Role of Plant Derived Alkaloids and Their Mechanism in Neurodegenerative Disorders

Abstract

Neurodegenerative diseases are conventionally demarcated as disorders with selective loss of neurons. Conventional as well as newer molecules have been tested but they offer just symptomatic advantages along with abundant side effects. The discovery of more compelling molecules that can halt the pathology of these diseases will be considered as a miracle of present time. Several synthetic compounds are available but they may cause several other health issues. Therefore, natural molecules from the plants and other sources are being discovered to replace available medicines. In conventional medicational therapies, several plants have been reported to bestow remedial effects. Phytochemicals from medicinal plants can provide a better and safer alternative to synthetic molecules. Many phytochemicals have been identified that cure the human body from a number of diseases. The present article reviews the potential efficacy of plant-derived alkaloids, which possess potential therapeutic effects against several NDDs including Alzheimer's disease (AD), Huntington disease (HD), Parkinson's disease (PD), Epilepsy, Schizophrenia, and stroke. Alkaloids include isoquinoline, indole, pyrroloindole, oxindole, piperidine, pyridine, aporphine, vinca, β-carboline, methylxanthene, lycopodium, and erythrine byproducts. Alkaloids constitute positive roles in ameliorating pathophysiology of these illnesses by functioning as muscarinic and adenosine receptors agonists, anti-oxidant, anti-amyloid and MAO inhibitors, acetylcholinestrase and butyrylcholinesterase inhibitor, inhibitor of α-synuclein aggregation, dopaminergic and nicotine agonist, and NMDA antagonist.

Keywords: Neurodegenerative diseases; Phytochemicals; Plant derived alkaloids; acetylcholinestrase; butyrylcholinesterase; monoamine oxidase..

FIGURE 1

ALKALOIDS IN NEURODEGENERATIVE DISEASES. Because of the influential and multiple actions of alkaloids, they possess a variety of pharmacological potentials in modern medicine and the effects includes analgesic (e.g., morphine), anti-hyperglycemic (e.g., piperine), anticancer (e.g., berberine), antiarrhythmic (e.g., quinidine), antibacterial (e.g., ciprofloxacin). Some other alkaloids exhibit stimulant effects to CNS (e.g., cocaine, caffeine, and nicotine) as well as psychotropic effects (e.g., psilocin). Although alkaloids have an extensive history and numerous applications but only a few are promoted as active medicine . Alkaloids exert numerous neuro-protective activities in numerous diseases such as epilepsy, psychological disorders, cerebral ischemia, dementia and memory impairment, depression, anxiety, HD, PD, AD and many others . Alkaloids attenuates the development of NDDs through their vast mode of action, i.e., via inhibiting the activity of acetyl-cholinesterase (AChE) enzyme , by increasing the level of gamma-aminobutyric acid (GABA) , by acting as antagonist of NMDA and many more as described in Fig 2.

FIGURE 2

NEUROPROTECTIVE EFFICACY OF ALKALOIDS. Ach = Acetylcholine; AchE = Acetylcholinestrase; APP = Amyoid precursor protein; COMT = Catechol-O-methyltransferase; MAO-B = Monoamine oxidase B; NMDA = N-methyl-D-aspartate; IL-1 = Interleukin 1; ROS = Reactive oxygen species; RNS = Reactive nitrogen species; NO = Nitric oxide; Nrf = Nuclear factor erthyroid; BDNF = Brain derived neurotropic factor

FIGURE 3

PLANT SOURCE AND CHEMICAL STRUCTURE OF ALKALOIDS