Garcinol, an effective monoamine oxidase-B inhibitor for the treatment of Parkinson's disease

Mazumder, Muhammed Khairujjaman; Paul, Rajib; Phukan, Banashree Chetia; Dutta, Ankumoni; Chakrabarty, Jayasree; Bhattacharya, Pallab; Borah, Anupom

doi:10.1016/j.mehy.2018.06.009

Cited by 28 publications

(16 citation statements)

References 36 publications

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“…Further, more the free energy of binding, i.e., docking score, more is the stability of the ligand-receptor complex. Thus, the ligand may block the receptor’s activity (Paul and Choudhury, 2010; Mazumder et al, 2013, 2014, 2015, 2018a, 2018b; Mazumder and Borah, 2014, 2015; Mazumder and Choudhury, 2019). The present computational modeling study demonstrated that all the phytochemicals and / or metabolites of PJ, except punicalagin, could effectively interact with the active sites of the respective receptors (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The amount of energy liberated upon docking of a ligand with a receptor is a measure of stability of the complex, and indicates how strongly a ligand may inhibit an enzyme (Paul and Choudhury, 2010; Mazumder et al, 2013, 2014, 2015, 2018a, 2018b; Mazumder and Borah, 2014, 2015; Mazumder and Choudhury, 2019). In the present study, molecular docking was performed between the active sites of the enzymes and the selected phytochemicals of the PJ, using the respective known inhibitors as the reference ligands, following Mazumder et al (2013, 2014, 2015, 2018a, 2018b). The docking was performed using Molegro Virtual Docker 2.1 package, which uses MolDock / PLP scoring function (Thomsen and Christensen, 2006).…”

Section: Methodsmentioning

confidence: 99%

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An in silico investigation on the inhibitory potential of the constituents of Pomegranate juice on antioxidant defense mechanism: Relevance to neurodegenerative diseases

2019

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Elevation in the levels of reactive oxygen and nitrogen species (RONS), and downregulation of cellular antixoidants, have ubiquitously been reported from studies in animal models of neurodegenerative diseases, including Parkinson’s disease (PD) and Alzheimer’s disease (AD). Thus, plant-derived compounds are widely being investigated for their beneficial effects in these models. However, while studies have reported antioxidant potentials of several phytochemicals, a large number of studies have demonstrated different phytochemicals to be rather pro-oxidant and exaggerate oxidative stress (OS). One such study aimed to investigate possible ameliorative effect of Pomegranate juice (PJ) in rat model of toxin-induced parkinsonism revealed that PJ exacerbates OS, inflammation and promotes neurodegeneration. Thus, it remains to be investigated whether different constituents and metabolites of PJ are pro-oxidant or anti-oxidant. Using computational modeling, we investigated possible inhibitory potential of different constituents of PJ and their metabolites viz. delphinidin-3-glucoside, dimethylellagic acid-glucuronide, ellagic acid, ellagitannin, gallic acid, gallotannin 23, pelargonidin, punicalagin, urolithin A, urolithin A-glucuronide and urolithin B, on anti-oxidant defense system of the brain. The results indicate that the constituents of PJ have the potential to inhibit five key enzymes of the neuronal antioxidant defense system, viz. catalase, superoxide dismutase, glutathione peroxidase 4, glutathione reductase and glutathione-S-transferase. Thus, it is surmised that the constituents of PJ may contribute to OS and neurodegeneration by way of affecting antioxidant defense mechanism. This may particularly be more pronounced in neurodegenerative diseases, since neurons are known to be more vulnerable to OS. Thus, the present findings caution the use of PJ in patients prone to OS, especially those suffering from neurodegenerative diseases, and warrant further experimental studies to unveil the effects of individual components and metabolites of PJ on antioxidant defense system of brain.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

An in silico investigation on the inhibitory potential of the constituents of Pomegranate juice on antioxidant defense mechanism: Relevance to neurodegenerative diseases

2019

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“…Monoamine oxidase‐B (MAO−B) metabolizes dopamine and, thus, represents a suitable target for the treatment of Parkinson's disease (PD) based on dopamine depletion in certain parts of the brain. Garcinol exhibited a distinct MAO−B inhibition similar to known MAO−B inhibitors and together with its neuroprotective effects, this compound appears particularly promising for the treatment of PD . Garcinol also reduced the side‐effects of dopamine replacement therapy by L‐DOPA.…”

Section: New Effects On Inflammation Processes and Neurodegenerative mentioning

confidence: 90%

“…Garcinol exhibited a distinct MAOÀ B inhibition similar to known MAOÀ B inhibitors and together with its neuroprotective effects, this compound appears particularly promising for the treatment of PD. [83] Garcinol also reduced the side-effects of dopamine replacement therapy by L-DOPA. Dyskinesia induced by L-DOPA in 6-hydroxydopamine (6-OHDA)-lesioned mice was reduced by co-treatment with garcinol (5 mg/kg, orally).…”

Section: Epilepsymentioning

confidence: 99%

“…Suppression of inflammation factors in vitro and in vivo [82] downregulation of NF-κB signaling, reduced expression of COX-2/PGE2, iNOS and interleukins (IL-1b, IL-6) [82] Parkinson's disease Neuroprotective effects, [83] reduction of dopamine side-effects/dyskinesia [84,85] MAOÀ B inhibition, [83] inhibition of catechol-Omethyltransferase [85]…”

Section: Neuroinflammation Of Microgliamentioning

confidence: 99%

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Chemical and Biological Aspects of Garcinol and Isogarcinol: Recent Developments

Schobert

Biersack

2019

Chemistry & Biodiversity

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The natural polyisoprenylated benzophenone derivatives garcinol and isogarcinol are secondary plant metabolites isolated from various Garcinia species including Garcinia indica. This review takes stock of the recent chemical and biological research into these interesting natural compounds over the last five years. New biological sources and chemical syntheses are discussed followed by new insights into the activity of garcinol and isogarcinol against cancer, pathogenic bacteria, parasite infections and various inflammatory diseases.

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Therapeutic considerations of bioactive compounds in Alzheimer's disease and Parkinson's disease: Dissecting the molecular pathways

Phukan,

Roy,

Gahatraj

et al. 2023

Phytotherapy Research

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Leading neurodegenerative diseases Alzheimer's disease (AD) and Parkinson's disease (PD) are characterized by the impairment of memory and motor functions, respectively. Despite several breakthroughs, there exists a lack of disease‐modifying treatment strategies for these diseases, as the available drugs provide symptomatic relief and bring along side effects. Bioactive compounds are reported to bear neuroprotective properties with minimal toxicity, however, a detailed elucidation of their modes of neuroprotection is lacking. The review elucidates the neuroprotective mechanism(s) of some of the major phyto‐compounds in pre‐clinical and clinical studies of AD and PD to understand their potential in combating these diseases. Curcumin, eugenol, resveratrol, baicalein, sesamol and so on have proved efficient in countering the pathological hallmarks of AD and PD. Curcumin, resveratrol, caffeine and so on have reached the clinical phases of these diseases, while aromadendrin, delphinidin, cyanidin and xanthohumol are yet to be extensively explored in pre‐clinical phases. The review highlights the need for extensive investigation of these compounds in the clinical stages of these diseases so as to utilize their disease‐modifying abilities in the real field of treatment. Moreover, poor pharmacokinetic properties of natural compounds are constraints to their therapeutic yields and this review suggests a plausible contribution of nanotechnology in overcoming these limitations.

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Garcinol, an effective monoamine oxidase-B inhibitor for the treatment of Parkinson's disease

Cited by 28 publications

References 36 publications

An in silico investigation on the inhibitory potential of the constituents of Pomegranate juice on antioxidant defense mechanism: Relevance to neurodegenerative diseases

An in silico investigation on the inhibitory potential of the constituents of Pomegranate juice on antioxidant defense mechanism: Relevance to neurodegenerative diseases

Chemical and Biological Aspects of Garcinol and Isogarcinol: Recent Developments

Therapeutic considerations of bioactive compounds in Alzheimer's disease and Parkinson's disease: Dissecting the molecular pathways

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