Chrysin Modulates Genes Related to Inflammation, Tissue Remodeling, and Cell Proliferation in the Gastric Ulcer Healing

Abstract

Chrysin exhibits anti-inflammatory and antioxidant activities. Here, the gastroprotective effect of chrysin was investigated in mouse models of gastric ulcer induced by absolute ethanol, acetic acid, and ischemia-reperfusion injury. The gastric-healing effect was evaluated at 7 and 14 days after treatment; the mechanism of action was verified using the expression of metalloproteinase 2 (MMP-2) and 9 (MMP-9), caspase-3, cyclooxygenase 1 (COX-1) and 2 (COX-2), epidermal growth factor (EGF), and interleukin-10. Chrysin (10 mg/kg) inhibited macroscopic lesions and increased catalase activity in the mouse model established using absolute ethanol. It ameliorated the gastric ulcer caused by acetic acid by improving the expression of inflammatory genes such as COX-2, inhibiting negative remodeling promoted by MMP-9, increasing cell proliferation effect via EGF, and reducing cellular apoptosis by modulating caspase-3. A faster healing effect was evident in the first 7 days of treatment compared to 14 days of treatment, indicating the pharmacological potential of chrysin. Overall, these results demonstrate the potent effect of chrysin in the gastrointestinal tract and elucidate the genes involved in the healing of gastric ulcers. Moreover, an increase in the levels of gastric mucosa defensive factors is involved in the activity of chrysin in the gastric mucosa.

A Review of the Role of Flavonoids in Peptic Ulcer (2010–2020)

“…In addition, chrysin (10, 50 and 100 mg/kg, p.o.) and carbenoxolone (100 mg/kg, positive control) protected the gastric mucosa from ethanol-induced injury in mice [ 90 ]. Recently, Fagundes et al, (2020) [ 90 ] demonstrated the gastric healing effect of chrysin (10 mg/kg, p.o., mice) and lansoprazole (30 mg/kg, control group) in the acetic acid model, improving the expression of inflammatory genes such as COX-2, inhibiting the negative remodeling promoted by MMP-9, increasing the cell proliferation effect via epidermal growth factor (EGF) and reducing cell apoptosis by modulating caspase-3.…”

“…Their development involves changes in the levels of PGE 2 , NO, growth factors, and cytokines, as well as changes in the microcirculation and the mucus adhesion pattern [ 171 ]. Rutin [ 65 ], hesperdidin [ 121 ], chrysin [ 90 ], and baicalin [ 85 ] showed antiulcerogenic and healing activity in this model; it can be inferred that flavonoids were able to accelerate the healing of ulcers, thereby being an important mechanism to reduce disease recurrences.…”

“…PGs play a central role in the defense of the gastric epithelium, by inhibiting acid secretion, stimulating mucus and HCO 3 − secretion and increasing blood flow [ 185 ]. Many flavonoids exert gastroprotective effects through mechanisms that involve prostaglandins and the enzymatic activity of the COX, such as pinostrobin [ 109 ], chysin [ 90 ], and hesperidin [ 119 ], strengthening the defense mechanisms of the mucosa or slowing down the inflammatory process.…”

“…In the mitochondrial pathway, with ROS and TNF-α breaking the balance between pro and anti-apoptosis factors, Cit C is released from mitochondria into the cytosol, followed by caspase-9 and activation of caspase-3 [ 187 ]. Flavonoids diosmin [ 92 ], morin [ 60 ], chrysin [ 90 ] and naringin [ 107 ] modulate these markers apoptotic, protecting gastric tissue from inducing cell death.…”

“…Thus, MMP-9 is an important marker in the process of inflammation and ulcerations in the gastrointestinal tract [ 189 ]. Chrysin [ 90 ] and quercetin [ 53 ] promote a reduced expression of MMP-9 in ulcer models, which is considered a positive factor, as this enzyme causes damage by acting directly on tissue.…”