Natural products in drug discovery: advances and opportunities

Nature Reviews Drug Discovery, Год журнала: 2021, Номер 20(3), С. 200 - 216

Опубликована: Янв. 28, 2021

Язык: Английский

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Targeting oxidative stress in disease: promise and limitations of antioxidant therapy

Nature Reviews Drug Discovery, Год журнала: 2021, Номер 20(9), С. 689 - 709

Опубликована: Июнь 30, 2021

Язык: Английский

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Autism spectrum disorder

The Lancet, Год журнала: 2018, Номер 392(10146), С. 508 - 520

Опубликована: Авг. 1, 2018

Язык: Английский

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Antioxidants Maintain Cellular Redox Homeostasis by Elimination of Reactive Oxygen Species

Cellular Physiology and Biochemistry, Год журнала: 2017, Номер 44(2), С. 532 - 553

Опубликована: Янв. 1, 2017

Reactive oxygen species (ROS) are produced by living cells as normal cellular metabolic byproduct. Under excessive stress conditions, will produce numerous ROS, and the organisms eventually evolve series of response mechanisms to adapt ROS exposure well utilize it signaling molecules. molecules would trigger oxidative in a feedback mechanism involving many biological processes, such apoptosis, necrosis autophagy. Growing evidences have suggested that play critical role throughout entire cell death pathway. Overwhelming production can destroy organelles structure bio-molecules, which lead inflammatory is known underpinning for development diabetes cancer. Cytochrome P450 enzymes (CYP) regarded markers stress, transform toxic metabolites into superoxide anion, hydrogen peroxide hydroxyl radical might cause injury cells. Accordingly, evolved balanced system neutralize extra namely antioxidant systems consist enzymatic antioxidants dismutase (SOD), catalase (CAT) glutathione peroxidases (GPxs), thioredoxin (Trx) non-enzymatic collectively reduce state. Herein, we review recent novel findings processes induced summarize roles endogenous natural anti-oxidative compounds several human diseases caused order illustrate vital prevention against stress.

Язык: Английский

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The KEAP1-NRF2 System: a Thiol-Based Sensor-Effector Apparatus for Maintaining Redox Homeostasis

Physiological Reviews, Год журнала: 2018, Номер 98(3), С. 1169 - 1203

Опубликована: Май 2, 2018

The Kelch-like ECH-associated protein 1-NF-E2-related factor 2 (KEAP1-NRF2) system forms the major node of cellular and organismal defense against oxidative electrophilic stresses both exogenous endogenous origins. KEAP1 acts as a cysteine thiol-rich sensor redox insults, whereas NRF2 is transcription that robustly transduces chemical signals to regulate battery cytoprotective genes. represses activity under quiescent conditions, liberated from KEAP1-mediated repression on exposure stresses. rapid inducibility response based derepression mechanism an important feature KEAP1-NRF2 system. Recent studies have unveiled complexities functional contributions defined its broader involvement in biological processes, including cell proliferation differentiation, well cytoprotection. In this review, we describe historical milestones initial characterization provide comprehensive overview molecular mechanisms governing functions NRF2, their roles physiology pathology. We also refer clinical significance prophylactic therapeutic target for various diseases, particularly aging-related disorders. believe controlled harnessing key healthy aging well-being humans.

Язык: Английский

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Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases

Nature Reviews Drug Discovery, Год журнала: 2019, Номер 18(4), С. 295 - 317

Опубликована: Янв. 4, 2019

Язык: Английский

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Long-term benefit of Microbiota Transfer Therapy on autism symptoms and gut microbiota

Scientific Reports, Год журнала: 2019, Номер 9(1)

Опубликована: Апрель 9, 2019

Abstract Many studies have reported abnormal gut microbiota in individuals with Autism Spectrum Disorders (ASD), suggesting a link between microbiome and autism-like behaviors. Modifying the is potential route to improve gastrointestinal (GI) behavioral symptoms children ASD, fecal transplant could transform dysbiotic toward healthy one by delivering large number of commensal microbes from donor. We previously performed an open-label trial Microbiota Transfer Therapy (MTT) that combined antibiotics, bowel cleanse, stomach-acid suppressant, transplant, observed significant improvements GI symptoms, autism-related microbiota. Here, we report on follow-up same 18 participants two years after treatment was completed. Notably, most were maintained, improved even more end treatment. Important changes at remained follow-up, including increases bacterial diversity relative abundances Bifidobacteria Prevotella . Our observations demonstrate long-term safety efficacy MTT as therapy treat ASD who problems, warrant double-blind, placebo-controlled future.

Язык: Английский

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The multifaceted role of Nrf2 in mitochondrial function

Current Opinion in Toxicology, Год журнала: 2016, Номер 1, С. 80 - 91

Опубликована: Окт. 11, 2016

The transcription factor nuclear erythroid 2 p45-related (Nrf2) is the master regulator of cellular redox homeostasis. Nrf2 target genes comprise a large network antioxidant enzymes, proteins involved in xenobiotic detoxification, repair and removal damaged proteins, inhibition inflammation, as well other factors. In recent years it has emerged that part its role cytoprotective gene expression, impacts mitochondrial function. Increased activity defends against toxins. Reduced glutathione, principal small molecule mammalian cell product several downstream Nrf2, counterbalances ROS production. function suppressed mitochondria-related disorders, such Parkinson's disease Friedrich's ataxia. Studies using isolated mitochondria cultured cells have demonstrated deficiency leads to impaired fatty acid oxidation, respiration ATP Small activators support integrity by promoting mitophagy conferring resistance oxidative stress-mediated permeability transition. Excitingly, studies shown also affects stem with implications for self-renewal, cardiomyocyte regeneration, neural stem/progenitor survival.

Язык: Английский

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Sulforaphane reduces hepatic glucose production and improves glucose control in patients with type 2 diabetes

Science Translational Medicine, Год журнала: 2017, Номер 9(394)

Опубликована: Июнь 14, 2017

Sulforaphane, a natural compound identified by drug repurposing, reduces hepatic glucose production and improves control in type 2 diabetes.

Язык: Английский

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Keap1, the cysteine-based mammalian intracellular sensor for electrophiles and oxidants

Archives of Biochemistry and Biophysics, Год журнала: 2016, Номер 617, С. 84 - 93

Опубликована: Авг. 4, 2016

The Kelch-like ECH associated protein 1 (Keap1) is a component of Cullin3-based Cullin-RING E3 ubiquitin ligase (CRL) multisubunit complex. Within the CRL, homodimeric Keap1 functions as Cullin3 adaptor, and importantly, it also critical that performs substrate recognition. best-characterized transcription factor NF-E2 p45-related 2 (Nrf2), which orchestrates an elaborate transcriptional program in response to environmental challenges caused by oxidants, electrophiles pro-inflammatory agents, allowing adaptation survival under stress conditions. equipped with reactive cysteine residues act sensors for endogenously produced exogenously encountered small molecules (termed inducers), have characteristic chemical signature, reactivity sulfhydryl groups. Inducers modify impair its ability target Nrf2 ubiquitination degradation. Consequently, accumulates, enters nucleus drives genes, encode large network cytoprotective proteins. Here we summarize early studies leading prediction existence Keap1, followed discovery main negative regulator Nrf2. We then describe available structural information on assembly Cullin3, interaction discuss multiple allow detection wide range endogenous inducers, provide fine-tuning tight control Keap1/Nrf2 stress-sensing response.

Язык: Английский

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