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Parkinson’s disease is a progressive neurodegenerative disorder characterized by the loss of the nigrostriatal
system’s pigmented dopaminergic neurons with a subsequent drop in dopamine. PD refers to such motor
disorders such as resting tremor, muscle stiffness, and slow motion. Recent studies have shown that there
has been an increasing interest i...
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Context 1
... primary manifestation in persons with PD who will have lost more than 60 percent of the dopamine-producing cells in the brain includes rigidity, tremor, bradykinesia, Parkinsonian gait, and postural instability.Although movement-related manifestations of PD are the main symptoms, gradual muscle function deterioration and continuing brain injury can guide to secondary symptoms viz. dementia, memory loss, confusion, stress, anxiety, constipation, difficulty swallowing, depression, erectile dysfunction 11 ( Figure 1). PD is a condition that is generally based on symptoms and signs. ...
Context 2
... primary manifestation in persons with PD who will have lost more than 60 percent of the dopamine-producing cells in the brain includes rigidity, tremor, bradykinesia, Parkinsonian gait, and postural instability.Although movement-related manifestations of PD are the main symptoms, gradual muscle function deterioration and continuing brain injury can guide to secondary symptoms viz. dementia, memory loss, confusion, stress, anxiety, constipation, difficulty swallowing, depression, erectile dysfunction 11 ( Figure 1). PD is a condition that is generally based on symptoms and signs. ...
Context 3
... primary manifestation in persons with PD who will have lost more than 60 percent of the dopamine-producing cells in the brain includes rigidity, tremor, bradykinesia, Parkinsonian gait, and postural instability.Although movement-related manifestations of PD are the main symptoms, gradual muscle function deterioration and continuing brain injury can guide to secondary symptoms viz. dementia, memory loss, confusion, stress, anxiety, constipation, difficulty swallowing, depression, erectile dysfunction 11 ( Figure 1). PD is a condition that is generally based on symptoms and signs. ...
Citations
... Despite the accumulating studies reporting the multi-target potential of synthetic drugs, the use of natural products against multiple therapeutic targets is yet to be investigated in detail (Lu et al., 2012). Numerous studies have reported the potency of natural products from medicinal plants, fruits, and vegetables to act as antiparkinsonian agents such as alkaloids, glycosides, flavonoids, caffeine, xanthones, catechins and coumarins which demonstrated neuroprotective properties associated with strong antioxidant and monoamine oxidase inhibitory activity (Carradori et al., 2014;Khanam et al., 2021;Singla et al., 2021). ...
Coumarins are a highly privileged scaffold in medicinal chemistry. It is present in many natural products and is reported to display various pharmacological properties. A large plethora of compounds based on the coumarin ring system have been synthesized and were found to possess biological activities such as anticonvulsant, antiviral, anti-inflammatory, antibacterial, antioxidant as well as neuroprotective properties. Despite the wide activity spectrum of coumarins, its naturally occurring derivatives are yet to be investigated in detail. In the current study, a chemical library was created to assemble all chemical information related to naturally occurring coumarins from the literature. Additionally, a multi-stage virtual screening combining QSAR modeling, molecular docking, and ADMET prediction was conducted against monoamine oxidase B and acetylcholinesterase, two relevant targets known for their neuroprotective properties and 'disease-modifying' potential in Parkinson's and Alzheimer's disease. Our findings revealed ten coumarin derivatives that may act as dual-target drugs against MAO-B and AChE. Two coumarin candidates were selected from the molecular docking study: CDB0738 and CDB0046 displayed favorable interactions for both proteins as well as suitable ADMET profiles. The stability of the selected coumarins was assessed through 100 ns molecular dynamics simulations which revealed promising stability through key molecular interactions for CDB0738 to act as dual inhibitor of MAO-B and AChE. However, experimental studies are necessary to evaluate the bioactivity of the proposed candidate. The current results may generate an increasing interest in bioprospecting naturally occurring coumarins as potential candidates against relevant macromolecular targets by encouraging virtual screening studies against our chemical library.
... Several research confirmed that phytomedicines have the ability to treat PD, and some of them proved to be effective and more reliable than the current synthetic drugs. These herbs and nutraceuticals include Erythrina velutin (Fabaceae), Peganum harmal (Nitrariaceae), Curcuma longa (Zingiberaceae), Carthamus tinctorius L. (Asteraceae), Pueraria lobate (Fabaceae), Juglandis semen (Juglandaceae), Lycium barbarum L fruit (Solanaceae), Mucuna pruriens (Fabaceae), Bacopa monnieri (Schrophulariaceae), Camellia sinensis ( Theaceae), Coffea a rabica (Rubiaceae), Gingko b iloba (Ginkgoaceae), Fructus alpinia oxyphylla (Zingiberaceae), Delphinium denudatum (Ranunculaceae), Panax ginseng (Araliaceae), Chunghyuldan, Paeoniae Alba Radix, Tianma Gouteng Yin, Baicalei, and resveratrol [30,71]. Some important plants and their roles in PD are summarized in Table 17.2. ...
... There is a great deal of literature supporting the use and efficacy of natural products (NP) in PD such as flavonoids, xanthones, phenolic derivatives, alkaloids, and caffeine [21,22]. These natural resources and their derivatives have been reported for their potential to selectively inhibit MAO-B and may offer a safer alternative compared to conventional drugs [23]. ...
Parkinson’s disease is considered the second most frequent neurodegenerative disease. It is described by the loss of dopaminergic neurons in the mid-brain. For many decades, L-DOPA has been considered as the gold standard for treating Parkinson’s disease motor symptoms, however, due to the decrease of efficacy, in the long run, there is an urgent need for novel antiparkinsonian drugs. Caffeine derivatives have been reported several times for their neuroprotective properties and dual blockade of monoamine oxidase (MAO) and adenosine A 2A receptors (AA 2A R). Natural products are currently attracting more focus due to structural diversity and safety in contrast to synthetic drugs. In the present work, computational studies were conducted on natural product-like caffeine derivatives to search for novel potent candidates acting as dual MAO-B inhibitors/AA 2A R antagonists for Parkinson’s disease. Our findings revealed two natural products among the top hits: CNP0202316 and CNP0365210 fulfill the requirements of drugs acting on the brain. The selected lead compounds were further studied using molecular dynamics simulation to assess their stability with MAO-B. Current findings might shift the interest towards natural-based compounds and could be exploited to further optimize caffeine derivatives into a successful dual-target-directed drug for managing and halting the neuronal damage in Parkinson’s disease patients.
... Several plant species and their secondary metabolites have been identified to possess excellent therapeutic potential against neurodegenerative disorders [9,10]. Experimental and molecular mechanisms of natural PD inhibitors isolated from plants by experimental in vitro and in vivo analyses have been highlighted in several studies [10][11][12]. ...
... Several plant species and their secondary metabolites have been identified to possess excellent therapeutic potential against neurodegenerative disorders [9,10]. Experimental and molecular mechanisms of natural PD inhibitors isolated from plants by experimental in vitro and in vivo analyses have been highlighted in several studies [10][11][12]. These plants have been found to exert a diverse range of protective effects that soothe devastating neurodegeneration. ...
