Plant-Derived Bioactive Compounds in the Management of Neurodegenerative Disorders: Challenges, Future Directions and Molecular Mechanisms Involved in Neuroprotection

Abstract

Neurodegenerative disorders encompass a wide range of pathological conditions caused by progressive damage to the neuronal cells and nervous-system connections, which primarily target neuronal dysfunction and result in problems with mobility, cognition, coordination, sensation, and strength. Molecular insights have revealed that stress-related biochemical alterations such as abnormal protein aggregation, extensive generation of reactive oxygen and nitrogen species, mitochondrial dysfunction, and neuroinflammation may lead to damage to neuronal cells. Currently, no neurodegenerative disease is curable, and the available standard therapies can only provide symptomatic treatment and delay the progression of the disease. Interestingly, plant-derived bioactive compounds have drawn considerable attention due to their well-established medicinal properties, including anti-apoptotic, antioxidant, anti-inflammatory, anticancer, and antimicrobial properties, as well as neuroprotective, hepatoprotective, cardioprotective, and other health benefits. Plant-derived bioactive compounds have received far more attention in recent decades than synthetic bioactive compounds in the treatment of many diseases, including neurodegeneration. By selecting suitable plant-derived bioactive compounds and/or plant formulations, we can fine tune the standard therapies because the therapeutic efficacy of the drugs is greatly enhanced by combinations. A plethora of in vitro and in vivo studies have demonstrated plant-derived bioactive compounds’ immense potential, as proven by their capacity to influence the expression and activity of numerous proteins implicated in oxidative stress, neuroinflammation, apoptosis, and aggregation. Thus, this review mostly focuses on the antioxidant, anti-inflammatory, anti-aggregation, anti-cholinesterase, and anti-apoptotic properties of several plant formulations and plant-derived bioactive compounds and their molecular mechanisms against neurodegenerative disorders.

Identification and Characterization of Neuroprotective Properties of Thaumatin-like Protein 1a from Annurca Apple Flesh Polyphenol Extract

“…AChE and BuChE activity was assayed by the Ellman method [ 39 ], as previously reported [ 5 , 8 ], using acetylthiocholine and butyrylthiocholine as substrates, respectively. Donepezil was used as an internal control for the inhibition observed.…”

“…Inhibition of A β 1–40 self-aggregation was performed by incubating 96 µM peptide in 12 µL of 200 mM sodium phosphate buffer (pH 8.0) containing 0.5% ( v / v ) DMSO at 37 °C for 24 h, in the absence or in the presence of increasing concentrations of AFPE or Peaks 1–4, as previously reported [ 5 ]. To quantify amyloid fibrils’ formation, 0.5 mL of 1.6 µM thioflavin T in 50 mM glycine–NaOH buffer (pH 8.5) was added.…”

“…However, these drugs can ameliorate cognitive and motor dysfunctions without reverting the cause of the disorders, and they can cause various side effects; therefore, a promising strategy is represented by natural and diet plant compounds, either as lead structural compounds to develop new drugs or as molecules to be used against neurodegenerative disorders [ 3 , 4 , 5 , 6 ].…”

A review on a selected Ayurvedic herbal formula in the management of Kaphaja Unmada (Major depressive disorder): A critical analysis

“…The enormous potential of plant-derived bioactive compounds has been shown in a large number of in vitro and in vivo investigations, as evidenced by their ability to modulate the expression and activity of several proteins involved in oxidative stress, neuro-inflammation, apoptosis and aggregation. Therefore, the main focus of this review was on Evolvulus alsinoides protective antioxidant, anti-inflammatory, anti-aggregation, anti-cholinesterase, and anti-apoptotic effects [40] .…”

The Effects of Bioactive Compounds on Human Brain Structures and Diseases

“…Consequently, traditional medicines are believed to be effective and have minimal or no side effects [ 11 ]. Bioactive compounds derived from plants have garnered significant attention because of their firmly established medicinal properties, including anti-apoptotic, antioxidant, anti-inflammatory, anticancer, antimicrobial, neuroprotective, hepatoprotective, and cardioprotective, properties [ 13 ].…”