Dietary diosgenin attenuates subacute intestinal inflammation associated with indomethacin in rats

Abstract

We investigated the effects of dietary diosgenin (Dio), a plant-derived sapogenin, on indomethacin (Indo)-induced intestinal inflammation and alterations in bile secretion in rats. In anesthetized rats, bile secretion, intestinal inflammation, and blood chemistry were assessed 3 days after two subcutaneous injections of Indo given 24 h apart. Dio (> 80 mg.kg-1.day-1) pretreatment significantly inhibited weight and food intake decreases and intestinal inflammation. This protective effect was confirmed by examination of gross and histological findings and intestinal myeloperoxidase activity. Dio significantly increased biliary cholesterol (Chol) output and prevented the decreases in bile flow, bile acid output, and biliary alpha-muricholic acid and the increases in biliary hyodeoxycholic acid, deoxycholic acid, and hydrophobicity index of bile. Significantly more biliary Chol and phospholipids were present in macromolecules separate from bile acids and Indo in Dio-treated rats. Dio significantly increased the elimination constant of Indo and reduced plasma Indo levels at 3 and 12 h but did not influence biliary secretion of Indo for 3.5 h after injection. Although Dio dose-dependently attenuated subacute intestinal inflammation and normalized bile secretion in this model, it may also compromise the anti-inflammatory action of indo.

Chemoprevention of Azoxymethane/Dextran Sodium Sulfate–Induced Mouse Colon Carcinogenesis by Freeze-Dried YamSanyakuand Its Constituent Diosgenin

“…It has also been reported that diosgenin antagonistically suppressed the inflammatory process in various animal models (38). Diosgenin dose-dependently attenuated subacute intestinal inflammation and normalized bile secretion in indomethacin-induced intestinal inflammation in rats (38). In this study, we showed that oral administration of diosgenin and sanyaku markedly reduced the expression levels of inflammatory cytokine genes, including IL-1b, IL-6, IL-12b, and TNF-a, which were significantly elevated in the colonic mucosa of mice treated with AOM/DSS (Fig.…”

“…Diosgenin inhibited the activity and expression of COX-2 in human osteosarcoma 1547 cells (33) and also abrogated basal and TNF-induced expression of COX-2 in KBM-5 cells (34), but upregulated COX-2 expression in human erythroleukemia cells (35) and noncancerous human rheumatoid arthritis synoviocytes (36). It has also been reported that diosgenin antagonistically suppressed the inflammatory process in various animal models (38). Diosgenin dose-dependently attenuated subacute intestinal inflammation and normalized bile secretion in indomethacin-induced intestinal inflammation in rats (38).…”

Diosgenin, an Activator of 1,25D3-MARRS Receptor/ERp57, Attenuates the Effects of TNF-α by Causing ADAM10-Dependent Ectodomain Shedding of TNF Receptor 1

“…For example, diosgenin has anti-inflammatory effects in animal studies [27-29]. TNF-α, a proinflammatory cytokine, plays a pivotal role in the inflammatory processes [30], while diosgenin may have anti-inflammatory effects by reducing the responsiveness of the cells to TNF-α via ADAM10-dependent ectodomain shedding of TNFR1.…”

Diosgenin inhibits osteoclastogenesis, invasion, and proliferation through the downregulation of Akt, IκB kinase activation and NF-κB-regulated gene expression

“…Antiproliferative effects of diosgenin are mediated through cell cycle arrest (Moalic et al, 2001;Liu et al, 2005), disruption of Ca 2 þ homeostasis (Leger et al, 2004;Liu et al, 2005), the activation of p53, release of apoptosis-inducing factor, and modulation of caspase-3 activity . It also inhibits azoxymethane-induced aberrant colon crypt foci (Raju et al, 2004) and has been shown to inhibit intestinal inflammation (Yamada et al, 1997) and modulate the activity of lipoxygenase (LOX) (Nappez et al, 1995) and cyclooxygenase-2 (COX-2) (Moalic et al, 2001). More recently, diosgenin has been shown to bind to the chemokine receptor CXCR3, which mediates inflammatory responses (Ondeykal et al, 2005).…”