Table 5.

Curcuminoids, olive-associated polyphenols (including secoiridoids and 5-HT), coumarins, and flavonolignans

Subgroups	Compounds	Dietary/Exogenous sources	Mechanisms of action (Preclinical models)	Studies in humans (including observational and intervention studies	References
Curcuminoids	Curcumin	Turmeric	Is a potent anti-inflammatory and antioxidant with broad therapeutic potential, including anti-tumor, anti-apoptotic, and immunomodulatory effects. It modulates multiple inflammatory pathways, including NF-κB, COX, and various cytokines, and influences iron metabolism and autophagy in IBDs	Human studies show curcumin´s promise managing IBD, particularly UC. Clinical trials report significant improvements in disease activity, inflammatory markers, and quality of life with curcumin supplementation. However, some studies yielded mixed results, underscoring the need for standardized dosages, formulations, and further large-scale trials to validate curcumin´s efficacy as an adjunct therapy in IBd management	501-528
Secoiridoids and polyphenols from olives/EVOO	Extra virgin olive oil	Olives/EVOO	Preclinical studies demonstrated the potential of EVOO in managing IBD, with findings showing that EVOO can reduce inflammation, oxidative stress, and cell damage in various models. It has been found to modulates cytokines, COX-2, and iNOS while influencing signaling pathways like MAPk and PPARγ	Clinical trials on EVOO and its poluphenols for IBd are limited. Studies have shown that EVOO can reduce inflammation markers and gastrointestinal symptoms in Uc patients and that phenolic-rich EVOO can enhance cardioprotective benefits and gut microbiota. Also, Mediterranean diet, including EVOO, has demonstrated over all benefits for IBD management, such as improved BMI, reduced inflammation, and better disease management compared to other diets	533-535,537-545
	Hydroxytyrosol		Has shown promising results in preclinical IBD models. Studies demonstrate that HT reduces inflammation, oxidative stress, and apoptosis while enhancing antioxidant defenses and gut microbiota composition	-	546-551
	Oleuropein		Studies reveal that Ole reduces oxidative stress, inflammation, and apoptosis, and improves disease activity in UC models. It decreases pro-inflammatory cytokines and COX-2 expression while promoting healing and enhancing antioxidant defenses	-	552-554
Coumarins	Esculetin and 4- methylesculetin	Cinnamon; Vegetables, spices, fruits, and medicinal plants including all parts of the plants-fruits, roots, stems and leaves	Esculetin at 5 mg/kg in a rat TNBS-induced IBD model, exhibited strong anti-inflammatory effects, reducing MDA levels, preventing GSH depletion, and decreasing pro-inflammatory cytokines. It showed efficacy comparable to prednisolone and was 10 tomes more effective than sulfasalazine. Similarly, 4-methyl-esculetin demonstrated superior efficacy in reducing colitis symptoms, preventing GSH depletion, and inhibiting inflammation, with effects comparable to established treatments	-	557-562
	Aesculin		Showing minimal cytotoxicity, significantly alleviated DSS-induced colitis symptoms by reducing inflammatory factors like iNOS, IL-1β, and TNF-α. It also attenuated NF-κB signaling and enhanced PPARγ nuclear localization	-	563
	Daphnetin		He et al. found that daphnetin alleviated colitis severity in mice by improving intestinal structure, increasing ZO-1, occludin, and BCL-2 levels, and reducing Bax and cleaved caspase 3 expression. It also suppressed MAD, SOD activities, inflammatory cytokines, and apoptosis, while inhibiting JAK/STAT signaling via REG3A activation	-	565
	Fraxetin		Demonstrated notable efficacy in mitigating DSS-induced colitis symptoms, including body weight loss, colon shortening, tissue damage, and disease activity index. It also inhibits NF-κB pathway, suppression of NLRP3 inflammasome, restoration of Gut barrier function, and modulation of gut microbiota	-	566
	Umbelliferone		Improves macroscopic and histological damage in an acetic acid-induced UC rat model. It reduced inflammatory markers, downregulated TLR4, NF-κB, and iNOS, and upregulated SIRT1 and PPARγ signaling pathways	-	567
	Paepalantine		Alleviates TNBS-induced colonic damage in mice at 5 and 10 mg/kg. it improved mucosal recovery and reduced oxidative stress by preventing glutathione depletion and inhibiting nitric oxide activity	-	569
	Coumarin		Reduces colonic damage in TNBS-induced colitis models. Their protective effect was linked to preventing glutathione depletion caused by inflammation	-	570
Flavonolignanes	Silymarin	Milk thistle (Sylybum marianum)	Is a potent anti-inflammatory that inhibits NF-κB pathways and enhances antioxidant defenses via Nrf2 activation. It shows potential as a tool against viral-associated IBD due to its properties and effectiveness in reducing colitis symptoms	In a randomized, double-blinded trial with 80 UC patients, silibin supplementation improved hemoglobin levels, erythrocyte sedimentation rate, and disease activity index, helping maintain remission better than placebo	573,575-578,581
	Silibin	Sylybum marianum	Has ant-inflammatory and chemopreventine benefits I preclinical IBD models. In a TNBS-induced colitis rat model, silybin reduced NF-κB activity and inflammatory markers, enhancing antioxidant defenses	-	579,580