Glycosides as Potential Medicinal Components for Ulcerative Colitis: A Review

Abstract

Ulcerative colitis (UC) is a chronic, non-specific disease of unknown etiology. The disease develops mainly in the rectum or colon, and the main clinical symptoms include abdominal pain, diarrhea, and purulent bloody stools, with a wide variation in severity. The specific causative factors and pathogenesis of the disease are not yet clear, but most scholars believe that the disease is caused by the interaction of genetic, environmental, infectious, immune, and intestinal flora factors. As for the treatment of UC, medications are commonly used in clinical practice, mainly including aminosalicylates, glucocorticoids, and immunosuppressive drugs. However, due to the many complications associated with conventional drug therapy and the tendency for UC to recur, there is an urgent need to discover new, safer, and more effective drugs. Natural compounds with biodiversity and chemical structure diversity from medicinal plants are the most reliable source for the development of new drug precursors. Evidence suggests that glycosides may reduce the development and progression of UC by modulating anti-inflammatory responses, inhibiting oxidative stress, suppressing abnormal immune responses, and regulating signal transduction. In this manuscript, we provide a review of the epidemiology of UC and the available drugs for disease prevention and treatment. In addition, we demonstrate the protective or therapeutic role of glycosides in UC and describe the possible mechanisms of action to provide a theoretical basis for preclinical studies in drug development.

Keywords: epidemiology; glycosides; immune response; inflammatory response; oxidative stress; signal transduction; ulcerative colitis.

Figure 1

Structural formulae of several glycosides.

Figure 2

Glycosides and oxidative stress. All glycosides produced relief of UC by inhibited oxidative stress.

Figure 3

Glycosides and apoptosis. Salidroside 10 and polydatin 11 down-regulated the expression of Bax, caspase-3, and cleaved caspase-3 and up-regulated the expression of Bcl-2. Paeoniflorin 12, baicalin 2, and hyperoside 3 can down-regulate Bax. Aloin A 21 down-regulated cleaved caspase-3 expression.

Figure 4

Glycosides and intestinal epithelial barrier. Polydatin 11, baicalin 2, hyperoside 3, aloin A 21, linarin 5, vitexin 6, and naringin 7 can improve the expression of TJ proteins and mucin proteins, thus inhibiting the increase of the permeability of the intestinal mucosa to achieve regulation of intestinal epithelial barrier function.

Figure 5

Glycosides and Th17/Treg balance. Polydatin 11, salidroside 10, astragaloside Ⅳ 16, hyperoside 3, and mangiferin 4 produced relief of UC by regulating the balance of Th17/Treg cells.

Figure 6

Glycosides and UC-related receptors AND transcriptional regulation. Paeoniflorin 12, vitexin 6, and baicalin 2 produced relief of UC by reducing TLR4 expression and blocking the TLR4/NF-κB signaling pathway. Glycyrrhizin 15, convallatoxin 20, and naringin 7 produced relief of UC by suppressing the expression of NF-κB via activated PPARγ. Salidroside 10 and naringin 7 produced relief of UC by inhibiting the expression of inflammasome and thereby reducing the release of IL-1β. Punicalagin 8, paeoniflorin 12, pedunculoside 14, liriodendrin 19, baicalin 2, mangiferin 4, polydatin 11, and vitexin 6 produced relief of UC by blocking the NF-κB signaling pathway. Mangiferin 4, polydatin 11, pedunculoside 14, and paeoniflorin 12 produced relief of UC by blocking the MAPK signaling pathway. Asperuloside 13, hyperoside 3, and polydatin 11 produced relief of UC by blocking the Nrf2/HO-1 signaling pathway.

Figure 7

The mechanism of glycosides in the treatment of UC. Glycosides play a role in the treatment of UC through anti-inflammatory and antioxidant stress mechanisms, regulation of impaired intestinal epithelial barrier function, regulation of immune cells, and regulation of UC-related receptors and signal transduction.