The Effect of Thymoquinone, α7 Receptor Agonist and α7 Receptor Allosteric Modulator on the Cerebral Cortex in Experimentally Induced Alzheimer's Disease in Relation to MSCs Activation

Abstract

Background and ObjectivesAlzheimer’s disease (AD) is the most common form of dementia among older persons. Thymoquinone (TQ) has anti-inflammatory, anticonvulsant and antioxidant activity. A novel α7 nicotinic acetyl choline receptor (α7 nAChR ) agonist (PNU- 282987) have been identified to enhance the cognitive performance. An alternative treatment strategy via compounds known as nicotinic “positive allosteric modulators” (PAMs) has been reported. This study was designed to investigate the combination of PAM of α7 nAChRs with PNU- 282987 or with TQ as a possible treatment for AD in rat.Methods48 male albino rats were divided into 4 groups. Group I (Control), Group II received lipopolysaccharide, 0.8 mg/kg by intraperitoneal injection (IPI) once, Group III received TQ 10 mg/kg by IPI, Group IV received PNU-120596 1 mg/kg by IPI, in addition to PNU-282987 1 mg/kg by IPI in subgroup IVa and TQ in subgroup b. All treatment drugs were given for 5 days.ResultsAcidophilic masses, deformed neurons, Congo red +ve masses and reduced Phospho-CREB immunoexpression were seen in group II. All changes regressed by treatment. Some CD44 +ve cells were noticed in group II and few +ve cells in subgroup IVa, that became multiple in group III and subgroup IVb. The histological, histochemical and immunohistochemical changes were confirmed statistically and significant differences were recorded.ConclusionsTQ or α7 nAChR agonist combined with PAM can have an important role in treatment of AD that is superior to thymoquinone alone. Exceptionally, TQ single or combined with PAM proved activation of MSC.

Dissecting the Potential Roles of Nigella sativa and Its Constituent Thymoquinone on the Prevention and on the Progression of Alzheimer's Disease

“…Recently, in an animal model of AD [lipopolysaccharide(LPS)-induced neuroinflammation in rats] it was tested the combination of PNU-120596, a positive allosteric modulator (PAM) of α7 nicotine acetyl choline receptor (nAChR), with the specific nAChR agonist PNU-282987 or with TQ (Ibrahim AbdEl Fattah et al, 2016 ). Data reported that TQ or the α7 nAChR agonist in combination with the PAM had a pivotal role in the treatment of AD, by reducing the neuroinflammation, and by activating the mesenchymal stem cells (MSCs).…”

The Neuroprotective Effects of Thymoquinone: A Review

“…The PAM of α7 nAChRs is known as PNU-120596. 97 Recently, studies aimed at investigating the combination of PAM of α7 nAChRs with PNU-282987 (α7 nAChR agonist) or with TQ as a possible treatment for AD in an animal model using histological, histochemical, immunohistochemical, and morphometric methods.…”

Neuropharmacological Potential and Delivery Prospects of Thymoquinone for Neurological Disorders

“…LPS causes acidophilic masses, deformed neurons, Congo red (+ve) masses, and reduced cAMP response element-binding protein (CREB) phosphorylation (phospho-CREB) immunoexpression. Concerning histological, histochemical, and immunohistochemical studies, TQ or α 7 nicotinic acetylcholine receptor agonist combined with PAM can have an important role in treatment of AD [ 91 ]. In a recent study, TQ improves LPS-induced learning and memory impairments in rats by attenuating hippocampal cytokine levels and brain tissue oxidative damage [ 84 ].…”