Alzheimer’s disease (AD) is a progressive neurodegenerative disorder more prevalent among the elderly population. AD is characterised clinically by a progressive decline in cognitive functions and pathologically by the presence of neurofibrillary tangles (NFTs), deposition of beta-amyloid (Aβ) plaque and synaptic dysfunction in the brain. Centella asiatica (CA) is a valuable herb being used widely in African, Ayurvedic, and Chinese traditional medicine to reverse cognitive impairment and to enhance cognitive functions. This study aimed to evaluate the effectiveness of CA in preventing d-galactose/aluminium chloride (d-gal/AlCl₃) induced AD-like pathologies and the underlying mechanisms of action were further investigated for the first time. Results showed that co-administration of CA to d-gal/AlCl₃ induced AD-like rat models significantly increased the levels of protein phosphatase 2 (PP2A) and decreased the levels of glycogen synthase kinase-3 beta (GSK-3β). It was further observed that, CA increased the expression of mRNA of Bcl-2, while there was minimal effect on the expression of caspase 3 mRNA. The results also showed that, CA prevented morphological aberrations in the connus ammonis 3 (CA 3) sub-region of the rat’s hippocampus. The results clearly demonstrated for the first time that CA could alleviate d-gal/AlCl₃ induced AD-like pathologies in rats via inhibition of hyperphosphorylated tau (P-tau) bio-synthetic proteins, anti-apoptosis and maintenance of cytoarchitecture.

Neurotransmission and cognitive dysfunctions have been linked to old age disorders including Alzheimer’s disease (AD). Aluminium is a known neurotoxic metal, whereas d-galactose (d-gal) has been established as a senescence agent. WIN55,212-2 (WIN), is a potent cannabinoid agonist which partially restores neurogenesis in aged rats. The current study aimed to explore the therapeutic potentials of WIN on Aluminium chloride (AlCl₃) and d-gal-induced rat models with cognitive dysfunction. Healthy male albino Wistar rats weighing between 200–250 g were injected with d-gal 60 mg/kg intra peritoneally (i.p), while AlCl₃ (200 mg/kg) was orally administered once daily for 10 consecutive weeks. Subsequently, from weeks 8–11 rats were co-administered with WIN (0.5, 1 and 2 mg/kg/day) and donepezil 1 mg/kg. The cognitive functions of the rats were assessed with a Morris water maze (MWM). Furthermore, oxidative stress biomarkers; malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) and neurogenesis markers: Nestin and glial fibrillary acidic protein (GFAP) were also evaluated, as well as the histology of the hippocampus. The results revealed that rats exposed to AlCl₃ and d-gal alone showed cognitive impairments and marked neuronal loss (p < 0.05) in their hippocampal conus ammonis 1 (CA1). Additionally, a significant decrease in the expressions of GFAP and Nestin was also observed, including increased levels of MDA and decreased levels of SOD and GSH. However, administration of WIN irrespective of the doses given reversed the cognitive impairments and the associated biochemical derangements. As there were increases in the levels SOD, GSH, Nestin and GFAP (p < 0.05), while a significant decrease in the levels of MDA was observed, besides attenuation of the aberrant cytoarchitecture of the rat’s hippocampi. The biochemical profiles of the WIN-treated rats were normal. Thus, these findings offer possible scientific evidence of WIN being an effective candidate in the treatment of AD-related cognitive deficits.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with cholinergic dysfunctions and impaired redox homeostasis. The plant Centella asiatica (CA) is renowned for its nutritional benefits and herbal formulas for promoting health, enhancing cognition, and its neuroprotective effects. The present study aims to investigate the protective role of CA on D-gal/AlCl₃-induced cognitive deficits in rats. The rats were divided into six groups and administered with donepezil 1 mg/kg/day, CA (200, 400, and 800 mg/kg/day) and D-gal 60 mg/kg/day + AlCl₃ 200 mg/kg/day for 10 weeks. The ethology of the rats was evaluated by the Morris water maze test. The levels of acetylcholinesterase (AChE), phosphorylated tau (P-tau), malondialdehyde (MDA) and activities of superoxide dismutase (SOD), in the hippocampus and cerebral cortex were estimated by enzyme-linked immunosorbent assay (ELISA). Additionally, the ultrastructure of the prefrontal cortex of the rats’ was observed using transmission electron microscopy (TEM). Rats administered with D-gal/AlCl₃ exhibited cognitive deficits, decreased activities of SOD, and marked increase in AChE and MDA levels. Further, prominent alterations in the ultrastructure of the prefrontal cortex were observed. Conversely, co-administration of CA with D-gal/AlCl₃ improved cognitive impairment, decreased AChE levels, attenuated the oxidative stress in hippocampus and cerebral cortex, and prevented ultrastructural alteration of neurons in the prefrontal cortex. Irrespective of the dose of CA administered, the protective effects were comparable to donepezil. In conclusion, this study suggests that CA attenuated the cognitive deficits in rats by restoring cholinergic function, attenuating oxidative stress, and preventing the morphological aberrations.

Background: Cannabis and its extracts are now being explored due to their huge health benefits. Although, the effect they elicit, whether on humans or rodents, may vary based on the age of the animal/subject and or the time in which the extract is administered. However, several debates exist concerning the various medical applications of these compounds. Nonetheless, their applicability as therapeutics should not be clouded based on their perceived negative biological actions. Methods:: Articles from reliable databases such as Science Direct, PubMed, Google Scholar, Scopus, and Ovid were searched. Specific search methods were employed using multiple keywords: ‘‘Medicinal Cannabis; endocannabinoid system; cannabinoids receptors; cannabinoids and cognition; brain disorders; neurodegenerative diseases’’. For the inclusion/exclusion criteria, only relevant articles related to medicinal Cannabis and its various compounds were considered. Results:: The current review highlights the role, effects, and involvement of Cannabis, cannabinoids, and endocannabinoids in preventing selected neurodegenerative diseases and possible amelioration of cognitive impairments. Furthermore, it also focuses on Cannabis utilization in many disease conditions such as Alzheimer’s and Parkinson’s disease among others. Conclusion:: In conclusion, the usage of Cannabis should be further explored as accumulating evidence suggests that it could be effective and somewhat safe, especially when adhered to the recommended dosage. Furthermore, in-depth studies should be conducted in order to unravel the specific mechanism underpinning the involvement of cannabinoids at the cellular level and their therapeutic applications.

The present study evaluated the effect of Centella asiatica L. Urban (CA) extracts on ultrastructure and oxidative stress parameters on chronic unpredictable mild stress (CUMS) rat’s hippocampi. Rats were divided into six groups (n=6) and treated as follows: Group 1, Unstressed + normal saline (control); Group 2, CUMS + normal saline (Model); Group 3, CUMS + Flx (10 mg/kg) (FLX); Groups 4, CUMS + CA (200 mg/kg) (CA 200); Group 5, CUMS + CA (400 mg/kg) (CA 400) and Group 6, CUMS + CA (800 mg/kg) (CA 800). Nine different stressors were administered to the rats for 8 weeks consecutively, with concurrent administration of fluoxetine or CA. The hippocampi of the rats were evaluated by transmission electron microscopy (TEM) and oxidative stress biomarkers were also determined. Qualitative TEM results showed defective mitochondria, nucleus, myelin sheaths and reduced numbers of synapses in CUMS rats as well as increased oxidative stress biomarkers. Administration of CA prevented some of the structural and biochemical aberrations observed in response to stress in a manner comparable with fluoxetine, a selective serotonin-reuptake inhibitor. Conclusively, CA ameliorates structural defects induced by CUMS in the rat hippocampus, with a potential therapeutic importance in the treatment of stress and depression.

Neurodegenerative disorders represent a significant and escalating global healthcare challenge, characterized by the progressive degeneration of neurons and a consequent decline in cognitive and motor functions. Among older adults, Alzheimer’s disease (AD) is the most prevalent neurodegenerative condition, marked by hallmark neuropathological features such as intracellular hyperphosphorylated tau (p-tau) forming neurofibrillary tangles, synaptic dysfunction, neuronal loss, and extracellular amyloid beta (Aβ) plaque accumulation. Aluminium (Al), a known neurotoxic metal, can cross the blood-brain barrier and accumulate in brain tissue, inducing changes associated with neurodegeneration. Additionally, D-galactose (D-gal) is frequently used in animal models to accelerate aging by inducing oxidative stress and inflammation, thus serving as a valuable tool in anti-aging and neurodegenerative research. This study investigates the therapeutic potential of Ziziphus mauritiana extract (ZME), a traditional medicinal plant with recognized nutritional and pharmacological value, in mitigating cognitive dysfunction induced by Aluminium Chloride (AlCl₃) and D-galactose in Wistar rats. Thirty-five healthy adult male rats (80–120 g) were administered D-gal (60 mg/kg, intraperitoneally) and AlCl₃ (200 mg/kg, orally) to induce neurodegeneration. Two experimental groups received ZME at doses of 100 mg/kg and 50 mg/kg, respectively, while the positive control group was treated with donepezil (1 mg/kg). Cognitive function was assessed using the Novel Object Recognition (NOR) test, oxidative stress was evaluated via Superoxide Dismutase (SOD) activity, and histological examination of the prefrontal cortex was conducted to assess neuronal integrity. Results revealed that exposure to AlCl₃ and D-gal significantly impaired cognitive performance, reduced SOD levels (p < 0.05), and induced morphological alterations in the prefrontal cortex. Treatment with ZME significantly improved cognitive performance, elevated SOD activity, and restored cortical architecture, indicating neuroprotective effects. These findings support the potential of Ziziphus mauritiana as a therapeutic agent for mitigating AD-related cognitive impairments through its antioxidative and neuroprotective mechanisms.