Skip to content
2000
image of Natural Product-based Therapies for Inflammatory Bowel Disease: Targeting Key Signaling Pathways

Abstract

Inflammatory Bowel Disease (IBD), which includes ulcerative colitis and Crohn’s disease, accounts for chronic inflammation in the entire gastrointestinal tract. Conventional treatments, such as amino salicylates, corticosteroids, immunomodulators, and biologics, can all alleviate symptoms; however, they may cause unwanted side effects and are extremely expensive. Most of the time, long-term treatment is also less effective. This review aims to discuss natural products (NPs) with therapeutic potential for IBD, emphasizing flavonoids, terpenoids, polysaccharides, and alkaloids. The compounds have been chosen based on literature reporting anti-inflammatory, antioxidative, and immunomodulatory activities that relate to IBD pathophysiology. Preclinical evidence using and models and available clinical data provides the basis for the main pharmacological effects, mechanisms of action, and safety profiles of these NPs. The key molecular pathways that are targeted include the NF-κB, MAPK, and JAK/STAT signaling pathways, as well as the establishment of the gut microbiota and intestinal barrier functions. Standardization, bioavailability, and maximal dosing remain challenging issues even when experimental models show promising results for various NPs. Hence, this review stresses the urgency for well-designed clinical trials and suitable formulation approaches to translate these observations into efficacious and evidence-based therapies. Being a natural remedy option, NPs could be considered complementary or alternative treatments for IBD, demanding further interrogation within an integrated therapeutic paradigm.

Loading

Article metrics loading...

/content/journals/mrmc/10.2174/0113895575405061250923110348
2025-10-15
2025-11-08
Loading full text...

Full text loading...

References

  1. Park S.C. Jeen Y.T. Genetic studies of inflammatory bowel disease-focusing on Asian patients. Cells 2019 8 5 404 10.3390/cells8050404 31052430
    [Google Scholar]
  2. Larabi A. Barnich N. Nguyen H.T.T. New insights into the interplay between autophagy, gut microbiota and inflammatory responses in IBD. Autophagy 2020 16 1 38 51 10.1080/15548627.2019.1635384 31286804
    [Google Scholar]
  3. Lee M. Chang E.B. Inflammatory bowel diseases (IBD) and the microbiome—searching the crime scene for clues. Gastroenterology 2021 160 2 524 537 10.1053/j.gastro.2020.09.056 33253681
    [Google Scholar]
  4. Alatab, S.; Sepanlou, S.G.; Ikuta, K.; Vahedi, H.; Bisignano, C.; Safiri, S.; Sadeghi, A.; Nixon, M.R.; Abdoli, A.; Abolhassani, H.; Alipour, V.; Almadi, M.A.H.; Almasi-Hashiani, A.; Anushiravani, A.; Arabloo, J.; Atique, S.; Awasthi, A.; Badawi, A.; Baig, A.A.A.; Bhala, N.; Bijani, A.; Biondi, A.; Borzì, A.M.; Burke, K.E.; Carvalho, F.; Daryani, A.; Dubey, M.; Eftekhari, A.; Fernandes, E.; Fernandes, J.C.; Fischer, F.; Haj-Mirzaian, A.; Haj-Mirzaian, A.; Hasanzadeh, A.; Hashemian, M.; Hay, S.I.; Hoang, C.L.; Househ, M.; Ilesanmi, O.S.; Jafari Balalami, N.; James, S.L.; Kengne, A.P.; Malekzadeh, M.M.; Merat, S.; Meretoja, T.J.; Mestrovic, T.; Mirrakhimov, E.M.; Mirzaei, H.; Mohammad, K.A.; Mokdad, A.H.; Monasta, L.; Negoi, I.; Nguyen, T.H.; Nguyen, C.T.; Pourshams, A.; Poustchi, H.; Rabiee, M.; Rabiee, N.; Ramezanzadeh, K.; Rawaf, D.L.; Rawaf, S.; Rezaei, N.; Robinson, S.R.; Ronfani, L.; Saxena, S.; Sepehrimanesh, M.; Shaikh, M.A.; Sharafi, Z.; Sharif, M.; Siabani, S.; Sima, A.R.; Singh, J.A.; Soheili, A.; Sotoudehmanesh, R.; Suleria, H.A.R.; Tesfay, B.E.; Tran, B.; Tsoi, D.; Vacante, M.; Wondmieneh, A.B.; Zarghi, A.; Zhang, Z-J.; Dirac, M.; Malekzadeh, R.; Naghavi, M.The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990–2017: A systematic analysis for the global burden of disease study 2017. Lancet Gastroenterol. Hepatol., 2020, 5(1), 17-30.GBD 2017 Inflammatory Bowel Disease Collaborators. 2020 10.1016/S2468‑1253(19)30333‑4] 31648971
    [Google Scholar]
  5. Molodecky N.A. Soon I.S. Rabi D.M. Ghali W.A. Ferris M. Chernoff G. Benchimol E.I. Panaccione R. Ghosh S. Barkema H.W. Kaplan G.G. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 2012 142 1 46 54.e42 10.1053/j.gastro.2011.10.001 22001864
    [Google Scholar]
  6. Mak W.Y. Zhao M. Ng S.C. Burisch J. The epidemiology of inflammatory bowel disease: East meets west. J. Gastroenterol. Hepatol. 2020 35 3 380 389 10.1111/jgh.14872 31596960
    [Google Scholar]
  7. Kotze P.G. Underwood F.E. Damião A.O.M.C. Ferraz J.G.P. Saad-Hossne R. Toro M. Iade B. Bosques-Padilla F. Teixeira F.V. Juliao-Banos F. Simian D. Ghosh S. Panaccione R. Ng S.C. Kaplan G.G. Progression of inflammatory bowel diseases throughout Latin America and the Caribbean: A systematic review. Clin. Gastroenterol. Hepatol. 2020 18 2 304 312 10.1016/j.cgh.2019.06.030 31252191
    [Google Scholar]
  8. Verstockt B. Ferrante M. Vermeire S. Van Assche G. New treatment options for inflammatory bowel diseases. J. Gastroenterol. 2018 53 5 585 590 10.1007/s00535‑018‑1449‑z 29556726
    [Google Scholar]
  9. Kennedy N.A. Heap G.A. Green H.D. Hamilton B. Bewshea C. Walker G.J. Thomas A. Nice R. Perry M.H. Bouri S. Chanchlani N. Heerasing N.M. Hendy P. Lin S. Gaya D.R. Cummings J.R.F. Selinger C.P. Lees C.W. Hart A.L. Parkes M. Sebastian S. Mansfield J.C. Irving P.M. Lindsay J. Russell R.K. McDonald T.J. McGovern D. Goodhand J.R. Ahmad T. Patel V. Mazhar Z. Saich R. Colleypriest B. Tham T.C. Iqbal T.H. Kaushik V. Murugesan S. Singh S. Weaver S. Preston C. Butt A. Smith M. Basude D. Beale A. Langlands S. Direkze N. Parkes M. Torrente F. De La Revella Negro J. MacDonald C.E. Evans S.M. Gunasekera A.V.J. Thakur A. Elphick D. Shenoy A. Nwokolo C.U. Dhar A. Cole A.T. Agrawal A. Bridger S. Doherty J. Cooper S.C. de Silva S. Mowat C. Mayhead P. Lees C. Jones G. Ahmad T. Hart J.W. Gaya D.R. Russell R.K. Gervais L. Dunckley P. Mahmood T. Banim P.J.R. Sonwalkar S. Ghosh D. Phillips R.H. Azaz A. Sebastian S. Shenderey R. Armstrong L. Bell C. Hariraj R. Matthews H. Jafferbhoy H. Selinger C.P. Zamvar V. De Caestecker J.S. Willmott A. Miller R. Babu P.S. Tzivinikos C. Bloom S.L. Chung-Faye G. Croft N.M. Fell J.M.E. Harbord M. Hart A. Hope B. Irving P.M. Lindsay J.O. Mawdsley J.E. McNair A. Monahan K.J. Murray C.D. Orchard T. Paul T. Pollok R. Shah N. Bouri S. Johnson M.W. Modi A. Kabiru K.D. Baburajan B.K. Bhaduri B. Fagbemi A.A. Levison S. Limdi J.K. Watts G. Foley S. Ramadas A. MacFaul G. Mansfield J. Grellier L. Morris M-A. Tremelling M. Hawkey C. Kirkham S. Charlton C.P.J. Rodrigues A. Simmons A. Lewis S.J. Snook J. Tighe M. Goggin P.M. De Silva A.N. Lal S. Smith M.S. Panter S. Cummings J.R.F. Dharmisari S. Carter M. Watts D. Mahmood Z. McLain B. Sen S. Pigott A.J. Hobday D. Wesley E. Johnston R. Edwards C. Beckly J. Vani D. Ramakrishnan S. Chaudhary R. Trudgill N.J. Cooney R. Bell A. Prasad N. Gordon J.N. Brookes M.J. Li A. Gore S. Predictors of anti-TNF treatment failure in anti-TNF-naive patients with active luminal Crohn’s disease: A prospective, multicentre, cohort study. Lancet Gastroenterol. Hepatol. 2019 4 5 341 353 UK Inflammatory Bowel Disease Pharmacogenetics Study Group. 10.1016/S2468‑1253(19)30012‑3 30824404
    [Google Scholar]
  10. Danese S. Furfaro F. Vetrano S. Targeting S1P in inflammatory bowel disease: new avenues for modulating intestinal leukocyte migration. J. Crohn’s Colitis 2018 12 Suppl. 2 S678 S686 10.1093/ecco‑jcc/jjx107 28961752
    [Google Scholar]
  11. Zaidun N.H. Thent Z.C. Latiff A.A. Combating oxidative stress disorders with citrus flavonoid: Naringenin. Life Sci. 2018 208 111 122 10.1016/j.lfs.2018.07.017 30021118
    [Google Scholar]
  12. Den Hartogh D.J. Tsiani E. Antidiabetic properties of naringenin: A citrus fruit polyphenol. Biomolecules 2019 9 3 99 10.3390/biom9030099 30871083
    [Google Scholar]
  13. Pinho-Ribeiro F.A. Zarpelon A.C. Fattori V. Manchope M.F. Mizokami S.S. Casagrande R. Verri W.A. Naringenin reduces inflammatory pain in mice. Neuropharmacology 2016 105 508 519 10.1016/j.neuropharm.2016.02.019 26907804
    [Google Scholar]
  14. Zeng W. Jin L. Zhang F. Zhang C. Liang W. Naringenin as a potential immunomodulator in therapeutics. Pharmacol. Res. 2018 135 122 126 10.1016/j.phrs.2018.08.002 30081177
    [Google Scholar]
  15. Zobeiri M. Belwal T. Parvizi F. Naseri R. Farzaei M.H. Nabavi S.F. Sureda A. Nabavi S.M. Naringenin and its nano-formulations for fatty liver: Cellular modes of action and clinical perspective. Curr. Pharm. Biotechnol. 2018 19 3 196 205 10.2174/1389201019666180514170122 29766801
    [Google Scholar]
  16. Dou W. Zhang J. Sun A. Zhang E. Ding L. Mukherjee S. Wei X. Chou G. Wang Z.T. Mani S. Protective effect of naringenin against experimental colitis via suppression of toll-like receptor 4/NF-κB signalling. Br. J. Nutr. 2013 110 4 599 608 10.1017/S0007114512005594 23506745
    [Google Scholar]
  17. Fathima A. Rao J.R. Selective toxicity of Catechin—A natural flavonoid towards bacteria. Appl. Microbiol. Biotechnol. 2016 100 14 6395 6402 10.1007/s00253‑016‑7492‑x 27052380
    [Google Scholar]
  18. Martínez Leal J. Valenzuela Suárez L. Jayabalan R. Huerta Oros J. Escalante-Aburto A. A review on health benefits of kombucha nutritional compounds and metabolites. CYTA J. Food 2018 16 1 390 399 10.1080/19476337.2017.1410499
    [Google Scholar]
  19. Cardoso R.R. Neto R.O. dos Santos D’Almeida C.T. do Nascimento T.P. Pressete C.G. Azevedo L. Martino H.S.D. Cameron L.C. Ferreira M.S.L. Barros F.A.R. Kombuchas from green and black teas have different phenolic profile, which impacts their antioxidant capacities, antibacterial and antiproliferative activities. Food Res. Int. 2020 128 108782 10.1016/j.foodres.2019.108782 31955755
    [Google Scholar]
  20. Mascia C. Maina M. Chiarpotto E. Leonarduzzi G. Poli G. Biasi F. Proinflammatory effect of cholesterol and its oxidation products on CaCo-2 human enterocyte-like cells: Effective protection by epigallocatechin-3-gallate. Free Radic. Biol. Med. 2010 49 12 2049 2057 10.1016/j.freeradbiomed.2010.09.033 20923702
    [Google Scholar]
  21. Sergent T. Piront N. Meurice J. Toussaint O. Schneider Y.J. Anti-inflammatory effects of dietary phenolic compounds in an in vitro model of inflamed human intestinal epithelium. Chem. Biol. Interact. 2010 188 3 659 667 10.1016/j.cbi.2010.08.007 20816778
    [Google Scholar]
  22. Bing X. Xuelei L. Wanwei D. Linlang L. Keyan C. EGCG maintains Th1/Th2 balance and mitigates ulcerative colitis induced by dextran sulfate sodium through TLR4/MyD88/NF‐κB signaling pathway in rats. Can. J. Gastroenterol. Hepatol. 2017 2017 1 1 9 10.1155/2017/3057268 29404307
    [Google Scholar]
  23. Chen Y. Le T.H. Du Q. Zhao Z. Liu Y. Zou J. Hua W. Liu C. Zhu Y. Genistein protects against DSS-induced colitis by inhibiting NLRP3 inflammasome via TGR5-cAMP signaling. Int. Immunopharmacol. 2019 71 144 154 10.1016/j.intimp.2019.01.021 30901677
    [Google Scholar]
  24. Xue B. Xie J. Huang J. Chen L. Gao L. Ou S. Wang Y. Peng X. Plant polyphenols alter a pathway of energy metabolism by inhibiting fecal Bacteroidetes and Firmicutes in vitro. Food Funct. 2016 7 3 1501 1507 10.1039/C5FO01438G 26882962
    [Google Scholar]
  25. Bitzer Z.T. Elias R.J. Vijay-Kumar M. Lambert J.D. (‐)‐Epigallocatechin‐3‐gallate decreases colonic inflammation and permeability in a mouse model of colitis, but reduces macronutrient digestion and exacerbates weight loss. Mol. Nutr. Food Res. 2016 60 10 2267 2274 10.1002/mnfr.201501042 27218415
    [Google Scholar]
  26. Guan F. Liu A.B. Li G. Yang Z. Sun Y. Yang C.S. Ju J. Deleterious effects of high concentrations of (-)-epigallocatechin-3-gallate and atorvastatin in mice with colon inflammation. Nutr. Cancer 2012 64 6 847 855 10.1080/01635581.2012.695424 22716294
    [Google Scholar]
  27. Dryden G.W. Lam A. Beatty K. Qazzaz H.H. McClain C.J. A pilot study to evaluate the safety and efficacy of an oral dose of (-)-epigallocatechin-3-gallate-rich polyphenon E in patients with mild to moderate ulcerative colitis. Inflamm. Bowel Dis. 2013 19 9 1 10.1097/MIB.0b013e31828f5198 23846486
    [Google Scholar]
  28. Liu D. Wu J. Xie H. Liu M. Takau I. Zhang H. Xiong Y. Xia C. Inhibitory effect of hesperetin and on human UDP-glucuronosyltransferase enzymes: Implications for herb–drug interactions. Biol. Pharm. Bull. 2016 39 12 2052 2059 10.1248/bpb.b16‑00581 27904048
    [Google Scholar]
  29. Shirzad M. Heidarian E. Beshkar P. Gholami-Arjenaki M. Biological effects of hesperetin on interleukin-6/phosphorylated signal transducer and activator of transcription 3 pathway signaling in prostate cancer PC3 cells. Pharmacognosy Res. 2017 9 2 188 194 28539744
    [Google Scholar]
  30. González-Alfonso J. Míguez N. Padilla J. Leemans L. Poveda A. Jiménez-Barbero J. Ballesteros A. Sandoval G. Plou F. Optimization of regioselective α-glucosylation of hesperetin catalyzed by cyclodextrin glucanotransferase. Molecules 2018 23 11 2885 10.3390/molecules23112885 30400664
    [Google Scholar]
  31. Parhiz H. Roohbakhsh A. Soltani F. Rezaee R. Iranshahi M. Antioxidant and anti-inflammatory properties of the citrus flavonoids hesperidin and hesperetin: An updated review of their molecular mechanisms and experimental models. Phytother. Res. 2015 29 3 323 331 10.1002/ptr.5256 25394264
    [Google Scholar]
  32. Alu’datt M.H. Rababah T. Alhamad M.N. Al-Mahasneh M.A. Ereifej K. Al-Karaki G. Al-Duais M. Andrade J.E. Tranchant C.C. Kubow S. Ghozlan K.A. Profiles of free and bound phenolics extracted from Citrus fruits and their roles in biological systems: Content, and antioxidant, anti-diabetic and anti-hypertensive properties. Food Funct. 2017 8 9 3187 3197 10.1039/C7FO00212B 28805834
    [Google Scholar]
  33. Chen F. Yin Y. Liu Y. Liu X. Liu F. Zhang X. Zhao H. Liu D. Oxymatrine alleviates the inflammatory damage and its mechanism in rats with TNBS-induced colitis. Xi bao yu fen zi Mian yi xue za zhi= Chinese. J. Cell. Mol. Immunol. 2019 35 1 1 5
    [Google Scholar]
  34. Li Q. Miao Z. Wang R. Yang J. Zhang D. Hesperetin induces apoptosis in human glioblastoma cells via p38 MAPK activation. Nutr. Cancer 2020 72 3 538 545 10.1080/01635581.2019.1638424 31295040
    [Google Scholar]
  35. Elhennawy M.G. Abdelaleem E.A. Zaki A.A. Mohamed W.R. Cinnamaldehyde and hesperetin attenuate TNBS‐induced ulcerative colitis in rats through modulation of the JAk2/STAT3/SOCS3 pathway. J. Biochem. Mol. Toxicol. 2021 35 5 e22730 10.1002/jbt.22730 33522063
    [Google Scholar]
  36. Polat F.R. Karaboğa I. Polat M.S. Erboğa Z. Yilmaz A. Güzel S. Effect of hesperetin on inflammatory and oxidative status in trinitrobenzene sulfonic acid-induced experimental colitis model. Cell. Mol. Biol. 2018 64 11 58 65 10.14715/cmb/2018.64.11.11 30213290
    [Google Scholar]
  37. Guazelli C.F.S. Fattori V. Ferraz C.R. Borghi S.M. Casagrande R. Baracat M.M. Verri W.A. Antioxidant and anti-inflammatory effects of hesperidin methyl chalcone in experimental ulcerative colitis. Chem. Biol. Interact. 2021 333 109315 10.1016/j.cbi.2020.109315 33171134
    [Google Scholar]
  38. Erlund I. Meririnne E. Alfthan G. Aro A. Plasma kinetics and urinary excretion of the flavanones naringenin and hesperetin in humans after ingestion of orange juice and grapefruit juice. J. Nutr. 2001 131 2 235 241 10.1093/jn/131.2.235 11160539
    [Google Scholar]
  39. Ganai A.A. Farooqi H. Bioactivity of genistein: A review of in vitro and in vivo studies. Biomed. Pharmacother. 2015 76 30 38 10.1016/j.biopha.2015.10.026 26653547
    [Google Scholar]
  40. Sahin I. Bilir B. Ali S. Sahin K. Kucuk O. Soy isoflavones in integrative oncology: Increased efficacy and decreased toxicity of cancer therapy. Integr. Cancer Ther. 2019 18 1534735419835310 10.1177/1534735419835310 30897972
    [Google Scholar]
  41. Sefrina L.R. Briawan D. Sinaga T. Permaesih D. Flavonoid database based on Indonesian foods. J. Nutr. Sci. Vitaminol. (Tokyo) 2020 66 Suppl. S251 S255 10.3177/jnsv.66.S251 33612606
    [Google Scholar]
  42. Spagnuolo C. Russo G.L. Orhan I.E. Habtemariam S. Daglia M. Sureda A. Nabavi S.F. Devi K.P. Loizzo M.R. Tundis R. Nabavi S.M. Genistein and cancer: Current status, challenges, and future directions. Adv. Nutr. 2015 6 4 408 419 10.3945/an.114.008052 26178025
    [Google Scholar]
  43. Chen Q. Duan X. Fan H. Xu M. Tang Q. Zhang L. Shou Z. Liu X. Zuo D. Yang J. Deng S. Dong Y. Wu H. Liu Y. Nan Z. Oxymatrine protects against DSS-induced colitis via inhibiting the PI3K/AKT signaling pathway. Int. Immunopharmacol. 2017 53 149 157 10.1016/j.intimp.2017.10.025 29107215
    [Google Scholar]
  44. Abron J.D. Singh N.P. Price R.L. Nagarkatti M. Nagarkatti P.S. Singh U.P. Genistein induces macrophage polarization and systemic cytokine to ameliorate experimental colitis. PLoS One 2018 13 7 e0199631 10.1371/journal.pone.0199631 30024891
    [Google Scholar]
  45. Cao W. Kayama H. Chen M.L. Delmas A. Sun A. Kim S.Y. Rangarajan E.S. McKevitt K. Beck A.P. Jackson C.B. Crynen G. Oikonomopoulos A. Lacey P.N. Martinez G.J. Izard T. Lorenz R.G. Rodriguez-Palacios A. Cominelli F. Abreu M.T. Hommes D.W. Koralov S.B. Takeda K. Sundrud M.S. The xenobiotic transporter Mdr1 enforces T cell homeostasis in the presence of intestinal bile acids. Immunity 2017 47 6 1182 1196.e10 10.1016/j.immuni.2017.11.012 29262351
    [Google Scholar]
  46. Schneider L.S. Hernandez G. Zhao L. Franke A.A. Chen Y.L. Pawluczyk S. Mack W.J. Brinton R.D. Safety and feasibility of estrogen receptor-β targeted phytoSERM formulation for menopausal symptoms: Phase 1b/2a randomized clinical trial. Menopause 2019 26 8 874 884 10.1097/GME.0000000000001325 30889096
    [Google Scholar]
  47. Jaakola L. New insights into the regulation of anthocyanin biosynthesis in fruits. Trends Plant Sci. 2013 18 9 477 483 10.1016/j.tplants.2013.06.003 23870661
    [Google Scholar]
  48. Sui X. Zhang Y. Zhou W. Bread fortified with anthocyanin-rich extract from black rice as nutraceutical sources: Its quality attributes and in vitro digestibility. Food Chem. 2016 196 910 916 10.1016/j.foodchem.2015.09.113 26593572
    [Google Scholar]
  49. Silva S. Costa E.M. Calhau C. Morais R.M. Pintado M.E. Anthocyanin extraction from plant tissues: A review. Crit. Rev. Food Sci. Nutr. 2017 57 14 3072 3083 10.1080/10408398.2015.1087963 26529399
    [Google Scholar]
  50. Fang J. Bioavailability of anthocyanins. Drug Metab. Rev. 2014 46 4 508 520 10.3109/03602532.2014.978080 25347327
    [Google Scholar]
  51. Chun O.K. Chung S.J. Song W.O. Estimated dietary flavonoid intake and major food sources of U.S. adults. J. Nutr. 2007 137 5 1244 1252 10.1093/jn/137.5.1244 17449588
    [Google Scholar]
  52. Del Rio D. Borges G. Crozier A. Berry flavonoids and phenolics: Bioavailability and evidence of protective effects. Br. J. Nutr. 2010 104 S3 S67 S90 10.1017/S0007114510003958 20955651
    [Google Scholar]
  53. Sharma P. McClees S. Afaq F. Pomegranate for prevention and treatment of cancer: An update. Molecules 2017 22 1 177 10.3390/molecules22010177 28125044
    [Google Scholar]
  54. Thumann T.A. Pferschy-Wenzig E.M. Moissl-Eichinger C. Bauer R. The role of gut microbiota for the activity of medicinal plants traditionally used in the European Union for gastrointestinal disorders. J. Ethnopharmacol. 2019 245 112153 10.1016/j.jep.2019.112153 31408679
    [Google Scholar]
  55. Tian L. Tan Y. Chen G. Wang G. Sun J. Ou S. Chen W. Bai W. Metabolism of anthocyanins and consequent effects on the gut microbiota. Crit. Rev. Food Sci. Nutr. 2019 59 6 982 991 10.1080/10408398.2018.1533517 30595029
    [Google Scholar]
  56. Khan M.S. Ikram M. Park J.S. Park T.J. Kim M.O. Gut microbiota, its role in induction of Alzheimer’s disease pathology, and possible therapeutic interventions: Special focus on anthocyanins. Cells 2020 9 4 853 10.3390/cells9040853 32244729
    [Google Scholar]
  57. Peng Y. Yan Y. Wan P. Chen D. Ding Y. Ran L. Mi J. Lu L. Zhang Z. Li X. Zeng X. Cao Y. Gut microbiota modulation and anti-inflammatory properties of anthocyanins from the fruits of Lycium ruthenicum Murray in dextran sodium sulfate-induced colitis in mice. Free Radic. Biol. Med. 2019 136 96 108 10.1016/j.freeradbiomed.2019.04.005 30959170
    [Google Scholar]
  58. Wu L.H. Xu Z.L. Dong D. He S.A. Yu H. Protective effect of anthocyanins extract from blueberry on TNBS‐induced IBD model of mice. Evid. Based Complement. Alternat. Med. 2011 2011 1 525462 10.1093/ecam/neq040 21785630
    [Google Scholar]
  59. Piberger H. Oehme A. Hofmann C. Dreiseitel A. Sand P.G. Obermeier F. Schoelmerich J. Schreier P. Krammer G. Rogler G. Bilberries and their anthocyanins ameliorate experimental colitis. Mol. Nutr. Food Res. 2011 55 11 1724 1729 10.1002/mnfr.201100380 21957076
    [Google Scholar]
  60. Jiao Y.F. Lu M. Zhao Y.P. Liu N. Niu Y.T. Niu Y. Zhou R. Yu J.Q. N-methylcytisine ameliorates dextran-sulfate-sodium-induced colitis in mice by inhibiting the inflammatory response. Molecules 2018 23 3 510 10.3390/molecules23030510 29495327
    [Google Scholar]
  61. Nomi Y. Iwasaki-Kurashige K. Matsumoto H. Therapeutic effects of anthocyanins for vision and eye health. Molecules 2019 24 18 3311 10.3390/molecules24183311 31514422
    [Google Scholar]
  62. Lai Y. Zeng H. He M. Qian H. Wu Z. Luo Z. Xue Y. Yao G. Zhang Y. 6,8-Di-C-methyl-flavonoids with neuroprotective activities from Rhododendron fortunei. Fitoterapia 2016 112 237 243 10.1016/j.fitote.2016.06.008 27345941
    [Google Scholar]
  63. Nishitani Y. Yamamoto K. Yoshida M. Azuma T. Kanazawa K. Hashimoto T. Mizuno M. Intestinal anti‐inflammatory activity of luteolin: Role of the aglycone in NF‐κB inactivation in macrophages co‐cultured with intestinal epithelial cells. Biofactors 2013 39 5 522 533 10.1002/biof.1091 23460110
    [Google Scholar]
  64. Ran X. Li Y. Chen G. Fu S. He D. Huang B. Wei L. Lin Y. Guo Y. Hu G. Farrerol ameliorates TNBS-induced colonic inflammation by inhibiting ERK1/2, JNK1/2, and NF-κB signaling pathway. Int. J. Mol. Sci. 2018 19 7 2037 10.3390/ijms19072037 30011811
    [Google Scholar]
  65. Shi H.J. Song H.B. Wang L. Xiao S.X. Bo K.P. Ma W. The synergy of diammonium glycyrrhizinate remarkably reduces the toxicity of oxymatrine in ICR mice. Biomed. Pharmacother. 2018 97 19 25 10.1016/j.biopha.2017.09.039 29080454
    [Google Scholar]
  66. Tao F. Qian C. Guo W. Luo Q. Xu Q. Sun Y. Inhibition of Th1/Th17 responses via suppression of STAT1 and STAT3 activation contributes to the amelioration of murine experimental colitis by a natural flavonoid glucoside icariin. Biochem. Pharmacol. 2013 85 6 798 807 10.1016/j.bcp.2012.12.002 23261528
    [Google Scholar]
  67. Ju S. Ge Y. Li P. Tian X. Wang H. Zheng X. Ju S. Dietary quercetin ameliorates experimental colitis in mouse by remodeling the function of colonic macrophages via a heme oxygenase-1-dependent pathway. Cell Cycle 2018 17 1 53 63 10.1080/15384101.2017.1387701 28976231
    [Google Scholar]
  68. He C. Wang Z. Shi J. Pharmacological effects of icariin. Adv. Pharmacol. 2020 87 179 203 10.1016/bs.apha.2019.10.004 32089233
    [Google Scholar]
  69. Huang Y. Xing K. Qiu L. Wu Q. Wei H. Therapeutic implications of functional tea ingredients for ameliorating inflammatory bowel disease: A focused review. Crit. Rev. Food Sci. Nutr. 2022 62 19 5307 5321 10.1080/10408398.2021.1884532 33635174
    [Google Scholar]
  70. Liu C. Wang J. Yang Y. Liu X. Zhu Y. Zou J. Peng S. Le T.H. Chen Y. Zhao S. He B. Mi Q. Zhang X. Du Q. Ginsenoside Rd ameliorates colitis by inducing p62-driven mitophagy-mediated NLRP3 inflammasome inactivation in mice. Biochem. Pharmacol. 2018 155 366 379 10.1016/j.bcp.2018.07.010 30012462
    [Google Scholar]
  71. Kim J.K. Kim J.Y. Jang S.E. Choi M.S. Jang H.M. Yoo H.H. Kim D.H. Fermented red ginseng alleviates cyclophosphamide-induced immunosuppression and 2, 4, 6-trinitrobenzenesulfonic acid-induced colitis in mice by regulating macrophage activation and T cell differentiation. Am. J. Chin. Med. 2018 46 8 1879 1897 10.1142/S0192415X18500945 30518233
    [Google Scholar]
  72. Xu L. Zhang Y. Xue X. Liu J. Li Z.S. Yang G.Y. Song Y. Pan Y. Ma Y. Hu S. Wen A. Jia Y. Rodriguez L.M. Tull M.B. Benante K. Khan S.A. Cao Y. Jovanovic B. Richmond E. Umar A. Bergan R. Wu K. A phase I trial of berberine in Chinese with ulcerative colitis. Cancer Prev. Res. 2020 13 1 117 126 10.1158/1940‑6207.CAPR‑19‑0258 31619442
    [Google Scholar]
  73. Lee S.Y. Jeong J.J. Eun S.H. Kim D.H. Anti-inflammatory effects of ginsenoside Rg1 and its metabolites ginsenoside Rh1 and 20(S)-protopanaxatriol in mice with TNBS-induced colitis. Eur. J. Pharmacol. 2015 762 333 343 10.1016/j.ejphar.2015.06.011 26054809
    [Google Scholar]
  74. Ryuk J.A. Zheng M.S. Lee M.Y. Seo C.S. Li Y. Lee S.H. Moon D.C. Lee H.W. Lee J.H. Park J.Y. Son J.K. Ko B.S. Discrimination of Phellodendron amurense and P. chinense based on DNA analysis and the simultaneous analysis of alkaloids. Arch. Pharm. Res. 2012 35 6 1045 1054 10.1007/s12272‑012‑0612‑y 22870814
    [Google Scholar]
  75. Ye H. Wu Q. Zhu Y. Guo C. Zheng X. Ginsenoside Rh2 alleviates dextran sulfate sodium-induced colitis via augmenting TGFβ signaling. Mol. Biol. Rep. 2014 41 8 5485 5490 10.1007/s11033‑014‑3422‑0 24893598
    [Google Scholar]
  76. Tian M. Ma P. Zhang Y. Mi Y. Fan D. Ginsenoside Rk3 alleviated DSS-induced ulcerative colitis by protecting colon barrier and inhibiting NLRP3 inflammasome pathway. Int. Immunopharmacol. 2020 85 106645 10.1016/j.intimp.2020.106645 32521491
    [Google Scholar]
  77. Joh E.H. Lee I.A. Jung I.H. Kim D.H. Ginsenoside Rb1 and its metabolite compound K inhibit IRAK-1 activation—The key step of inflammation. Biochem. Pharmacol. 2011 82 3 278 286 10.1016/j.bcp.2011.05.003 21600888
    [Google Scholar]
  78. Yang N. Liang G. Lin J. Zhang S. Lin Q. Ji X. Chen H. Li N. Jin S. Ginsenoside Rd therapy improves histological and functional recovery in a rat model of inflammatory bowel disease. Phytother. Res. 2020 34 11 3019 3028 10.1002/ptr.6734 32468636
    [Google Scholar]
  79. Zhang A. Wang H. Sun H. Zhang Y. An N. Yan G. Meng X. Wang X. Metabolomics strategy reveals therapeutical assessment of limonin on nonbacterial prostatitis. Food Funct. 2015 6 11 3540 3549 10.1039/C5FO00489F 26302114
    [Google Scholar]
  80. Cui H. Cai Y. Wang L. Jia B. Li J. Zhao S. Chu X. Lin J. Zhang X. Bian Y. Zhuang P. Berberine regulates Treg/Th17 balance to treat ulcerative colitis through modulating the gut microbiota in the colon. Front. Pharmacol. 2018 9 571 10.3389/fphar.2018.00571 29904348
    [Google Scholar]
  81. Fan S. Zhang C. Luo T. Wang J. Tang Y. Chen Z. Yu L. Limonin: A review of its pharmacology, toxicity, and pharmacokinetics. Molecules 2019 24 20 3679 10.3390/molecules24203679 31614806
    [Google Scholar]
  82. Liu S. Zhang S. Lv X. Lu J. Ren C. Zeng Z. Zheng L. Zhou X. Fu H. Zhou D. Chen Y. Limonin ameliorates ulcerative colitis by regulating STAT3/miR-214 signaling pathway. Int. Immunopharmacol. 2019 75 105768 10.1016/j.intimp.2019.105768 31382166
    [Google Scholar]
  83. Chrzanowski J. Chrzanowska A. Graboń W. Glycyrrhizin: An old weapon against a novel coronavirus. Phytother. Res. 2021 35 2 629 636 10.1002/ptr.6852 32902005
    [Google Scholar]
  84. Lv J. Zhang Y. Tian Z. Liu F. Shi Y. Liu Y. Xia P. Astragalus polysaccharides protect against dextran sulfate sodium-induced colitis by inhibiting NF-κB activation. Int. J. Biol. Macromol. 2017 98 723 729 10.1016/j.ijbiomac.2017.02.024 28188801
    [Google Scholar]
  85. Stronati L. Palone F. Negroni A. Colantoni E. Mancuso A.B. Cucchiara S. Cesi V. Isoldi S. Vitali R. Dipotassium glycyrrhizate improves intestinal mucosal healing by modulating extracellular matrix remodeling genes and restoring epithelial barrier functions. Front. Immunol. 2019 10 939 10.3389/fimmu.2019.00939 31105713
    [Google Scholar]
  86. Kudo T. Okamura S. Zhang Y. Masuo T. Mori M. Topical application of glycyrrhizin preparation ameliorates experimentally induced colitis in rats. World J. Gastroenterol. 2011 17 17 2223 2228 10.3748/wjg.v17.i17.2223 21633533
    [Google Scholar]
  87. de Putter R. Donck J. Low-dose liquorice ingestion resulting in severe hypokalaemic paraparesis, rhabdomyolysis and nephrogenic diabetes insipidus. Clin. Kidney J. 2014 7 1 73 75 10.1093/ckj/sft159 25859357
    [Google Scholar]
  88. Jin M. Zhao K. Huang Q. Shang P. Structural features and biological activities of the polysaccharides from Astragalus membranaceus. Int. J. Biol. Macromol. 2014 64 257 266 10.1016/j.ijbiomac.2013.12.002 24325861
    [Google Scholar]
  89. Auyeung K.K. Han Q.B. Ko J.K. Astragalus membranaceus: A review of its protection against inflammation and gastrointestinal cancers. Am. J. Chin. Med. 2016 44 1 1 22 10.1142/S0192415X16500014 26916911
    [Google Scholar]
  90. Yang H. Li Y. Wu W. Sun Q. Zhang Y. Zhao W. Lv H. Xia Q. Hu P. Li H. Qian J. The incidence of inflammatory bowel disease in Northern China: A prospective population-based study. PLoS One 2014 9 7 e101296 10.1371/journal.pone.0101296 25029440
    [Google Scholar]
  91. Yan X. Lu Q.G. Zeng L. Li X.H. Liu Y. Du X.F. Bai G.M. Synergistic protection of astragalus polysaccharides and matrine against ulcerative colitis and associated lung injury in rats. World J. Gastroenterol. 2020 26 1 55 69 10.3748/wjg.v26.i1.55 31933514
    [Google Scholar]
  92. Flórez N. Gonzalez-Munoz M. Ribeiro D. Fernandes E. Dominguez H. Freitas M. Algae polysaccharides’ chemical characterization and their role in the inflammatory process. Curr. Med. Chem. 2017 24 2 149 175 10.2174/0929867323666161028160416 27804878
    [Google Scholar]
  93. Rioux J.D. Xavier R.J. Taylor K.D. Silverberg M.S. Goyette P. Huett A. Green T. Kuballa P. Barmada M.M. Datta L.W. Shugart Y.Y. Griffiths A.M. Targan S.R. Ippoliti A.F. Bernard E.J. Mei L. Nicolae D.L. Regueiro M. Schumm L.P. Steinhart A.H. Rotter J.I. Duerr R.H. Cho J.H. Daly M.J. Brant S.R. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat. Genet. 2007 39 5 596 604 10.1038/ng2032 17435756
    [Google Scholar]
  94. Xia E.Q. Cui B. Xu X.R. Song Y. Ai X.X. Li H.B. Microwave-assisted extraction of oxymatrine from Sophora flavescens. Molecules 2011 16 9 7391 7400 10.3390/molecules16097391 21878859
    [Google Scholar]
  95. Cao X. He Q. Anti-tumor activities of bioactive phytochemicals in Sophora flavescens for breast cancer. Cancer Manag. Res. 2020 12 1457 1467 10.2147/CMAR.S243127 32161498
    [Google Scholar]
  96. Wen J.B. Zhu F.Q. Chen W.G. Jiang L.P. Chen J. Hu Z.P. Huang Y.J. Zhou Z.W. Wang G.L. Lin H. Zhou S.F. Oxymatrine improves intestinal epithelial barrier function involving NF-κB-mediated signaling pathway in CCl4-induced cirrhotic rats. PLoS One 2014 9 8 e106082 10.1371/journal.pone.0106082 25171482
    [Google Scholar]
  97. Guzman J.R. Koo J.S. Goldsmith J.R. Mühlbauer M. Narula A. Jobin C. Oxymatrine prevents NF-κB nuclear translocation and ameliorates acute intestinal inflammation. Sci. Rep. 2013 3 1 1629 10.1038/srep01629 23568217
    [Google Scholar]
  98. Danese S. New therapies for inflammatory bowel disease: From the bench to the bedside. Gut 2012 61 6 918 932 10.1136/gutjnl‑2011‑300904 22115827
    [Google Scholar]
  99. Qiu M. Liu J. Feng P. Su Y. Guo R. Shi F. Wang S. Zhao B. Cytochrome P450s regulates aloperine-induced pathological changes in mouse liver and kidney. Res. Vet. Sci. 2020 132 97 100 10.1016/j.rvsc.2020.06.005 32544634
    [Google Scholar]
  100. Wang R. Deng X. Gao Q. Wu X. Han L. Gao X. Zhao S. Chen W. Zhou R. Li Z. Bai C. Sophora alopecuroides L.: An ethnopharmacological, phytochemical, and pharmacological review. J. Ethnopharmacol. 2020 248 112172 10.1016/j.jep.2019.112172 31442619
    [Google Scholar]
  101. Fu X. Sun F. Wang F. Zhang J. Zheng B. Zhong J. Yue T. Zheng X. Xu J.F. Wang C.Y. Aloperine protects mice against DSS‐induced colitis by PP2A‐mediated PI3K/Akt/mTOR signaling suppression. Mediators Inflamm. 2017 2017 1 1 14 10.1155/2017/5706152 29056830
    [Google Scholar]
  102. Lee I.A. Low D. Kamba A. Llado V. Mizoguchi E. Oral caffeine administration ameliorates acute colitis by suppressing chitinase 3-like 1 expression in intestinal epithelial cells. J. Gastroenterol. 2014 49 8 1206 1216 10.1007/s00535‑013‑0865‑3 23925589
    [Google Scholar]
  103. Senchina D.S. Hallam J.E. Kohut M.L. Nguyen N.A. Perera M.A. Alkaloids and athlete immune function: Caffeine, theophylline, gingerol, ephedrine, and their congeners. Exerc. Immunol. Rev. 2014 20 68 93 24974722
    [Google Scholar]
  104. Singleton E.L. Le N. Ness G.L. Theophylline and caffeine as alternatives during an aminophylline shortage. Ann. Pharmacother. 2019 53 3 316 320 10.1177/1060028018806624 30304941
    [Google Scholar]
  105. Zhou B. Ma C. Ren X. Xia T. Li X. Wu Y. Production of theophylline via aerobic fermentation of pu-erh tea using tea-derived fungi. BMC Microbiol. 2019 19 1 261 10.1186/s12866‑019‑1640‑2 31771506
    [Google Scholar]
  106. Ghasemi-Pirbaluti M. Motaghi E. Najafi A. Hosseini M.J. The effect of theophylline on acetic acid induced ulcerative colitis in rats. Biomed. Pharmacother. 2017 90 153 159 10.1016/j.biopha.2017.03.038 28351778
    [Google Scholar]
  107. Annamaraju P. Patel P. Baradhi K.M. Pentoxifylline. In: StatPearls. Treasure Island, FL StatPearls Publishing 2024 32644522
    [Google Scholar]
  108. Hao Y. Huo J. Wang T. Sun G. Wang W. Chemical profiling of Coptis rootlet and screening of its bioactive compounds in inhibiting Staphylococcus aureus by UPLC-Q-TOF/MS. J. Pharm. Biomed. Anal. 2020 180 113089 10.1016/j.jpba.2019.113089 31901737
    [Google Scholar]
  109. Zhang X.J. Yuan Z.W. Qu C. Yu X.T. Huang T. Chen P.V. Su Z.R. Dou Y.X. Wu J.Z. Zeng H.F. Xie Y. Chen J.N. Palmatine ameliorated murine colitis by suppressing tryptophan metabolism and regulating gut microbiota. Pharmacol. Res. 2018 137 34 46 10.1016/j.phrs.2018.09.010 30243842
    [Google Scholar]
  110. Mai C.T. Wu M.M. Wang C.L. Su Z.R. Cheng Y.Y. Zhang X.J. Palmatine attenuated dextran sulfate sodium (DSS)-induced colitis via promoting mitophagy-mediated NLRP3 inflammasome inactivation. Mol. Immunol. 2019 105 76 85 10.1016/j.molimm.2018.10.015 30496979
    [Google Scholar]
  111. Bjarnason I. Macpherson A.J. Delivery, safety and efficacy of 5-aminosalicylate preparations. Inflammopharmacology 1993 2 3 277 287 10.1007/BF02660618
    [Google Scholar]
  112. Reyhan E. Irkorucu O. Surmelioglu A. Ozkara S. Deger K.C. Aziret M. Erdem H. Cetinkunar S. Demirturk P. Sehirli A.O. Efficacy of pentoxifylline and tadalafil in rat model of ischemic colitis. J. Invest. Surg. 2014 27 6 349 353 10.3109/08941939.2014.971204 25361018
    [Google Scholar]
  113. Karatay E. Gül Utku Ö. Erdal H. Arhan M. Önal İ.K. İbi̇ş M. Eki̇nci̇ Ö. Yilmaz Demi̇rtaş C. Dumlu G.Ş. Pentoxifylline attenuates mucosal damage in an experimental model of rat colitis by modulating tissue biomarkers of inflammation, oxidative stress, and fibrosis. Turk. J. Med. Sci. 2017 47 1 348 356 10.3906/sag‑1508‑98 28263514
    [Google Scholar]
  114. Dorrington A.M. Selinger C.P. Parkes G.C. Smith M. Pollok R.C. Raine T. The historical role and contemporary use of corticosteroids in inflammatory bowel disease. J. Crohn’s Colitis 2020 14 9 1316 1329 10.1093/ecco‑jcc/jjaa053 32170314
    [Google Scholar]
  115. Dubois-Camacho K. Ottum P.A. Franco-Muñoz D. De la Fuente M. Torres-Riquelme A. Díaz-Jiménez D. Olivares-Morales M. Astudillo G. Quera R. Hermoso M.A. Glucocorticosteroid therapy in inflammatory bowel diseases: From clinical practice to molecular biology. World J. Gastroenterol. 2017 23 36 6628 6638 10.3748/wjg.v23.i36.6628 29085208
    [Google Scholar]
  116. Kim K.U. Kim J. Kim W.H. Min H. Choi C.H. Treatments of inflammatory bowel disease toward personalized medicine. Arch. Pharm. Res. 2021 44 3 293 309 10.1007/s12272‑021‑01318‑6 33763844
    [Google Scholar]
  117. Sattler L. Hanauer S.B. Malter L. Immunomodulatory agents for treatment of patients with inflammatory bowel disease (review safety of anti-TNF, anti-integrin, anti IL-12/23, JAK inhibition, sphingosine 1-phosphate receptor modulator, azathioprine/6-MP and methotrexate). Curr. Gastroenterol. Rep. 2021 23 12 30 10.1007/s11894‑021‑00829‑y 34913108
    [Google Scholar]
  118. Cai Z. Wang S. Li J. Treatment of inflammatory bowel disease: A comprehensive review. Front. Med. 2021 8 765474 10.3389/fmed.2021.765474 34988090
    [Google Scholar]
  119. Tominaga K. Sugaya T. Tanaka T. Kanazawa M. Iijima M. Irisawa A. Thiopurines: Recent topics and their role in the treatment of inflammatory bowel diseases. Front. Pharmacol. 2021 11 582291 10.3389/fphar.2020.582291 33584261
    [Google Scholar]
  120. Herfarth H.H. Methotrexate for inflammatory bowel diseases-new developments. Dig. Dis. 2016 34 1-2 140 146 10.1159/000443129 26981630
    [Google Scholar]
  121. Mammoser A. Calcineurin inhibitor encephalopathy. Semin. Neurol. 2012 32 5 517 524 10.1055/s‑0033‑1334471 23677660
    [Google Scholar]
  122. Zhang W. Michalowski C.B. Beloqui A. Oral delivery of biologics in inflammatory bowel disease treatment. Front. Bioeng. Biotechnol. 2021 9 675194 10.3389/fbioe.2021.675194 34150733
    [Google Scholar]
  123. Queiroz N.S.F. Regueiro M. Safety considerations with biologics and new inflammatory bowel disease therapies. Curr. Opin. Gastroenterol. 2020 36 4 257 264 10.1097/MOG.0000000000000607 31895234
    [Google Scholar]
  124. Rakowsky S. Papamichael K. Cheifetz A.S. Choosing the right biologic for complications of inflammatory bowel disease. Expert Rev. Gastroenterol. Hepatol. 2022 16 3 235 249 10.1080/17474124.2022.2036122 35094628
    [Google Scholar]
  125. Zhang H.M. Yuan S. Meng H. Hou X.T. Li J. Xue J.C. Li Y. Wang Q. Nan J.X. Jin X.J. Zhang Q.G. Stem cell-based therapies for inflammatory bowel disease. Int. J. Mol. Sci. 2022 23 15 8494 10.3390/ijms23158494 35955628
    [Google Scholar]
  126. Kotlarz D. Beier R. Murugan D. Diestelhorst J. Jensen O. Boztug K. Pfeifer D. Kreipe H. Pfister E.D. Baumann U. Puchalka J. Bohne J. Egritas O. Dalgic B. Kolho K.L. Sauerbrey A. Buderus S. Güngör T. Enninger A. Koda Y.K.L. Guariso G. Weiss B. Corbacioglu S. Socha P. Uslu N. Metin A. Wahbeh G.T. Husain K. Ramadan D. Al-Herz W. Grimbacher B. Sauer M. Sykora K.W. Koletzko S. Klein C. Loss of interleukin-10 signaling and infantile inflammatory bowel disease: Implications for diagnosis and therapy. Gastroenterology 2012 143 2 347 355 10.1053/j.gastro.2012.04.045 22549091
    [Google Scholar]
  127. Pan X. Li Q. Zhu X. Li Z. Cai X. Pang R. Ruan G. Mechanism and therapeutic effect of umbilical cord mesenchymal stem cells in inflammatory bowel disease. Sci. Rep. 2019 9 1 17646 10.1038/s41598‑019‑54194‑y 31776475
    [Google Scholar]
  128. Wei H. Liu X. Ouyang C. Zhang J. Chen S. Lu F. Chen L. Complications following stem cell therapy in inflammatory bowel disease. Curr. Stem Cell Res. Ther. 2017 12 6 471 475 28302045
    [Google Scholar]
  129. Lalu M.M. McIntyre L. Pugliese C. Fergusson D. Winston B.W. Marshall J.C. Granton J. Stewart D.J. Safety of cell therapy with mesenchymal stromal cells (SafeCell): A systematic review and meta-analysis of clinical trials. PLoS One 2012 7 10 e47559 10.1371/journal.pone.0047559 23133515
    [Google Scholar]
  130. Gough E. Shaikh H. Manges A.R. Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection. Clin. Infect. Dis. 2011 53 10 994 1002 10.1093/cid/cir632 22002980
    [Google Scholar]
  131. Guo B. Harstall C. Louie T. Veldhuyzen van Zanten S. Dieleman L.A. Systematic review: Faecal transplantation for the treatment of Clostridium difficile ‐associated disease. Aliment. Pharmacol. Ther. 2012 35 8 865 875 10.1111/j.1365‑2036.2012.05033.x 22360412
    [Google Scholar]
  132. Colman R.J. Rubin D.T. Fecal microbiota transplantation as therapy for inflammatory bowel disease: A systematic review and meta-analysis. J. Crohn’s Colitis 2014 8 12 1569 1581 10.1016/j.crohns.2014.08.006 25223604
    [Google Scholar]
  133. Weingarden A.R. Vaughn B.P. Intestinal microbiota, fecal microbiota transplantation, and inflammatory bowel disease. Gut Microbes 2017 8 3 238 252 10.1080/19490976.2017.1290757 28609251
    [Google Scholar]
  134. Büning J. Homann N. von Smolinski D. Borcherding F. Noack F. Stolte M. Kohl M. Lehnert H. Ludwig D. Helminths as governors of inflammatory bowel disease. Gut 2008 57 8 1182 1183 10.1136/gut.2008.152355 18628388
    [Google Scholar]
  135. Summers RW. Elliott DE. Qadir K. Urban JF. Thompson R. Weinstock J.V. Trichuris suis seems to be safe and possibly effective in the treatment of inflammatory bowel disease. Am. J. Gastroenterol. 2003 98 9 2034 2041 10.1111/j.1572‑0241.2003.07660.x
    [Google Scholar]
  136. Hunter M.M. Mckay D.M. Helminths as therapeutic agents for inflammatory bowel disease. Aliment. Pharmacol. Ther. 2004 19 2 167 177 10.1111/j.0269‑2813.2004.01803.x 14723608
    [Google Scholar]
  137. Bemelman W.A. Adamina M. Buskens C. DHoore, A.; Kotze, P.G.; Oresland, T.; Panis, Y.; Samprieto, G.; Spinelli, A.; Tulchinsky, H.; Warusavitarne, J.; Zmora, O. Evolving role of IBD surgery. J. Crohn’s Colitis 2018 12 8 1005 1007 10.1093/ecco‑jcc/jjy056
    [Google Scholar]
  138. Kühn F. Klar E. Surgical principles in the treatment of ulcerative colitis. Viszeralmedizin 2015 31 4 246 250 26557832
    [Google Scholar]
  139. Herlihy N. Feakins R. Gut inflammation induced by drugs: Can pathology help to differentiate from inflammatory bowel disease? United European Gastroenterol. J. 2022 10 5 451 464 10.1002/ueg2.12242 35633273
    [Google Scholar]
  140. Kiesler P. Fuss I.J. Strober W. Experimental models of inflammatory bowel diseases. Cell. Mol. Gastroenterol. Hepatol. 2015 1 2 154 170 10.1016/j.jcmgh.2015.01.006 26000334
    [Google Scholar]
  141. Shen Z.H. Zhu C.X. Quan Y.S. Yang Z.Y. Wu S. Luo W.W. Tan B. Wang X.Y. Relationship between intestinal microbiota and ulcerative colitis: Mechanisms and clinical application of probiotics and fecal microbiota transplantation. World J. Gastroenterol. 2018 24 1 5 14 10.3748/wjg.v24.i1.5 29358877
    [Google Scholar]
  142. Zhang Y.J. Li S. Gan R.Y. Zhou T. Xu D.P. Li H.B. Impacts of gut bacteria on human health and diseases. Int. J. Mol. Sci. 2015 16 4 7493 7519 10.3390/ijms16047493 25849657
    [Google Scholar]
  143. Nascimento R.P. Machado A.P.F. Galvez J. Cazarin C.B.B. Maróstica M.R. Junior Ulcerative colitis: Gut microbiota, immunopathogenesis and application of natural products in animal models. Life Sci. 2020 378 118129 10.1016/j.lfs.2020.118129 32717271
    [Google Scholar]
  144. Wang L. Gao M. Kang G. Huang H. The potential role of phytonutrients flavonoids influencing gut microbiota in the prophylaxis and treatment of inflammatory bowel disease. Front. Nutr. 2021 8 798038 10.3389/fnut.2021.798038 34970585
    [Google Scholar]
  145. Alrafas H.R. Busbee P.B. Nagarkatti M. Nagarkatti P.S. Resveratrol modulates the gut microbiota to prevent murine colitis development through induction of Tregs and suppression of Th17 cells. J. Leukoc. Biol. 2019 106 2 467 480 10.1002/JLB.3A1218‑476RR 30897248
    [Google Scholar]
  146. Wu X. Wang L. Tang L. Wang L. Cao S. Wu Q. Zhang Z. Li L. Salvianolic acid B alters the gut microbiota and mitigates colitis severity and associated inflammation. J. Funct. Foods 2018 46 312 319 10.1016/j.jff.2018.04.068
    [Google Scholar]
  147. Cheng H. Liu J. Zhang D. Wang J. Tan Y. Feng W. Peng C. Ginsenoside Rg1 alleviates acute ulcerative colitis by modulating gut microbiota and microbial tryptophan metabolism. Front. Immunol. 2022 13 817600 10.3389/fimmu.2022.817600 35655785
    [Google Scholar]
  148. Ji J. Ge X. Chen Y. Zhu B. Wu Q. Zhang J. Shan J. Cheng H. Shi L. Daphnetin ameliorates experimental colitis by modulating microbiota composition and Treg/Th17 balance. FASEB J. 2019 33 8 9308 9322 10.1096/fj.201802659RR 31145641
    [Google Scholar]
  149. Yuan S. Li Y. Li J. Xue J.C. Wang Q. Hou X.T. Meng H. Nan J.X. Zhang Q.G. Traditional Chinese medicine and natural products: Potential approaches for inflammatory bowel disease. Front. Pharmacol. 2022 13 892790 10.3389/fphar.2022.892790 35873579
    [Google Scholar]
  150. Zhang J. Lei H. Hu X. Dong W. Hesperetin ameliorates DSS-induced colitis by maintaining the epithelial barrier via blocking RIPK3/MLKL necroptosis signaling. Eur. J. Pharmacol. 2020 873 172992 10.1016/j.ejphar.2020.172992 32035144
    [Google Scholar]
  151. Araki Y. Mukaisyo K. Sugihara H. Fujiyama Y. Hattori T. Increased apoptosis and decreased proliferation of colonic epithelium in dextran sulfate sodium-induced colitis in mice. Oncol. Rep. 2010 24 4 869 874 10.3892/or.2010.869 20811666
    [Google Scholar]
  152. Wu Z. Huang S. Li T. Li N. Han D. Zhang B. Xu Z.Z. Zhang S. Pang J. Wang S. Zhang G. Zhao J. Wang J. Gut microbiota from green tea polyphenol-dosed mice improves intestinal epithelial homeostasis and ameliorates experimental colitis. Microbiome 2021 9 1 184 10.1186/s40168‑021‑01115‑9 34493333
    [Google Scholar]
  153. Liu C. Zeng Y. Wen Y. Huang X. Liu Y. Natural products modulate cell apoptosis: A promising way for the treatment of ulcerative colitis. Front. Pharmacol. 2022 13 806148 10.3389/fphar.2022.806148 35173617
    [Google Scholar]
  154. Yousef M. Pichyangkura R. Soodvilai S. Chatsudthipong V. Muanprasat C. Chitosan oligosaccharide as potential therapy of inflammatory bowel disease: Therapeutic efficacy and possible mechanisms of action. Pharmacol. Res. 2012 66 1 66 79 10.1016/j.phrs.2012.03.013 22475725
    [Google Scholar]
  155. Hou C. Chen L. Yang L. Ji X. An insight into anti-inflammatory effects of natural polysaccharides. Int. J. Biol. Macromol. 2020 153 248 255 10.1016/j.ijbiomac.2020.02.315 32114173
    [Google Scholar]
  156. Paunovic V. Harnett M.M. Mitogen-activated protein kinases as therapeutic targets for rheumatoid arthritis. Drugs 2013 73 2 101 115 10.1007/s40265‑013‑0014‑6 23371304
    [Google Scholar]
  157. Zhu L. Shen H. Gu P.Q. Liu Y.J. Zhang L. Cheng J.F. Baicalin alleviates TNBS induced colitis by inhibiting PI3K/AKT pathway activation. Exp. Ther. Med. 2020 20 1 581 590 10.3892/etm.2020.8718 32537016
    [Google Scholar]
  158. Yuan D. Li C. Huang Q. Fu X. Dong H. Current advances in the anti-inflammatory effects and mechanisms of natural polysaccharides. Crit. Rev. Food Sci. Nutr. 2023 63 22 5890 5910 10.1080/10408398.2022.2025535 35021901
    [Google Scholar]
  159. El-Akabawy G. El-Sherif N.M. Zeaxanthin exerts protective effects on acetic acid-induced colitis in rats via modulation of pro-inflammatory cytokines and oxidative stress. Biomed. Pharmacother. 2019 111 841 851 10.1016/j.biopha.2019.01.001 30616083
    [Google Scholar]
  160. Grzybowska-Chlebowczyk U. Wysocka-Wojakiewicz P. Jasielska M. Cukrowska B. Więcek S. Kniażewska M. Chudek J. Oxidative and antioxidative stress status in children with inflammatory bowel disease as a result of a chronic inflammatory process. Mediators Inflamm. 2018 2018 1 1 7 10.1155/2018/4120973 30116148
    [Google Scholar]
  161. Piechota-Polanczyk A. Fichna J. Review article: The role of oxidative stress in pathogenesis and treatment of inflammatory bowel diseases. Naunyn Schmiedebergs Arch. Pharmacol. 2014 387 7 605 620 10.1007/s00210‑014‑0985‑1 24798211
    [Google Scholar]
  162. Zhu X. Tian X. Yang M. Yu Y. Zhou Y. Gao Y. Zhang L. Li Z. Xiao Y. Moses R.E. Li X. Zhang B. Procyanidin B2 promotes intestinal injury repair and attenuates colitis-associated tumorigenesis via suppression of oxidative stress in mice. Antioxid. Redox Signal. 2021 35 2 75 92 10.1089/ars.2019.7911 32940048
    [Google Scholar]
  163. Lv T. Shen L. Yang L. Diao W. Yang Z. Zhang Y. Yu S. Li Y. Polydatin ameliorates dextran sulfate sodium-induced colitis by decreasing oxidative stress and apoptosis partially via sonic hedgehog signaling pathway. Int. Immunopharmacol. 2018 64 256 263 10.1016/j.intimp.2018.09.009 30218952
    [Google Scholar]
  164. Sangaraju R. Nalban N. Alavala S. Rajendran V. Jerald M.K. Sistla R. Protective effect of galangin against dextran sulfate sodium (DSS)-induced ulcerative colitis in Balb/c mice. Inflamm. Res. 2019 68 8 691 704 10.1007/s00011‑019‑01252‑w 31147743
    [Google Scholar]
  165. Wang Y. Ji X. Yan M. Chen X. Kang M. Teng L. Wu X. Chen J. Deng C. Protective effect and mechanism of polysaccharide from Dictyophora indusiata on dextran sodium sulfate-induced colitis in C57BL/6 mice. Int. J. Biol. Macromol. 2019 140 973 984 10.1016/j.ijbiomac.2019.08.198 31449863
    [Google Scholar]
  166. Silva F.A.R. Rodrigues B.L. Ayrizono M.L.S. Leal R.F. The immunological basis of inflammatory bowel disease. Gastroenterol. Res. Pract. 2016 2016 1 1 11 10.1155/2016/2097274 28070181
    [Google Scholar]
  167. Zaiatz Bittencourt V. Jones F. Doherty G. Ryan E.J. Targeting immune cell metabolism in the treatment of inflammatory bowel disease. Inflamm. Bowel Dis. 2021 27 10 1684 1693 10.1093/ibd/izab024 33693743
    [Google Scholar]
  168. Zhu Y. Zhao Q. Huang Q. Li Y. Yu J. Zhang R. Liu J. Yan P. Xia J. Guo L. Liu G. Yang X. Zeng J. Nuciferine regulates immune function and gut microbiota in DSS-induced ulcerative colitis. Front. Vet. Sci. 2022 9 939377 10.3389/fvets.2022.939377 35909691
    [Google Scholar]
  169. Li M. Guo W. Dong Y. Wang W. Tian C. Zhang Z. Yu T. Zhou H. Gui Y. Xue K. Li J. Jiang F. Sarapultsev A. Wang H. Zhang G. Luo S. Fan H. Hu D. Beneficial effects of celastrol on immune balance by modulating gut microbiota in experimental ulcerative colitis mice. Genomics Proteomics Bioinformatics 2022 20 2 288 303 10.1016/j.gpb.2022.05.002 35609771
    [Google Scholar]
  170. Wei B. Zhang R. Zhai J. Zhu J. Yang F. Yue D. Liu X. Lu C. Sun X. Suppression of Th17 cell response in the alleviation of dextran sulfate sodium-induced colitis by Ganoderma lucidum polysaccharides. J. Immunol. Res. 2018 2018 1 1 10 10.1155/2018/2906494 29888292
    [Google Scholar]
  171. Zhu H. Li Y.R. Oxidative stress and redox signaling mechanisms of inflammatory bowel disease: Updated experimental and clinical evidence. Exp. Biol. Med. 2012 237 5 474 480 10.1258/ebm.2011.011358 22442342
    [Google Scholar]
  172. Scott O. Roifman C.M. NF-κB pathway and the Goldilocks principle: Lessons from human disorders of immunity and inflammation. J. Allergy Clin. Immunol. 2019 143 5 1688 1701 10.1016/j.jaci.2019.03.016 30940520
    [Google Scholar]
  173. Cui L. Wang W. Luo Y. Ning Q. Xia Z. Chen J. Feng L. Wang H. Song J. Tan X. Tan W. Wang C. Jia X. Polysaccharide from Scutellaria baicalensis Georgi ameliorates colitis via suppressing NF-κB signaling and NLRP3 inflammasome activation. Int. J. Biol. Macromol. 2019 132 393 405 10.1016/j.ijbiomac.2019.03.230 30936012
    [Google Scholar]
  174. Liu C. Dunkin D. Lai J. Song Y. Ceballos C. Benkov K. Li X.M. Anti-inflammatory effects of Ganoderma lucidum triterpenoid in human crohn’s disease associated with downregulation of NF-κB signaling. Inflamm. Bowel Dis. 2015 21 8 1918 1925 10.1097/MIB.0000000000000439 25993687
    [Google Scholar]
  175. Zhou Y. Zhong B. Min X. Hou Y. Lin L. Wu Q. Shi J. Chen X. Therapeutic potential of isobavachalcone, a natural flavonoid, in murine experimental colitis by inhibiting NF‐κB p65. Phytother. Res. 2021 35 10 5861 5870 10.1002/ptr.7246 34435401
    [Google Scholar]
  176. Liu M. Zhang G. Zheng C. Song M. Liu F. Huang X. Bai S. Huang X. Lin C. Zhu C. Hu Y. Mi S. Liu C. Activating the pregnane X receptor by imperatorin attenuates dextran sulphate sodium‐induced colitis in mice. Br. J. Pharmacol. 2018 175 17 3563 3580 10.1111/bph.14424 29945292
    [Google Scholar]
  177. Villarino A.V. Kanno Y. O’Shea J.J. Mechanisms and consequences of Jak–STAT signaling in the immune system. Nat. Immunol. 2017 18 4 374 384 10.1038/ni.3691 28323260
    [Google Scholar]
  178. Zhang X. Xu F. Liu L. Feng L. Wu X. Shen Y. Sun Y. Wu X. Xu Q. (+)-Borneol improves the efficacy of edaravone against DSS-induced colitis by promoting M2 macrophages polarization via JAK2-STAT3 signaling pathway. Int. Immunopharmacol. 2017 53 1 10 10.1016/j.intimp.2017.10.002 29028547
    [Google Scholar]
  179. Tao J.H. Duan J.A. Zhang W. Jiang S. Guo J.M. Wei D.D. Polysaccharides from Chrysanthemum morifolium Ramat ameliorate colitis rats via regulation of the metabolic profiling and NF-κ B/TLR4 and IL-6/JAK2/STAT3 signaling pathways. Front. Pharmacol. 2018 9 746 10.3389/fphar.2018.00746 30042683
    [Google Scholar]
  180. Direito R. Rocha J. Lima A. Gonçalves M.M. Duarte M.P. Mateus V. Sousa C. Fernandes A. Pinto R. Boavida Ferreira R. Sepodes B. Figueira M.E. Reduction of inflammation and colon injury by a spearmint phenolic extract in experimental bowel disease in mice. Medicines 2019 6 2 65 10.3390/medicines6020065 31174376
    [Google Scholar]
  181. Zhu F. Zheng J. Xu F. Xi Y. Chen J. Xu X. Resveratrol alleviates dextran sulfate sodium-induced acute ulcerative colitis in mice by mediating PI3K/Akt/VEGFA pathway. Front. Pharmacol. 2021 12 693982 10.3389/fphar.2021.693982 34497510
    [Google Scholar]
  182. Hu L.H. Liu J.Y. Yin J.B. Eriodictyol attenuates TNBS ‐induced ulcerative colitis through repressing TLR4/NF‐kB signaling pathway in rats. Kaohsiung J. Med. Sci. 2021 37 9 812 818 10.1002/kjm2.12400 34042266
    [Google Scholar]
  183. El-Sherbiny M. Eisa N.H. Abo El-Magd N.F. Elsherbiny N.M. Said E. Khodir A.E. Anti-inflammatory/anti-apoptotic impact of betulin attenuates experimentally induced ulcerative colitis: An insight into TLR4/NF-kB/caspase signalling modulation. Environ. Toxicol. Pharmacol. 2021 88 103750 10.1016/j.etap.2021.103750 34597787
    [Google Scholar]
  184. Wang Y.J. Li Q.M. Zha X.Q. Luo J.P. Dendrobium fimbriatum hook polysaccharide ameliorates dextran-sodium-sulfate-induced colitis in mice via improving intestinal barrier function, modulating intestinal microbiota, and reducing oxidative stress and inflammatory responses. Food Funct. 2022 13 1 143 160 10.1039/D1FO03003E 34874039
    [Google Scholar]
  185. Venkataraman B. Ojha S. Belur P.D. Bhongade B. Raj V. Collin P.D. Adrian T.E. Subramanya S.B. Phytochemical drug candidates for the modulation of peroxisome proliferator‐activated receptor γ in inflammatory bowel diseases. Phytother. Res. 2020 34 7 1530 1549 10.1002/ptr.6625 32009281
    [Google Scholar]
  186. Dubuquoy L. Rousseaux C. Thuru X. Peyrin-Biroulet L. Romano O. Chavatte P. Chamaillard M. Desreumaux P. PPAR as a new therapeutic target in inflammatory bowel diseases. Gut 2006 55 9 1341 1349 10.1136/gut.2006.093484 16905700
    [Google Scholar]
  187. Venkataraman B. Almarzooqi S. Raj V. Alhassani A.T. Alhassani A.S. Ahmed K.J. Subramanian V.S. Ojha S.K. Attoub S. Adrian T.E. Subramanya S.B. Thymoquinone, a dietary bioactive compound, exerts anti-inflammatory effects in colitis by stimulating expression of the colonic epithelial PPAR-γ transcription factor. Nutrients 2021 13 4 1343 10.3390/nu13041343 33920708
    [Google Scholar]
  188. Venkataraman B. Almarzooqi S. Raj V. Dudeja P.K. Bhongade B.A. Patil R.B. Ojha S.K. Attoub S. Adrian T.E. Subramanya S.B. α-Bisabolol Mitigates Colon Inflammation by Stimulating Colon PPAR-γ Transcription Factor: In Vivo and In Vitro Study. PPAR Res. 2022 2022 1 1 22 10.1155/2022/5498115 35465355
    [Google Scholar]
  189. Xu B. Huang S. Chen Y. Wang Q. Luo S. Li Y. Wang X. Chen J. Luo X. Zhou L. Synergistic effect of combined treatment with baicalin and emodin on DSS ‐induced colitis in mouse. Phytother. Res. 2021 35 10 5708 5719 10.1002/ptr.7230 34379340
    [Google Scholar]
  190. Zhou Y. Wang D. Yan W. Treatment effects of natural products on inflammatory bowel disease in vivo and their mechanisms: Based on animal experiments. Nutrients 2023 15 4 1031 10.3390/nu15041031 36839389
    [Google Scholar]
  191. Duan L. Cheng S. Li L. Liu Y. Wang D. Liu G. Natural anti-inflammatory compounds as drug candidates for inflammatory bowel disease. Front. Pharmacol. 2021 12 684486 10.3389/fphar.2021.684486 34335253
    [Google Scholar]
/content/journals/mrmc/10.2174/0113895575405061250923110348
Loading
/content/journals/mrmc/10.2174/0113895575405061250923110348
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test