[1] CHEN C Q,FICHNA J,BASHASHATI M,et al.Distribution,function and physiological role of melatonin in the lower gut[J].World Journal of Gastroenterology,2011,17(34):3888-3898.

[2] BONNEFONT-ROUSSELOT D,COLLIN F.Melatonin:action as antioxidant and potential applications in human disease and aging[J].Toxicology,2010,278(1):55-67.

[3] KASIMAY O,CAKIR B,DEVERSEN E,et al.Exogenous melatonin delays gastric emptying rate in rats:role of CCK2 and 5-HT3 receptors[J].Journal of Physiology and Pharmacology,2005,56(4):543-553.
[4] KIM J B,JUNG J Y,AHN J C,et al.Antioxidant and anti-apoptotic effect of melatonin on the vestibular hair cells of rat utricles[J].Clinical and Experimental Otorhinolaryngology,2009,2(1):6-12.

[5] DOBOCOVICH M L,MANKOWSHA M.Functimal MT
1 and MT
2 melatonin receptors in mammals[J].Endocrine,2005,27(2):101-110.

[6] BUBENIK G A.Localization,physiological significance and possible clinical implication of gastrointestinal melatonin[J].Biological Signals and Receptors,2001,10(6):350-366.

[7] BERTRAND P P,BERTRAND R L,CAMELLO P J,et al.Simultaneous measurement of serotonin and melatonin from the intestine of old mice:the effects of daily melatonin supple-mentation[J].Journal of Pineal Research,2010,49(1):23-34.

[8] MOTILVA V,CABEZA J,DE LA LASTRA C A.New issues about melatonin and its effects on the digestive system[J].Current Pharmaceutical Design,2001,7(10):909-931.

[9] MUÑOZ-PÉREZ J L,LÓPEZ-PATIÑO M A,ÁLVAREZ-OTERO R,et al.Characterization of melatonin synthesis in the gastrointestinal tract of rainbow trout (
Oncorhynchus mykiss):distribution,relation with serotonin,daily rhythms and photoperiod regulation[J].Journal of Comparative Physiology B,2016,186(4):471-484.

[10] STEBELOVÁ K,HERICHOVÁ I,ZEMAN M.Diabetes induces changes in melatonin concentrations in peripheral tissues of rat[J].Neuro Endocrinology Letters,2007,28(2):159-165.
[11] HUETHER G.Melatonin synthesis in the gastrointestinal tract and the impact of nutritional factors on circulating melatonin[J].Annals of the New York Academy of Sciences,1994,719:146-158.
[12] TAN D X,MANCHESTER L C,ESTEBAN-ZUBERO E,et al.Melatonin as a potent and inducible endogenous antioxidant:synthesis and metabolism[J].Molecules,2015,20(10):18886-18906.

[13] KVETNOY I M,INGEL I E,KVETNAIA T V,et al.Gastrointestinal melatonin:cellular identification and biological role[J].Neuro Endocrinology Letters,2002,23(2):121-132.
[14] YANO J M,YU K,DONALDSON G P,et al.Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis[J].Cell,2015,161(2):264-276.

[15] LEE P P,PANG S F.Melatonin and its receptors in the gastrointestinal tract[J].Neurosignals,1993,2(4):181-193.

[16] NOSJEAN O,FERROM,COGE F,et al.Identification of the melatonin binding site MT3 as the Quinone reductase 2[J].Journal of Biological Chemistry,2000,275(40):31311-31317.

[17] SALLINEN P,SAARELA S,ILVES M,et al.The expression of MT1 and MT2 melatonin receptor mRNA in several rat tissues[J].Life Science,2005,76(10):1123-1134.

[18] STEBELOVÁ K,ANTTILA K,MÄNTTÄRI S,et al.Immunohistochemical definition of MT2 receptors and melatonin in the gastrointestinal tissues of rat[J].Acta Histochemica,2010,112(1):26-33.

[19] SÖDERQUIST F,HELLSTRÖM P M,CUNNINGHAM J L.Human gastroenteropancreatic expression of melatonin and its receptors MT1 and MT2[J].PLoS One,2015,10(3):e0120195.
[20] SOTÁK M,MRNKA L,PÁCHA J.Heterogeneous expression of melatonin receptor
MT1 mRNA in the rat intestine under control and fasting conditions[J].Journal of Pineal Research,2006,41(2):183-188.

[21] WIESENBERG I,MISSBACH M,CARLBERG C.The potential role of the transcription factor RZR/ROR as a mediator of nuclear melatonin signaling[J].Restorative Neurology and Neuroscience,1998,12(2/3):143-150.
[22] MERLE A,DELAGRANGE P,RENARD P,et al.Effect of melatonin on motility pattern of small intestine in rats and its inhibition by melatonin receptor antagonist S 22153[J].Journal of Pineal Research,2000,29(2):116-124.

[23] DRAGO F,MACAUDA S,SALEHI S.Small doses of melatonin increase intestinal motility in rats[J].Digestive Diseases and Sciences,2002,47(9):1969-1974.

[24] CHOJNACKI C,WALECKA-KAPICA E,LOKIE C ' K,et al.Influence of melatonin on symptoms of irritable bowel syndrome in postmenopausal women[J].Endokrynologia Polska,2013,64(2):114-120.
[25] SONG G H,LENG P H,GWEE K A,et al.Melatonin improves abdominal pain in irritable bowel syndrome patients who have sleep disturbances:a randomized,double blind,placebo controlled study[J].Gut,2005,54(10):1402-1407.

[26] SJÖBLOM M.The duodenal mucosal bicarbonate secretion[J].Upsala Journal of Medical Sciences,2005,110(2):115-149.

[27] REITER R J.Melatonin:lowering the high price of free radicals[J].News in Physiological Sciences,2000,15(5):246-250.
[28] REITER R J,PAREDES S D,MANCHESTER L C,et al.Reducing oxidative/nitrosative stress:a newly-discovered genre for melatonin[J].Critical Reviews in Biochemistry and Molecular Biology,2009,44(4):175-200.

[29] TAN D X,REITER R J,MANCHESTER L C,et al.Chemical and physical properties and potential mechanisms:melatonin as a broad spectrum antioxidant and free radical scavenger[J].Current Topics in Medicinal Chemistry,2002,2(2):181-197.

[30] ESPOSITO E,CUZZOCREA S.Antiinflammatory activity of melatonin in central nervous system[J].Current Neuropharmacology,2010,8(3):228-242.

[31] MEI Q,DIAO L,XU J M,et al.A protective effect of melatonin on intestinal permeability is induced by diclofenac
via regulation of mitochondrial function in mice[J].Acta Pharmacologica Sinica,2011,32(4):495-502.

[32] REITER R J,ROSALES-CORRAL S,TAN D X,et al.Melatonin as a mitochondria-targeted antioxidant:one of evolution's best ideas[J].Cellular and Molecular Life Sciences,2017,74(21):3863-3881.

[33] TAMURA E K,SILVA C L M,MARKUS R P.Melatonin inhibits endothelial nitric oxide production
in vitro[J].Journal of Pineal Research,2006,41(3):267-274.

[34] BRAZÃO V,DEL VECCHIO FILIPIN M,SANTELLO F H,et al.Immunomodulatory properties and anti-apoptotic effects of zinc and melatonin in an experimental model of chronic Chagas disease[J].Immunobiology,2015,220(5):626-633.

[35] CHETSAWANG B,PUTTHAPRASART C,PHANSUWAN-PUJITO P,et al.Melatonin protects against hydrogen peroxide-induced cell death signaling in SH-SY5Y cultured cells:involvement of nuclear factor kappa B,Bax and Bcl-2[J].Journal of Pineal Research,2006,41(2):116-123.

[36] GUHA M,MAITY P,CHOUBEY V,et al.Melatonin inhibits free radical-mediated mitochondrial-dependent hepatocyteapoptosis and liver damage induced during malarial infection[J].Journal of Pineal Research,2007,43(4):372-381.

[37] KIM C H,KIM K H,YOO Y M.Melatonin protects against apoptotic and autophagic cell death in C2C12 murine myoblast cells[J].Journal of Pineal Research,2011,50(3):241-249.

[38] ANDRABI S A,SAYEED I,SIEMEN D,et al.Direct inhibition of the mitochondrial permeability transition pore:a possible mechanism responsible for anti-apoptotic effects of melatonin[J].FASEB Journal,2004,18(7):869-871.

[39] REN W K,LIU G,CHEN S,et al.Melatonin signaling in T cells:functions and applications[J].Journal of Pineal Research,2017,62(3):e12394.
[40] HALDAR C,RAI S,SINGH R.Melatonin blocks dexamethasone-induced immunosuppression in a seasonally breeding rodent Indian palm squirrel,
Funambulus pennanti[J].Steroids,2004,69(6):367-377.

[41] CAPELLI E,CAMPO I,PANELLI S,et al.Evaluation of gene expression in human lymphocytes activated in the presence of melatonin[J].International Immunopharmacology,2002,2(7):885-892.

[42] MUXEL S M,PIRES-LAPA M A,MONTEIRO A W,et al.NF-κB drives the synthesis of melatonin in RAW 264.7 macrophages by inducing the transcription of the arylalkylamine-N-acetyltransferase (
AA-
NAT) gene[J].PLoS One,2012,7(12):e52010.
[43] RAGHAVENDRA V,SINGH V,KULKARNI S K,et al.Melatonin enhances Th2 cell mediated immune responses:lack of sensitivity to reversal by naltrexone or benzodiazepine receptor antagonists[J].Molecular and Cellular Biochemistry,2001,221(1/2):57-62.

[44] YU Q N,MILLER S C,OSMOND D G.Melatonin inhibits apoptosis during early B-cell development in mouse bone marrow[J].Journal of Pineal Research,2000,29(2):86-93.

[45] CARRILLO-VICO A,LARDONE P J,ÁLVAREZ-SÁNCHEZ N,et al.Melatonin:buffering the immune system[J].International Journal of Molecular Sciences,2013,14(4):8638-8683.

[46] TIAN Y M,ZHANG G Y,DAI Y R.Melatonin rejuvenates degenerated thymus and redresses peripheral immune functions in aged mice[J].Immunology Letters,2003,88(2):101-104.

[47] LIU F,NG T B,FUNG M C.Pineal indoles stimulate the gene expression of immunomodulating cytokines[J].Journal of Neural Transmission,2001,108(4):397-405.

[48] CURRIER N L,SUN L Z Y,MILLER S C.Exogenous melatonin:quantitative enhancement
in vivo of cells mediating non-specific immunity[J].Journal of Neuroimmunology,2000,104(2):101-108.

[49] SANTELLO F H,FRARE E O,DOS SANTOS C D,et al.Suppressive action of melatonin on the TH-2 immune response in rats infected with
Trypanosoma cruzi[J].Journal of Pineal Research,2008,45(3):291-296.

[50] BRAZÃO V,DEL VECCHIO FILIPIN M,SANTELLO F H,et al.Melatonin and zinc treatment:distinctive modulation of cytokine production in chronic experimental Trypanosoma cruzi infection[J].Cytokine,2011,56(3):627-632.

[51] POHANKA M.Impact of melatonin on immunity:a review[J].Central European Journal of Medicine,2013,8(4):369-376.
[52] CARRILLO-VICO A,LARDONE P J,FERNÁNDEZ-SANTOS J M,et al.Human lymphocyte-synthesized melatonin is involved in the regulation of the interleukin-2/interleukin-2 receptor system[J].Journal of Clinical Endocrinology and Metabolism,2005,90(2):992-1000.

[53] CHEN Y,ZHANG J,ZHAO Q,et al.Melatonin induces anti-inflammatory effects to play a protective role via endoplasmic reticulum stress in acute pancreatitis[J].Cellular Physiology and Biochemistry,2016,40(5):1094-1104.

[54] DONG W G,MEI Q,YU J P,et al.Effects of melatonin on the expression of
iNOS and
COX-2 in rat models of colitis[J].World Journal of Gastroenterology,2003,9(6):1307-1311.

[55] ESPOSITO E,MAZZON E,RICCARDI L,et al.Matrix metalloproteinase-9 and metalloproteinase-2 activity and expression is reduced by melatonin during experimental colitis[J].Journal of Pineal Research,2008,45(2):166-173.

[56] LI J H,YU J P,YU H G,et al.Melatonin reduces inflammatory injury through inhibiting NF-κB activation in rats with colitis[J].Mediators of Inflammation,2005,2005(4):185-193.

[57] MAHMOOD N M A,JUMMA K M,HUSSAIN S A.Dose-dependent anti-inflammatory activity of melatonin in experimental animal model of chronic inflammation[J].Global Journal of Pharmacology,2010,4(2):66-70.
[58] MOZAFFARI S,ABDOLLAHI M.Melatonin,a promising supplement in inflammatory bowel disease:a comprehensive review of evidences[J].Current Pharmaceutical Design,2011,17(38):4372-4378.

[59] NOSÁL'OVÁ V,ZEMAN M, ?ERNÁ S,et al.Protective effect of melatonin in acetic acid induced colitis in rats[J].Journal of Pineal Research,2007,42(4):364-370.

[60] TRIANTAFILLIDIS A,TRIANTAFILLIDIS J K.Melatonin:a potent antioxidant agent with anti-inflammatory and anti-apoptotic effects that might be useful in the treatment of IBD patients[J].Annals of Gastroenterology,2009,22(1):10-12.
[61] GITTO E,MARSEGLIA L,MANTI S,et al.Protective role of melatonin in neonatal diseases[J].Oxidative Medicine and Cellular Longevity,2013,2013:980374.
[62] MAURIZ J L,COLLADO P S,VENEROSO C,et al.A review of the molecular aspects of melatonin's anti-inflammatory actions:recent insights and new perspectives[J].Journal of Pineal Research,2013,54(1):1-14.

[63] YU G M,KUBOTA H,OKITA M,et al.The anti-inflammatory and antioxidant effects of melatonin on LPS-stimulated bovine mammary epithelial cells[J].PLoS One,2017,12(5):e0178525.
[64] MEI Q,YU J P,XU J M,et al.Melatonin reduces colon immunological injury in rats by regulating activity of macrophages[J].Acta Pharmacologica Sinica,2002,23(10):882-886.
[65] MAZZON E,ESPOSITO E,CRISAFULLI C,et al.Melatonin modulates signal transduction pathways and apoptosis in experimental colitis[J].Journal of Pineal Research,2006,41(4):363-373.

[66] SUN X C,SHAO Y Y,JIN Y,et al.Melatonin reduces bacterial translocation by preventing damage to the intestinal mucosa in an experimental severe acute pancreatitis rat model[J].Experimental and Therapeutic Medicine,2013,6(6):1343-1349.

[67] LIU T,ZHANG L Y,JOO D,et al.NF-κB signaling in inflammation[J].Signal Transduction and Targeted Therapy,2017,2:17023.
[68] XU P,WANG J,HONG F,et al.Melatonin prevents obesity through modulation of gut microbiota in mice[J].Journal of Pineal Research,2017,62(4):e12399.
[69] REN W K,WANG P,YAN J M,et al.Melatonin alleviates weanling stress in mice:involvement of intestinal microbiota[J].Journal of Pineal Research,2017,doi:10.1111/jpi.12448.
[70] ANDERSON G,MAES M.The gut-brain axis:the role of melatonin in linking psychiatric,inflammatory and neurodegenerative conditions[J].Advances in Integrative Medicine,2015,2(1):31-37.