Abstract
Plant-derived (phyto) carbazole alkaloids are an important class of compounds, presented in the family of Rutaceae (Genera Murraya, Clausena, Glycosmis, Micromelum and Zanthoxylum). Due to several significant biological activities, such as antitumor, antibacterial, antiviral, antidiabetic, anti-HIV and neuroprotective activities of the parent skeleton (3-methylcarbazole), carbazole alkaloids are recognized as an important class of potential therapeutic agents. Neurodegenerative diseases (NDs) may exhibit a vast range of conditions, affecting neurons primarily and leading ultimately to the progressive losses of normal motor and cognitive functions. The main pathophysiological indicators of NDs comprise increasing atypical protein folding, oxidative stresses, mitochondrial dysfunctions, deranged neurotransmissions and neuronal losses. Phyto-carbazole alkaloids can be investigated for exerting multitarget approaches to ameliorating NDs. This review presents a comprehensive evaluation of the available scientific literature on the neuroprotective mechanisms of phyto-carbazole alkaloids from the Rutaceae family in ameliorating NDs.
Highlights
Neurodegenerative diseases (NDs) belong to a heterogeneous groups of disorders (Alzheimer’s, Parkinson’s, multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s disease, etc.), which could result in progressive loss of structure or function of the neurons.These neurological changes in the brain could lead to logical and/or functional deterioration over time
Claulansine F (Clau F), a pyrano[3,2-a] carbazole alkaloid, revealed protection against sodium nitroprusside (SNP)-induced apoptosis in pheochromocytoma (PC12) cells [74], which exerted a significant effect on hydroxyl free radical scavenging and mitochondrial integrity
These results suggest the importance of groups at C-3, C-6 and N-9; the lipophilic groups in the compounds are the crucial factors for neuroprotective activity of carbazoles [75]
Summary
Neurodegenerative diseases (NDs) belong to a heterogeneous groups of disorders (Alzheimer’s, Parkinson’s, multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s disease, etc.), which could result in progressive loss of structure or function of the neurons. Among the naturally occurring phyto-carbazole alkaloids, mahanimbine, koenimbine, koenigicine and clausazoline-K were reported to possess anti-lipase activity [14,15], while mahanine, pyrayafoline-D and murrafoline-I displayed anticancer activities by inducing apoptosis through activating the caspase-9/caspase-3 pathway [16]. Both natural and synthetic derivatives of carbazole alkaloids have revealed numerous pharmacological activities, such as anticancer [17], antioxidant [18], anti-inflammatory [19], antibacterial [20], antifungal [21], antidiabetic [22], antiangiogenic [23], larvicidal [24], antiplant virus [25], anti-HIV [26], and neuroprotective activities [13].
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