Combination of paeoniflorin and calycosin-7-glucoside alleviates ischaemic stroke injury via the PI3K/AKT signalling pathway.

CONTEXT: Paeoniflorin (PF) and calycosin-7-glucoside (CG, Paeonia lactiflora Pall. extract) have demonstrated protective effects in ischaemic stroke. OBJECTIVE: To investigate the synergistic effects of PF + CG on ischaemia/reperfusion injury in vivo and in vitro. MATERIALS AND METHODS: Male Sprague-Dawley rats were subjected to the middle cerebral artery occlusion/reperfusion (MCAO/R). After MCAO/R for 24 h, rats were randomly subdivided into 5 groups: sham, model (MCAO/R), study treatment (PF + CG, 40 + 20 mg/kg), LY294002 (20 mg/kg), and study treatment + LY294002. Males were given via intragastric administration; the duration of the in vivo experiment was 8 days. Neurologic deficits, cerebral infarction, brain edoema, and protein levels were assessed in vivo. Hippocampal neurons (HT22) were refreshed with glucose-free DMEM and placed in an anaerobic chamber for 8 h. Subsequently, HT22 cells were reoxygenated in a 37 °C incubator with 5% CO2 for 6 h. SOD, MDA, ROS, LDH and protein levels were measured in vitro. RESULTS: PF + CG significantly reduced neurobehavioral outcomes (21%), cerebral infarct volume (44%), brain edoema (1.6%) compared with the MCAO/R group. Moreover, PF + CG increased p-PI3K/PI3K (4.69%, 7.4%), p-AKT/AKT (6.25%, 60.6%) and Bcl-2/BAX (33%, 49%) expression in vivo and in vitro, and reduced GSK-3ß (10.5%, 9.6%) expression. In vitro, PF + CG suppressed apoptosis in HT22 cells and decreased ROS and MDA levels (20%, 50%, respectively). CONCLUSIONS: PF + CG showed a synergistic protective effect against ischaemic brain injury, potentially being a future treatment for ischaemic stroke.

Sodium Tanshinone IIA Sulfonate Attenuates Scopolamine-Induced Cognitive Dysfunctions via Improving Cholinergic System.

Sodium Tanshinone IIA sulfonate (STS) is a derivative of Tanshinone IIA (Tan IIA). Tan IIA has been reported to possess neuroprotective effects against Alzheimer's disease (AD). However, whether STS possesses effect on AD remains unclear. This study aims to estimate whether STS could protect against scopolamine- (SCOP-) induced learning and memory deficit in Kunming mice. Morris water maze results showed that oral administration of STS (10 mg/kg and 20 mg/kg) and Donepezil shortened escape latency, increased crossing times of the original position of the platform, and increased the time spent in the target quadrant. STS decreased the activity of acetylcholinesterase (AChE) and increased the activity of choline acetyltransferase (ChAT) in the hippocampus and cortex of SCOP-treated mice. Oxidative stress results showed that STS increased the activity of superoxide dismutase (SOD) and decreased the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) in hippocampus and cortex. In addition, western blot was carried out to detect the expression of apoptosis related proteins (Bcl-2, Bax, and Caspase-3). STS upregulated the protein expression of Bcl-2 and downregulated the proteins expression of Bax and Caspase-3. These results indicated that STS might become a promising therapeutic candidate for attenuating AD-like pathological dysfunction.

[Metabonomics Study on Urine 1H-NMR in Chronic Superficial Gastritis Patients with Pi-qi Deficiency Syndrome/Pi-Wei Dampness-heat Syndrome].

OBJECTIVE: To observe metabolomic changes in urine of chronic superficial gastritis (CSG) patients with Pi-qi deficiency syndrome (PQDS) or Pi-Wei dampness-heat syndrome (PWDHS), thereby providing scientific evidence for syndrome typing of them. METHODS: Urine samples were collected from CSG patients with PQDS/PWDHS and healthy volunteers, 10 in each group. Proton nuclear magnetic resonance spectroscopy (1H-NMR) based metabonomic analysis was performed on urine samples. Contents of related biomarkers were analyzed by principal component analysis (PCA), partial least square discriminant analysis (PLS-DA), and urivariate statistical analysis. RESULTS: PLS-DA analysis showed that metabolites among CSG patients with PQDS/PWDHS and healthy volunteers could be mutually distinguished. Seven differentially identified metabolites were screened from urines of CSG patients with PQDS and healthy volunteers included glutamate, methionine, α-oxoglutarate, dimethylglycine, creatinine, taurine, and glucose. Four differentially identified metabolites were screened from urines of CSG patients with PWDHS and healthy volunteers included 2-hydroxybutyric acid, trimethylamine oxide, taurine, and hippuric acid. Eleven differentially identified metabolites were screened from urines of CSG patients with PQDS and PWDHS included fucose, ß-hydroxybutyric acid, alanine, glutamate, methionine, succinic acid, citric acid, creatinine, glucose, hippuric acid, and lactic acid. CONCLUSION: The metabolic differences of CSG patients PQDS and PWDHS mainly manifested in glycometabolism, lipid metabolism, and amino acids catabolism, and 1H-NMR based metabonomics may be used in classified study of Chinese medical syndrome typing.

Inhibitory effect of hydroxysafflor yellow a on mouse skin photoaging induced by ultraviolet irradiation.

Chronic exposure to ultraviolet (UV) irradiation is believed to be the major cause of skin damage that results in premature aging of the skin, so called photoaging, characterized by increases in skin thickness, formation of wrinkles, and loss of skin elasticity. UV induces damage to skin mainly by oxidative stress and collagen degradation. In this study, we examined the photo-protective effect of hydroxysafflor yellow A (HSYA), a major active chemical component isolated from Carthamus tinctorius L., by topical application on the skin of mice. Exposure of the dorsal depilated skin of mice to UV radiation four times a week for 10 weeks induced epidermal hyperplasia, elastin accumulation, collagen degradation, etc. HSYA at the doses of 50, 100, and 200 µg/mouse was topically applied immediately following each UV exposure. The effects of HSYA were evaluated by a series of tests, including macroscopic and histopathological evaluation of skin, pinch test, and redox homeostasis of skin homogenates. Results showed that the UV-induced skin damage was significantly improved after HSYA treatment, especially at doses of 100 and 200 µg/mouse. This protective effect is possibly related to the anti-oxidative property of HSYA and mediated by promoting endogenous collagen synthesis. This is the first study providing preclinical evidence for the protective effect of HSYA against photoaging.

Protective effects of hydroxysafflor yellow A on ß-amyloid-induced neurotoxicity in PC12 cells.

The accumulation of extracellular amyloid-ß peptide (Aß) has been considered as one of the important causes of Alzheimer's disease (AD), the most prevalent form of dementia. Hydroxysafflor yellow A (HSYA), a major active chemical component isolated from Carthamus tinctorius L., has been shown to possess neuroprotective actions in various ischemic models in vivo. The present study aimed to investigate the potential protective effect of HSYA against Aß-induced neurotoxicity in cultured rat pheochromocytoma (PC12) cells. The PC12 cells were pretreated with different concentrations (20, 40 and 80 µM) of HSYA for 2 h and then further treated with Aß (20 µM) for 24 h. The results showed that Aß could significantly decrease cell viability, glutathione level, mitochondrial membrane potential and the ratio of Bcl-2/Bax protein expression, while elevate the release of lactate dehydrogenase, the formation of DNA fragmentation, the levels of malondialdehyde and intracellular reactive oxygen species in PC12 cells. However, pretreatment with HSYA could effectively reverse these changes induced by Aß in PC12 cells. Our experimental results demonstrate that HSYA may be a potential neuroprotective agent warranting further development for treatment of AD.

[The empirical study of Maxingganshi decoction and its compatibility in acute lung injury rats].

OBJECTIVE: To explore the pharmacodyniamic action and the mechanism of action of the Maxingganshi decoction in acute lung injury rats in order to supply the pharmacology evidence to cure the SIRS-ALI of Maxingganshi decoction. METHODS: The study designed by orthogonal design. The SIRS-ALI model were Conseructed by the LPS intravenous injection and the effects of Maxingganshi decoction and it's different compatibilities to the SIRS-ALI model were observed. The experiments results were analvsised in order to reveal the compatibility rules of the Maxingganshi decocotion. RESULTS: Maxingganshi decocotion and its different compatibilities had good effects of prevention and cure the SIRS-ALI. The mechanism maybe concerned with the Maxingganshi decocotion can decrease the TNF-alpha and increase the IL-10. The experiments results also indicated that the action of the full formula was the best. The principal drug was the most important in the formula. CONCLUSION: Maxingganshitang has a good effect in anti the ALI; the results indicat that the principal drug is the predominant therapeutic action in the formula ministerial drug. Adjuvant drug and messenger drug can strengthen pharmacodynamic action.

[Influence of compatibility on content of berberine in Maxingganshi decoction].

OBJECTIVE: To set up the quantitative method of herberine in decoctions prepared from various combinations of Maxingganshi decotion by HPLC and to determine the change of general contents in different decoction. METHODS: The study was designed by L8 (2(7)) orthogonal and to determine the change of general contents in different decoction by HPLC. RESULTS: In full formula remove Glycyrrhiza uralensis group, the contents of L-ephedrine, d-pseudephedrine and the amygdaloside cut down significantly. In full formula remove armeniacae semen group, the content of glycyrrhetic acid cut down significantly. Four chemical composition in full formula group had higher contents. CONCLUSION: Armeniacae semen can decrease the content of L-ephedrine, D-pseudephedrine. Glycyrrhiza uralensis can help decoctum amygdaloside and armeniacae semen can help decoctum glycyrrhizic acid.