RÉSUMÉ
Sujet(s)
Animaux , Souris , Apoptose , Technique de Western , Encéphalopathie ischémique , Encéphale , Caspase-3 , DNA nucleotidylexotransferase , Heme oxygenase-1 , Infarctus du territoire de l'artère cérébrale moyenne , Espèces réactives de l'oxygène , Reperfusion , Accident vasculaire cérébral , Régulation positive , EauRÉSUMÉ
Post-menopausal osteoporosis (PMO) is a major global human health concern. Owing to the need for therapeutic drugs without side effects, natural extracts containing various polyphenolic compounds that may exert estrogenic effects have been studied in depth. Rhus verniciflua Stokes (RVS), which has been used as a traditional herbal medicine for centuries in Korea, was recently revealed to exert estrogenic effects attributable to its bioactive ingredients sulfuretin and butein, which have strong estrogen receptor–binding affinities. In this study, the protective potential of RVS in PMO was evaluated by using an experimental animal model of PMO, which was established by ovariectomy (OVX) of female Sprague Dawley rats. The oral administration of RVS at 20 mg/kg or 100 mg/kg for 8 weeks markedly protected against OVX-induced atrophy of the uterine tube and reversed the elevation in the ratio of serum receptor activator of nuclear factor-κB ligand to osteoprotegerin, which is a marker of disease severity. In addition, RVS inhibited OVX-induced tibia bone loss, activated osteogenic activity, and suppressed osteoclastic activity in the tibial epiphyseal plate, a region of bone remodeling. Collectively, these factors indicated that the oral intake of RVS might be beneficial for the prevention of PMO.
Sujet(s)
Femelle , Humains , Administration par voie orale , Atrophie , Remodelage osseux , Oestrogènes , Trompes utérines , Lame épiphysaire , Science des plantes médicinales , Corée , Modèles animaux , Modèles théoriques , Ostéoclastes , Ostéoporose post-ménopausique , Ostéoprotégérine , Ovariectomie , Rat Sprague-Dawley , Rhus , TibiaRÉSUMÉ
Cholestatic liver cirrhosis (CLC) eventually proceeds to end-stage liver failure by mediating overwhelming deposition of collagen, which is produced by activated interstitial myofibroblasts. Although the beneficial effects of Rhus verniciflua Stokes (RVS) on various diseases are well-known, its therapeutic effect and possible underlying mechanism on interstitial fibrosis associated with CLC are not elucidated. This study was designed to assess the protective effects of RVS and its possible underlying mechanisms in rat models of CLC established by bile duct ligation (BDL). We demonstrated that BDL markedly elevated the serological parameters such as aspartate aminotransferase, alanine transaminase, total bilirubin, and direct bilirubin, all of which were significantly attenuated by the daily uptake of RVS (2 mg/kg/day) for 28 days (14 days before and after operation) via intragastric route. We observed that BDL drastically induced the deterioration of liver histoarchitecture and excessive deposition of extracellular matrix (ECM), both of which were significantly attenuated by RVS. In addition, we revealed that RVS inhibited BDL-induced proliferation and activation of interstitial myofibroblasts, a highly suggestive cell type for ECM production, as shown by immunohistochemical and semi-quantitative detection of α-smooth muscle actin and vimentin. Finally, we demonstrated that the anti-fibrotic effect of RVS was associated with the inactivation of Smad3, the key downstream target of a major fibrogenic cytokine, i.e., transforming growth factor β (TGF-β). Simultaneously, we also found that RVS reciprocally increased the expression of Smad7, a negative regulatory protein of the TGF-β/Smad3 pathway. Taken together, these results suggested that RVS has a therapeutic effect on CLC, and these effects are, at least partly, due to the inhibition of liver fibrosis by the downregulation of Smad3 and upregulation of Smad7.
Sujet(s)
Actines , Alanine transaminase , Aspartate aminotransferases , Conduits biliaires , Bilirubine , Collagène , Régulation négative , Matrice extracellulaire , Fibrose , Ligature , Cirrhose du foie , Défaillance hépatique , Foie , Modèles animaux , Myofibroblastes , Négociation , Rhus , Facteurs de croissance transformants , Régulation positive , VimentineRÉSUMÉ
Helicobacter pylori colonizes the gastric mucosa of about half of the world's population, causing chronic gastritis and gastric cancer. An increasing emergence of antibiotic-resistant H. pylori arouses demand on alternative non-antibiotic-based therapies. In this study, we freshly prepared crude N-acetylneuraminic acid obtained from glycomacropeptide (G-NANA) of whey through a neuraminidase-mediated reaction and evaluated its antibacterial ability against H. pylori and H. felis. Overnight cultures of the H. pylori were diluted with fresh media and different concentrations (1-150 mg/mL) of crude G-NANA were added directly to the culture tube. Bacterial growth was evaluated by measuring the optical density of the culture medium and the number of viable bacteria was determined by a direct count of the colony forming units (CFU) on agar plates. For the in vivo study, mice were orally infected with 100 µL (5×108 cfu/mL) of H. felis four times at a day's interval, accompanied by a daily administration of crude G-NANA or vehicle. A day after the last infection, the mice were daily administered the crude G-NANA (0, 75, and 300 mg/mL) for 10 days and euthanized. Their stomachs were collected and bacterial colonization was determined by quantitative real-time PCR. Crude G-NANA inhibited H. pylori's growth and reduced the number of viable bacteria in a dose-dependent manner. Furthermore, crude G-NANA inhibited bacterial colonization in the mice. These results showed that crude G-NANA has antibacterial activity against Helicobacter and demonstrated its therapeutic potential for the prevention of chronic gastritis and gastric carcinogenesis induced by Helicobacter infection in humans.