Suggesting 7,8-dihydroxyflavone as a promising nutraceutical against CNS disorders

Paul, Rajib; Nath, Joyobrato; Paul, Satinath; Mazumder, Muhammed Khairujjaman; Phukan, Banashree Chetiya; Roy, Rubina; Bhattacharya, Pallab; Borah, Anupom

doi:10.1016/j.neuint.2021.105068

Cited by 13 publications

(12 citation statements)

References 112 publications

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“…However, data awareness in terms of pharmacological HD drug targets and potential agents is also crucial for novel drug discovery, design, and development. In fact, the target landscape with respect to HD is rich and diverse, which leaves much space for rational drug design approaches [ 2 , 14 , 15 , 17 , 20 , 21 , 22 , 27 , 35 , 79 ]. Many compounds with affinities to one or several of these targets have also been identified.…”

Section: Resultsmentioning

confidence: 99%

“…(v) Novel, diverse targets reducing muHTT production, enhancing muHTT degradation, and generally lowering muHTT-conferred (long-term) toxicity, and thus, positively affect HD onset and progression. These targets include CASPs [ 2 , 14 , 15 , 17 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 79 ], HSPs [ 2 , 22 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ], HDACs [ 2 , 14 , 15 , 17 , 20 , 79 , 105 ], PDEs [ 14 , 15 , 17 , 31 , 35 , 36 ], and σRs [ 14 , 15 , 35 , 37 , 79 ], but also the adenosine 2A receptor (A2AR) [ 14 , 36 ], the AMP-activated protein kinase (AMPK) [ 20 , 31 , 79 ], the ERG-associated protein with SET domain (ESET) [ 106 , 107 , 108 ], the Kelch-like ECH-associated protein (KEAP) [ 31 , 56 , 109 ,…”

Section: Resultsmentioning

confidence: 99%

“…However, no causative, disease-modifying treatment is to this date available to stop, slow down, or reverse the disease progression or even delay HD onset [ 6 ]. Several promising target structures apart from HTT have been identified to potentially be involved in the HD pathogenesis, including cysteine aspartases (caspases, CASPs) [ 2 , 14 , 15 , 17 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ], heat shock proteins (HSPs) [ 2 , 22 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ], histone deacetylases (HDACs) [ 2 , 14 , 15 , 17 , 20 ], phosphodiesterases (PDEs) [ 14 , 15 , 17 , 31 , 35 , 36 ], or sigma-receptors (σRs) [ 14 , 15 , 35 , 37 ], amongst several others. Many interesting drug candidates were discovered targeting these and other cerebral targets, however, the reason for their positive effect on in vitro or in vivo HD models remains unclear, and the mechanisms of action toward their primary targets still need to be elucidated [ 38 , 39 ].…”

Section: Introductionmentioning

confidence: 99%

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A Novel Huntington’s Disease Assessment Platform to Support Future Drug Discovery and Development

Möhle

Brüning

et al. 2022

IJMS

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Huntington’s disease (HD) is a lethal neurodegenerative disorder without efficient therapeutic options. The inefficient translation from preclinical and clinical research into clinical use is mainly attributed to the lack of (i) understanding of disease initiation, progression, and involved molecular mechanisms; (ii) knowledge of the possible HD target space and general data awareness; (iii) detailed characterizations of available disease models; (iv) better suitable models; and (v) reliable and sensitive biomarkers. To generate robust HD-like symptoms in a mouse model, the neomycin resistance cassette was excised from zQ175 mice, generating a new line: zQ175Δneo. We entirely describe the dynamics of behavioral, neuropathological, and immunohistological changes from 15–57 weeks of age. Specifically, zQ175Δneo mice showed early astrogliosis from 15 weeks; growth retardation, body weight loss, and anxiety-like behaviors from 29 weeks; motor deficits and reduced muscular strength from 36 weeks; and finally slight microgliosis at 57 weeks of age. Additionally, we collected the entire bioactivity network of small-molecule HD modulators in a multitarget dataset (HD_MDS). Hereby, we uncovered 358 unique compounds addressing over 80 different pharmacological targets and pathways. Our data will support future drug discovery approaches and may serve as useful assessment platform for drug discovery and development against HD.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Novel Huntington’s Disease Assessment Platform to Support Future Drug Discovery and Development

Möhle

Brüning

et al. 2022

IJMS

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“…Previously, the flavones compound mimicked neurotrophin’s binding ability by inducing the tyrosine phosphorylation and dimerization of TrkB. Moreover, it can mimic BDNF’s ability to activate the downstream pathways essential in neurogenesis and synaptic plasticity ( Jang et al, 2010 ; Gupta et al, 2013 ; Wurzelmann et al, 2017 ; Paul et al, 2021 ). Furthermore, a study on SBH supplementation showed that it could induce synaptic plasticity and synaptogenesis, thus improving learning and memory performance in the brain ( Mustafa et al, 2018 ).…”

Section: Cognitive Learning and Memory Function And Sbh Bioactive Com...mentioning

confidence: 99%

The potential neuroprotective effects of stingless bee honey

Zulkifli

Hassan

Mustafa

et al. 2023

Front. Aging Neurosci.

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Tropical Meliponini bees produce stingless bee honey (SBH). Studies have shown beneficial properties, including antibacterial, bacteriostatic, anti-inflammatory, neurotherapeutic, neuroprotective, wound, and sunburn healing capabilities. High phenolic acid and flavonoid concentrations offer SBH its benefits. SBH can include flavonoids, phenolic acids, ascorbic acid, tocopherol, organic acids, amino acids, and protein, depending on its botanical and geographic origins. Ursolic acid, p-coumaric acid, and gallic acid may diminish apoptotic signals in neuronal cells, such as nuclear morphological alterations and DNA fragmentation. Antioxidant activity minimizes reactive oxygen species (ROS) formation and lowers oxidative stress, inhibiting inflammation by decreasing enzymes generated during inflammation. Flavonoids in honey reduce neuroinflammation by decreasing proinflammatory cytokine and free radical production. Phytochemical components in honey, such as luteolin and phenylalanine, may aid neurological problems. A dietary amino acid, phenylalanine, may improve memory by functioning on brain-derived neurotrophic factor (BDNF) pathways. Neurotrophin BDNF binds to its major receptor, TrkB, and stimulates downstream signaling cascades, which are crucial for neurogenesis and synaptic plasticity. Through BDNF, SBH can stimulate synaptic plasticity and synaptogenesis, promoting learning and memory. Moreover, BDNF contributes to the adult brain’s lasting structural and functional changes during limbic epileptogenesis by acting through the cognate receptor tyrosine receptor kinase B (TrkB). Given the higher antioxidants activity of SBH than the Apis sp. honey, it may be more therapeutically helpful. There is minimal research on SBH’s neuroprotective effects, and the related pathways contribute to it is unclear. More research is needed to elucidate the underlying molecular process of SBH on BDNF/TrkB pathways in producing neuroprotective effects.

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“…Since 7,8-DHF was found to have TrkB agonistic activity in 2010, the research literature related to the TrkB signaling pathway has extensively increased, especially in the treatment of neuroprotection and neuropsychiatric disorders [ 153 ]. As 7,8-DHF has a definite neuronal protective effect, studies on 7,8-DHF are no longer limited to common neuropsychiatric disorders such as depression, AD, and PD, and even appear in the studies on schizophrenia, HD, and DS.…”

Section: Development Potential and Challenges Coexistmentioning

confidence: 99%

7,8-Dihydroxyflavone and Neuropsychiatric Disorders: A Translational Perspective from the Mechanism to Drug Development

Yang

Zhu

2022

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: 7,8-Dihydroxyflavone (7,8-DHF) is a kind of natural flavonoids, with the potential to cross the blood-brain barrier. 7,8-DHF effectively mimics the effect of brain-derived neurotrophic factor (BDNF) in the brain to selectively activate tyrosine kinase receptor B (TrkB) and downstream signaling pathways, thus playing a neuroprotective role. The preclinical effects of 7,8-DHF have been widely investigated in the neuropsychiatric disorders, including Alzheimer’s disease (AD), Parkinson’s disease (PD), depression and memory impairment. Besides the effect on TrkB, 7,8-DHF could also function through fighting against oxidative stress, cooperating with estrogen receptors or regulating intestinal flora. This review focuses on the recent experimental studies on depression, neurodegenerative diseases and learning and memory function. Additionally, the structural modification and preparation of 7,8-DHF were also concluded and proposed, hoping to provide reference for the follow-up research and clinical drug development of 7,8-DHF in the field of neuropsychiatric disorders.

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Suggesting 7,8-dihydroxyflavone as a promising nutraceutical against CNS disorders

Cited by 13 publications

References 112 publications

A Novel Huntington’s Disease Assessment Platform to Support Future Drug Discovery and Development

A Novel Huntington’s Disease Assessment Platform to Support Future Drug Discovery and Development

The potential neuroprotective effects of stingless bee honey

7,8-Dihydroxyflavone and Neuropsychiatric Disorders: A Translational Perspective from the Mechanism to Drug Development

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