Polysaccharide from Paris polyphylla improves learning and memory ability in D-galactose-induced aging model mice based on antioxidation, p19/p53/p21, and Wnt/ß-catenin signaling pathways.

The current study aimed to investigate the effects and mechanisms of Paris polyphylla polysaccharide component 1 (PPPm-1) to improve learning and memory in D-galactose-induced aging model mice. We determined the effects of PPPm-1 on the brain, organ index, and behavior in the aging model mice induced by D-galactose to study learning and memory improvement. UV-Vis spectrophotometry helped determine the PPPm-1 effect on antioxidant parameters associated with learning and memory in the brain and related organs of aging mice. Moreover, in the hippocampi of aging model mice, PPPm-1 effect on the mRNA and protein expressions of p19, p53, p21, P16, Rb, Wnt/1, ß-catenin, CyclinD1, TCF-4, and GSK-3ß were detected using the quantitative real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. The results indicated that PPPm-1 could increase the brain and organ indexes, the avoidance latency, the total distance and average speed in the water maze, and the SOD and GSH-PX activities in the brain, liver tissues, and plasma. Moreover, the mRNA and protein expressions of Wnt/1, ß-catenin, CyclinD1, and TCF-4 were also elevated in the hippocampi of aging model mice. However, the error times in step-through tests, the MDA content in the brain and liver tissues, the AChE activity in the brain tissue, the protein expressions of P16, Rb in the hippocampi, and the mRNA and protein expressions of p19, p53, p21, and GSK-3ß in the hippocampi of aging model mice were significantly decreased. Thus, PPPm-1 significantly enhanced the learning and memory impairment induced by D-galactose in mice. The action mechanisms were associated with anti-oxidative stress, cholinergic nervous system function regulation, LTP enhancement in long-term memory, down-regulated expression of p19/p53/p21 signaling pathway factors, and Wnt/ß-catenin signaling pathway activation.

Study on the antithrombotic effect and physiological mechanism of okanin.

The objectives of this study were to investigate the antithrombotic effect and physiological mechanism of okanin, a flavonoid monomer in Coreopsis tinctoria Nutt. The antithrombotic effects of okanin were determined by the anticoagulant activity test in vitro and in vivo, the venous thrombosis and arterial thrombosis test in rats. To study the antithrombotic physiological mechanisms of okanin, UV spectrophotometer and enzyme-linked immunosorbent assay (ELISA) were used to determine the effects of three concentrations of okanin on the contents of 6-keto-prostaglandin F1α (6-Keto-PGF1α), thromboxane B2 (TXB2), endothelin-1 (ET-1), antithrombin III (AT-Ⅲ), protein C (PC) and von willebrand factor (vWF) in the plasma of rats with arterial thrombosis; ELISA was used to detect the effects of okanin on the contents of plasminogen (PLG), tissue plasminogen activator (t-PA) and type-1 plasminogen activator inhibitor (PAI-1) in the plasma of mice and Chinese white rabbits. The results showed that okanin could prolong the coagulation time in vitro and in vivo of animals (P < 0.01 in the high dose group) and the activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT) of human venous blood (ATPP of medium dose group P < 0.01; PT, TT P < 0.05. P < 0.01 in the high dose group); inhibit the maximum platelet aggregation rate of rabbits (P < 0.05 in the low dose group; P < 0.01 in the medium and high dose groups), decrease the dry and wet weight of venous thrombosis and the wet weight of common carotid artery thrombosis in rats (low dose group, P < 0.05; medium and high dose groups, P < 0.01); increase the levels of 6-Keto-PGF1α, AT-Ⅲ, PLG and t-PA in animal plasma; decrease the levels of TXB2, ET-1, vWF and PAI-1 in animal plasma. It is concluded that okanin can significantly inhibit thrombosis, and its physiological mechanisms were related to affecting the activation of related coagulation factors in endogenous and exogenous coagulation pathways, affecting the physiological characteristics of platelets, repairing damaged vascular endothelial cells and enhancing the activity of the fibrinolytic system.