Comparative Studies of Phytochemical Screening, HPLC-PDA-ESI-MS/MS-LC/HR-ESI-MS Analysis, Antioxidant Capacity and in Vitro Fermentation of Officinal Sage (Salvia officinalis L.) Cultivated in Different Biotopes of Northwestern Tunisia.

We aimed in the present study to investigate the chemical composition, the antioxidant capacities as well as the in vitro fermentation properties of Salvia officinalis leaves aqueous extract (SOLAE) grown in four regions of northwestern Tunisia. Our data firstly indicated a spatial variation (P<0.05) in condensed tannins, total lipids, polyphenols and flavonoids contents. The HPLC-PDA-ESI-MS/MS-LC/HR-ESI-MS technique allowed to the identification of 13 phenolic compounds and showed that protocatechuic acid is the major constituent of the plant leaves grown in Tabarka, Ain Draham and Testour. The SOLAE of the plant grown in Tabarka presents the most potent scavenging activity against DPPH radical and had the highest percentage of inhibition. More importantly, we found in the present study that the digestibility of dry matter and in vitro fermentation showed a significant variation between the regions and the animal species. Also, we showed a very positive correlation between antioxidant properties and phenolic compounds contents. In conclusion, we suggest that SOLAE had potential beneficial effects owing in part to its antioxidant and ROS scavenging activities. Therefore, S. officinalis can be proposed as an additive food for animals' nutrition and health.

Phytochemical Properties of Crataegus azarolus Berries Decoction Extract and Evaluation of its Protective Activity Against Acetic Acid-Induced Ulcerative Colitis in Rats.

The present study aims to evaluate the protective effect of Crataegus azarolus berries decoction extract (CAB-DE) against acetic acid-induced ulcerative colitis as well as the mechanisms implicated in such protection. Adult male Wistar rats were separated into seven groups: Control (H2O), acetic acid (AA), AA + various doses of CAB-DE (100, 200, and 400 mg/kg, b.w.,p.o.), and AA + sulfasalazine (100 mg/kg, b.w.,p.o.) or gallic acid (50 mg/kg, b.w.,p.o.) during 10 days. All rats were kept fasting overnight and ulcerative colitis was induced by rectal infusion of AA (300 mg kg-1, b.w.) (3%, v/v, 5 mL kg-1 b.w), for 30 s. The colon was rapidly excised and macroscopically examined to measure ulcerated surfaces and the ulcer index. In vitro, we found that CAB-DE exhibited a high antioxidant activity against DPPH radical (IC50 = 164.17 ± 4.78 µg/mL). In vivo, pretreatment with CAB-DE significantly protected the colonic mucosa against AA-induced damage by stimulating mucus secretion, reducing ulcer index as well as histopathological changes. Also, CAB-DE limited the oxidative status induced by AA in the colonic mucosa, as assessed by MDA and H2O2 increased levels and the depletion of both enzymatic activities and non-enzymatic levels. In addition, AA intoxication increased iron and calcium levels in colonic mucosa and plasma, while CAB-DE pretreatment regulated all intracellular mediators deregulation and significantly reduced inflammatory markers such as CRP (1.175 ± .04 ─ .734 ± .06 µg/dl) and ALP (161.53 ± 5.02 ─ 98.60 ± 4.21 UI/L) levels. We suggest that CAB-DE protected against AA-induced ulcerative colitis due in part to its antioxidant and anti-inflammatory properties.

Hepato-Nephroprotective Actions of Salvia officinalis Decoction Extract Against Extraintestinal Alterations Induced with Acetic Acid-Colitis Model in Rats.

Inflammatory bowel disease is associated with multiple extraintestinal disorders, including hepato-nephrological disruptions. The aim of this study was to evaluate the hepato-nephroprotective effect of Salvia officinalis leaf decoction extract (SLDE) on acetic acid (AA)-induced colitis accompanied with liver and kidney injuries. Wistar albinos rats were pretreated with SLDE (50, 100, and 200 mg kg-1, b.w., p.o.) during 10 days and intoxicated for 24 h by acute rectal administration of AA (3%, v/v, 5 mL kg-1, b.w.). Our results showed that S. officinalis treatment protected against AA-induced liver and kidney injuries by plasma transaminase activities and preservation of the hepatic and renal tissue structures. The level of high-density lipoprotein-cholesterol was also reverted back to near normalcy by treatment. Lipid peroxidation was decreased significantly by officinal sage supplementation. Treatment with SLDE increased enzymatic (superoxide dismutase, catalase, and glutathione peroxidase) and nonenzymatic (-SH groups and reduced glutathione) antioxidants in liver and kidney tissues. Also, SLDE treatment significantly protected against inflammation markers and reversed all intracellular mediator perturbations. This study suggests that the S. officinalis has a beneficial effect in controlling kidney and liver injuries by reducing lipid peroxidation and increasing antioxidant enzyme activities and nonenzymatic contents, which reduce the risk of developing extraintestinal complications.

Salvia officinalis flowers extract ameliorates liver and kidney injuries induced by simultaneous intoxication with ethanol/castor oil.

The current study investigated the possible mechanisms of aqueous extract Salvia officinalis flowers (SF-AE) and its protective effects against hepatorenal toxicities produced by simultaneous acute administration of ethanol (EtOH)/castor oil (CO). Healthy male rats (N = 50) were separated into five equal groups: control, Ethanol (EtOH) + Castor oil (CO), doses of increasing orders of SF-AE (50, 100, and 200 mg/kg, b.w., p.o.) during 15 days. Liver and kidney injuries were induced by EtOH (4 g/kg, b.w., p.o.) combined with CO (5 mL/kg, b.w., p.o.). Compared to the control group, SF-AE pretreatment protected against simultaneous administration of EtOH and CO-caused serious histological alterations in liver and kidney tissues. SF-AE also reversed liver and kidney biochemical parameters and lipid profile alterations. More importantly, SF-AE significantly reduced the malondialdehyde (MDA) level and counteracted the depletion of both enzymatic and non-enzymatic antioxidants. SF-AE also prevents against inflammation induced by EtOH combined with CO, expressed by the rise of inflammation biomarkers (C-reactive protein: CRP and alkaline phosphatase: ALP). Additionally, combined EtOH intoxication and CO poisoning exerted an increase in H2 O2 , free iron and calcium levels. Impressively, SF-AE treatment regulated levels of these studied intracellular mediators in a dose-dependent manner. In conclusion, SF-AE can potentially improve liver and kidney injuries associated with biochemical parameter deregulations, possibly by controlling oxidative stress and inflammation.

Antioxidant Properties, Phytoactive Compounds and Potential Protective Action of Salvia officinalis Flowers Against Combined Gastro-Intestinal Ulcer and Diarrhea Experimentally Induced in Rat.

The present study was conducted to investigate the protective action of Salvia officinalis flowers aqueous extract (SOFAE) against combined gastro-intestinal (GI) disorders-induced by ethanol and castor oil administration in rats. Adult male Wistar rats were divided into seven groups of ten each and various doses of SOFAE (50, 100, and 200 mg kg-1, b.w., p.o.) and sulfasalazine (100 mg kg-1, b.w., p.o.) were daily administrated during 15 days. After, animals were intoxicated with a single oral administration of ethanol (4 g kg-1, b.w., p.o.) and castor oil (5 mL kg-1, b.w., p.o.). We found that SOFAE contains several phytoactive compounds with a strong ABTS scavenging ability. In vivo, we showed that SOFAE protected against EtOH/CO-induced macroscopic and histological alterations in GI tract accompanied by intestinal fluid accumulation and gastric juice decrease. SOFAE significantly counteracted lipoperoxydation increase and reversed the depletion of both enzymatic and non-enzymatic antioxidants. More importantly, SOFAE significantly reduced the levels of inflammatory markers (CRP and ALP) in plasma and mucosal GI tract. In conclusion, our data clearly indicate that the SOFAE exerted a potential protective effect against EtOH-induced peptic ulcer combined with CO-induced diarrhea in rats. These effects could be associated with its antioxidant and anti-inflammatory properties.

Antioxidant Properties of Salvia officinalis Decoction Extract and Mechanism of Its Protective Effects on Ethanol-Induced Liver and Kidney Injuries.

This study assessed the hepato- and nephroprotective effects of Salvia officinalis flowers decoction extract (SODE) against ethanol (EtOH)-induced oxidative stress in rats as well as the possible mechanism implicated in such protection. Animals were divided into four groups: control, EtOH, and EtOH+SODE. Wistar rats were pretreated with SODE (50, 100, and 200 mg/kg, body weight [b.w.], p.o.) for 15 days and intoxicated during 2 h by acute oral administration of EtOH (4 g/kg, b.w.) 60 min after the last dose of SODE. We found that SODE pretreatment, in vivo, protected against EtOH-induced liver and kidney injuries evident by plasma transaminases activity and preservation of the hepatic tissue structure. Compared with the control group, the animals treated with the SODE showed a significant decrease (68.81 ± 6.89-50.65 ± 3.97 UI/L) of alanine aminotransferase (ALT) and aspartate aminotransferase (AST; 144.38 ± 6.58-113.64 ± 8.03 UI/L) in a dose-dependent manner. By contrast, the plant extract significantly and dose dependently increased (0.175 ± 0.077-0.302 ± 0.011 mmol/L) the uric acid. The SODE counteracted EtOH-induced liver and kidney lipoperoxidation, preserved sulfhydryl groups (-SH) and glutathione reduced (GSH) contents. Our extract prevented the depletion of antioxidant enzyme activities such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). We also showed that acute alcohol administration increased tissue and plasma hydrogen peroxide (H2O2), calcium and free iron levels. Of interest, SODE pretreatment reversed all EtOH-induced disturbances in intracellular mediators. More importantly, SODE treatment significantly protected against alcohol-induced inflammation by reducing C-reactive protein (CRP) and alkaline phosphatase (ALP) activities in plasma. It was concluded that the SODE exerted a potential protective effect against EtOH-induced inflammation and oxidative stress in the rat organs. This study recommends that the consumption of sage flowers is useful for patients who suffer from hepato- and nephrotoxicity.

Protective effects of Crataegus azarolus L. berries aqueous extract against castor oil-induced diarrhea, oxidative stress, and inflammation in rat.

BACKGROUND: Diarrhea is a multifactorial gastrointestinal disorder responsible for about 5 million deaths annually. The chemical composition, the antioxidant activity of Crataegus azarolus berries aqueous extract (CABAE) as well as its protective effects against castor oil-induced diarrhea, oxidative stress, and inflammation in rat were studied. METHODS: Sixty male rats were used and divided into six groups of ten animals in each: Control (C), castor oil (CO), CO+various doses of CABAE (100, 200, and 400 mg/kg b.w., p.o.), and CO+loperamide (LOP, 10 mg/kg b.w., p.o.). KEY RESULTS: The CABAE showed relatively high levels of total polyphenols, flavonoids, and tannins. The LC-HRESIMS technique allowed the identification of 5 phenolic compounds and the major component is quinic acid. In vivo studies showed that CABAE protected against castor oil-induced diarrhea and intestinal fluid accumulation. The CABAE counteracted castor oil-induced lipoperoxidation, preserved GSH and thiol groups levels, and prevented the depletion of antioxidant enzyme activities, such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). The CABAE administration also protected against castor oil-induced inflammatory markers (ALP and CRP) increase. More importantly, castor oil induced an increase of intracellular mediators, such as hydrogen peroxide, free iron, and calcium, while CABAE pretreatment significantly reversed them to near control levels. CONCLUSION: The Crataegus azarolus berries aqueous extract significantly protected against diarrhea due in part to its antioxidant and anti-inflammatory properties.

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

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 ß-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.

Phytochemical/Antioxidant Properties and Individual/Synergistic Actions of Salvia officinalis L. Aqueous Extract and Loperamide on Gastrointestinal Altering Motor Function.

Medicinal plants are known by pharmacological relevance and were used for long time to prevent/treat numerous gastrointestinal (GI) disorders. The current study focuses on the phytochemical/antioxidant characteristics of sage aqueous extract (SAE), as well as its pharmacological actions on altering motor function in the intestine and related disruptions. In vitro phytochemical/antioxidant properties were investigated by colorimetric/biochemical methods. Male rats were divided into seven groups of six animals in each: control (C), castor oil (CO), CO + loperamide (LOP, 10 mg/kg, b.w., p.o.), CO + various doses of SAE (50, 100, and 200 mg/kg, b.w., p.o.), and the mixture (MIX: SAE, 50 mg/kg, b.w., p.o. + LOP, 5 mg/kg, b.w., i.p.) group. In vivo GI/physiological/pharmacological actions of SAE were explored based on the watery/frequent stools, enteropooling, and GI transit time, as well as their associated disturbances. The aqueous extract of S. officinalis contains high tannins/flavonols/anthocyanin contents and a strong, free radical scavenging activity (EC50 = 48.56 ± 0.34 µg/mL). SAE/MIX significantly reduced CO-induced diarrhea in a dose-dependent manner. SAE/MIX decreased also the gastric and intestinal mucosal malondialdehyde/hydrogen peroxide levels and preserved the normal activities/levels of enzymatic/nonenzymatic antioxidants. Added to that, we showed that SAE/MIX pretreatment provided stability of lipid profile (cholesterol and triglycerides), hepatic transaminases, renal injury indicators, and C-reactive protein/alkaline phosphatase levels changed by CO intoxication. These findings suggested that SAE/MIX exerted benefic individual/synergistic effects confirming their use as a strategy in the treatment of GI physiological disorders.