Alzheimer’s disease, a major and increasing global health challenge, is an irreversible, progressive form of dementia, associated with an ongoing decline of brain functioning. The etiology of this disease is not completely understood, and no safe and effective anti-Alzheimer’s disease drug to prevent, stop, or reverse its evolution is currently available. Current pharmacotherapy concentrated on drugs that aimed to improve the cerebral acetylcholine levels by facilitating cholinergic neurotransmission through inhibiting cholinesterase. These compounds, recognized as cholinesterase inhibitors, offer a viable target across key sign domains of Alzheimer’s disease, but have a modest influence on improving the progression of this condition. In this paper, we sought to highlight the current understanding of the cholinergic system involvement in Alzheimer’s disease progression in relation to the recent status of the available cholinesterase inhibitors as effective therapeutics.

Diabetes and Alzheimer’s disease are two highly prevalent diseases among the aging population and have become major public health concerns in the 21st century, with a significant risk to each other. Both of these diseases are increasingly recognized to be multifactorial conditions. The terms “diabetes type 3” or “brain diabetes” have been proposed in recent years to provide a complete view of the potential common pathogenic mechanisms between these diseases. While insulin resistance or deficiency remains the salient hallmarks of diabetes, cognitive decline and non-cognitive abnormalities such as impairments in visuospatial function, attention, cognitive flexibility, and psychomotor speed are also present. Furthermore, amyloid aggregation and deposition may also be drivers for diabetes pathology. Here, we offer a brief appraisal of social impact and economic burden of these chronic diseases and provide insight into amyloidogenesis through considering recent advances of amyloid-β aggregates on diabetes pathology and islet amyloid polypeptide on Alzheimer’s disease. Exploring the detailed knowledge of molecular interaction between these two amyloidogenic proteins opens new opportunities for therapies and biomarker development.

The most important discoveries in pharmacology, such as certain classes of analgesics or chemotherapeutics, started from natural extracts which have been found to have effects in traditional medicine. Cannabis, traditionally used in Asia for the treatment of pain, nausea, spasms, sleep, depression, and low appetite, is still a good candidate for the development of new compounds. If initially all attention was directed to the endocannabinoid system, recent studies suggest that many of the clinically proven effects are based on an intrinsic chain of mechanisms that do not necessarily involve only cannabinoid receptors. Recent research has shown that major phytocannabinoids and their derivatives also interact with non-cannabinoid receptors such as vanilloid receptor 1, transient receptor ankyrin 1 potential, peroxisome proliferator-activated receptor-gamma or glitazone receptor, G55 protein-coupled receptor, and nuclear receptor, producing pharmacological effects in diseases such as Alzheimer’s, epilepsy, depression, neuropathic pain, cancer, and diabetes. Nonetheless, further studies are needed to elucidate the precise mechanisms of these compounds. Structure modulation of phytocannabinoids, in order to improve pharmacological effects, should not be limited to the exploration of cannabinoid receptors, and it should target other courses of action discovered through recent research.

Alzheimer’s disease (AD) affects tens of millions of people worldwide. Despite the advances in understanding the disease, there is an increased urgency for pharmacological approaches able of impacting its onset and progression. With a multifactorial nature, high incidence and prevalence in later years of life, there is growing evidence highlighting a relationship between metabolic dysfunction related to diabetes and subject’s susceptibility to develop AD. The link seems so solid that sometimes AD and type 3 diabetes are used interchangeably. A candidate for a shared pathogenic mechanism linking these conditions is chronically-activated mechanistic target of rapamycin (mTOR). Chronic activation of unrestrained mTOR could be responsible for sustaining metabolic dysfunction that causes the breakdown of the blood-brain barrier, tau hyperphosphorylation and senile plaques formation in AD. It has been suggested that inhibition of sodium glucose cotransporter 2 (SGLT2) mediated by constant glucose loss, may restore mTOR cycle via nutrient-driven, preventing or even decreasing the AD progression. Currently, there is an unmet need for further research insight into molecular mechanisms that drive the onset and AD advancement as well as an increase in efforts to expand the testing of potential therapeutic strategies aimed to counteract disease progression in order to structure effective therapies.

Neurodegenerative diseases are an increasing cause of global morbidity and mortality. They occur in the central nervous system (CNS) and lead to functional and mental impairment due to loss of neurons. Recent evidence highlights the link between neurodegenerative and inflammatory diseases of the CNS. These are typically associated with several neurological disorders. These diseases have fundamental differences regarding their underlying physiology and clinical manifestations, although there are aspects that overlap. The endocannabinoid system (ECS) is comprised of receptors (type-1 (CB1R) and type-2 (CB2R) cannabinoid-receptors, as well as transient receptor potential vanilloid 1 (TRPV1)), endogenous ligands and enzymes that synthesize and degrade endocannabinoids (ECBs). Recent studies revealed the involvement of the ECS in different pathological aspects of these neurodegenerative disorders. The present review will explore the roles of cannabinoid receptors (CBRs) and pharmacological agents that modulate CBRs or ECS activity with reference to Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Huntington’s Disease (HD) and multiple sclerosis (MS).

The present study evaluated the chemical composition and the in vitro and in vivo antioxidant potential of Ammi visnaga L. essential oil to provide a scientific basis for the use of this plant in the traditional pharmacopoeia. Gas chromatography-mass spectrometry was used to identify the volatile constituents present of the oil. The in vitro antioxidant capacity was evaluated by the DPPH and the reducing power assays. For the in vivo tests, oral administration of Ammi visnaga L. oil (600 and 1200 mg/kg body weight) was performed in Swiss albino mice treated with acetaminophen (400 mg/kg). The toxic effect of acetaminophen and the action of the essential oil were measured by determining the levels of lipid peroxidation and antioxidant enzymes in liver and kidneys homogenates. The major components identified were butanoic acid, 2-methyl-, pentyl ester, (Z)-β-ocimene, D-limonene, linalool, pulegone and lavandulyl-butyrate. The in vitro DPPH and reducing power assays showed moderate to low free radical scavenging activity and the antioxidant power was positively correlated with the polyphenols’ concentration. In vivo, the Ammi visnaga L. essential oil showed a high antioxidant capacity at both concentrations (600 and 1200 mg/kg), effectively increasing the levels of reduced glutathione, superoxide dismutase, and catalase and significantly reducing the lipid peroxidation. The results obtained from this study suggest that Ammi visnaga L. could represent a source of molecules with antioxidant potential in the prevention of free radical-related diseases.