Toxicological and Genotoxicity Assessment of a Dihydroquercetin-Rich Dahurian Larch Tree (<i>Larix gmelinii</i> Rupr) Extract (Lavitol)

Schauss, Alexander G.; Tselyico, Sergei S.; Kuznetsova, V.A.; Yegorova, Inna

doi:10.1177/1091581815576975

Cited by 37 publications

(33 citation statements)

References 14 publications

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“…Furthermore, it still remains unclear whether taxifolin has therapeutic effects on established CAA. Since the safety profile of taxifolin has been reported (5,6), future studies to address these issues would be helpful for translating the research findings to clinical practice.…”

Section: Discussionmentioning

confidence: 99%

“…Taxifolin, also known as dihydroquercetin, is a natural bioactive flavonoid found in various foods and herbs (4). The safety profile of taxifolin has been established (5,6), and taxifolin has been reported to exhibit various pharmacological effects, including antioxidative, antinitrosative, and antiinflammatory effects (7,8). In vitro studies have demonstrated that taxifolin had an inhibitory effect on the aggregation of the 42-residue amyloidβ protein (amyloid-β ) involved in the pathogenesis of AD (9,10), suggesting that taxifolin may have the potential to help prevent or treat AD.…”

mentioning

confidence: 99%

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Pleiotropic neuroprotective effects of taxifolin in cerebral amyloid angiopathy

Inoue

Saitô

Tanaka

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Cerebral amyloid angiopathy (CAA) results from amyloid-β deposition in the cerebrovasculature. It is frequently accompanied by Alzheimer's disease and causes dementia. We recently demonstrated that in a mouse model of CAA, taxifolin improved cerebral blood flow, promoted amyloid-β removal from the brain, and prevented cognitive dysfunction when administered orally. Here we showed that taxifolin inhibited the intracerebral production of amyloid-β through suppressing the ApoE-ERK1/2-amyloid-β precursor protein axis, despite the low permeability of the bloodbrain barrier to taxifolin. Higher expression levels of triggering receptor expressed on myeloid cell 2 (TREM2) were associated with the exacerbation of inflammation in the brain. Taxifolin suppressed inflammation, alleviating the accumulation of TREM2expressing cells in the brain. It also mitigated glutamate levels and oxidative tissue damage and reduced brain levels of active caspases, indicative of apoptotic cell death. Thus, the oral administration of taxifolin had intracerebral pleiotropic neuroprotective effects on CAA through suppressing amyloid-β production and beneficially modulating proinflammatory microglial phenotypes.cerebral amyloid angiopathy | neuroprotection | taxifolin | triggering receptor expressed on myeloid cell 2

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Pleiotropic neuroprotective effects of taxifolin in cerebral amyloid angiopathy

Inoue

Saitô

Tanaka

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…One of these is taxifolin, a flavonoid found in various plants such as milk thistle, onions, and Douglas fir bark [12,50]. This is an advantageous target to study because the biochemical and safety profiles of taxifolin have been established [12,51,52].…”

Section: Inhibitory Effects Of Taxifolin On Aβ Aggregationmentioning

confidence: 99%

“…Taken together, this basic and preclinical evidence highlights the beneficial effects of taxifolin. The safety of using taxifolin has already been established [51,52], so clinical trials to examine the efficacy of taxifolin for treating CAA and AD are of significance.…”

Section: Effects Of Taxifolin In a Mouse Model Of Admentioning

confidence: 99%

Potential Therapeutic Approaches for Cerebral Amyloid Angiopathy and Alzheimer’s Disease

Tanaka

Saitô

Inoue

et al. 2020

IJMS

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Cerebral amyloid angiopathy (CAA) is a cerebrovascular disease directly implicated in Alzheimer’s disease (AD) pathogenesis through amyloid-β (Aβ) deposition, which may cause the development and progression of dementia. Despite extensive studies to explore drugs targeting Aβ, clinical benefits have not been reported in large clinical trials in AD patients or presymptomatic individuals at a risk for AD. However, recent studies on CAA and AD have provided novel insights regarding CAA- and AD-related pathogenesis. This work has revealed potential therapeutic targets, including Aβ drainage pathways, Aβ aggregation, oxidative stress, and neuroinflammation. The functional significance and therapeutic potential of bioactive molecules such as cilostazol and taxifolin have also become increasingly evident. Furthermore, recent epidemiological studies have demonstrated that serum levels of a soluble form of triggering receptor expressed on myeloid cells 2 (TREM2) may have clinical significance as a potential novel predictive biomarker for dementia incidence. This review summarizes recent advances in CAA and AD research with a focus on discussing future research directions regarding novel therapeutic approaches and predictive biomarkers for CAA and AD.

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“…В качестве сырья для получения ДКВ используется комлевая часть древесины лиственницы даурской (Larix dahurica Turcz.). ДКВ обладает выраженными антиоксидантными свойствами [5], приемлемым профилем безопасности [6] и является основой лекарственных средств "Диквертин" и "Асковертин" [7]. Некоторые фармакологические эффекты ДКВ были выявлены как в рамках целенаправленного анализа in silico, так и в полномасштабных трансляционных исследованиях, включающих молекулярное моделирование [8][9].…”

Section: Introductionunclassified

Analysis of dihydroquercetin physical modification via in vitro and in silico methods

et al. 2019

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Flavonoid-mediated materials are promising substances for the design of new functional materials because of their bioactivity, eco-friendliness, and cost-effectiveness. Dihydroquercetin (DHQ) is the major flavonoid in the wood of Larix dahurica Turcz. Previously some new modifications were created on the basis of DHQ, they were characterized by different morphological, physico-chemical and biopharmaceutical properties. This study was performed to research the influence of the solvent on the formation of the solid phase in DHQ microtubes and crystal form as commercially available active pharmaceutical ingredient (API). The choice of the models for the computational simulation was based on the data of differential scanning calorimetry. All calculations were performed using Materials Science Suite. In silico analysis demonstrated that the molecules of solvent are a key player in the formation of the solid phase of the flavonoid-mediated material. Also the comparative analysis of physical characteristics between DHQ microtubes and crystal form was performed. These data give an opportunity to suggest, that DHQ microtubes may have a grate application as the dressing material and in the drug delivering. The results of this study could be helpful for the design of the new flavonoid-mediated materials by crystal engineering.

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Toxicological and Genotoxicity Assessment of a Dihydroquercetin-Rich Dahurian Larch Tree (Larix gmelinii Rupr) Extract (Lavitol)

Cited by 37 publications

References 14 publications

Pleiotropic neuroprotective effects of taxifolin in cerebral amyloid angiopathy

Pleiotropic neuroprotective effects of taxifolin in cerebral amyloid angiopathy

Potential Therapeutic Approaches for Cerebral Amyloid Angiopathy and Alzheimer’s Disease

Analysis of dihydroquercetin physical modification via in vitro and in silico methods

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