Costus root granules improve ulcerative colitis through regulation of TGF-β mediation of the PI3K/AKT signaling pathway

Abstract

Ulcerative colitis is a chronic nonspecific inflammatory disease that occurs in the colon and rectum. Costus root is a type of traditional Chinese medicine that exhibits antibacterial properties and serves an inhibitory role in the regeneration of gut bacteria. However, the molecular mechanisms underlying Costus root-mediated improvements in ulcerative colitis remain unclear. A complex formula of Costus root granules was created and investigated in the present study for its therapeutic effects in a rat model of ulcerative colitis. Ingredient dissolution into a traditional water decoction was used as a control. The potential mechanism mediated by Costus root granules was also analyzed in colonic epithelial cells isolated from the experimental rats. The results of the present study demonstrated that Costus root granule treatment inhibited inflammation in colonic tissue. Costus root granule treatment also suppressed the apoptosis of colonic epithelial cells isolated from the rat model of ulcerative colitis. Analyses of the underlying mechanisms of these effects indicated that the administration of Costus root granules increased transforming growth factor β expression, which activated the phosphoinositide 3-kinase/RAC-α serine/threonine-protein kinase signaling pathway in colonic epithelial cells. Notably, the administration of Costus root granules improved stomachache, diarrhea and hematochezia in and increased the body weight of, the ulcerative colitis rats. In conclusion, these results indicate that Costus root granules markedly ameliorate inflammation of the colonic epithelium, decrease the apoptosis of colonic epithelial cells and improve colonic function, which suggests that Costus root granules are an efficient agent for the treatment of ulcerative colitis.

Molecular Targets and Mechanisms of Scutellariae radix-Coptidis rhizoma Drug Pair for the Treatment of Ulcerative Colitis Based on Network Pharmacology and Molecular Docking

“…The PI3K-AKT signaling pathway is involved in the regulation and release of proinflammatory cytokines, including TNF- α and other cytokines closely related to the inflammatory response of UC [ 67 ], and plays an important role in the development and progression of UC. TCMs inhibit transforming growth factor- β (TGF- β ) expression and lead to a decrease in PI3K/AKT activation, thereby alleviating the symptoms of UC by regulating TGF- β expression [ 68 ]. AGE and RAGE are involved in and mediate various signaling pathways of oxidative stress, induce ROS production, and activate NF- κ B, leading to inflammatory responses, cell apoptosis, and microvascular diseases [ 69 ].…”

Yu Shi An Chang Fang Ameliorates TNBS-Induced Colitis in Mice by Reducing Inflammatory Response and Protecting the Intestinal Mucosal Barrier

“…Although western medicine can instantly relieve symptoms of patients in previous treatments, the relapse of disease and the toxic and side effects of repeated drugs after treatment, all affect the treatment effect, safety, physical tolerance, and cooperation duration of UC patients. Thanks to minor side effects, Chinese medicine possessing anti-inflammatory effects has been increasingly investigated in recent decades [ 21 – 24 ]. The main ingredients of YST are Scutellaria baicalensis 20 g, Astragalus 15 g, Atractylodes 10 g, Licorice 10 g, Radix Paeoniae Alba 20 g, Cinnamon 5 g, Pueraria 15 g, Carbonized Catnip 15 g, Radix Sanguisorbae 30 g, Bletilla Striata 10 g, Frankincense 5 g, Herba Patriniae 30 g, Sargent Gloryvine 15 g, Panax Notoginseng powder 3 g. Scutellaria baicalensis Georgi ,and Paeonia lactiflora Pall could treat UC [ 25 , 26 ].…”

The Role of Extracellular Matrix Components in Inflammatory Bowel Diseases

“…Researchers also bring attention to the MMP inhibitors that show therapeutic potential in the treatment of IBD. The tested inhibitors are expected to reduce the expression of MMPs and therefore positively affect the course of the disease [ 37 , 39 , 40 ]. For example, administration of mesalamine may result in reduced MMP-2 expression and inflammation in the course of UC [ 39 ].…”

“…The tested inhibitors are expected to reduce the expression of MMPs and therefore positively affect the course of the disease [ 37 , 39 , 40 ]. For example, administration of mesalamine may result in reduced MMP-2 expression and inflammation in the course of UC [ 39 ]. Moreover, treatment of CD patients with immunosuppressives such as methotrexate, corticosteroids or anti-TNF therapeutics resulted in a decrease in epithelial MMP-7 and stromal MMP-9 and -26 which also led to improvement of patients [ 40 ].…”