Neuroprotective Effects of Black Pepper and Its Bioactive Compounds in Age-Related Neurological Disorders

Age-related neurological disorders (ANDs), including neurodegenerative diseases, are multifactorial disorders whose risk increases with age. The main pathological hallmarks of ANDs include behavioral changes, excessive oxidative stress, progressive functional declines, impaired mitochondrial function, protein misfolding, neuroinflammation, and neuronal cell death. Recently, efforts have been made to overcome ANDs because of their increased age-dependent prevalence. Black pepper, the fruit of Piper nigrum L. in the family Piperaceae, is an important food spice that has long been used in traditional medicine to treat various human diseases. Consumption of black pepper and black pepper-enriched products is associated with numerous health benefits due to its antioxidant, antidiabetic, anti-obesity, antihypertensive, anti-inflammatory, anticancer, hepatoprotective, and neuroprotective properties. This review shows that black pepper's major bioactive neuroprotective compounds, such as piperine, effectively prevent AND symptoms and pathological conditions by modulating cell survival signaling and death. Relevant molecular mechanisms are also discussed. In addition, we highlight how recently developed novel nanodelivery systems are vital for improving the efficacy, solubility, bioavailability, and neuroprotective properties of black pepper (and thus piperine) in different experimental AND models, including clinical trials. This extensive review shows that black pepper and its active ingredients have therapeutic potential for ANDs.