Individual and synergistic protective properties of Salvia officinalis decoction extract and sulfasalazine against ethanol-induced gastric and small bowel injuries

Abstract

The present study was carried out to determine the phytochemical composition of Salvia officinalis flowers decoction extract (SOFDE) as well as its individual and/or synergistic actions with sulfasalazine against ethanol (EtOH)-induced peptic ulcer in Wistar rats. In this respect, rats were divided into six groups of eight animals each: control, EtOH, EtOH + sulfasalazine (SULF, 100 mg kg⁻¹, b.w., p.o.), mixture: MIX (SOFDE, 50 mg kg⁻¹ b.w., p.o. + SULF, 50 mg kg⁻¹, b.w., p.o.) and EtOH + two doses of SOFDE (100 and 200 mg kg⁻¹ b.w., p.o.). In vitro, the phytochemical and the antioxidant properties were determined using colorimetric analysis. HPLC-PDA/ESI-MS assay was used to identify the distinctive qualitative profile of phenolic compounds. Our results firstly indicated that SOFDE is rich in total tannins, flavonols, anthocyanins and a moderate concentration of total carotenoids. Chromatographic techniques allowed the identification of 13 phenolic compounds and the major ones are quinic acid, protocatechuic acid, gallic acid and salviolinic acid. SOFDE also exhibited an important in vitro antioxidant activity using the β-carotene bleaching method. In vivo, SOFDE and the mixture provide significant protection against ethanol-induced gastric and duodenal macroscopic and histological alterations. Also, SOFDE alone or in combination with SULF, showed a significant protection against the secretory profile disturbances, lipid peroxidation, antioxidant enzyme activities and non-enzymatic antioxidant level depletion induced by alcohol administration. Importantly, we showed that EtOH acute intoxication increased gastric and intestinal calcium, free iron, magnesium and hydrogen peroxide (H₂O₂) levels, while SOFDE/MIX treatment protected against all these intracellular mediators' deregulation. We also showed that alcohol treatment significantly increased the C-reactive protein (CRP) and alkaline phosphatase (ALP) activities in plasma. The SOFDE and MIX treatment significantly protected against alcohol-induced inflammation. More importantly, we showed in the present work that the mixture exerted a more important effect than SOFDE and SULF each alone indicating a possible synergism between these two molecules. In conclusion, our data suggests that SOFDE and SULF exerted a potential synergistic protective effect against all the macroscopic, histological and biochemical disturbances induced by EtOH intoxication. This protection might be related in part to its antioxidant and anti-inflammatory properties as well as by negatively regulating Fenton reaction components such as H₂O₂ and free iron.