Sesaminol prevents Parkinson's disease by activating the Nrf2-ARE signaling pathway

Kaji, Haruka; Matsui–Yuasa, Isao; Matsumoto, Kayo; Omura, Ayano; Kiyomoto, Kunio; Kojima‐Yuasa, Akiko

doi:10.1016/j.heliyon.2020.e05342

Cited by 22 publications

(8 citation statements)

References 39 publications

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“…Sesaminol is one type of sesame lignan compound commonly found in sesame seeds and well known for its strong antioxidant and anticancer properties (Miyahara et al, 2001;Watanabe et al, 2017). Using in vitro and in vivo models, Kaji et al (2020) reported the preventive effect of sesaminol on a neurodegenerative disease named as Parkinson's disease (PD). Sesamolin, the second major lignan, found in sesame oil has been regarded as a natural therapeutic agent because of its various therapeutic properties (Michailidis et al, 2019).…”

Section: Compoundmentioning

confidence: 99%

Inhibition Potencies of Phytochemicals Derived from Sesame Against SARS-CoV-2 Main Protease: A Molecular Docking and Simulation Study

et al. 2021

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The ongoing COVID-19 pandemic, caused by SARS-CoV-2, has now spread across the nations with high mortality rates and multifaceted impact on human life. The proper treatment methods to overcome this contagious disease are still limited. The main protease enzyme (Mpro, also called 3CLpro) is essential for viral replication and has been considered as one of the potent drug targets for treating COVID-19. In this study, virtual screening was performed to find out the molecular interactions between 36 natural compounds derived from sesame and the Mpro of COVID-19. Four natural metabolites, namely, sesamin, sesaminol, sesamolin, and sesamolinol have been ranked as the top interacting molecules to Mpro based on the affinity of molecular docking. Moreover, stability of these four sesame-specific natural compounds has also been evaluated using molecular dynamics (MD) simulations for 200 nanoseconds. The molecular dynamics simulations and free energy calculations revealed that these compounds have stable and favorable energies, causing strong binding with Mpro. These screened natural metabolites also meet the essential conditions for drug likeness such as absorption, distribution, metabolism, and excretion (ADME) properties as well as Lipinski’s rule of five. Our finding suggests that these screened natural compounds may be evolved as promising therapeutics against COVID-19.

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Section: Compoundmentioning

confidence: 99%

Inhibition Potencies of Phytochemicals Derived from Sesame Against SARS-CoV-2 Main Protease: A Molecular Docking and Simulation Study

et al. 2021

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“…Both polyphenols showed improved binding affinity at the binding interface of the BA.3 SGp RBD–ACE2 complex due to the multiple interactions with residues such as His14, Glu17, Arg373, and Lys333. Medicinally, sesaminol showed powerful antioxidant and anticancer properties, as well as the ability to prevent Parkinson's disease by activating the Nrf2–ARE signaling pathway 53 . Further, the molecular docking results of the standard drug chloroquine at the SGp RBDs of BA.1, BA.2, and BA.3 with minimum binding energies of −4.7, −4.9, and −4.4 kcal/mol, respectively, were also compared with the screened polyphenols, 16 which clearly supported the importance of polyphenols in suppressing the host–pathogen mediation of SARS‐CoV‐2 by obstructing the interaction between Omicron SGp RBD and hACE2.…”

Section: Resultsmentioning

confidence: 99%

Computational studies on the interaction of Omicron subvariants (BA.1, BA.2, and BA.3) with ACE2 and polyphenols

Vardhan

Sahoo

2023

Phytochemical Analysis

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IntroductionThe SARS‐CoV‐2 Omicron variant BA.2 is spreading widely across the globe. The World Health Organization (WHO) designated BA.2 as a variant of concern due to its high transmission rate and pathogenicity. To elucidate the structural changes caused by mutations, we conducted a comparative analysis of BA.2 with variants BA.1 and BA.3.ObjectiveIn the present study, we aimed to investigate the interactions of the spike glycoprotein receptor‐binding domain (SGp RBD) of Omicron variants BA.1, BA.2, and BA.3 with the human receptor hACE2. Further, a library of 233 polyphenols was screened by molecular docking with the SGp RBDs of Omicron variants BA.1, BA.2, and BA.3.MethodsProtein–protein and protein–ligand molecular docking simulations were performed with AutoDock Vina and the ClusPro 2.0 server, respectively. The protein–ligand interactions were evaluated by BIOVIA Discovery Studio and ChimeraX 1.4. The molecular dynamics simulations for 100 ns were performed using GROMACS 2021.ResultsCompared to other variants of concern, the structural changes in Omicron caused by mutations at key positions improved its ability to cause infection. Despite multiple mutations, many important polyphenols bind effectively at the RBDs of Omicron variants, with the required pharmacokinetic and ADME features and obeying the Lipinski rule.ConclusionEven though Omicron variants have multiple mutations and their transmission rate is relatively high, the computed binding affinities of lead polyphenols like epigallocatechin‐3‐O‐gallate (EGCG) and luteolin‐7‐O‐glucuronide (L7G) indicate that traditional medicines and proper immunity booster diets may be useful in the long‐term fight against SARS‐CoV‐2.

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“…Many compounds with known neuroprotective effects have shown to exert their actions through the activation of the NRF2 pathway ( Table 1 ) [ 207 , 208 , 209 ] and chemical screening used to discover new cytoprotective drugs show that their effect is mediated by the NRF2 pathway. Some screening assays have been designed to find NRF2 activators [ 128 , 210 ] or modifying known NRF2 activators, such as sulforaphane [ 211 ], flavonoids [ 212 ], or chalcones [ 213 ], among others, to provide therapeutic effects in cellular models of PD [ 214 , 215 ].…”

Section: Therapeutic Approaches Using Nrf2 For Neuroprotectionmentioning

confidence: 99%

NRF2 Activation and Downstream Effects: Focus on Parkinson’s Disease and Brain Angiotensin

et al. 2021

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Reactive oxygen species (ROS) are signalling molecules used to regulate cellular metabolism and homeostasis. However, excessive ROS production causes oxidative stress, one of the main mechanisms associated with the origin and progression of neurodegenerative disorders such as Parkinson’s disease. NRF2 (Nuclear Factor-Erythroid 2 Like 2) is a transcription factor that orchestrates the cellular response to oxidative stress. The regulation of NRF2 signalling has been shown to be a promising strategy to modulate the progression of the neurodegeneration associated to Parkinson’s disease. The NRF2 pathway has been shown to be affected in patients with this disease, and activation of NRF2 has neuroprotective effects in preclinical models, demonstrating the therapeutic potential of this pathway. In this review, we highlight recent advances regarding the regulation of NRF2, including the effect of Angiotensin II as an endogenous signalling molecule able to regulate ROS production and oxidative stress in dopaminergic neurons. The genes regulated and the downstream effects of activation, with special focus on Kruppel Like Factor 9 (KLF9) transcription factor, provide clues about the mechanisms involved in the neurodegenerative process as well as future therapeutic approaches.

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Sesaminol prevents Parkinson's disease by activating the Nrf2-ARE signaling pathway

Cited by 22 publications

References 39 publications

Inhibition Potencies of Phytochemicals Derived from Sesame Against SARS-CoV-2 Main Protease: A Molecular Docking and Simulation Study

Inhibition Potencies of Phytochemicals Derived from Sesame Against SARS-CoV-2 Main Protease: A Molecular Docking and Simulation Study

Computational studies on the interaction of Omicron subvariants (BA.1, BA.2, and BA.3) with ACE2 and polyphenols

NRF2 Activation and Downstream Effects: Focus on Parkinson’s Disease and Brain Angiotensin

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