ABSTRACT
Gallic acid (3,4,5-trihydroxybenzoic acid, GA) is a phenolic compound found in many medicinal plants traditionally used in China or patent medicine such as Feiyangchangweiyan capsule (FY capsule) for the treatment of gastrointestinal diseases for decades. However, the evidence for the gastroprotective effect of GA is deficient and the pharmacological mechanisms remain limited. The present investigation was initiated to demonstrate the gastroprotective effect and to understand potential underlying mechanism of GA on ethanol-induced gastric ulcer in rats. Gastric ulcers were induced by absolute ethanol (5 mL/kg, i.g.) in male Sprague-Dawley rats, GA (10, 30, and 50 mg/kg), FY capsule (0.4 g/kg) and 30 mg/kg Lansoprazole was administered orally. Physiological saline and lansoprazole were used as negative and positive control, respectively. Induction of rats with ethanol resulted in a significant rise in ulcer index, serum levels of inflammatory cytokines markers (IL-1ß, IL-6 and TNF-α), TBARS, protein expression of Bax and Caspase-3 and a significant reduction in the activities or levels of endogenous antioxidants (SOD, CAT and GSH), gastric mucosal protective factors (PGE2 and NO) and protein expression of Bcl-2. Pretreatment with GA showed a remarkable decrease in ulcer index, inflammatory cytokines markers, TBARS, protein expression of Bax and Caspase-3 and a significant increase in the activities of endogenous antioxidants, levels of PGE2 and NO, and protein expression of Bcl-2, Nrf2 and HO-1 when compared with ethanol treated groups. This study demonstrated the gastroprotective effect of Gallic acid and FY capsule on ethanol-induced gastric ulcer in rats. The underlying mechanism of GA and FY capsule against gastric ulcer in rats caused by ethanol might be involved in Nrf2/HO-1 anti-oxidative pathway and ultimately played an anti-apoptotic role through regulating Bax, Bcl-2 and Caspase-3.
Subject(s)
Anti-Ulcer Agents/pharmacology , Ethanol/adverse effects , Gallic Acid/pharmacology , Stomach Ulcer/etiology , Stomach Ulcer/metabolism , Animals , Antioxidants/metabolism , Apoptosis/drug effects , Biopsy , Cytokines/metabolism , Dinoprostone/metabolism , Disease Models, Animal , Gastric Juice/metabolism , Heme Oxygenase (Decyclizing)/metabolism , Hydrogen-Ion Concentration , Inflammation Mediators/metabolism , Lipid Peroxidation/drug effects , Male , NF-E2-Related Factor 2/metabolism , Nitric Oxide/metabolism , Rats , Severity of Illness Index , Signal Transduction/drug effects , Stomach Ulcer/drug therapy , Stomach Ulcer/pathologyABSTRACT
Paeonol and danshensu is the representative active ingredient of traditional Chinese medicinal herbs Cortex Moutan and Radix Salviae Milthiorrhizae, respectively. Paeonol and danshensu combination (PDSS) has putative cardioprotective effects in treating ischemic heart disease (IHD). However, the evidence for the protective effect is scarce and the pharmacological mechanisms of the combination remain unclear. The present study was designed to investigate the protective effect of PDSS on isoproterenol (ISO)-induced myocardial infarction in rats and to elucidate the potential mechanism. Assays of creatine kinase-MB, cardiac troponin I and T and histopathological analysis revealed PDSS significantly prevented myocardial injury induced by ISO. The ISO-induced profound elevation of oxidative stress was also suppressed by PDSS. TUNEL and caspase-3 activity assay showed that PDSS significantly inhibited apoptosis in myocardia. In exploring the underlying mechanisms of PDSS, we found PDSS enhanced the nuclear translocation of Nrf2 in myocardial injured rats. Furthermore, PDSS increased phosphorylated PI3K and Akt, which may in turn activate antioxidative and antiapoptotic signaling events in rat. These present findings demonstrated that PDSS exerts significant cardioprotective effects against ISO-induced myocardial infarction in rats. The protective effect is, at least partly, via activation of Nrf2/HO-1 signaling and involvement of the PI3K/Akt cell survival signaling pathway.
Subject(s)
Acetophenones/pharmacology , Apoptosis/drug effects , Lactates/pharmacology , Oxidative Stress/drug effects , Signal Transduction/drug effects , Acetophenones/administration & dosage , Acetophenones/chemistry , Animals , Blotting, Western , Cardiotonic Agents/chemistry , Cardiotonic Agents/pharmacology , Creatine Kinase, MB Form/metabolism , Drug Therapy, Combination , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Heme Oxygenase-1/metabolism , Isoproterenol , Lactates/administration & dosage , Lactates/chemistry , Male , Microscopy, Electron, Transmission , Molecular Structure , Myocardial Infarction/chemically induced , Myocardial Infarction/drug therapy , Myocardial Infarction/pathology , Myocardium/metabolism , Myocardium/pathology , Myocardium/ultrastructure , NF-E2-Related Factor 2/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Phytotherapy , Proto-Oncogene Proteins c-akt/metabolism , Rats, Sprague-Dawley , Signal Transduction/physiology , Troponin I/metabolism , Troponin T/metabolismABSTRACT
OBJECTIVE: To study the HPLC fingerprint of toad skin and provide a reliable method for quality control and identification. METHODS: It used HPLC for detection and computer aided similarity evaluation system for processing and analysing HPLC fingerprint. RESULTS: The common pattern of HPLC fingerprint of toad skin was astablished, 29 peaks were identified as the characteristic fingerprints, in which 9 peaks corresponded to 9 bufogenins. (2) Each samples' similarity of relative retention time was all above 0.99, but the similarity of relative peak areas was low. CONCLUSION: (1) The method is accurate and with good reproducibility. The fingerprints can be used for the identification and quality control of toad skin. (2) The toad skin from different regions are stable in composition, but the contents of the components are different.