Abstract
Gastric ulcers are a common problem in upper gastrointestinal tract (GI) disorders. Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most aggressive factors leading to inducing gastric ulcers. Natural products with lower toxicity and safety are currently sought as a potential source to minimize the effect of the gastric ulcers. Perilla frutescens or Nga-mon (in Thai) leaves are rich in rosmarinic acid (RA), which has antioxidant, anti-inflammatory, and anticancer effects. This study investigates the protective effect of ethanolic extract (EE) and aqueous fraction (AF) from Perilla frutescens leaves, which are rich in RA, on indomethacin- (IND-) induced gastric ulcer in a rat model. The EE at the doses of 50 and 500 mg/kg body weight, AF at the doses of 50, 250, and 500 mg/kg body weight, or famotidine (a standard drug) were administered for 14 days prior to ulcer induction. The ulceration was performed by intragastric administration of IND. Gross gastric ulcers and biological and histological parameters were examined. The pretreatment with AF had more significant effects than EE, including reduced ulcer index, decreased gastric secretion volume and decreased acidity, but it had an elevated gastric pH relative to the IND-induced gastric ulcer. In a histopathological study, the EE and AF decreased mucosal ulcer, inflammatory infiltration, and degenerative lining cells. The IND-induced expression of inflammatory mediators was significantly attenuated with EE and AF. The experiment also remarkably showed the preservation of mucus and apoptosis protection of EE and AF on a gastric mucosal ulcer. The findings demonstrated that the EE and AF of perilla leaves were capable of protecting the stomach against gastric ulcers induced by IND through anti-inflammatory and antiapoptotic mechanisms that should be further investigated. It is suggested that Perilla frutescens leaf could be a potential alternative source of RA as a therapeutic agent and food supplement for NSAID-induced gastric injuries.
Highlights
Gastric ulcers, which result from an imbalance between the protective and damaging factors in the stomach, are a common problem in upper gastrointestinal (GI) tract disorders [1, 2]
This study found that the mRNA expressions of TNF-α, IL-1β, and IL-6 (Figures 6(a)–6(c)) were all significantly elevated after administration of IND compared to the normal control rats (P < 0.01); the pretreatment with ethanolic extract (EE) and aqueous fraction (AF) significantly suppressed the expressions of TNF-α and IL-1β (P < 0.05), which was similar to pretreatment with famotidine
Further research on anti-inflammatory effects and antiapoptosis effects of Perilla frutescens leaves might lead to the discovery of new pharmacological products in the prevention and clinical treatment of inflammatory diseases in the GI tract and other tissue ulcers. This is the first report to provide scientific evidence of the gastroprotective activities of the traditional medicine of rosmarinic acid (RA) enriched extracts from Perilla frutescens leaves through the mechanism of anti-inflammatory activity, an increase in mucus production, and protection of apoptosis in gastric mucosa
Summary
Gastric ulcers, which result from an imbalance between the protective and damaging factors in the stomach, are a common problem in upper gastrointestinal (GI) tract disorders [1, 2]. The long-term use of NSAIDs has many adverse effects, including GI toxicity and cardiovascular complications [5, 6]. Indomethacin (IND) is a well-known NSAID, and it produces gastric damage that is related to loss of gastric mucosal integrity, generates oxidative stress, suppresses of mucus production, induces apoptosis, and activates inflammation [7, 8]. Proton-pump inhibitors (PPIs) and H2 receptor antagonists have been used for the prevention of NSAID-induced gastric ulcers; several adverse effects have been reported with prolonged PPI use [5, 9]. Several natural products, especially from medicinal herbs with gastroprotective effects, have been intensively sought and reported [10,11,12,13,14,15,16]
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