Homocysteine (Hcy) is a nonproteogenic sulfur containing amino acid derived from dietary methionine through demethylation. Homocysteine can be re-methylated to methionine [precursor of S-adenosylmethionine (SAM)] via the re-methylation or 5-methyltetrahydrofolate pathway or undergoes transsulfuration to form cysteine by the action of metabolic enzymes and cofactors. Impaired metabolism due to genetic alteration in metabolic enzymes (methionine synthase, methyltetrahydrofolate reductase (MTHFR), cystathionine β-synthase (CβS), and cystathionine-γ-lyase (CγL) or deficiency in cofactors (vitamin B6 , B12 , folate) may lead to acquired metabolic anomaly known as hyperhomocysteinemia. Hcy excess decreases the S-adenosylmethionine (SAM)-dependent synthesis of catecholamines, viz. dopamine, norepinephrine, epinephrine, and noncatecholamine, viz. serotonin (5-HT), due to genetic alteration in key enzyme MTHFR in the homocysteine metabolism pathway that leads to depression. Thus, hyperhomocysteinemia (HHcy)-induced SAM level is influenced by the single nucleotide polymorphism (SNP) MTHFR C677T. Furthermore, HHcy leads to production of precarious neurotoxic product homocysteic acid (HCA) and cysteine sulfinic acid (CSA) which acts as an N-methyl-D-aspartate (NMDA) receptor agonist and has neurotoxic effects on dopaminergic neurons. In the current review, an attempt has been made to discuss the neurotoxic effects of HHcy in the pathogenesis of depression.

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The present study investigates the potential of Carnosine, a histamine precursor in rat model of bilateral common carotid artery occlusion (BCCAo)-induced vascular dementia (VaD). Wistar rats were subjected to BCCAo procedure under anaesthesia to induce VaD. The rats were subjected to Morris water maze (MWM) test (6th day onwards post-surgery). MWM test was employed to assess learning and memory of the animals whereby escape latency time, time spent in target quadrant and Path length (distance travelled) taken as important parameters. Serum nitrite level; Brain thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) levels; Brain acetylcholinesterase (AChE) activity; brain Myeloperoxidase activity (MPO) and neutrophil count were estimated as per standard procedures. BCCAo in rats produced a significant vascular endothelial dysfunction, as reflected by decrease in serum nitrite levels. Further, these animals showed poor performance on MWM, depicting impairment of learning and memory. There was a significant rise in brain oxidative stress level as indicated by increase in TBARS and decrease in GSH levels. An increase in brain AChE activity was also observed. Moreover, these rats also exhibited an increase in MPO activity and neutrophil infiltration in brain (as marker of inflammation). Treatment of Carnosine (200 and 400 mg/kg, i.p.)/Donepezil (0.3 mg/kg, i.p.) ameliorated BCCAo-induced memory deficits; endothelial dysfunction; biochemical and histopathological changes. It is concluded that Carnosine has shown efficacy in rat model of BCCAo-induced VaD and can be considered as an important therapeutic agent for the treatment of VaD.

The present study investigates the effect of ozagrel, a selective thromboxane A2 (TXA2) inhibitor, in rat model of hyperhomocysteinemia (HHcy)‐induced vascular cognitive impairment and dementia (VCID). Wistar rats were administered L‐methionine (1.7 g/kg/day; p.o. × 8 weeks) to induce VCID. Morris water maze (MWM) test was employed to assess learning and memory. Endothelial dysfunction was assessed in the isolated aorta by observing endothelial‐dependent vasorelaxation and levels of serum nitrite. Various biochemical and histopathological estimations were also performed. L‐methionine produced significant impairment in endothelium‐dependent vasorelaxation and decreases serum nitrite levels indicating endothelial dysfunction. Further, these animals performed poorly on MWM, depicting impairment of learning and memory. Further, a significant rise in brain oxidative stress level (indicated by increase in brain thiobarbituric acid‐reactive species and decrease in reduced glutathione levels), brain acetylcholinesterase activity, brain myeloperoxidase activity, brain TNF‐α and IL‐6 levels, and brain leukocyte (neutrophil) infiltration was also observed. Treatment of ozagrel (10 and 20 mg/kg, p. o.)/donepezil (0.5 mg/kg, i.p., serving as standard) ameliorated L‐methionine‐induced endothelial dysfunction, memory deficits, and biochemical and histopathological changes. It may be concluded that ozagrel markedly improved endothelial dysfunction, learning and memory, and biochemical and histopathological alteration associated with L‐methionine‐induced VCID and that TXA2 can be considered as an important therapeutic target for the management of VCID.

New receptor Phenylene‐Bis‐Methylfuran‐yl‐2‐Methyele Acetohydrazide (PBMMA) has been synthesized by condensation of hydrazide and 5‐methyl furfural. Synthesized receptor has been fully characterized by IR, 1H NMR, 13C NMR, mass spectroscopic and thermo gravimetric analysis. The receptor PBMMA shows selective recognition potential towards Gd3+ ion when tested with several metal ions such as Na+, K+, Mg2+, Cu2+, Cd2+, Hg2+, Y3+, La3+, Eu3+, Sm3+, Gd3+, Re6+ and Th4+ ion as their sulfates by UV–visible and fluorescence spectroscopic studies. Binding nature of PBMMA with Gd3+ ion was further studied by mass spectroscopic and cyclic voltammetric studies. The stoichiometry of PBMMA‐Gd3+ ion has been established, 1:1 by Benesi‐Hildebrand plot method and method of continuous variation (Job's plot) with association affinity K = 6.491 × 104 M−1. In addition to these, molecular docking, molecular dynamic stimulation and binding energy of complex; through Density Function theory −595.66 kcal/mol has also indication of strong binding. The electron transfer energy of Higher occupied molecular orbital (HOMO) to Lower unoccupied molecular orbital (LUMO) is about 4.186 eV and 295 nm for PBMMA‐Gd3+ Complex.