Emerging Epigenetic Therapies

Kaypee, Stephanie; Mandal, Somnath; Chatterjee, Snehajyoti; Kundu, Tapas K.

doi:10.1016/b978-0-12-800206-3.00021-5

Cited by 3 publications

(3 citation statements)

References 175 publications

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“…Moreover, quercetin inhibits COX-2 and TLR4 activity to reduce inflammatory responses [6,39,148]. Interestingly, quercetin may have epigenetic mechanisms by inhibiting lysine acetyltransferase (KAT) activity [150,151] and increasing lysine deacetylase (KDAC) activity [152], suggesting that the flavonoid can bidirectionally regulate autophagy [153], neuroinflammation, and apoptosis [154]. Quercetin also inhibits acetylcholinesterase (AChE) [155], which can enhance alertness and cognitive function in AD patients.…”

Section: Quercetinmentioning

confidence: 99%

Polyherbal and Multimodal Treatments: Kaempferol- and Quercetin-Rich Herbs Alleviate Symptoms of Alzheimer’s Disease

Alexander,

Parsaee,

Vasefi

2023

Biology

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Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder impairing cognition and memory in the elderly. This disorder has a complex etiology, including senile plaque and neurofibrillary tangle formation, neuroinflammation, oxidative stress, and damaged neuroplasticity. Current treatment options are limited, so alternative treatments such as herbal medicine could suppress symptoms while slowing cognitive decline. We followed PRISMA guidelines to identify potential herbal treatments, their associated medicinal phytochemicals, and the potential mechanisms of these treatments. Common herbs, including Ginkgo biloba, Camellia sinensis, Glycyrrhiza uralensis, Cyperus rotundus, and Buplerum falcatum, produced promising pre-clinical results. These herbs are rich in kaempferol and quercetin, flavonoids with a polyphenolic structure that facilitate multiple mechanisms of action. These mechanisms include the inhibition of Aβ plaque formation, a reduction in tau hyperphosphorylation, the suppression of oxidative stress, and the modulation of BDNF and PI3K/AKT pathways. Using pre-clinical findings from quercetin research and the comparatively limited data on kaempferol, we proposed that kaempferol ameliorates the neuroinflammatory state, maintains proper cellular function, and restores pro-neuroplastic signaling. In this review, we discuss the anti-AD mechanisms of quercetin and kaempferol and their limitations, and we suggest a potential alternative treatment for AD. Our findings lead us to conclude that a polyherbal kaempferol- and quercetin-rich cocktail could treat AD-related brain damage.

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Section: Quercetinmentioning

confidence: 99%

Polyherbal and Multimodal Treatments: Kaempferol- and Quercetin-Rich Herbs Alleviate Symptoms of Alzheimer’s Disease

Alexander,

Parsaee,

Vasefi

2023

Biology

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“…By interacting with CREBB binding protein (CBP), PCAF can activate the transcription depending on PCAF intrinsic histone acetyltransferase (HAT) activity 3 . PCAF is also a coactivator of the p53 gene target; acetylating K320 standardizes p53 enzymatic activity, promoting p53‐dependent p21 transcription and cell cycle arrest during the DNA damage process 4 . Structurally, PCAF (KAT2B) is a multidomain protein, the domains are namely, bromodomain (Brd), N‐terminal domain and HAT domain which is associated with CBP and p300 while in transcription and mis regulation of PCAF connected with cancer, HIV and neuroinflammation 5,6 …”

Section: Introductionmentioning

confidence: 99%

“…3 PCAF is also a coactivator of the p53 gene target; acetylating K320 standardizes p53 enzymatic activity, promoting p53-dependent p21 transcription and cell cycle arrest during the DNA damage process. 4 Structurally, PCAF (KAT2B) is a multidomain protein, the domains are namely, bromodomain (Brd), N-terminal domain and HAT domain which is associated with CBP and p300 while in transcription and mis regulation of PCAF connected with cancer, HIV and neuroinflammation. 5,6 Bromodomains are protein interaction modules, which recognize acetylation motifs, now it is emerged as an important therapeutic targets for many diseases, including inflammation and oncology.…”

Section: Introductionmentioning

confidence: 99%

Binding mechanism of anacardic acid, carnosol and garcinol with PCAF: A comprehensive study using molecular docking and molecular dynamics simulations and binding free energy analysis

Ramakrishnan

Kumaradhas

2023

J of Cellular Biochemistry

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The p300/CBP associated factor bromodomain (PCAF Brd) is emerged as one of the promising target proteins for different types of cancers. PCAF is one among the histone acetyltransferase enzymes which involved in the regulation of transcriptase process by modifying the chromatin structure. Anacardic acid, carnosol, garcinol are the experimentally reported inhibitors of PCAF Brd; however, their detailed binding mechanism these inhibitors are not yet known. The intermolecular interaction, binding energy, and the stability of these inhibitors with the active site of PCAF Brd are playing the key role in the binding of these inhibitors with PCAF. The in silico study incorporates the molecular docking and dynamics simulations; these molecular level simulations allow to understand the binding mechanism. In the present study, the induced fit molecular docking and molecular dynamics of anacardic acid, carnosol and garcinol molecules against the PCAF Brd have been performed.The docking score values of these molecules are −5.112 (anacardic acid), −5.141 (carnosol), −5.199 (garcinol) and −3.641 (L45) kcal/mol, respectively. Further, the molecular dynamics simulation was carried out for these docked complexes to understand their conformational their stability and binding energy from the roots means square deviation (RMSD) and root means square of fluctuation (RMSF), and molecular mechanics with the generalized born and surface area solvation (MM/GBSA) binding free energy calculations. The intermolecular interactions and binding free energy values confirm that garcinol forms key interactions and has high binding affinity towards PCAF Brd on compare with the other two inhibitors. Therefore, garcinol may be considered as a potential inhibitor of PCAF Brd.

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