharmaceutical research. Iran J Pharm Res  2011; 10(1): 97-104.
[PMID:  24363687] 
[122] 
Zhang M, Long Y, Sun Y, et al. Evidence for the complementary and synergistic effects of the three-alkaloid combination regimen containing berberine, hypaconitine and skimmianine on the ulcerative colitis rats induced by trinitrobenzene-sulfonic acid. Eur J Pharmacol  2011; 651(1-3): 187-96.
[http://dx.doi.org/10.1016/j.ejphar.2010.10.030] [PMID:  20969848] 
[123] 
Lee I-A, Hyun Y-J, Kim D-H. Berberine ameliorates TNBS induced colitis by inhibiting lipid peroxidation, enterobacterial growth and NF-κB activation. Eur J Pharmacol  2010; 648(1-3): 162-70.
[http://dx.doi.org/10.1016/j.ejphar.2010.08.046] [PMID:  20828550] 
[124] 
Zhou H, Mineshita S. The effect of berberine chloride on experimental colitis in rats in vivo and in vitro. J Pharmacol Exp Ther  2000; 294(3): 822-9.
[PMID:  10945829] 
[125] 
Huls M, Russel FG, Masereeuw R. The role of ATP binding cassette transporters in tissue defense and organ regeneration. J Pharmacol Exp Ther  2009; 328(1): 3-9.
[http://dx.doi.org/10.1124/jpet.107.132225] [PMID:  18791064] 
[126] 
Sharom FJ. The P-glycoprotein multidrug transporter. Essays Biochem  2011; 50(1): 161-78.
[http://dx.doi.org/10.1042/bse0500161] [PMID:  21967057] 
[127] 
Johnstone RW, Ruefli AA, Smyth MJ. Multiple physiological functions for multidrug transporter P-glycoprotein? Trends Biochem Sci  2000; 25(1): 1-6.
[http://dx.doi.org/10.1016/S0968-0004(99)01493-0] [PMID:  10637601] 
[128] 
Banner KH, Cattaneo C, Le Net JL, Popovic A, Collins D, Gale JD. Macroscopic, microscopic and biochemical characterisation of spontaneous colitis in a transgenic mouse, deficient in the multiple drug resistance 1a gene. Br J Pharmacol  2004; 143(5): 590-8.
[http://dx.doi.org/10.1038/sj.bjp.0705982] [PMID:  15466445] 
[129] 
Blokzijl H, Vander Borght S, Bok LI, et al. Decreased P-glycoprotein (P-gp/MDR1) expression in inflamed human intestinal epithelium is independent of PXR protein levels. Inflamm Bowel Dis  2007; 13(6): 710-20.
[http://dx.doi.org/10.1002/ibd.20088] [PMID:  17262809] 
[130] 
Xu L, Zhang Y, Xue X, Liu J, Li ZS, Yang GY, et al. A Phase I Trial of Berberine in Chinese with Ulcerative Colitis. Cancer prevention research (Philadelphia, Pa) 2019.
[131] 
Song HY, Sik Kim W, Kim JM, et al. A hydroxyethyl derivative of chrysin exhibits anti-inflammatory activity in dendritic cells and protective effects against dextran sodium salt-induced colitis in mice. Int Immunopharmacol 2019.77105958
[http://dx.doi.org/10.1016/j.intimp.2019.105958] [PMID:  31639615] 
[132] 
Lleal M, Sarrabayrouse G, Willamil J, Santiago A, Pozuelo M, Manichanh C. A single faecal microbiota transplantation modulates the microbiome and improves clinical manifestations in a rat model of colitis. EBioMedicine  2019; 48: 630-41.
[http://dx.doi.org/10.1016/j.ebiom.2019.10.002] [PMID:  31628021] 
[133] 
Samarghandian S, Azimi-Nezhad M, Borji A, Samini M and, Farkhondeh T. 2017. Protective effects of carnosol against oxidative stress induced brain damage by chronic stress in rats.BMC complementary and alternative medicine.  17(1), pp.1-7.
[134] 
Samarghandian S, Azimi-Nezhad M and, Farkhondeh T. 2017. Immunomodulatory and antioxidant effects of saffron aqueous extract (Crocus sativus L.) on streptozotocin-induced diabetes in rats.Indian heart journal.  69(2), pp.151-159.
[135] 
Shakib Z, Shahraki N, Razavi BM, Hosseinzadeh H. Aloe vera as an herbal medicine in the treatment of metabolic syndrome: A review. Phytother Res  2019; 33(10): 2649-60.
[http://dx.doi.org/10.1002/ptr.6465] [PMID:  31456283] 
[136] 
Farkhondeh T, Samarghandian S. Antidotal effects of curcumin against agents-induced cardiovascular toxicity Cardiovascular Haematological Disorders-Drug Targets (Formerly Current Drug Targets- Cardiovascular Hematological Disorders) 2016;16(1):30-7. 16(1): 30-7.
[http://dx.doi.org/10.2174/1871529X16666160802144510] 
[137] 
Samarghandian S, Azimi-Nezhad M, Borji A, et al. Inhibitory and cytotoxic activities of chrysin on human breast adenocarcinoma cells by induction of apoptosis. Pharmacogn Mag  2016; 12(Suppl. 4): S436-40.
[http://dx.doi.org/10.4103/0973-1296.191453] [PMID:  27761071] 
Cite As