Protective role of flavonoids quercetin and silymarin in the viral-associated inflammatory bowel disease: an updated review

Abstract

Inflammatory bowel disease (IBD) is a chronic recurrent inflammation of the gastrointestinal tract (GIT). IBD patients are susceptible to various infections such as viral infections due to the long-term consumption of immunosuppressive drugs and biologics. The antiviral and IBD protective traits of flavonoids have not been entirely investigated. This study objective included an overview of the protective role of flavonoids quercetin and silymarin in viral-associated IBD. Several viral agents such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV) and enteric viruses can be reactivated and thus develop or exacerbate the IBD conditions or eventually facilitate the disease remission. Flavonoids such as quercetin and silymarin are non-toxic and safe bioactive compounds with remarkable anti-oxidant, anti-inflammatory and anti-viral effects. Mechanisms of anti-inflammatory and antiviral effects of silymarin and quercetin mainly include immune modulation and inhibition of caspase enzymes, viral binding and replication, RNA synthesis, viral proteases and viral assembly. In the nutraceutical sector, natural flavonoids low bioavailability and solubility necessitate the application of delivery systems to enhance their efficacy. This review study provided an updated understanding of the protective role of quercetin and silymarin against viral-associated IBD.

Keywords: Antiviral traits; Inflammatory bowel diseases; Quercetin; Silymarin; Viral infections.

Fig. 1

The role of gut microbiota in GIT (gastrointestinal tract) health and IBD (inflammatory bowel disease) prevention; the consumption of vegetables and fruits, fiber, vitamins and n-3 PUFAs (polyunsaturated fatty acids) results in the gut microbiota prospering and proliferation exerting anti-inflammatory effects and offering the GIT protection. Additionally, these healthy foods directly regulate the Th1/Th2 cells and increase Treg and anti-inflammatory cytokines providing health conditions for the epithelial barrier. On the contrary, unhealthy foods such as SFAs, n-6 PUFAs, trans-FAs, sugar, red meat, processed meat and food additives decrease the microbial diversity and also beneficial bacteria. These conditions lead to the pathobionts population increase and subsequent development of epithelial inflammation (Jostins et al. ; Wallace et al. ; Cui and Yuan ; Andreou et al. ; Li et al. ; Liu et al. 2022). PUFAs poly-unsaturated fatty acids, TH1 T helper 1 or cytotoxic T cells, TH2 T helper 2 cells, Treg regulatory T cells, FAs fatty acids, SFAs saturated fatty acids

Fig. 2

The imbalance of Gut microbiota causing the IBD progression; a healthy gut preserves intestinal homeostasis via sufficient production of short-chain fatty acids (SCFAs) and vitamins and bile acid metabolism which maintain the balance within the gut microbiota and lessens the inflammation. However, in IBD conditions, these products are decreased leading to a low diversity of beneficial bacteria and their metabolites, resulting in gut inflammation. Th T helper cell, Treg regulatory T cell

Fig. 3

Structure of quercetin and silymarin

Fig. 4

The anti-inflammatory effects of quercetin via regulation of various signaling pathways such as TXNIP-NLRP3 inflammasome, SIRT1-NLRP3 pathway, NLRP3/ASC caspase activating, gut microbiome maintenance and T cells and cytokines/chemokines regulation; TXNIP thioredoxin (TRX)-interacting protein, NLRP3 NOD-like receptor family pyrin domain-containing 3, SIRT1 sirtuin (silent mating-type information regulation 2 homolog) 1, ASC apoptotic speck-like protein containing a caspase recruitment domain, Th T helper cell, Treg regulatory T cell, IL interleukin, TNF-α tumor necrosis factor α, PGE-2 prostaglandin E2, COX-2 cyclooxygenase-2, iNOS inducible nitric oxide synthase. Silibinin is the major active component of silymarin which also exhibits antioxidative, anticancer and antimicrobial traits (Ravichandran et al. ; Mariño et al. ; Rendina et al. 2014)

Fig. 5

The protective and effects of silymarin including antiviral, antioxidant, anti-arthritis, anti-inflammatory, antidiabetic protective and wound healing mechanisms; GPx glutathione peroxidase, CAT catalase, MDA malondialdehyde, GSH glutathione, SOD superoxide dismutase, PGA prostaglandin, IL interleukin, TNF-α tumor necrosis factor α, HMG-CoA 3-hydroxy-3-methylglutaryl coenzyme A (Saeed et al. 2017). Details of association of various viral agents in IBD and each flavonoid antiviral effects have not been evaluated. The objective of this review was to provide an update regarding the effects of viral agents on IBD development and antiviral properties of quercetin and silymarin considering their anti-inflammatory effects

Fig. 6

Flowchart of the methodology applied in this review