Polyhydroxycurcuminoids but not curcumin upregulate neprilysin and can be applied to the prevention of Alzheimer’s disease

Chen, Po-Ting; Chen, Zih Ten; Hou, Wen Chi; Yu, Lung; Chen, Rita P Y

doi:10.1038/srep29760

Cited by 35 publications

(32 citation statements)

References 46 publications

(62 reference statements)

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“…Using, a sensitive fluorescence-based amyloid-β digestion assay, Chen and colleagues (2016) [98] screened 25 compounds for their ability to upregulate neprilysin (NEP) activity. To our surprise, four compounds, dihydroxylated curcumin, monohydroxylated demethoxycurcumin, and mono- and di-hydroxylated bisdemethoxycurcumin, increased NEP activity, while curcumin did not.…”

Section: Research On Curcumin In Mouse Models Of Alzheimer’s Diseasementioning

confidence: 99%

“…Finally, feeding monohydroxylated demethoxycurcumin (also named demethylcurcumin) or dihydroxylated bisdemethoxycurcumin (also named bisdemethylcurcumin) to APPswe/PS1dE9 double transgenic mice upregulated NEP levels in the brain and reduced Aβ accumulation in the hippocampus and cortex. These polyhydroxy curcuminoids offer hope in the prevention of AD [98]. …”

Section: Research On Curcumin In Mouse Models Of Alzheimer’s Diseasementioning

confidence: 99%

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Protective Effects of Indian Spice Curcumin Against Amyloid-β in Alzheimer’s Disease

Reddy

Mańczak

Yin

et al. 2018

JAD

277

138

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The purpose of our article is to assess the current understanding of Indian spice ‘Curcumin’ against amyloid-β (Aβ)-induced toxicity in Alzheimer’s disease (AD) pathogenesis. Natural products, such as ginger, curcumin and gingko biloba have been used as diets and dietary supplements to treat human diseases, including cancer, cardiovascular, respiratory, infectious, diabetes, obesity, metabolic syndromes and neurological disorders. Products derived from plants are known to have protective effects, including anti-inflammatory, anti-oxidant, anti-arthritis, pro-healing and boosting memory cognitive functions. In the last decade, several groups have designed and synthesized curcumin and its derivatives and extensively tested using cell and mouse models of AD. Recent research on amyloid-β and curcumin has revealed that curcumin prevents amyloid-β aggregation and crosses the blood brain barrier (BBB), reach brain cells and protect neurons from various toxic insults of aging and amyloid-β in humans. Recent research has also reported that curcumin ameliorates cognitive decline and improves synaptic functions in mouse models of AD. Further, recent groups have initiated studies on elderly individuals and patients with AD and the outcome of these studies is currently being assessed. This article highlights the beneficial effects of curcumin on AD. This article also critically assesses the current limitations of curcumin’s bioavailability and urgent need for new formulation to increase its brain levels to treat patients with AD.

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Section: Research On Curcumin In Mouse Models Of Alzheimer’s Diseasementioning

confidence: 99%

Section: Research On Curcumin In Mouse Models Of Alzheimer’s Diseasementioning

confidence: 99%

Protective Effects of Indian Spice Curcumin Against Amyloid-β in Alzheimer’s Disease

Reddy

Mańczak

Yin

et al. 2018

JAD

277

138

View full text Add to dashboard Cite

show abstract

“…They found that phenyl methoxy groups can contribute to the suppression of Aβ42 and to the suppression of APP. The researchers found that different curcuminoids presented different effects on the BACE1 expressions, for example, curcumin did not affect BACE1 mRNA (messenger RNA) and protein levels, AB12 suppressed BACE1 mRNA level, and AB9 suppressed Chen et al [54] found that poly-substituted hydroxylcurcuminoids are able to upregulate neprilysin, the most important Aβ-degrading enzyme. Thus, these compounds can be used to prevent AD.…”

Section: In Vitromentioning

confidence: 99%

Curcumin in Health and Diseases: Alzheimer’s Disease and Curcumin Analogues, Derivatives, and Hybrids

Chainoglou

Hadjipavlou‐Litina

2020

IJMS

105

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Worldwide, Alzheimer’s disease (AD) is the most common neurodegenerative multifactorial disease influencing the elderly population. Nowadays, several medications, among them curcumin, are used in the treatment of AD. Curcumin, which is the principal component of Curcuma longa, has shown favorable effects forsignificantly preventing or treating AD. During the last decade, the scientific community has focused their research on the optimization of therapeutic properties and on the improvement of pharmacokinetic properties of curcumin. This review summarizes bibliographical data from 2009 to 2019 on curcumin analogues, derivatives, and hybrids, as well as their therapeutic, preventic, and diagnostic applications in AD. Recent advances in the field have revealed that the phenolic hydroxyl group could contribute to the anti-amyloidogenic activity. Phenyl methoxy groups seem to contribute to the suppression of amyloid-β peptide (Aβ42) and to the suppression of amyloid precursor protein (APP) andhydrophobic interactions have also revealed a growing role. Furthermore, flexible moieties, at the linker, are crucial for the inhibition of Aβ aggregation. The inhibitory activity of derivatives is increased with the expansion of the aromatic rings. The promising role of curcumin-based compounds in diagnostic imaging is highlighted. The keto-enol tautomerism seems to be a novel modification for the design of amyloid-binding agents. Molecular docking results, (Q)SAR, as well as in vitro and in vivo tests highlight the structures and chemical moieties that are correlated with specific activity. As a result, the knowledge gained from the existing research should lead to the design and synthesis ofinnovative and multitargetedcurcumin analogues, derivatives, or curcumin hybrids, which would be very useful drug and tools in medicine for both diagnosis and treatment of AD.

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“…When administered as the co-crystalized compound sacubitril/valsartan, the individual agents valsartan and LBQ657 dissociate, and have a blood elimination half-life of around 11 hours, reaching a plasma steady state concentration in three days. This makes sacubitril/valsartan suitable for twice daily dosing [63, 65, 66]. Pharmaceutical chemist and clinical pharmacologists have highly developed skills in drug synthesis and optimizing the pharmacodynamic effect of a drug, while physicians are uniquely qualified to evaluate the gaps in drug efficacy.…”

Section: What We Always Hoped For: a Pharmaceutical Breakthrough In Hmentioning

confidence: 99%

“…Accumulation of amyloid peptide closely mimics the phenotype of Alzheimer’s disease in a murine model [62] and, in fact, an active area of investigation in the treatment of Alzheimer’s disease is to employ therapeutic agents to augment neprilysin activity [63]. This raises the very real concern that in our quest to find the next ‘silver bullet’ for the treatment of HF, we may inadvertently be predisposing patients to neurological and ophthalmic dysfunction from the off-target effects that are inevitable for any therapeutic agent, and occasionally underappreciated until the stage of post-marketing surveillance of the drug by the Food and Drug Administration Adverse Event Reporting System (FAERS).…”

Section: Neprilysin Inhibition With An Angiotensin Receptor Antagonismentioning

confidence: 99%

Neprilysin inhibition: A brief review of past pharmacological strategies for heart failure treatment and future directions

Howell

Cameron

2016

Cardiol J.

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Heart failure (HF) is a manifestation of aberrant vascular responses and remains a public health concern with a worldwide prevalence of around 23 million and a 5-year mortality numerically equivalent to many cancers. Over the last two decades, mortality from HF reached a plateau with current pharmaceutical agents and mechanical cardiac support. In the last several years, various “novel” pharmaceutical agents have been tested in clinical trials and ultimately met with disappointment, showing only incremental benefit in the treatment of HF. Designing a HF drug with enhanced efficacy over existing agents seemed like a Sisyphean task. Yet again, pharmaceutical chemists have demonstrated their prowess in lateral thinking by developing a vasoactive agent which is a co-crystallized compound of valsartan and sacubitril in a one-to-one molar ratio; the former molecule belongs to a family of agents that are the current standard of care for HF and the latter molecule is a novel agent which inhibits neprilysin — a neutral endopeptidase found in human plasma which alters neurohumoral responses. In July of 2015, a drug which is a combination of valsartan and sacubitril was formally licensed by the United States Food and Drug Administration for the treatment of HF. This review describes the evolution of HF medications focusing on rational drug design with the first HF medication, the beta adrenergic receptor antagonist. We then discuss the biochemical and physiological properties of sacubitril/valsartan which likely lead to its dramatic ability to ameliorate HF mortality.

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Polyhydroxycurcuminoids but not curcumin upregulate neprilysin and can be applied to the prevention of Alzheimer’s disease

Cited by 35 publications

References 46 publications

Protective Effects of Indian Spice Curcumin Against Amyloid-β in Alzheimer’s Disease

Protective Effects of Indian Spice Curcumin Against Amyloid-β in Alzheimer’s Disease

Curcumin in Health and Diseases: Alzheimer’s Disease and Curcumin Analogues, Derivatives, and Hybrids

Neprilysin inhibition: A brief review of past pharmacological strategies for heart failure treatment and future directions

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