Protective effects of vincamine against ethanol-induced gastric ulcer by attenuation of IL-6, IL-1β, and TNF-α mRNA expression levels in the gastric mucosa of BALB/c mice

Abstract

Vincamine, a monoterpenoid alkaloid, and an active constituent of plant Catharanthus roseus Linn, has been proclaimed for antioxidant and anti-inflammatory activities. This study was designed to evaluate the gastroprotective activity of Vincamine by ameliorating gastric ulcer in BALB/c mice. The study was also designed to find the possible mechanism of gastric protection by exploring the impact of Vincamine on gastric pH, acidic content, observing histopathology and molecular expression of inflammatory mediators like Interleukin- β (IL-1β), Interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF- α) and oxidative stress markers in the gastric tissue. A total number of 36 BALB/c mice were divided into 6 groups mainly normal control (NC) treated with normal saline, disease control (DC) treated with high dose of absolute ethanol (5ml/kg) while treatment groups involved pretreatment with low- dose Vincamine (VLD) at 10mg/kg body weight, medium-dose vincamine (VMD) at 20mg/kg body weight and high- dose vincamine (VHD) at 40mg/kg body weight before ethanol high dose administration and reference drug control, omeprazole (OMT) at the dose of 20 mg/kg body weight. Molecular expression levels of mRNA expressions of inflammatory cytokines like IL-1β, IL-6 and TNF- α were evaluated by using reverse transcription real time polymerase chain reaction method (RT-PCR). Pre-treatment of DC group with low (VLD), medium (VMD) and high doses (VHD) of vincamine improved gastric ulcer score and ameliorated histopathological parameter such as, infiltration of inflammatory cells, edema, fibrinoid necrosis, hemorrhage, and erosion score when compared to DC group. Induction of gastric model significantly increased (all P < 0.05) the mRNA expression of IL-1β, IL-6 and TNF- α in the gastric tissue when same was compared to normal control group (NC). Pretreatment of DC group with different doses of vincamine (VLD, VMD and VHD) significantly downregulated (all P < 0.05) the mRNA expressions of IL-1β, IL-6 and TNF- α and ameliorated oxidative stress marker MDA and increased antioxidant markers like SOD and GSH in the gastric tissue when same was compared to the DC group. In a nutshell, vincamine provide gastric protection in the BALB/c mice of gastric ulcer group by increasing the gastric pH, attenuated total acidity of the stomach and modulated infiltration of inflammatory cells, edema, fibrinoid necrosis, hemorrhage, and erosion score when compared to the DC group. Furthermore, vincamine possesses antiulcer and gastroprotective activity which may be ascribed to down-regulation the mRNA expression of IL-1β, IL-6 and TNF- α in the gastric tissue of disease control group. Vincamine also provide gastroprotective role by increasing the concentration of SOD and GSH while decreasing the MDA in gastric tissue.