Inhibition of resveratrol glucosides (REs) on advanced glycation endproducts (AGEs) formation: inhibitory mechanism and structure-activity relationship.

The study on inhibitory effects of resveratrol glucosides (REs) on advanced glycation endproducts (AGEs) formation is still unmet. Herein, for the first time, the antiglycation activities of five REs in the fetal bovine serum proteins (FBS)/fructose system were evaluated, and its structure-activity relationship and antiglycation mechanism were further explored. These REs showed remarkable inhibition toward AGEs formation. Among them, Piceatannol-3'-O-glucoside (PG) exhibited highest antiglycation activity as reflected in approximately 80% inhibition of fluorescent AGEs at the concentration of 1.0 mM. The structure-activity relationship analysis indicated that glucoside attached to the B ring of resveratrol displays a superior antiglycation activity. Moreover, the results of antiglycation mechanism showed that the antiglycation activity of REs was proportional to their antioxidant capacity and methylglyoxal (MGO) trapping capacity. Therefore, the REs are promising candidates worthy of further exploration for preventing AGEs accumulation in vivo, thereby treating AGEs-associated diseases.

[Salidroside via ERK1/2 and PI3K/AKT/mTOR signal pathway induces mouse bone marrow mesenchymal stem cells differentiation into neural cells].

To investigate the role of the extracellular signal-regulated kinase (ERK1/2) and PI3K/AKT/ mTOR signal pathway inducing bone marrow mesenchymal stem cells (BMSCs) differentiation into neural cells, mouse bone marrow-derived mesenchymal stem cell lines D1 cells were used as research object. And they were divided into control groups and salidroside (SD) groups. Different concentrations (5, 25, 50, 100 and 200 microg x mL(-1) of SD were used and SD (100 microg x mL(-1)) was used to induce at different time (0.5, 1, 3, 6, 9, 12, 24, 48 and 72 h). The immunofluorescence staining chemical technology, real-time PCR and Western blotting were used to detect the positive rates of NSE, MAP2, beta-Tubulin III, NES, GFAP and the expression levels of beta-Tubulin III, NSE, ERK1/2, AKT. The expression of ERK1/2 and NSE was detected when the ERK1/2 and PI3K/AKT/ mTOR signal pathway was blocked by PD98059 and LY294002. It indicated that the positive rates of NSE, MAP2, beta-Tubulin III, NES and GFAP were gradually enhanced with time increased. The expression level of NSE and beta-Tubulin III protein were significantly higher than those in control groups (P < 0.01). The expression of ERK1/2, AKT mRNA and protein were higher with concentration and time increased. When the ERK1/2 and PI3K/AKT/mTOR signal pathway were blocked, the expression levels of NSE, NES and beta-Tubulin III mRNA and NSE protein were inhibited significantly. It points out that SD can stimulate the ERK1/2 and PI3K/AKT/mTOR signal pathway to promote BMSCs differentiation into neural cells.

The effects of daidzin and its aglycon, daidzein, on the scopolamine-induced memory impairment in male mice.

In this study, the effect of daidzin or daidzein isolated from Pueraria lobata on the memory impairments induced by scopolamine was assessed in male mice using the passive avoidance and the Morris water maze tasks. Administration of daidzin (5 mg/kg) or daidzein (5 mg/kg) significantly reversed the scopolamine (1 mg/kg)-induced cognitive impairments in male mice as evidenced by the passive avoidance test (p < 0.05) and on the Morris water maze test (p < 0.05). Moreover, the ameliorating effects of daidzin or daidzein were antagonized by tamoxifen (1 mg/kg), the nonspecific estrogen receptor antagonist. These results indicate that daidzin or daidzein may be useful in cognitive impairment induced by cholinergic dysfunction, and this beneficial effect is mediated, in part, via estrogen receptor.

Tetrahydroxystilbene glucoside ameliorates diabetic nephropathy in rats: involvement of SIRT1 and TGF-ß1 pathway.

Oxidative stress caused by hyperglycaemia is believed to be a major molecular mechanism underlying diabetic nephropathy. 2,3,5,4'-tetrahydroxystilbene-2-O-ß-d-glucoside (TSG), an active component extract from Polygonum multiflorum Thunb, exhibits antioxidative and anti-inflammatory effects. Possible protective mechanisms of TSG on diabetic nephropathy were investigated in rats and cultured rat mesangial cells. Total cholesterol and triglyceride levels of diabetic rats were clearly increased and these increases were diminished by treatment with TSG. Treatment of diabetic rats with TSG also significantly reduced blood urea nitrogen, creatinine, 24 h urinary protein levels, and kidney weight/body weight. The activities of superoxide dismutase and glutathione peroxidase in renal homogenate were increased markedly, whereas malonaldehyde levels were decreased significantly in TSG-treated diabetic rats. TSG dramatically inhibited diabetes-induced overexpression of TGF-ß1 and COX-2, and restored the decrease of SIRT1 expression in diabetic rats. High glucose-induced overexpression of TGF-ß1 in cultured mesangial cells was significantly inhibited, whereas the decease of SIRT1 expression was restored by pretreatment of TSG. Nicotinamide, the inhibitor of SIRT1, partially relieved the inhibitory effect of TSG on TGF-ß1 expression under high glucose condition. These findings indicate that the protective mechanisms of TSG on diabetic nephropathy are involved in the alleviation of oxidative stress injury and overexpression of COX-2 and TGF-ß1, partially via activation of SIRT1.

[Resistant effect of water decoction of root of Crataegus cuneata on male infertility induced by GTW in rats].

OBJECTIVE: To observe the effects of water decoction of the root of Crataegus cuneata on infertility induced by multi-glucoside of Tripterygium wilfordii (GTW) in rats. METHOD: Male adult rats were randomly divided into five groups, which were treated via gastric gavage of distilled water (1 mL x kg(-1)) , solution of GTW (10 mg x kg(-1)) and three doses of water decoction of root of C. cuneata (1.8, 5.4, 18 g x kg(-1)) + GTW (10 mg x kg(-1)), respectively. 8 weeks later, GTW was stopped and the decoction and water continued for another 4 weeks. And then, all the male rats were copulated with adult female rats. The rates of pregnancy, average numbers of embryos and luteum of female rats, relative weights of reproductive organs, sperm counts, sperm motility and viability were compared among all the groups. The histology and ultrastructure of testis and epididymis were observed, while the concentrations of follicle stimulating hormone (FSH), luteinizing hormone (LH) and testostorone (T) in serum and T in testicular homogenate were detected by radioimmunoassay. RESULT: Compared with those in GTW model group, the embryo numbers, the relative weight of testis and epididymis and sperm counts and motility in C. cuneata groups were increased obviously (P < 0.05). After treatment, the morphological damages of seminiferous tubules and sperms were recovered, while concentrations of T in testicular homogenate were also significantly increased (P < 0.01). CONCLUSION: C. cuneata could relieve the reproductive lesions induced by GTW, and hence improve the uberty of the male infertile model rats.

Restorative effect of repetitive administration of Shaoyao-Gancao-tang on bioavailability of paeoniflorin reduced by antibacterial synthetic drugs treatment in rats.

Paeoniflorin (PF) is an active glucoside in Shaoyao (peony root), and is transformed into an antispasmodic metabolite, paeonimetabolin-I (PM-I), by intestinal bacteria in the gut after oral administration of Shaoyao or Shaoyao-Gancao-tang (SGT, Shakuyaku-Kanzo-To in Japanese). SGT is a pain-relieving traditional Chinese formulation (Kampo-medicine in Japanese) and is often used together with antibacterial synthetic drugs, such as amoxicillin and metronidazole (AMPC-MET), in peptic ulcer therapy. Since the bioavailability of PF in SGT has been reported to be significantly reduced by co-administered antibacterial drugs, we investigated how to minimize this reducing effect of antibacterial treatment in the present study. We found that repetitive administration of SGT starting 24 h after AMPC-MET treatment rapidly restored the plasma PM-I concentration from SGT reduced by AMPC-MET, due to its restorative effect on the decreased PF-metabolizing activity of intestinal bacteria in rat feces. The present findings suggest that it may be clinically useful to administer SGT repetitively, starting 1 or 2 d after treatment with a mixture of AMPC-MET during their combination therapy, to accelerate the recovery of the reduced bioavailability of PF in SGT. Similar administration regimens may also be useful in other combination therapies involving traditional Chinese formulations and antibacterial synthetic drugs to ensure the efficacy of the bioactive glycosides in the formulations.

Chemical constituents of Gentianaceae XIX: CNS-depressant effects of swertiamarin.

CNS activity of swertiamarin, a secoiridoid glucoside from Swertia chirata, was evaluated. An apparent anomaly, associated with the unanticipated finding that the alcoholic extracts (excluding mangiferin) of S. chirata significantly reversed the mangiferin-induced CNS-stimulating effects in albino mice and rats, was resolved. The results indicate that swertiamarin and mangiferin antagonize each other in vivo and thereby reverse their CNS effects.