Methanolic extract of Tamarix Gallica attenuates hyperhomocysteinemia induced AD-like pathology and cognitive impairments in rats

Abstract

Although few drugs are available today for the management of Alzheimer’s disease (AD) and many plants and their extracts are extensively employed in animals’ studies and AD patients, yet no drug or plant extract is able to reverse AD symptoms adequately. In the present study, Tamarix gallica (TG), a naturally occurring plant known for its strong antioxidative, anti-inflammatory and anti-amyloidogenic properties, was evaluated on homocysteine (Hcy) induced AD-like pathology and cognitive impairments in rats. We found that TG attenuated Hcy-induced oxidative stress and memory deficits. TG also improved neurodegeneration and neuroinflammation by upregulating synaptic proteins such as PSD95 and synapsin 1 and downregulating inflammatory markers including CD68 and GFAP with concomitant decrease in proinflammatory mediators interlukin-1β (IL1β) and tumor necrosis factor α (TNFα). TG attenuated tau hyperphosphorylation at multiple AD-related sites through decreasing some kinases and increasing phosphatase activities. Moreover, TG rescued amyloid-β (Aβ) pathology through downregulating BACE1. Our data for the first time provide evidence that TG attenuates Hcy-induced AD-like pathological changes and cognitive impairments, making TG a promising candidate for the treatment of AD-associated pathological changes.

Protein Phosphatase 2A as a Drug Target in the Treatment of Cancer and Alzheimer’s Disease

“…Till now, a number of natural plant extracts have shown the ability to reduce tau hyperphosphorylation and the formation of Aβ deposits. We have found that Moringa oleifera (MO), Tamarix gallica (TG), Codonopsis pilosula polysaccharide (CPPs) and Ginkgo biloba extract EGb761 can attenuate memory deficits in AD animal model [83][84][85][86] . These natural plant extracts have the ability to decrease tau phosphorylation and increase PP2A activity but the exact mechanism is unclear.…”

Prenatal Hyperhomocysteinemia Induces Glial Activation and Alters Neuroinflammatory Marker Expression in Infant Rat Hippocampus

“…In adult animals, HHC was shown to induce some mitochondria dysfunction and ultrastructural changes in the hippocampus and cortex [ 81 ]. The treatment of adult rats with Hcy led to significant reduction in the number of neuronal cells, degradation of their synapses and dendritic spines, indicating Hcy-associated neurodegeneration [ 82 ]. Furthermore, methionine-enriched diet was shown to alter the volume of adult rat CA1 hippocampus, astroglial activation, and swelling of soma and nuclei of neurons [ 83 ].…”

Direct Activation of Protein Phosphatase 2A (PP2A) by Tricyclic Sulfonamides Ameliorates Alzheimer's Disease Pathogenesis in Cell and Animal Models

“…We and others have established a sporadic AD rat model through inducing hyperhomocysteinemia in rats. These rats exhibit typical AD-like pathogenesis such as tau hyperphosphorylation, Aβ overproduction, PP2A inhibition, and cognitive deficits [35,36,[43][44][45][46]. To explore the effect of SMAPs in AD model in vivo, HHcy rat model was established after 14 days injection of Hcy (400 μg/kg/day) via the vena caudalis, together with (preventive) or followed with the treatment of DBK-1160 (35 mg/kg, twice a day) or SCR-1693(1 mg/kg/day, treatment positive control) ( Table 2 and Fig.…”