CLC number:
On-line Access: 2022-06-08
Received: 2021-12-01
Revision Accepted: 2022-02-16
Crosschecked: 2022-06-08
Cited: 0
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Citations: Bibtex RefMan EndNote GB/T7714
Jian WANG, Liqian SU, Lun ZHANG, Jiali ZENG, Qingru CHEN, Rui DENG, Ziyan WANG, Weidong KUANG, Xiaobao JIN, Shuiqing GUI, Yinghua XU, Xuemei LU. Spirulina platensis aqueous extracts ameliorate colonic mucosal damage and modulate gut microbiota disorder in mice with ulcerative colitis by inhibiting inflammation and oxidative stress[J]. Journal of Zhejiang University Science B, 2022, 23(6): 481-501.
@article{title="Spirulina platensis aqueous extracts ameliorate colonic mucosal damage and modulate gut microbiota disorder in mice with ulcerative colitis by inhibiting inflammation and oxidative stress",
author="Jian WANG, Liqian SU, Lun ZHANG, Jiali ZENG, Qingru CHEN, Rui DENG, Ziyan WANG, Weidong KUANG, Xiaobao JIN, Shuiqing GUI, Yinghua XU, Xuemei LU",
journal="Journal of Zhejiang University Science B",
volume="23",
number="6",
pages="481-501",
year="2022",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2100988"
}
%0 Journal Article
%T Spirulina platensis aqueous extracts ameliorate colonic mucosal damage and modulate gut microbiota disorder in mice with ulcerative colitis by inhibiting inflammation and oxidative stress
%A Jian WANG
%A Liqian SU
%A Lun ZHANG
%A Jiali ZENG
%A Qingru CHEN
%A Rui DENG
%A Ziyan WANG
%A Weidong KUANG
%A Xiaobao JIN
%A Shuiqing GUI
%A Yinghua XU
%A Xuemei LU
%J Journal of Zhejiang University SCIENCE B
%V 23
%N 6
%P 481-501
%@ 1673-1581
%D 2022
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2100988
TY - JOUR
T1 - Spirulina platensis aqueous extracts ameliorate colonic mucosal damage and modulate gut microbiota disorder in mice with ulcerative colitis by inhibiting inflammation and oxidative stress
A1 - Jian WANG
A1 - Liqian SU
A1 - Lun ZHANG
A1 - Jiali ZENG
A1 - Qingru CHEN
A1 - Rui DENG
A1 - Ziyan WANG
A1 - Weidong KUANG
A1 - Xiaobao JIN
A1 - Shuiqing GUI
A1 - Yinghua XU
A1 - Xuemei LU
J0 - Journal of Zhejiang University Science B
VL - 23
IS - 6
SP - 481
EP - 501
%@ 1673-1581
Y1 - 2022
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2100988
Abstract: ulcerative colitis (UC) is a chronic and recurrent inflammatory bowel disease (IBD) that has become a major gastroenterologic problem during recent decades. Numerous complicating factors are involved in UC development such as oxidative stress, inflammation, and microbiota disorder. These factors exacerbate damage to the intestinal mucosal barrier. Spirulina platensis is a commercial alga with various biological activity that is widely used as a functional ingredient in food and beverage products. However, there have been few studies on the treatment of UC using S. platensis aqueous extracts (SP), and the underlying mechanism of action of SP against UC has not yet been elucidated. Herein, we aimed to investigate the modulatory effect of SP on microbiota disorders in UC mice and clarify the underlying mechanisms by which SP alleviates damage to the intestinal mucosal barrier. Dextran sulfate sodium (DSS) was used to establish a normal human colonic epithelial cell (NCM460) injury model and UC animal model. The mitochondrial membrane potential assay 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and staining with Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) and Hoechst 33258 were carried out to determine the effects of SP on the NCM460 cell injury model. Moreover, hematoxylin and eosin (H&E) staining, transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qPCR), western blot, and 16S ribosomal DNA (rDNA) sequencing were used to explore the effects and underlying mechanisms of action of SP on UC in C57BL/6 mice. In vitro studies showed that SP alleviated DSS-induced NCM460 cell injury. SP also significantly reduced the excessive generation of intracellular reactive oxygen species (ROS) and prevented mitochondrial membrane potential reduction after DSS challenge. In vivo studies indicated that SP administration could alleviate the severity of DSS-induced colonic mucosal damage compared with the control group. Inhibition of inflammation and oxidative stress was associated with increases in the activity of antioxidant enzymes and the expression of tight junction proteins (TJs) post-SP treatment. SP improved gut microbiota disorder mainly by increasing antioxidant enzyme activity and the expression of TJs in the colon. Our findings demonstrate that the protective effect of SP against UC is based on its inhibition of pro-inflammatory cytokine overproduction, inhibition of DSS-induced ROS production, and enhanced expression of antioxidant enzymes and TJs in the colonic mucosal barrier.
[1]AkimotoT, TakasawaA, MurataM, et al., 2016. Analysis of the expression and localization of tight junction transmembrane proteins, claudin-1, -4, -7, occludin and JAM-A, in human cervical adenocarcinoma. Histol Histopathol, 31(8):921-931.
[2]AlwaleedEA, El-SheekhM, Abdel-DaimMM, et al., 2021. Effects of Spirulina platensis and Amphora coffeaeformis as dietary supplements on blood biochemical parameters, intestinal microbial population, and productive performance in broiler chickens. Environ Sci Pollut Res Int, 28(2):1801-1811.
[3]BerruienNNA, SmithCL, 2020. Emerging roles of melanocortin receptor accessory proteins (MRAP and MRAP2) in physiology and pathophysiology. Gene, 757:144949.
[4]BetanzosA, Javier-ReynaR, Garcia-RiveraG, et al., 2013. The EhCPADH112 complex of Entamoeba histolytica interacts with tight junction proteins occludin and claudin-1 to produce epithelial damage. PLoS ONE, 8(6):e65100.
[5]BradleyPP, PriebatDA, ChristensenRD, et al., 1982. Meas
[6]urement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol, 78(3):206-209.
[7]CaniPD, PossemiersS, van de WieleT, et al., 2009. Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut, 58(8):1091-1103.
[8]Castro-OchoaKF, Vargas-RoblesH, Chánez-ParedesS, et al., 2019. Homoectoine protects against colitis by preventing a claudin switch in epithelial tight junctions. Dig Dis Sci, 64(2):409-420.
[9]CiapettiG, CenniE, PratelliL, et al., 1993. In vitro evaluation of cell/biomaterial interaction by MTT assay. Biomaterials, 14(5):359-364.
[10]da CunhaVP, PreisserTM, SantanaMP, et al., 2020. Invasive Lactococcus lactis producing mycobacterial Hsp65 ameliorates intestinal inflammation in acute TNBS-induced colitis in mice by increasing the levels of the cytokine IL-10 and secretory IgA. J Appl Microbiol, 129(5):1389-1401.
[11]DavaatserenM, HwangJT, ParkJH, et al., 2014. Allyl isothiocyanate ameliorates angiogenesis and inflammation in dextran sulfate sodium-induced acute colitis. PLoS ONE, 9(7):e102975.
[12]DingSJ, MaY, LiuG, et al., 2019. Lactobacillus brevis alleviates DSS-induced colitis by reprograming intestinal microbiota and influencing serum metabolome in murine model. Front Physiol, 10:1152.
[13]DobiA, RosanalyS, DevinA, et al., 2021. Advanced glycation end-products disrupt brain microvascular endothelial cell barrier: the role of mitochondria and oxidative stress. Microvasc Res, 133:104098.
[14]EicheleDD, KharbandaKK, 2017. Dextran sodium sulfate colitis murine model: an indispensable tool for advancing our understanding of inflammatory bowel diseases pathogenesis. World J Gastroenterol, 23(33):6016-6029.
[15]EmamieAD, RajabpourM, GhanavatiR, et al., 2021. The effects of probiotics, prebiotics and synbiotics on the reduction of IBD complications, a periodic review during 2009‒2020. J Appl Microbiol, 130(6):1823-1838.
[16]ErayM, MättöM, KaartinenM, et al., 2001. Flow cytometric analysis of apoptotic subpopulations with a combination of annexin V-FITC, propidium iodide, and SYTO 17. Cytometry, 43(2):134-142.
[17]GuinaneCM, CotterPD, 2013. Role of the gut microbiota in health and chronic gastrointestinal disease: understanding a hidden metabolic organ. Therap Adv Gastroenterol, 6(4):295-308.
[18]HalfvarsonJ, BrislawnCJ, LamendellaR, et al., 2017. Dynamics of the human gut microbiome in inflammatory bowel disease. Nat Microbiol, 2(5):17004.
[19]HayesCL, DongJ, GalipeauHJ, et al., 2018. Commensal microbiota induces colonic barrier structure and functions that contribute to homeostasis. Sci Rep, 8:14184.
[20]IdaN, HartmannT, PantelJ, et al., 1996. Analysis of heterogeneous βA4 peptides in human cerebrospinal fluid and blood by a newly developed sensitive western blot assay. J Biol Chem, 271(37):22908-22914.
[21]KaplanGG, 2015. The global burden of IBD: from 2015 to 2025. Nat Rev Gastroenterol Hepatol, 12(12):720-727.
[22]KariyilBJ, AyyappanUPT, GopalakrishnanA, et al., 2021. Chloroform fraction of methanolic extract of seeds of Annona muricata induce S phase arrest and ROS dependent caspase activated mitochondria-mediated apoptosis in triple-negative breast cancer. Anticancer Agents Med Chem, 21(10):1250-1265.
[23]KoseA, OzenMO, ElibolM, et al., 2017. Investigation of in vitro digestibility of dietary microalga Chlorella vulgaris and cyanobacterium Spirulina platensis as a nutritional supplement. 3 Biotech, 7(3):170.
[24]KruidenierL, KuiperI, LamersCB, et al., 2003. Intestinal oxidative damage in inflammatory bowel disease: semi-quantification, localization, and association with mucosal antioxidants. J Pathol, 201(1):28-36.
[25]LaparraJM, SanzY, 2010. Interactions of gut microbiota with functional food components and nutraceuticals. Pharmacol Res, 61(3):219-225.
[26]LiLH, YangF, JiaRJ, et al., 2020. Velvet antler polypeptide prevents the disruption of hepatic tight junctions via inhibiting oxidative stress in cholestatic mice and liver cell lines. Food Funct, 11(11):9752-9763.
[27]LiuQQ, ZengXL, GuanYL, et al., 2020. Verticillin A inhibits colon cancer cell migration and invasion by targeting c-Met. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 21(10):779-795.
[28]LuJ, ChenXN, XuXH, et al., 2019. Active polypeptides from Hirudo inhibit endothelial cell inflammation and macrophage foam cell formation by regulating the LOX-1/LXR-α/ABCA1 pathway. Biomed Pharmacother, 115:108840.
[29]LuoM, LuoY, 2021. Imperatorin relieved ulcerative colitis by regulating the Nrf-2/ARE/HO-1 pathway in rats. Inflammation, 44(2):558-569.
[30]MishraSK, KangJH, KimDK, et al., 2012. Orally administered aqueous extract of Inonotus obliquus ameliorates acute inflammation in dextran sulfate sodium (DSS)-induced colitis in mice. J Ethnopharmacol, 143(2):524-532.
[31]NielsenTS, FredborgM, TheilPK, et al., 2020. Dietary red meat adversely affects disease severity in a pig model of DSS-induced colitis despite reduction in colonic pro-inflammatory gene expression. Nutrients, 12(6):1728.
[32]PardhasaradhiBVV, AliAM, KumariAL, et al., 2003. Phycocyanin-mediated apoptosis in AK-5 tumor cells involves down-regulation of Bcl-2 and generation of ROS. Mol Cancer Ther, 2(11):1165-1170.
[33]ParkJH, LeeSI, KimIH, 2018. Effect of dietary Spirulina (Arthrospira) platensis on the growth performance, antioxidant enzyme activity, nutrient digestibility, cecal microflora, excreta noxious gas emission, and breast meat quality of broiler chickens. Poult Sci, 97(7):2451-2459.
[34]PayneCM, WeberC, Crowley-SkillicornC, et al., 2007. Deoxycholate induces mitochondrial oxidative stress and activates NF-κB through multiple mechanisms in HCT-116 colon epithelial cells. Carcinogenesis,28(1):215-222.
[35]PrasadA, PospisilP, TadaM, 2019. Editorial: reactive oxygen species (ROS) detection methods in biological system. Front Physiol, 10:1316.
[36]RaoXY, HuangXL, ZhouZC, et al., 2013. An improvement of the 2^(-delta delta CT) method for quantitative real-time polymerase chain reaction data analysis. Biostat Bioinforma Biomath, 3(3):71-85.
[37]ReersM, SmileyST, Mottola-HartshornC, et al., 1995. Mitochondrial membrane potential monitored by JC-1 dye. Methods Enzymol, 260:406-414, IN1-IN3, 415-417.
[38]SiddiquiH, NederbragtAJ, LagesenK, et al., 2011. Assessing diversity of the female urine microbiota by high throughput sequencing of 16S rDNA amplicons. BMC Microbiol, 11:244.
[39]SokolH, BeaugerieL, 2010. Body mass index and disease activity at treatment initiation: potential new predictors of response to azathioprine therapy in IBD. Inflamm Bowel Dis, 16(4):714-715.
[40]SpeckmannB, SteinbrennerH, 2014. Selenium and selenoproteins in inflammatory bowel diseases and experimental colitis. Inflamm Bowel Dis, 20(6):1110-1119.
[41]SunY, GeX, LiX, et al., 2020a. High-fat diet promotes renal injury by inducing oxidative stress and mitochondrial dysfunction. Cell Death Dis, 11(10):914.
[42]SunY, LiLW, LaiAY, et al., 2020b. Does ulcerative colitis influence the inter-individual heterogeneity of the human intestinal mucosal microbiome? Evol Bioinform, 16:1176934320948848.
[43]SzulinskaM, Gibas-DornaM, Miller-KasprzakE, et al., 2017. Spirulina maxima improves insulin sensitivity, lipid profile, and total antioxidant status in obese patients with well-treated hypertension: a randomized double-blind placebo-controlled study. Eur Rev Med Pharmacol Sci, 21(10):2473-2481.
[44]TaghipourN, MosaffaN, AghdaeiHA, et al., 2019. Immunomodulatory effect of Syphacia obvelata in treatment of experimental DSS-induced colitis in mouse model. Sci Rep, 9:19127.
[45]TakagiT, NaitoY, UchiyamaK, et al., 2011. Carbon monoxide liberated from carbon monoxide-releasing molecule exerts an anti-inflammatory effect on dextran sulfate sodium-induced colitis in mice. Dig Dis Sci, 56(6):1663-1671.
[46]TsangL, BanerjeeN, TabibianJH, 2019. Bloody diarrhea and weight loss in a patient in remission from ulcerative colitis. Gastroenterology, 157(5):1207-1209.
[47]UnnoN, WangH, MenconiMJ, et al., 1997. Inhibition of inducible nitric oxide synthase ameliorates endotoxin-induced gut mucosal barrier dysfunction in rats. Gastroenterology, 113(4):1246-1257.
[48]VinoloMAR, RodriguesHG, NachbarRT, et al., 2011. Regulation of inflammation by short chain fatty acids. Nutrients, 3(10):858-876.
[49]WargoJA, 2020. Modulating gut microbes. Science, 369(6509):1302-1303.
[50]XuLL, LiuT, WangL, et al., 2018. 3-(1H-Benzo[d]imidazol-6-yl)-5-(4-fluorophenyl)-1,2,4-oxadiazole (DDO7232), a novel potent Nrf2/ARE inducer, ameliorates DSS-induced murine colitis and protects NCM460 cells against oxidative stress via ERK1/2 phosphorylation. Oxid Med Cell Longev, 2018:3271617.
[51]XuePP, WangLF, XuJW, et al., 2020. Temperature-sensitive hydrogel for rectal perfusion improved the therapeutic effect of Kangfuxin liquid on DSS-induced ulcerative colitis mice: the inflammation alleviation and the colonic mucosal barriers repair. Int J Pharm, 589:119846.
[52]YeZH, NingK, AnderBP, et al., 2020. Therapeutic effect of methane and its mechanism in disease treatment. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 21(8):593-602.
[53]YousefiR, SaidpourA, MottaghiA, 2019. The effects of Spirulina supplementation on metabolic syndrome components, its liver manifestation and related inflammatory markers: a systematic review. Complement Ther Med, 42:137-144.
[54]YusufMS, HassanMA, Abdel-DaimMM, et al., 2016. Value added by Spirulina platensis in two different diets on growth performance, gut microbiota, and meat quality of Japanese quails. Vet World, 9(11):1287-1293.
[55]ZarepoorL, LuJT, ZhangC, et al., 2014. Dietary flaxseed intake exacerbates acute colonic mucosal injury and inflammation induced by dextran sodium sulfate. Am J Physiol Gastrointest Liver Physiol, 306(12):G1042-G1055.
[56]ZhangFX, WuWM, DengZY, et al., 2015. High altitude increases the expression of hypoxia-inducible factor 1α and inducible nitric oxide synthase with intestinal mucosal barrier failure in rats. Int J Clin Exp Pathol, 8(5):5189-5195.
[57]ZhangL, GuiSQ, LiangZB, et al., 2019. Musca domestica cecropin (Mdc) alleviates Salmonella typhimurium-induced colonic mucosal barrier impairment: associating with inflammatory and oxidative stress response, tight junction as well as intestinal flora. Front Microbiol, 10:522.
[58]ZhangL, GuiSQ, XuYH, et al., 2021. Colon tissue-accumulating mesoporous carbon nanoparticles loaded with Musca domestica cecropin for ulcerative colitis therapy. Theranostics, 11(7):3417-3438.
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