β‐secretase inhibitory effects of furanocoumarins from the root of <i>Angelica dahurica</i>

Marumoto, Shinsuke; Miyazawa, Mitsuo

doi:10.1002/ptr.2967

Cited by 50 publications

(30 citation statements)

References 18 publications

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“…The IMPcontaining herbs are widely used in China for the treatment of osteoporosis and relief of swelling and pain (Zhang et al, 2003). The reported pharmacological activities of IMP include anti-inflammatory properties (Garcia-Argaez et al, 2000), antiosteoporosis (Tang et al, 2008), antibacterial effects (Rosselli et al, 2007), antitumor (Kim et al, 2007), b-secretase inhibition (Marumoto and Miyazawa, 2010), and inhibition of myocardial hypertrophy (Zhang et al, 2010). Recent studies have demonstrated that IMP participates in hypertension treatment by inhibiting voltage-dependent calcium channels and receptor-mediated Ca 2+ influx and release (He et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Imperatorin Is a Mechanism-Based Inactivator of CYP2B6

et al. 2014

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Imperatorin (IMP) is the major active ingredient in many common medicinal herbs. We examined the irreversible inhibitory effect of IMP on CYP2B6. IMP produced a time-and concentrationdependent inactivation of CYP2B6. About 70% of activity of CYP2B6 was suppressed after its incubation with 1.5 mM IMP for 9 minutes. K I and k inact were found to be 0.498 mM and 0.079 min 21 , respectively. The loss of CYP2B6 activity required the presence of NADPH. Glutathione and catalase/superoxide dismutase showed little protection against the IMP-induced enzyme inactivation.Ticlopidine, a substrate of CYP2B6, showed protection of the enzyme against the inactivation induced by IMP. The estimated partition ratio of the inactivation was approximately 4. Additionally, a g-ketoenal intermediate was identified in microsomal incubations with IMP. CYP1A2, CYP2A6, CYP2B6, CYP2D6, CYP2E1, CYP3A4, and CYP3A5 were found to be involved in bioactivation of IMP. In conclusion, IMP is a mechanism-based inactivator of CYP2B6. The formation of g-ketoenal intermediate may account for the enzyme inactivation

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Section: Introductionmentioning

confidence: 99%

Imperatorin Is a Mechanism-Based Inactivator of CYP2B6

et al. 2014

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“…aloeresin D) [29]; isoflavones (bavachinin, neocorylin) and chalcone flavonoids (e.g. bavachromene, bavachalcone) [36]; (+)-vitisinol E, (+)-ampelopsin A, and (+)-vitisin [37]; furanocoumarins (imperatorin, (+)-byakangelicol) [38]; amentoflavone-type biflavonoids (e.g. 2,3-dihydroamentoflavone, 2,3-dihydro-6-methylginkgetin) [39]; resveratrol and its derivatives [40].…”

Section: Discussionmentioning

confidence: 99%

Effects of curcuminoids identified in rhizomes of Curcuma longa on BACE-1 inhibitory and behavioral activity and lifespan of Alzheimer’s disease Drosophila models

Wang

Kim

Lee

et al. 2014

BMC Complement Altern Med

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BackgroundAlzheimer’s disease (AD) is the most common type of presenile and senile dementia. The human β-amyloid precursor cleavage enzyme (BACE-1) is a key enzyme responsible for amyloid plaque production, which implicates the progress and symptoms of AD. Here we assessed the anti-BACE-1 and behavioral activities of curcuminoids from rhizomes of Curcuma longa (Zingiberaceae), diarylalkyls curcumin (CCN), demethoxycurcumin (DMCCN), and bisdemethoxycurcumin (BDMCCN) against AD Drosophila melanogaster models.MethodsNeuro-protective ability of the curcuminoids was assessed using Drosophila melanogaster model system overexpressing BACE-1 and its substrate APP in compound eyes and entire neurons. Feeding and climbing activity, lifespan, and morphostructural changes in fly eyes also were evaluated.ResultsBDMCCN has the strongest inhibitory activity toward BACE-1 with 17 μM IC50, which was 20 and 13 times lower than those of CCN and DMCCN respectively. Overexpression of APP/BACE-1 resulted in the progressive and measurable defects in morphology of eyes and locomotion. Remarkably, supplementing diet with either 1 mM BDMCCN or 1 mM CCN rescued APP/BACE1-expressing flies and kept them from developing both morphological and behavioral defects. Our results suggest that structural characteristics, such as degrees of saturation, types of carbon skeleton and functional group, and hydrophobicity appear to play a role in determining inhibitory potency of curcuminoids on BACE-1.ConclusionFurther studies will warrant possible applications of curcuminoids as therapeutic BACE-1 blockers.

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“…β-Secretase inhibitors isolated from A. dahurica roots were types of furanocoumarins (Fig. 3) including isoimperatorin (6), imperatorin (7), (+)-oxypeucedanin (8), (+)-bakangelicol (9) and (+)-byakangelicin (10) (Marumoto and Miyazawa, 2010). Owing to their low molecular weight, these compounds can easily cross the blood-brain-barrier (BBB) and reach the brain.…”

Section: β-Secretase Inhibitorsmentioning

confidence: 99%

Potential therapeutic agents against Alzheimer’s disease from natural sources

Park

2010

Arch. Pharm. Res.

106

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The average human life span in developed countries has increased to more than 80 years following rapid breakthrough and developments in modern medicine and science, resulting in prolonged life expectancy and increase in the population counts of the geriatric age group. This translates into a dramatic increase in disease burden of elderly patients suffering from senile disorders including neurodegenerative diseases, particularly Alzheimer's disease (AD). AD is characterized by the death of nerve cells in the cerebral cortex and is the most common subtype of dementia that affected 25 million people worldwide in 2000 and is expected to increase to 114 million by 2050. Despite the exponential growth in the number of AD patients, only acetylcholinesterase (AChE) inhibitors are being currently used to treat AD. It is well known that AChE inhibitors can alleviate the symptoms of AD but not halt the disease progression. Consequently, therapeutic agents against AD acting at various pathologic levels are needed. In the recent decade, natural products with anti-AD properties have attracted much attention. But very few natural products have been investigated in a scientifically justifiable method for these biological activities. Following a detailed research process, it is certain that natural products have a strong potential to develop biologically active compounds with new chemical structures. Many studies have been carried out to identify the naturally occurring anti-AD agents. This review article describes the molecular targets aiming at developing the anti-AD agents including the inhibition of AChE, inhibition of Aβ production by enhancing α-secretase (non-amyloidogenic pathway) or inhibiting β- and γ-secretases (amyloidogenic pathway), alleviating Aβ-induced neurotoxicity or reducing Aβ-induced neuroinflammation. In addition, this paper summarizes the potential of some of the natural products that might inhibit specific molecular targets and slow the progression of this disease.

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β‐secretase inhibitory effects of furanocoumarins from the root of Angelica dahurica

Cited by 50 publications

References 18 publications

Imperatorin Is a Mechanism-Based Inactivator of CYP2B6

Imperatorin Is a Mechanism-Based Inactivator of CYP2B6

Effects of curcuminoids identified in rhizomes of Curcuma longa on BACE-1 inhibitory and behavioral activity and lifespan of Alzheimer’s disease Drosophila models

Potential therapeutic agents against Alzheimer’s disease from natural sources

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