Extract of Rhus verniciflua stokes protects against renal ischemia-reperfusion injury by enhancing Nrf2-mediated induction of antioxidant enzymes.

Ischemia-reperfusion injury (IRI) may cause acute kidney disease (AKD) by mediating the oxidative stress-induced apoptosis of parenchymal cells. The extract of Rhus verniciflua Stokes (RVS) is used as a traditional herbal medicine as it exhibits anti-oxidant, anti-apoptotic and anti-inflammatory properties. Therefore, the current study investigated the therapeutic effect and the underlying mechanism of RVS on IRI-induced AKD in vivo and in vitro. The current study assessed the effects of RVS on a mouse model of renal IRI and in hypoxic human renal tubular epithelial HK-2 cells. The results demonstrated that the IRI-induced elevation of blood urea nitrogen, serum creatinine and lactate dehydrogenase was significantly attenuated by the intraoral administration of RVS (20 mg/kg/day) for 14 days prior to surgery. It was demonstrated that IRI surgery induced histological damage and cellular apoptosis in renal parenchyma, which were attenuated by pretreatment with RVS. Furthermore, in HK-2 cells incubated with 300 µM CoCl2 to induce chemical hypoxia, it was demonstrated that RVS treatment significantly inhibited cell death and the production of reactive oxygen species (ROS). Furthermore, RVS treatment upregulated the levels of endogenous antioxidant enzymes, including heme oxygenase-1 and catalase, as well as their upstream regulator nuclear factor erythroid 2-related factor 2, in HK-2 cells. Taken together, these results suggested that the intraoral administration of RVS induces a therapeutic effect on IRI-induced AKD. These effects are at least partly due to the attenuation of ROS production via upregulation of the antioxidant defense system in renal tubular cells.

Protective effect of Rhus verniciflua Stokes extract in an experimental model of post-menopausal osteoporosis.

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.

Rhus verniciflua Stokes attenuates cholestatic liver cirrhosis-induced interstitial fibrosis via Smad3 down-regulation and Smad7 up-regulation.

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 ß (TGF-ß). Simultaneously, we also found that RVS reciprocally increased the expression of Smad7, a negative regulatory protein of the TGF-ß/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.

Anti-Helicobacter pylori activity of crude N-acetylneuraminic acid isolated from glycomacropeptide of whey.

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 (5×10(8) 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.

Extract of Rhus verniciflua stokes protects the diet-induced hyperlipidemia in mice.

Rhus verniciflua stokes (RVS) is a popular medicinal plant in oriental medicines which is commonly used to resolve extravasated blood. To elucidate the molecular mechanism of the role of RVS extracts on the regulation of lipid and cholesterol biosynthesis, we investigated whether RVS extract protect the hyperlipidemia in western diet-induced C57BL6/J mice. Mice fed a western diet and additionally RVS extracts was administered orally at a dose of 0.1 or 1 g/kg/day for 2 weeks respectively. Group with higher dose of RVS extract showed a significantly decreased body weight compared with western diet fed mice groups. And total cholesterol, LDL-cholesterol levels and fatty liver formation were also improved especially in group of mice fed western diet supplemented high dose RVS extracts. Next, synthesis of hepatic bile acids were significantly increased in RVS extract fed groups. Furthermore, RVS extracts significantly increase promoter activity of Cyp7a1 via up-regulate the transcriptional expression level of LXRα. Our data suggest that RVS extracts could be a potent therapeutic ingredient for prevent a hyperlipidemia via increase of bile acids biosynthesis.

Anti-fatigue activity of Hovenia dulcis on a swimming mouse model through the inhibition of stress hormone expression and antioxidation.

Hovenia dulcis (H. dulcis) Thunb., which is distributed in Korea, China, and Japan, has been known to show hepatoprotective and free radical scavenging effects and enhance physical activity. Therefore, the objectives of this present study were to determine the anti-fatigue activity of hot-water extract from H. dulcis peduncle, and to find the reason why H. dulcis extract (HDE)-ingested mice had enhanced physical activity against swimming performance. The mice orally administrated with HDE (HDE-mice) dramatically enhanced their swimming time compared to the control mice. HDE significantly decreased serum levels of stress hormones, such as cortisol and adrenocorticotropic hormone (ACTH) in mice. The levels of thiobarbituric acid reactive substances (TBARS) were dramatically decreased in gastrocnemius muscle from both 100 mg/kg of HDE (LHDE) and 200 mg/kg of HDE (HHDE)-ingested mice compared to the control mice. The liver activities of superoxide dismutase (SOD) were significantly increased in HHDE-mice with increasing tendency in LHDE-mice. In addition, HHDE-mice significantly decreased the levels of blood glucose, total cholesterol (T-Chol), and triglyceride (TG). These results suggest that HDE had a significant anti-fatigue effect via its anti-stress and antioxidant activities, and thereby enhanced physical activity in swimming performance.