Oxidative stress is known to be associated with various age-related diseases. D-galactose (D-gal) has been considered a senescent model which induces oxidative stress response resulting in memory dysfunction. Pyrroloquinoline quinone (PQQ) is a redox cofactor which is found in various foods. In our previous study, we found that PQQ may be converted into a derivative by binding with amino acid, which is beneficial to several pathological processes. In this study, we found a beneficial glutamate mixture which may diminish neurotoxicity by oxidative stress in D-gal induced mouse. Our results showed that PQQ may influence the generation of proinflammatory mediators, including cytokines and prostaglandins during aging process. D-gal-induced mouse showed increased MDA and ROS levels, and decreased T-AOC activities in the hippocampus, these changes were reversed by PQQ supplementation. Furthermore, PQQ statistically enhanced Superoxide Dismutase SOD2 mRNA expression. PQQ could ameliorate the memory deficits and neurotoxicity induced by D-gal via binding with excess glutamate, which provide a link between glutamate-mediated neurotoxicity, inflammation and oxidative stress. In addition, PQQ reduced the up-regulated expression of p-Akt by D-gal and maintained the activity of GSK-3β, resulting in a down-regulation of p-Tau level in hippocampus. PQQ modulated memory ability partly via Akt/GSK-3β pathway.

1 In a recent in vivo study, liriodenine, an aporphine alkaloid, has been identi®ed as a prominent anti-arrhythmic agent that can prevent rats' sudden deaths, even at the dose as low as 10 77 g kg 71 .The aim of this study was to determine whether liriodenine at its e ective anti-arrhythmic dose of 10 77 g kg 71 had e ects on the left ventricular (LV)-arterial coupling in Wistar rats. 2 LV pressure and ascending aortic¯ow signals were recorded to construct the ventricular and arterial end-systolic pressure-stroke volume relationships to calculate LV end-systolic elastance (E es ) and e ective arterial volume elastance (E a ), respectively. The optimal afterload (Q load ) determined by the ratio of E a to E es was used to measure the optimality of energy transmission from the left ventricle to the arterial system. 3 Liriodenine at the dose of 10 77 g kg 71 showed no signi®cant changes in basal heart rate (HR), cardiac output (CO), LV end-systolic pressure (P es ), E a , E es , and Q load . 4 By contrast, liriodenine at the dose of 10 76 g kg 71 produced a signi®cant fall of 2.0% in HR and a signi®cant rise of 5.8% in CO, but no signi®cant change in P es . Moreover, liriodenine administration of 10 76 g kg 71 to rats signi®cantly decreased E es by 8.5% and E a by 10.6%, but did not change Q load . 5 We conclude that liriodenine at the dose of 10 77 g kg 71 has no e ects on the mechanical properties of the heart and the vasculature and the matching condition for the left ventricle coupled to its vasculature in rats. Even at 10 times the e ective anti-arrhythmic dose, liriodenine shows no e ects on the e ciency of energy transferred from the left ventricle to the arterial system. British Journal of Pharmacology (2001) 133, 29 ± 36 Keywords: Left ventricular-arterial coupling; left ventricular end-systolic elastance; e ective arterial volume elastance; optimal afterloadAbbreviations: APD, action potential duration; BA, basal state; CO, cardiac output (ml s 71 ); DMSO, dimethylsulphoxide; E a , e ective arterial volume elastance (mmHg ml 71 ); E es , left ventricular end-systolic elastance (mmHg ml 71 ); HR, basal heart rate (beats min 71 ); P es , end-systolic pressure of the left ventricle (mmHg); P isomax , peak isovolumic pressure of the left ventricle (mmHg); P max , peak pressure of the left ventricle (mmHg); Q load , optimal afterload; R p , total peripheral resistance (mmHg s ml 71 ); SV, stroke volume (ml beat 71 ); V ed , end-diastolic volume of the left ventricle (ml); V eed , e ective end-diastolic volume of the left ventricle (ml); V 0 , the zero-pressure volume (ml)

Iridoid glycosides (IGs) are found in many medicinal and edible plants, such as Gardenia jasminoides, Cistanche tubulosa, Eucommia ulmoides, Rehmanniae Radix, Lonicera japonica, and Cornus officinalis. Loganin, an IG, is one of the main active ingredient of Cornus officinalis Sieb. et Zucc., which approved as a medicinal and edible plant in China. Loganin has been widely concerned due to its extensive pharmacological effects, including anti‐diabetic, antiinflammatory, neuroprotective, and anti‐tumor activities, etc. Studies have shown that these underlying mechanisms include anti‐oxidation, antiinflammation and anti‐apoptosis by regulating a variety of signaling pathways, such as STAT3/NF‐κB, JAK/STAT3, TLR4/NF‐κB, PI3K/Akt, MCP‐1/CCR2, and RAGE/Nox4/p65 NF‐κB signaling pathways. In order to better understand the research status of loganin and promote its application in human health, this paper systematically summarized the phytochemistry, analysis methods, synthesis, pharmacological properties and related mechanisms, and pharmacokinetics based on the research in the past decades.

It was previously reported that cytokines and neurotoxins released from activated inflammatory cells induced the loss of projecting dopaminergic neurons in the substantia nigra, which triggered the pathogenesis of PD. The present study investigated the effect of treatment with tetramethylpyrazine (TMP) on the central cytokine synthesis, striatal dopamine content and glutamatergic transmission, and behavioral performance in the rotarod task in mice injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Treatment with TMP significantly improved the behavioral performance in the rotarod task in mice injected with MPTP. It also decreased the upregulation of cytokines (tumor necrosis factor-α and interleukin-1β) in the substantia nigra and striatum in these modeled mice. Furthermore, treatment with TMP significantly improved the dopamine deficits and attenuated the upregulation of striatal basal glutamatergic strength in the striatum of mice injected with MPTP. These results indicated that TMP might serve as a novel approach for the treatment of patients with PD.

Glutamate transporter-1 (GLT-1) plays a dual role in glutamate transportation: both normally devotion to the clearance of glutamate and during some pathological conditions extruding glutamate to the extracellular space. Therefore, it is uncertain whether increased expression of GLT-1 will actually be helpful against glutamate excitotoxicity. In this study, GLT-1 up-regulation was induced by ceftriaxone, and L-glutamate was added to induce glutamate toxicity in primary cultured rat cortical cells. The results showed that up-regulated GLT-1 induced by 1 lM ceftriaxone for 2 days markedly increased cell viability, decreased apoptotic cell death and alleviated ultrastructural damage induced by 50 lM glutamate 15 min. as well as promoted L-[ 3 H]-glutamate uptake in cultured cells. GLT-1 up-regulation had no effect on the intracellular free calcium concentration ([Ca 2+ ] i ) in the resting situation, while relieved intracellular calcium overloading by reducing the elevation and promoting the recovery of [Ca 2+ ] i following stimulation of 50 lM glutamate for 2 min. Applying 100 lM dihydrokainic acid (GLT-1 antagonist) 30 sec. before glutamate eliminated the above effect of GLT-1 up-regulation on [Ca 2+ ] i . In conclusion, GLT-1 up-regulation induced by ceftriaxone plays a positive glutamate transporting role against glutamate toxicity in primary cultured rat cortical cells.Glutamate excitotoxicity causes neuronal death by means of over-stimulation of glutamate receptors, especially the N-methyl-D-aspartate (NMDA) receptor subtype which is largely permeable to calcium leading to intracellular calcium overloading [1]. The extracellular concentration of glutamate is mainly regulated by glutamate transporters situated in neurons and glial cells, which normally eliminate glutamate from the synaptic space and terminate glutamate action on the postsynaptic receptors [2,3]. However, in some pathological conditions (e.g. ischaemia and hypoxia), glutamate transporters were found to extrude glutamate to the extracellular space, operating in the opposite direction and contributing to neuronal damage [4].In the glutamate transporter family, glutamate transporter-1 (GLT-1) highly expresses in astrocytes [5] and accounts for 90% of all glutamate uptake in the brain [6]. Alterations in GLT-1 expression and activity can exert profound influence in neuroprotection and neuropathology. On the one hand, several recent studies suggest that up-regulating GLT-1 expression may be beneficial because of the simultaneously increased positive transporter function in pathological conditions. For example, upregulation of GLT-1 expression by some agents [7] (e.g. b-lactam compounds ceftriaxone and the group II mGluR agonist 4-aminopyrrolidine-2,4-dicarboxylate) increased glutamate intake and attenuated the Huntington's disease phenotype in the R6/2 mouse [8], alleviated motor neurone degeneration and delayed loss of neurons in an animal model of amyotrophic lateral sclerosis (ALS) [9], and played an anti-nociceptive role in a c...