Journal of Research in Medical Sciences

: 2019  |  Volume : 24  |  Issue : 1  |  Page : 42-

Phytotherapies in inflammatory bowel disease

Mahboube Ganji-Arjenaki, Mahmoud Rafieian-Kopaei 
 Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran

Correspondence Address:
Mahmoud Rafieian-Kopaei
Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord


Inflammatory bowel disease (IBD) has been considered as a group of heterogeneous intestinal diseases that affects multiple organs outside of the gastrointestinal tract and is due to an uncontrolled inflammatory response mediated by the immune system. The IBD etiology has not been clearly defined, and it is considered as a multifactorial disease. Due to side effects of some conventional therapies, the consumption of complementary and alternative medicines, and in particular, the herbal therapy, more than before is increasing. Herbal therapy results for management of IBD by various mechanisms including leukotriene B4 inhibition, antioxidant activity, immune system regulation of nuclear factor-kappa B, as well as antiplatelet activity are favorable, and no unfortunate events have been yet reported. In this article, we aimed to review and report the herbal therapies established for management of human IBD or evaluated by animal IBD models. Their possible mechanisms of actions are also discussed.

How to cite this article:
Ganji-Arjenaki M, Rafieian-Kopaei M. Phytotherapies in inflammatory bowel disease.J Res Med Sci 2019;24:42-42

How to cite this URL:
Ganji-Arjenaki M, Rafieian-Kopaei M. Phytotherapies in inflammatory bowel disease. J Res Med Sci [serial online] 2019 [cited 2021 Oct 18 ];24:42-42
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Inflammatory bowel disease (IBD) has been considered as a group of heterogeneous intestinal diseases that affects multiple organs outside of the gastrointestinal (GI) tract and is due to an imbalance in intestinal microbiota and uncontrolled inflammatory response mediated by the immune system.[1],[2] Two main types within IBD can be distinguished and are in focus of attention because of their increasing incidence: Crohn's disease (CD) and ulcerative colitis (UC).[3] IBD is clinically designated by abdominal pain and cramps which may be associated with bloody diarrhea. Patients with IBD also have extraintestinal manifestations including arthritis, sacroiliitis, and ankylosing spondylitis. Low body mass index is also usual in these patients.[4],[5],[6] The clinical diagnosis of disease is usually supported by histologic, laboratory data, sonography, endoscopy, and radiology.[7]

Clinicians who treat IBD patients should be severely attentive of extraintestinal signs and symptoms to decrease morbidity.[8] Establishment and maintenance of a condition with steroid-free remission should be the main goal of medical therapy.[7] New classes drugs for IBD treatment including janus kinase inhibitors, anti-SMAD7 oligonucleotides, anti-tumor necrosis factor-α (TNF-α), peroxisome proliferator-activated receptor-γ ligand, anti-α four integrins, probiotics, and cell-based therapies are under clinical utilization.[9]

The existing IBD therapies unfortunately are not responsive for a lot of patients. There are serious demands for other therapies with induction and maintenance of remission. Hence, complementary and alternative medicines demands, particularly of herbal therapies, are reported to be higher among patients with IBD (21%–60%), due to their perceived natural effects.[10],[11]

Although not all commonly used phytomedicines are safe, most of the herbal products available are fairly safe in comparison to conventional drugs.[12],[13] Therefore, investigations on medicinal plants have been resulted in discovery of highly effective drugs such as opiate anesthetics, aspirin, and taxol.[14] Many medicinal plants have been used for thousands of years to treat or prevent bloody diarrhea. Therefore, in this article, we tried to present the effects of the most important medicinal plants on IBD. In this regards, we searched the herbal therapies for investiture and maintenance of IBD remission in both UC and CD.

 Materials and Methods

A search was done on electronic databases such as Google Scholar, PubMed, Web of Science, Cochrane Library, and CINHAL to review the evidence of herbal medicines with IBD Databases. Bothin vivo andin vitro data were collected on major herbal medicines using the search terms of “IBD” combined with the search terms “medicinal plants” or “herbal medicine,” in addition to hand searching the literature.

Pathogenesis of inflammatory bowel disease

The IBD etiopathogenesis is multifactorial and involves a dysregulated, immune-mediated inflammatory response (such as overexpression of multiple inflammatory cytokines and TNF-α), environmental changes, susceptibility gene variants, and an abnormal amount and kind of bowel microbiota.[15],[16] CD and UC both have common aspects including symptoms, organic damages, and therapy; however, each one exhibits its own distinct pathophysiological phenomenons.[17] For example, “Immunochip” studies have shown that the UC has maximum genetic association at single-nucleotide polymorphism (SNP) rs6927022 (between DQB1 and DRB1) mapped adjacent to HLA-DQA1 Class II gene, but for CD, no evidence of SNP[18],[19] or beta-defensins that is antimicrobial peptide secrete by the epithelium underexpression in CD can be found.[20]

Mechanism action of herbal medicines

Herbal therapies effective in IBD act through several mechanisms which are discussed below. The propriety of the cells mediating innate immunity including natural killer cells, dendritic cells, neutrophils, and macrophages are altered in IBD. The responses of mucosal T helper cells as well as overexpression of some cytokines including interferon gamma (IFN-γ), TNF-α, interleukin (IL)-1b, IL-6 and IL-12 are determined in IBD patients.[21] TNF-α secretion induces alterations in ion transport and epithelial permeability that may lead to lesions and mucosal inflammation.[22] Therefore, factors the regulating T-cells and pro-inflammatory cytokines have the potential to decrease inflammation scores and then improve the patient's IBD.

Some trials have revealed that Curcuma longa has potential to decrease the pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-1β, and IL-12 [Table 1].[23],[24]{Table 1}

Leukotriene B4 (LTB4) is a potent proinflammatory mediator playing an important role in IBD,[32] overexpression of LTB4 has been reported in IBD.[33] Nicotine derived from Nicotiana tabacum has been revealed to moderate LTB4 level in dinitrobenzene–sulfonic acid-induced colitis, therefore, it may help to improve IBD.[34]

The microbial content of the GI tract has essential role in the pathogenesis of IBD. It appears that in areas of GI tract that the level of luminal bacteria is more than normal, the possibility of disease progress.[35] Garlic (Allium sativum)withthe antibacterial properties can help to decrease microbial content then improve IBD.[36]

Overexpression of nuclear factor-kappa B (NF-κB) has been observed in IBD. The NF-κB proteins are eukaryotic transcription factors which usually play crucial roles in regulation of inflammation as well as in inflammatory responses in IBD.[37],[38] In response to proinflammatory stimuli, the NF-κB Kinase (IKK) induces transcriptional factor NF-κB.[39] Therefore, the suppressors of IKK and NF-κB can be employed for IBD treatment. Curcumin derived from C. longa,[24] a medicinal plant from Commiphora,[40] and the aflavin-3,3′-digallate derived from Camellia sinensis[28]can recede IKK and NF-κB. Boswellic acid, derived from Boswellia spp. can cause suppression of NF-κB activation and reduction of the proinflammatory cytokines such as IFN-γ, ILs 1, 2, 4, and 6 as well as an enhancement in macrophages phagocytosis.[41],[42]

Nitric oxide (NO) as well as inducible isoform of NO synthase (iNOS in IBD is increased.[43],[44],[45] Some herbal remedies, including a glycoside derived from Polygonum multiflorum,[46] a glycoprotein derived from Gardenia jasminoides,[27] theaflavin-3,3′-digallate derived from Clonorchis sinensis,[28] and curcumin,[23] are effective against IBD by decreasing the levels of NO and iNOS [Table 1].

Two isoforms of cyclooxygenase, i.e., Cox-1 and Cox-2 catalyze the synthesis of prostaglandins. Prostaglandins produced through Cox-1 play an important role in GI homeostasis maintenance such as blood flow and gastric cytoprotection. Prostaglandins synthesized through Cox-2 moderate inflammatory responses.[47],[48] Some trials have revealed that curcumin and G. jasminoides are able to reduce Cox-2 level.[6],[23],[24],[27]

Patients with IBD exacerbations have shown an enhancement in platelet numbers.[49] Platelets have several important roles such as modulatory role for the activity of other inflammatory cells, release of inflammatory mediators, recruitment, and chemotaxis.[50] Therefore, herbal antiplatelet drugs such as Angelica sinensis can suppress platelet activation, moderate the injury of endothelial cells, and improve microtransmission in IBD patients.[51],[52]

 Clinical Trials

The clinical trials on the effects of herbal medicines for IBD patients are promising. Clinical remission and positive responses were detected in more number of UC patients who used gel of Aloe vera in comparison to placebo group. Components of the gel, mainly used for control of intestinal inflammatory process, are anthraquinones (aloe-emodin), aloesin, and aloin which were able to decrease myeloperoxidase (MPO), LTB4, pro-inflammatory cytokines such as TNF-α and IL-1β activities that their effects are blockage of the activation of the NF-κB pathway, and downexpression of TNF-α gene. Therefore, they greatly reduce the index of clinical colitis, activities, progression, and histological scores of these patients.[53],[54],[55],[56],[57]

Distribution of the capsules containing components of cardamonin and wormwood decreased TNF-α serum level and pro-inflammatory cytokines such as IL-1β or IL-6, NF-κB, PGE2, COX-2 expression, iNOS, and NO. In CD patients, the symptoms were completely remitted in 65% of the patients in comparison to placebo group.[58],[59],[60],[61]

The diterpene lactone, andrographolide from Andrographis paniculata and A. paniculata reduced the cytokines of multiple pro-inflammation, including NF-κB, cysteine 62 of p50 subunit, inducible NO synthase (iNOS), TNF-α, IL-1β, IL-2 release and ERK1/2 phosphorylation following modulation of PKC-pathway, and reduction in the levels of several genes expressions such as TNF-α, p35, p40, IL-12, IL-16, and IL-12.[62],[63],[64],[65],[66],[67],[68],[69] The results revealed a significant reduction in the CD Activity Index in the patients who treated with the extract of the plant in comparison to placebo group.[70],[71] [Table 2] demonstrates detailed data of clinical trials from the use of herbal medicines in IBD patients.{Table 2}

Histopathology and scanning in electron microscopy have shown improvement in most of the parameters such as stool properties in UC patients that treated by Boswellia serrata extract for 6 weeks.[76] Boswellic acid component reduces lipid peroxidation, NF-κB activation, block the 5-lipoxygenase pathway, and increase the levels of superoxide dismutase in intestinal inflammation.[79],[80],[81]

Curcumin (the active component of C. longa)is effective in modification of signaling pathways such as MAPK and ERK, in expression of cascade, such as MPO, COX-2, iNOS, and LOX, and in decreasing the expression of TNFα, IL-1β, IL-12, or IFNγ, and NF-κB, but it is able to increasing the expression ofanti-inflammatory cytokines.[82],[83],[84],[85],[86] Potential of curcumin in modulating the NF-κB activity may hinder inflammatory responses and prevent the colonic mucosa damage.

Two clinical trials investigated the effects of Tripterygium wilfordii on prevention of postoperative recurrence in CD patients. In this trial, 45 CD patients received T. wilfordii extract. No recurrence was occurred during 3 months with no significant difference in relapse during 6–12 months of trial.[87] In the second trial, the CD patients were subjected to T. wilfordii extract 2 weeks after operation. The clinical recurrence was reported in 6%, however, endoscopic recurrence in these patients was 22%.[88]

Grass juice derived from Triticum aestivum improved the index of total disease activity and the severity of bowel bleeding of UC patients.[89]

The marijuana plant Cannabis sativa use in human IBD; there are very few controlled trials. In a study that cannabis was used in 291 patients with IBD, the pain and diarrhea were improved in CD patients [Table 2].[90],[91]


Side effects and acceptable safety of conventional therapies have caused an increased interest in herbal therapies for the management of IBD and other diseases. Herbal remedies have been shown to decrease histological damage, increase the disease activity index as well as the level of clinical response, improve the remission and decrease the relapse rates, improve stool consistency, and ameliorate rectal bleeding in IBD patients. Oxidative stress, allergy, psychological factors, platelets, LTB4, iNOS, and NF-κB are involved in pathogenesis of IBD.[92],[93],[94],[95] Herbal medicines have shown to improve these parameters by several mechanisms, including antioxidant activity, inhibition of IKK or NF-κB, suppression of LTB4, inhibition of platelets, and iNOS activities.

In UC patients, the extract of A. paniculata, gel of Aloe vera, powder of curcumin, and juiceofwheat grass (T. aestivum) in comparison to placebo significantly increased the remission maintenance or response. Seeds of Plantago ovata and gum resin of Boswellia serrata showed efficacy the same as mesalazine, whereas in UC therapy, the oil ofevening primrose (Oenothera biennis) had the relapse rate the same as omega-3 fatty acids. In CD therapy, T. wilfordii and Artemisia absinthium both were superior to placebo group in induction of remission, as well as in clinical recurrence prevention of postoperative CD.

Although some herbal remedies have been used for treatment of IBD patients were effective, there is no strong evidence for recommendation of these drugs in IBD as a single effective treatment. It must be emphasized that the role of phytotherapies is limited to supplementary component. The most IBD patients have good response to conventional therapy. The problem is refractory and complicated cases that almost always excluded in the herbal treatment research. Lack of reproducibility, the licensing requirements, lack of scientific knowledge of indications for the products of medicinal plants, are some problems in the use of herbal medicines in IBD.[53] Furthermore, because of ethical issues in these studies patients with low or moderate activity index have been selected. Moreover, in many of these researches, the effect of herbal drugs has been compared with placebo. There is a lack of studies with large sample size and head to head comparison of phytotherapy and conventional drug therapy for IBD. Other problem is that most studies have been performed in animal models and clinical trials, as mentioned in the manuscript, are limited with low sample size. Therefore, more clinical studies are suggested to obtain reliable results for the use of medicinal plants in IBD. It also should be emphasized that these herbal drugs have not magic effect in treatment of IBD and there is no significant effect as a single therapy.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


1de Mattos BR, Garcia MP, Nogueira JB, Paiatto LN, Albuquerque CG, Souza CL, et al. Inflammatory bowel disease: An overview of immune mechanisms and biological treatments. Mediators Inflamm 2015;2015:493012.
2Mizoguchi A, Takeuchi T, Himuro H, Okada T, Mizoguchi E. Genetically engineered mouse models for studying inflammatory bowel disease. J Pathol 2016;238:205-19.
3Stepaniuk P, Bernstein CN, Targownik LE, Singh H. Characterization of inflammatory bowel disease in elderly patients: A review of epidemiology, current practices and outcomes of current management strategies. Can J Gastroenterol Hepatol 2015;29:327-33.
4Dong J, Chen Y, Tang Y, Xu F, Yu C, Li Y, et al. Body mass index is associated with inflammatory bowel disease: A systematic review and meta-analysis. PLoS One 2015;10:e0144872.
5Ribaldone DG, Fagoonee S, Astegiano M, De Angelis C, Smedile A, Caviglia GP, et al. Coxib's safety in patients with inflammatory bowel diseases: A meta-analysis. Pain Physician 2015;18:599-607.
6Kozuch PL, Hanauer SB. Treatment of inflammatory bowel disease: A review of medical therapy. World J Gastroenterol 2008;14:354-77.
7Atreya R, Neumann H, Neurath MF. Update: Chronic inflammatory bowel disease. Dtsch Med Wochenschr 2015;140:1762-72.
8Brown SR, Coviello LC. Extraintestinal manifestations associated with inflammatory bowel disease. Surg Clin North Am 2015;95:1245-59, vii.
9Vanhove W, Nys K, Vermeire S. Therapeutic innovations in inflammatory bowel diseases. Clin Pharmacol Ther 2016;99:49-58.
10Hilsden RJ, Verhoef MJ, Rasmussen H, Porcino A, DeBruyn JC. Use of complementary and alternative medicine by patients with inflammatory bowel disease. Inflamm Bowel Dis 2011;17:655-62.
11Hung A, Kang N, Bollom A, Wolf JL, Lembo A. Complementary and alternative medicine use is prevalent among patients with gastrointestinal diseases. Dig Dis Sci 2015;60:1883-8.
12Nasri H, Shirzad H. Toxicity and safety of medicinal plants. J Herbmed Plarmacol 2013;2:21-2.
13Papakostas GI. Tolerability of modern antidepressants. J Clin Psychiatry 2008;69 Suppl E1:8-13.
14Panossian A, Seo EJ, Wikman G, Efferth T. Synergy assessment of fixed combinations of herba andrographidis and radix eleutherococci extracts by transcriptome-wide microarray profiling. Phytomedicine 2015;22:981-92.
15Malik TA. Inflammatory bowel disease: Historical perspective, epidemiology, and risk factors. Surg Clin North Am 2015;95:1105-22, v.
16Danese S, Grisham M, Hodge J, Telliez JB. JAK inhibition using tofacitinib for inflammatory bowel disease treatment: A hub for multiple inflammatory cytokines. Am J Physiol Gastrointest Liver Physiol 2016;310:G155-62.
17de Souza HS, Fiocchi C. Immunopathogenesis of IBD: Current state of the art. Nat Rev Gastroenterol Hepatol 2016;13:13-27.
18Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, Hui KY, et al. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 2012;491:119-24.
19Muro M, López-Hernández R, Mrowiec A. Immunogenetic biomarkers in inflammatory bowel diseases: Role of the IBD3 region. World J Gastroenterol 2014;20:15037-48.
20Gersemann M, Wehkamp J, Stange EF. Innate immune dysfunction in inflammatory bowel disease. J Intern Med 2012;271:421-8.
21Liu QL, Huang L, Zhao QJ, Li Q, He Z. Relationship between serum interleukin-17 level and inflammatory bowel disease. J Biol Regul Homeost Agents 2016;30:181-8.
22Hlavaty T, Krajcovicova A, Letkovsky J, Sturdik I, Koller T, Toth J, et al. Relapse rates of inflammatory bowel disease patients in deep and clinical remission after discontinuing anti-tumor necrosis factor alpha therapy. Bratisl Lek Listy 2016;117:205-11.
23Zhang M, Deng CS, Zheng JJ, Xia J. Curcumin regulated shift from th1 to th2 in trinitrobenzene sulphonic acid-induced chronic colitis. Acta Pharmacol Sin 2006;27:1071-7.
24Jiang H, Deng CS, Zhang M, Xia J. Curcumin-attenuated trinitrobenzene sulphonic acid induces chronic colitis by inhibiting expression of cyclooxygenase-2. World J Gastroenterol 2006;12:3848-53.
25Deguchi Y, Andoh A, Inatomi O, Yagi Y, Bamba S, Araki Y, et al. Curcumin prevents the development of dextran sulfate sodium (DSS)-induced experimental colitis. Dig Dis Sci 2007;52:2993-8.
26Camacho-Barquero L, Villegas I, Sánchez-Calvo JM, Talero E, Sánchez-Fidalgo S, Motilva V, et al. Curcumin, a curcuma longa constituent, acts on MAPK p38 pathway modulating COX-2 and iNOS expression in chronic experimental colitis. Int Immunopharmacol 2007;7:333-42.
27Oh PS, Lim KT. Plant originated glycoprotein has anti-oxidative and anti-inflammatory effects on dextran sulfate sodium-induced colitis in mouse. J Biomed Sci 2006;13:549-60.
28Ukil A, Maity S, Das PK. Protection from experimental colitis by theaflavin-3,3'-digallate correlates with inhibition of IKK and NF-kappaB activation. Br J Pharmacol 2006;149:121-31.
29Maity S, Ukil A, Karmakar S, Datta N, Chaudhuri T, Vedasiromoni JR, et al. Thearubigin, the major polyphenol of black tea, ameliorates mucosal injury in trinitrobenzene sulfonic acid-induced colitis. Eur J Pharmacol 2003;470:103-12.
30Micallef MJ, Iwaki K, Ishihara T, Ushio S, Aga M, Kunikata T, et al. The natural plant product tryptanthrin ameliorates dextran sodium sulfate-induced colitis in mice. Int Immunopharmacol 2002;2:565-78.
31Murakami A, Hayashi R, Tanaka T, Kwon KH, Ohigashi H, Safitri R, et al. Suppression of dextran sodium sulfate-induced colitis in mice by zerumbone, a subtropical ginger sesquiterpene, and nimesulide: Separately and in combination. Biochem Pharmacol 2003;66:1253-61.
32Yousefi B, Jadidi-Niaragh F, Azizi G, Hajighasemi F, Mirshafiey A. The role of leukotrienes in immunopathogenesis of rheumatoid arthritis. Mod Rheumatol 2014;24:225-35.
33Jupp J, Hillier K, Elliott DH, Fine DR, Bateman AC, Johnson PA, et al. Colonic expression of leukotriene-pathway enzymes in inflammatory bowel diseases. Inflamm Bowel Dis 2007;13:537-46.
34Chernyavsky AI, Galitovskiy V, Shchepotin IB, Grando SA. Anti-inflammatory effects of the nicotinergic peptides SLURP-1 and SLURP-2 on human intestinal epithelial cells and immunocytes. Biomed Res Int 2014;2014:609086.
35Kirk KF, Nielsen HL, Thorlacius-Ussing O, Nielsen H. Optimized cultivation of campylobacter concisus from gut mucosal biopsies in inflammatory bowel disease. Gut Pathog 2016;8:27.
36Vilahur G, Badimon L. Antiplatelet properties of natural products. Vascul Pharmacol 2013;59:67-75.
37D'Ignazio L, Bandarra D, Rocha S. NF-κB and HIF crosstalk in immune responses. FEBS J 2016;283:413-24.
38Vlantis K, Wullaert A, Polykratis A, Kondylis V, Dannappel M, Schwarzer R, et al. NEMO prevents RIP kinase 1-mediated epithelial cell death and chronic intestinal inflammation by NF-κB-dependent and -independent functions. Immunity 2016;44:553-67.
39Baratchian M, Davis CA, Shimizu A, Escors D, Bagnéris C, Barrett T, et al. Distinct activation mechanisms of NF-κB regulator inhibitor of NF-κB kinase (IKK) by isoforms of the cell death regulator cellular FLICE-like inhibitory protein (cFLIP). J Biol Chem 2016;291:7608-20.
40Cheon JH, Kim JS, Kim JM, Kim N, Jung HC, Song IS, et al. Plant sterol guggulsterone inhibits nuclear factor-kappaB signaling in intestinal epithelial cells by blocking ikappaB kinase and ameliorates acute murine colitis. Inflamm Bowel Dis 2006;12:1152-61.
41Zhang Y, Duan RD. Boswellic acid inhibits expression of acid sphingomyelinase in intestinal cells. Lipids Health Dis 2009;8:51.
42Goel A, Ahmad FJ, Singh RM, Singh GN. 3-acetyl-11-keto-beta-boswellic acid loaded-polymeric nanomicelles for topical anti-inflammatory and anti-arthritic activity. J Pharm Pharmacol 2010;62:273-8.
43Martín MC, Martinez A, Mendoza JL, Taxonera C, Díaz-Rubio M, Fernández-Arquero M, et al. Influence of the inducible nitric oxide synthase gene (NOS2A) on inflammatory bowel disease susceptibility. Immunogenetics 2007;59:833-7.
44Wan Saudi WS, Halim MA, Rudholm-Feldreich T, Gillberg L, Rosenqvist E, Tengholm A, et al. Neuropeptide S inhibits gastrointestinal motility and increases mucosal permeability through nitric oxide. Am J Physiol Gastrointest Liver Physiol 2015;309:G625-34.
45Rezaie A, Khalaj S, Shabihkhani M, Nikfar S, Zamani MJ, Mohammadirad A, et al. Study on the correlations among disease activity index and salivary transforming growth factor-beta 1 and nitric oxide in ulcerative colitis patients. Ann N Y Acad Sci 2007;1095:305-14.
46Wang X, Zhao L, Han T, Chen S, Wang J. Protective effects of 2,3,5,4'-tetrahydroxystilbene-2-O-beta-d-glucoside, an active component of Polygonum multiflorum thunb, on experimental colitis in mice. Eur J Pharmacol 2008;578:339-48.
47Miao XP, Li JS, Ouyang Q, Hu RW, Zhang Y, Li HY, et al. Tolerability of selective cyclooxygenase 2 inhibitors used for the treatment of rheumatological manifestations of inflammatory bowel disease. Cochrane Database Syst Rev 2014;(10):CD007744.
48El Miedany Y, Youssef S, Ahmed I, El Gaafary M. The gastrointestinal safety and effect on disease activity of etoricoxib, a selective cox-2 inhibitor in inflammatory bowel diseases. Am J Gastroenterol 2006;101:311-7.
49Giannotta M, Tapete G, Emmi G, Silvestri E, Milla M. Thrombosis in inflammatory bowel diseases: What's the link? Thromb J 2015;13:14.
50Voudoukis E, Karmiris K, Koutroubakis IE. Multipotent role of platelets in inflammatory bowel diseases: A clinical approach. World J Gastroenterol 2014;20:3180-90.
51Pitchford SC. Novel uses for anti-platelet agents as anti-inflammatory drugs. Br J Pharmacol 2007;152:987-1002.
52Kulnigg-Dabsch S, Schmid W, Howaldt S, Stein J, Mickisch O, Waldhör T, et al. Iron deficiency generates secondary thrombocytosis and platelet activation in IBD: The randomized, controlled thromboVIT trial. Inflamm Bowel Dis 2013;19:1609-16.
53Langhorst J, Wulfert H, Lauche R, Klose P, Cramer H, Dobos GJ, et al. Systematic review of complementary and alternative medicine treatments in inflammatory bowel diseases. J Crohns Colitis 2015;9:86-106.
54Rahimi R, Mozaffari S, Abdollahi M. On the use of herbal medicines in management of inflammatory bowel diseases: A systematic review of animal and human studies. Dig Dis Sci 2009;54:471-80.
55Park MY, Kwon HJ, Sung MK. Dietary aloin, aloesin, or aloe-gel exerts anti-inflammatory activity in a rat colitis model. Life Sci 2011;88:486-92.
56Stenson WF. Role of eicosanoids as mediators of inflammation in inflammatory bowel disease. Scand J Gastroenterol Suppl 1990;172:13-8.
57Kumar S, Singh BK, Pandey AK, Kumar A, Sharma SK, Raj HG, et al. Achromone analog inhibits TNF-alpha induced expression of cell adhesion molecules on human endothelial cells via blocking NF-kappaB activation. Bioorg Med Chem 2007;15:2952-62.
58Omer B, Krebs S, Omer H, Noor TO. Steroid-sparing effect of wormwood (Artemisia absinthium) in Crohn's disease: A double-blind placebo-controlled study. Phytomedicine 2007;14:87-95.
59Altwegg R, Vincent T. TNF blocking therapies and immunomonitoring in patients with inflammatory bowel disease. Mediators Inflamm 2014;2014:172821.
60Lee HG, Kim H, Oh WK, Yu KA, Choe YK, Ahn JS, et al. Tetramethoxy hydroxyflavone p7F downregulates inflammatory mediators via the inhibition of nuclear factor kappaB. Ann N Y Acad Sci 2004;1030:555-68.
61Hatziieremia S, Gray AI, Ferro VA, Paul A, Plevin R. The effects of cardamonin on lipopolysaccharide-induced inflammatory protein production and MAP kinase and NFkappaB signalling pathways in monocytes/macrophages. Br J Pharmacol 2006;149:188-98.
62Denzler KL, Waters R, Jacobs BL, Rochon Y, Langland JO. Regulation of inflammatory gene expression in PBMCs by immunostimulatory botanicals. PLoS One 2010;5:e12561.
63Xia YF, Ye BQ, Li YD, Wang JG, He XJ, Lin X, et al. Andrographolide attenuates inflammation by inhibition of NF-kappa B activation through covalent modification of reduced cysteine 62 of p50. J Immunol 2004;173:4207-17.
64Levita J, Nawawi AA, Mutalib A, Ibrahim S. Andrographolide: A review of its anti-inflammatory activity via inhibition of NF-kappaB activation from computational chemistry aspects. Int J Pharmacol 2010;6:569-76.
65Chiou WF, Chen CF, Lin JJ. Mechanisms of suppression of inducible nitric oxide synthase (iNOS) expression in RAW 264.7 cells by andrographolide. Br J Pharmacol 2000;129:1553-60.
66Shen YC, Chen CF, Chiou WF. Andrographolide prevents oxygen radical production by human neutrophils: Possible mechanism(s) involved in its anti-inflammatory effect. Br J Pharmacol 2002;135:399-406.
67Burgos RA, Seguel K, Perez M, Meneses A, Ortega M, Guarda MI, et al. Andrographolide inhibits IFN-gamma and IL-2 cytokine production and protects against cell apoptosis. Planta Med 2005;71:429-34.
68Iruretagoyena MI, Tobar JA, González PA, Sepúlveda SE, Figueroa CA, Burgos RA, et al. Andrographolide interferes with T cell activation and reduces experimental autoimmune encephalomyelitis in the mouse. J Pharmacol Exp Ther 2005;312:366-72.
69Liu J, Wang ZT, Ge BX. Andrograpanin, isolated from andrographis paniculata, exhibits anti-inflammatory property in lipopolysaccharide-induced macrophage cells through down-regulating the p38 MAPKs signaling pathways. Int Immunopharmacol 2008;8:951-8.
70Tang T, Targan SR, Li ZS, Xu C, Byers VS, Sandborn WJ, et al. Randomised clinical trial: Herbal extract HMPL-004 in active ulcerative colitis – A double-blind comparison with sustained release mesalazine. Aliment Pharmacol Ther 2011;33:194-202.
71Recio MC, Andujar I, Rios JL. Anti-inflammatory agents from plants: Progress and potential. Curr Med Chem 2012;19:2088-103.
72Langmead L, Feakins RM, Goldthorpe S, Holt H, Tsironi E, De Silva A, et al. Randomized, double-blind, placebo-controlled trial of oral Aloe vera gel for active ulcerative colitis. Aliment Pharmacol Ther 2004;19:739-47.
73Ben-Arye E, Goldin E, Wengrower D, Stamper A, Kohn R, Berry E, et al. Wheat grass juice in the treatment of active distal ulcerative colitis: A randomized double-blind placebo-controlled trial. Scand J Gastroenterol 2002;37:444-9.
74Sandborn WJ, Targan SR, Byers VS, Rutty DA, Mu H, Zhang X, et al. Andrographis paniculata extract (HMPL-004) for active ulcerative colitis. Am J Gastroenterol 2013;108:90-8.
75Rodríguez-Cabezas ME, Gálvez J, Camuesco D, Lorente MD, Concha A, Martinez-Augustin O, et al. Intestinal anti-inflammatory activity of dietary fiber (Plantago ovata seeds) in HLA-B27 transgenic rats. Clin Nutr 2003;22:463-71.
76Gupta I, Parihar A, Malhotra P, Gupta S, Lüdtke R, Safayhi H, et al. Effects of gum resin of boswellia serrata in patients with chronic colitis. Planta Med 2001;67:391-5.
77Greenfield SM, Green AT, Teare JP, Jenkins AP, Punchard NA, Ainley CC, et al. Arandomized controlled study of evening primrose oil and fish oil in ulcerative colitis. Aliment Pharmacol Ther 1993;7:159-66.
78Algieri F, Rodriguez-Nogales A, Rodriguez-Cabezas ME, Risco S, Ocete MA, Galvez J, et al. Botanical drugs as an emerging strategy in inflammatory bowel disease: A review. Mediators Inflamm 2015;2015:179616.
79Stanke-Labesque F, Pofelski J, Moreau-Gaudry A, Bessard G, Bonaz B. Urinary leukotriene E4 excretion: A biomarker of inflammatory bowel disease activity. Inflamm Bowel Dis 2008;14:769-74.
80Takada Y, Ichikawa H, Badmaev V, Aggarwal BB. Acetyl-11-keto-beta-boswellic acid potentiates apoptosis, inhibits invasion, and abolishes osteoclastogenesis by suppressing NF-kappa B and NF-kappa B-regulated gene expression. J Immunol 2006;176:3127-40.
81Wang H, Syrovets T, Kess D, Büchele B, Hainzl H, Lunov O, et al. Targeting NF-kappa B with a natural triterpenoid alleviates skin inflammation in a mouse model of psoriasis. J Immunol 2009;183:4755-63.
82Chattopadhyay I, Biswas K, Bandyopadhyay U, Banerjee RK. Turmeric and curcumin: Biological actions and medicinal applications. Curr Sci 2004;87:44-53.
83Ukil A, Maity S, Karmakar S, Datta N, Vedasiromoni JR, Das PK, et al. Curcumin, the major component of food flavour turmeric, reduces mucosal injury in trinitrobenzene sulphonic acid-induced colitis. Br J Pharmacol 2003;139:209-18.
84Larmonier CB, Uno JK, Lee KM, Karrasch T, Laubitz D, Thurston R, et al. Limited effects of dietary curcumin on th-1 driven colitis in IL-10 deficient mice suggest an IL-10-dependent mechanism of protection. Am J Physiol Gastrointest Liver Physiol 2008;295:G1079-91.
85Epstein J, Docena G, MacDonald TT, Sanderson IR. Curcumin suppresses p38 mitogen-activated protein kinase activation, reduces IL-1beta and matrix metalloproteinase-3 and enhances IL-10 in the mucosa of children and adults with inflammatory bowel disease. Br J Nutr 2010;103:824-32.
86Venkataranganna MV, Rafiq M, Gopumadhavan S, Peer G, Babu UV, Mitra SK, et al. NCB-02 (standardized curcumin preparation) protects dinitrochlorobenzene- induced colitis through down-regulation of NFkappa-B and iNOS. World J Gastroenterol 2007;13:1103-7.
87Tao QS, Ren JA, Ji ZL, Li JS, Wang XB, Jiang XH, et al. Maintenance effect of polyglycosides of Tripterygium wilfordii on remission in postoperative Crohn disease. Zhonghua Wei Chang Wai Ke Za Zhi 2009;12:491-3.
88Liao NS, Ren JA, Fan CG, Wang GF, Zhao YZ, Li JS, et al. Efficacy of polyglycosides of Tripterygium wilfordii in preventing postoperative recurrence of Crohn disease. Zhonghua Wei Chang Wai Ke Za Zhi 2009;12:167-9.
89Rahimi R, Nikfar S, Abdollahi M. Induction of clinical response and remission of inflammatory bowel disease by use of herbal medicines: A meta-analysis. World J Gastroenterol 2013;19:5738-49.
90Lal S, Prasad N, Ryan M, Tangri S, Silverberg MS, Gordon A, et al. Cannabis use amongst patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol 2011;23:891-6.
91Naftali T, Mechulam R, Lev LB, Konikoff FM. Cannabis for inflammatory bowel disease. Dig Dis 2014;32:468-74.
92Imanzadeh F, Nasri P, Sadeghi S, Sayyari A, Dara N, Abdollah K, et al. Food allergy among Iranian children with inflammatory bowel disease: A preliminary report. J Res Med Sci 2015;20:855-9.
93Tabatabaeian M, Afshar H, Roohafza HR, Daghaghzadeh H, Feizi A, Sharbafchi MR, et al. Psychological status in Iranian patients with ulcerative colitis and its relation to disease activity and quality of life. J Res Med Sci 2015;20:577-84.
94Tabatabaeian M, Afshar H, Roohafza HR, Daghaghzadeh H, Feizi A, Sharbafchi MR, et al. Psychological status in Iranian patients with ulcerative colitis and its relation to disease activity and quality of life. J Res Med Sci 2015;20:577-84. doi: 10.4103/1735-1995.165962.
95Minaiyan M, Mostaghel E, Mahzouni P. Preventive therapy of experimental colitis with selected iron chelators and anti-oxidants. Int J Prev Med 2012;3:S162-9.