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A comprehensive review and update on the pathogenesis of inflammatory bowel disease. <i>J. Immunol. Res.<\/i>, <b>2019<\/b>, 7247238 (2019).","DOI":"10.1155\/2019\/7247238"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2) Bopanna S, Ananthakrishnan AN, Kedia S, Yajnik V, Ahuja V. Risk of colorectal cancer in Asian patients with ulcerative colitis: a systematic review and meta-analysis. <i>Lancet Gastroenterol. Hepatol.<\/i>, <b>2<\/b>, 269\u2013276 (2017).","DOI":"10.1016\/S2468-1253(17)30004-3"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3) Ungaro R, Mehandru S, Allen PB, Peyrin-Biroulet L, Colombel JF. Ulcerative colitis. <i>Lancet<\/i>, <b>389<\/b>, 1756\u20131770 (2017).","DOI":"10.1016\/S0140-6736(16)32126-2"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4) Yu C, Zhang S, Wang Y, Zhang S, Luo L, Thorlacius H. Platelet-derived CCL5 regulates CXC chemokine formation and neutrophil recruitment in acute experimental colitis. <i>J. Cell. Physiol.<\/i>, <b>231<\/b>, 370\u2013376 (2016).","DOI":"10.1002\/jcp.25081"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5) Kayal M, Shah S. Ulcerative colitis: current and emerging treatment strategies. <i>J. Clin. Med.<\/i>, <b>9<\/b>, 94 (2019).","DOI":"10.3390\/jcm9010094"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6) He G, Wang X, Liu W, Li Y, Shao Y, Liu W, Liang X, Bao X. Chemical constituents, pharmacological effects, toxicology, processing and compatibility of Fuzi (lateral root of Aconitum carmichaelii Debx): a review. <i>J. Ethnopharmacol.<\/i>, <b>307<\/b>, 116160 (2023).","DOI":"10.1016\/j.jep.2023.116160"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7) Zhang Z, Yang S, Lin X, Huang Y, Wei X, Zhou J, Li R, Deng B, Fu C. Metabolomics of Spleen-Yang deficiency syndrome and the therapeutic effect of Fuzi Lizhong pill on regulating endogenous metabolism. <i>J. Ethnopharmacol.<\/i>, <b>278<\/b>, 114281 (2021).","DOI":"10.1016\/j.jep.2021.114281"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8) Zhang Z, Jiang M, Wei X, Shi J, Geng Z, Yang S, Fu C, Guo L. Rapid discovery of chemical constituents and absorbed components in rat serum after oral administration of Fuzi-Lizhong pill based on high-throughput HPLC-Q-TOF\/MS analysis. <i>Chin. Med.<\/i>, <b>14<\/b>, 6 (2019).","DOI":"10.1186\/s13020-019-0227-z"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9) Huang C, Dong J, Jin X, Ma H, Zhang D, Wang F, Cheng L, Feng Y, Xiong X, Jiang J, Hu L, Lei M, Wu B, Zhang G. Intestinal anti-inflammatory effects of fuzi-ganjiang herb pair against DSS-induced ulcerative colitis in mice. <i>J. Ethnopharmacol.<\/i>, <b>261<\/b>, 112951 (2020).","DOI":"10.1016\/j.jep.2020.112951"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10) Kosuge T, Yokota M. Studies on cardiac principle of aconite root. <i>Chem. Pharm. Bull.<\/i>, <b>24<\/b>, 176\u2013178 (1976).","DOI":"10.1248\/cpb.24.176"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11) Duan W, Chen J, Wu Y, Zhang Y, Xu Y. Protective effect of higenamine ameliorates collagen-induced arthritis through heme oxygenase-1 and PI3K\/Akt\/Nrf-2 signaling pathways. <i>Exp. Ther. Med.<\/i>, <b>12<\/b>, 3107\u20133112 (2016).","DOI":"10.3892\/etm.2016.3730"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12) Jin C, Chai Y, Hu Z, Tian W, Ling W, Li J, Wu M. Higenamine attenuates doxorubicin-induced cardiac remodeling and myocyte apoptosis by suppressing AMPK activation. <i>Front. Cell Dev. Biol.<\/i>, <b>10<\/b>, 809996 (2022).","DOI":"10.3389\/fcell.2022.809996"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13) Liu C, Zhu C, Wang G, Xu R, Zhu Y. Higenamine regulates Nrf2-HO-1-Hmgb1 axis and attenuates intestinal ischemia-reperfusion injury in mice. <i>Inflamm. Res.<\/i>, <b>64<\/b>, 395\u2013403 (2015).","DOI":"10.1007\/s00011-015-0817-x"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14) Ru J, Li P, Wang J, Zhou W, Li B, Huang C, Li P, Guo Z, Tao W, Yang Y, Xu X, Li Y, Wang Y, Yang L. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. <i>J. Cheminform.<\/i>, <b>6<\/b>, 13 (2014).","DOI":"10.1186\/1758-2946-6-13"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15) Liu X, Ouyang S, Yu B, Liu Y, Huang K, Gong J, Zheng S, Li Z, Li H, Jiang H. PharmMapper server: a web server for potential drug target identification using pharmacophore mapping approach. <i>Nucleic Acids Res.<\/i>, <b>38<\/b> (suppl._2), W609\u201314 (2010).","DOI":"10.1093\/nar\/gkq300"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16) Szklarczyk D, Santos A, von Mering C, Jensen LJ, Bork P, Kuhn M. STITCH 5: augmenting protein-chemical interaction networks with tissue and affinity data. <i>Nucleic Acids Res.<\/i>, <b>44<\/b> (D1), D380\u2013D384 (2016).","DOI":"10.1093\/nar\/gkv1277"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17) Li YH, Yu CY, Li XX, Zhang P, Tang J, Yang Q, Fu T, Zhang X, Cui X, Tu G, Zhang Y, Li S, Yang F, Sun Q, Qin C, Zeng X, Chen Z, Chen YZ, Zhu F. Therapeutic target database update 2018: enriched resource for facilitating bench-to-clinic research of targeted therapeutics. <i>Nucleic Acids Res.<\/i>, <b>46<\/b> (D1), D1121\u2013D1127 (2018).","DOI":"10.1093\/nar\/gkx1076"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18) Liu Y, Grimm M, Dai WT, Hou MC, Xiao ZX, Cao Y. CB-Dock: a web server for cavity detection-guided protein-ligand blind docking. <i>Acta Pharmacol. Sin.<\/i>, <b>41<\/b>, 138\u2013144 (2020).","DOI":"10.1038\/s41401-019-0228-6"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19) Dann SM, Spehlmann ME, Hammond DC, Iimura M, Hase K, Choi LJ, Hanson E, Eckmann L. IL-6-dependent mucosal protection prevents establishment of a microbial niche for attaching\/effacing lesion-forming enteric bacterial pathogens. <i>J. Immunol.<\/i>, <b>180<\/b>, 6816\u20136826 (2008).","DOI":"10.4049\/jimmunol.180.10.6816"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20) Kangwan N, Kongkarnka S, Pintha K, Saenjum C, Suttajit M. Protective effect of red rice extract rich in proanthocyanidins in a murine colitis model. <i>Biomedicines<\/i>, <b>11<\/b>, 265 (2023).","DOI":"10.3390\/biomedicines11020265"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21) Chen L, Zhang C, Cao J, Bei G, Wang X, Miao Z. Yiyi fuzi baijiang decoction alleviates ulcerative colitis partly by regulating TLR4-mediated PI3K\/Akt and NF-kappaB pathways. <i>Evid. Based Complement. Alternat. Med.<\/i>, <b>2022<\/b>, 8780514 (2022).","DOI":"10.1155\/2022\/8780514"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22) Wang J, Zhang Z, Fang A, Wu K, Chen X, Wang G, Mao F. Resveratrol attenuates inflammatory bowel disease in mice by regulating SUMO1. <i>Biol. Pharm. Bull.<\/i>, <b>43<\/b>, 450\u2013457 (2020).","DOI":"10.1248\/bpb.b19-00786"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23) Murakami S, Tasaka Y, Takatori S, Tanaka A, Kawasaki H, Araki H. Effect of Eucommia ulmoides leaf extract on chronic dextran sodium sulfate-induced colitis in mice. <i>Biol. Pharm. Bull.<\/i>, <b>41<\/b>, 864\u2013868 (2018).","DOI":"10.1248\/bpb.b17-00878"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24) Luchini AC, Rodrigues-Orsi P, Cestari SH, Seito LN, Witaicenis A, Pellizzon CH, Di Stasi LC. Intestinal anti-inflammatory activity of coumarin and 4-hydroxycoumarin in the trinitrobenzenesulphonic acid model of rat colitis. <i>Biol. Pharm. Bull.<\/i>, <b>31<\/b>, 1343\u20131350 (2008).","DOI":"10.1248\/bpb.31.1343"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25) Kageyama-Yahara N, Wang P, Wang X, Yamamoto T, Kadowaki M. The inhibitory effect of ergosterol, a bioactive constituent of a traditional Japanese herbal medicine saireito on the activity of mucosal-type mast cells. <i>Biol. Pharm. Bull.<\/i>, <b>33<\/b>, 142\u2013145 (2010).","DOI":"10.1248\/bpb.33.142"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26) Chen DT, Rao W, Shen X, Chen L, Wan ZJ, Sheng XP, Fan TY. Pharmacological effects of higenamine based on signalling pathways and mechanism of action. <i>Front. Pharmacol.<\/i>, <b>13<\/b>, 981048 (2022).","DOI":"10.3389\/fphar.2022.981048"},{"key":"27","doi-asserted-by":"crossref","unstructured":"27) Wei X, Zhang B, Liang X, Liu C, Xia T, Xie Y, Deng X, Tan X. Higenamine alleviates allergic rhinitis by activating AKT1 and suppressing the EGFR\/JAK2\/c-JUN signaling. <i>Phytomedicine<\/i>, <b>86<\/b>, 153565 (2021).","DOI":"10.1016\/j.phymed.2021.153565"},{"key":"28","doi-asserted-by":"crossref","unstructured":"28) Yang S, Chu S, Ai Q, Zhang Z, Gao Y, Lin M, Liu Y, Hu Y, Li X, Peng Y, Pan Y, He Q, Chen N. Anti-inflammatory effects of higenamine (Hig) on LPS-activated mouse microglia (BV2) through NF-kappaB and Nrf2\/HO-1 signaling pathways. <i>Int. Immunopharmacol.<\/i>, <b>85<\/b>, 106629 (2020).","DOI":"10.1016\/j.intimp.2020.106629"},{"key":"29","doi-asserted-by":"crossref","unstructured":"29) Shao XX, Xu Y, Xiao HY, Hu Y, Jiang Y. Higenamine improves DSS-induced ulcerative colitis in mice through the Galectin-3\/TLR4\/NF-kappaB pathway. <i>Tissue Cell<\/i>, <b>82<\/b>, 102111 (2023).","DOI":"10.1016\/j.tice.2023.102111"},{"key":"30","doi-asserted-by":"crossref","unstructured":"30) S\u00e1nchez de Medina F, Romero-Calvo I, Mascaraque C, Mart\u00ednez-Augustin O. Intestinal inflammation and mucosal barrier function. <i>Inflamm. Bowel Dis.<\/i>, <b>20<\/b>, 2394\u20132404 (2014).","DOI":"10.1097\/MIB.0000000000000204"},{"key":"31","doi-asserted-by":"crossref","unstructured":"31) Chen SJ, Liu XW, Liu JP, Yang XY, Lu FG. Ulcerative colitis as a polymicrobial infection characterized by sustained broken mucus barrier. <i>World J. Gastroenterol.<\/i>, <b>20<\/b>, 9468\u20139475 (2014).","DOI":"10.3748\/wjg.v20.i28.9468"},{"key":"32","doi-asserted-by":"crossref","unstructured":"32) Kawashima H. Roles of the gel-forming MUC2 mucin and its O-glycosylation in the protection against colitis and colorectal cancer. <i>Biol. Pharm. Bull.<\/i>, <b>35<\/b>, 1637\u20131641 (2012).","DOI":"10.1248\/bpb.b12-00412"},{"key":"33","doi-asserted-by":"crossref","unstructured":"33) Dharmani P, Srivastava V, Kissoon-Singh V, Chadee K. Role of intestinal mucins in innate host defense mechanisms against pathogens. <i>J. Innate Immun<\/i>., <b>1<\/b>, 123\u2013135 (2009).","DOI":"10.1159\/000163037"},{"key":"34","doi-asserted-by":"crossref","unstructured":"34) Turner JR. Intestinal mucosal barrier function in health and disease. <i>Nat. Rev. Immunol.<\/i>, <b>9<\/b>, 799\u2013809 (2009).","DOI":"10.1038\/nri2653"},{"key":"35","doi-asserted-by":"crossref","unstructured":"35) Chen HQ, Yang J, Zhang M, Zhou YK, Shen TY, Chu ZX, Zhang M, Hang XM, Jiang YQ, Qin HL. Lactobacillus plantarum ameliorates colonic epithelial barrier dysfunction by modulating the apical junctional complex and PepT1 in IL-10 knockout mice. <i>Am. J. Physiol. Gastrointest. Liver Physiol<\/i>., 1165, G1287\u2013G1297 (2010).","DOI":"10.1152\/ajpgi.00196.2010"},{"key":"36","doi-asserted-by":"crossref","unstructured":"36) Schulzke JD, Ploeger S, Amasheh M, Fromm A, Zeissig S, Troeger H, Richter J, Bojarski C, Schumann M, Fromm M. Epithelial tight junctions in intestinal inflammation. <i>Ann. N. Y. Acad. Sci.<\/i>, <b>1165<\/b>, 294\u2013300 (2009).","DOI":"10.1111\/j.1749-6632.2009.04062.x"},{"key":"37","doi-asserted-by":"crossref","unstructured":"37) Huang E, Liu R, Lu Z, Liu J, Liu X, Zhang D, Chu Y. NKT cells mediate the recruitment of neutrophils by stimulating epithelial chemokine secretion during colitis. <i>Biochem. Biophys. Res. Commun.<\/i>, <b>474<\/b>, 252\u2013258 (2016).","DOI":"10.1016\/j.bbrc.2016.04.024"},{"key":"38","doi-asserted-by":"crossref","unstructured":"38) Park S, Abdi T, Gentry M, Laine L. Histological disease activity as a predictor of clinical relapse among patients with ulcerative colitis: systematic review and meta-analysis. <i>Am. J. Gastroenterol.<\/i>, <b>111<\/b>, 1692\u20131701 (2016).","DOI":"10.1038\/ajg.2016.418"},{"key":"39","doi-asserted-by":"crossref","unstructured":"39) Huang XL, Xu J, Zhang XH, Qiu BY, Peng L, Zhang M, Gan HT. PI3K\/Akt signaling pathway is involved in the pathogenesis of ulcerative colitis. <i>Inflamm. Res.<\/i>, <b>60<\/b>, 727\u2013734 (2011).","DOI":"10.1007\/s00011-011-0325-6"},{"key":"40","doi-asserted-by":"crossref","unstructured":"40) Wu MP, Zhang YS, Zhou QM, Xiong J, Dong YR, Yan C. Higenamine protects ischemia\/reperfusion induced cardiac injury and myocyte apoptosis through activation of beta2-AR\/PI3K\/AKT signaling pathway. <i>Pharmacol. 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