Amyloid β aggregation inhibitory activity of triterpene saponins from the cactus Stenocereus pruinosus

Fujihara, Koji; Shimoyama, Takefumi; Kawazu, Ryo; Sasaki, Hiroaki; Koyama, Kiyotaka; Takahashi, Kunio; Kinoshita, Kaoru

doi:10.1007/s11418-020-01463-0

Cited by 11 publications

(8 citation statements)

References 48 publications

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“…This amphipathic property of saponin has drawn pharmacological attention to this group of compounds because it can cause diverse cellular activities by known pathways, including pore formation, direct membrane lysis, permeabilization of membrane, induced raft activity and direct protein binding [ 5 ]. Interestingly, various naturally occurring saponins have been reported to bind with the pathogenic proteins and cause an inhibitory aggregation effect, expected to solve protein aggregation-induced neurodegeneration disorders such as Huntington’s disease, Alzheimer’s disease, and Parkinson’s disease [ 6 ]. Ginsenoside Rg1, a plant triterpene saponin found in Panax ginseng , displayed protective effects in PC12 cell and mouse PD models by modulating antiapoptotic protein Bcl-2 and iNOS expressions [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Neurorescue Effects of Frondoside A and Ginsenoside Rg3 in C. elegans Model of Parkinson’s Disease

et al. 2021

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Parkinson’s disease (PD) is a currently incurable neurodegenerative disorder characterized by the loss of dopaminergic (DAergic) neurons in the substantia nigra pars compacta and α-synuclein aggregation. Accumulated evidence indicates that the saponins, especially from ginseng, have neuroprotective effects against neurodegenerative disorders. Interestingly, saponin can also be found in marine organisms such as the sea cucumber, but little is known about its effect in neurodegenerative disease, including PD. In this study, we investigated the anti-Parkinson effects of frondoside A (FA) from Cucumaria frondosa and ginsenoside Rg3 (Rg3) from Panax notoginseng in C. elegans PD model. Both saponins were tested for toxicity and optimal concentration by food clearance assay and used to treat 6-OHDA-induced BZ555 and transgenic α-synuclein NL5901 strains in C. elegans. Treatment with FA and Rg3 significantly attenuated DAergic neurodegeneration induced by 6-OHDA in BZ555 strain, improved basal slowing rate, and prolonged lifespan in the 6-OHDA-induced wild-type strain with downregulation of the apoptosis mediators, egl-1 and ced-3, and upregulation of sod-3 and cat-2. Interestingly, only FA reduced α-synuclein aggregation, rescued lifespan in NL5901, and upregulated the protein degradation regulators, including ubh-4, hsf-1, hsp-16.1 and hsp-16.2. This study indicates that both FA and Rg3 possess beneficial effects in rescuing DAergic neurodegeneration in the 6-OHDA-induced C. elegans model through suppressing apoptosis mediators and stimulating antioxidant enzymes. In addition, FA could attenuate α-synuclein aggregation through the protein degradation process.

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Section: Introductionmentioning

confidence: 99%

Neurorescue Effects of Frondoside A and Ginsenoside Rg3 in C. elegans Model of Parkinson’s Disease

et al. 2021

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“… a NA indicates “Not active.” b Myricetin and inhibitor IV were used as a positive control for the Th-T assay and the BACE1 FRET assay, respectively. Those activities were described in our previous reports [ 6 , 7 ] …”

Section: Resultsmentioning

confidence: 99%

“…The assay was conducted at final concentration of 10 μg/mL with each fraction. Th-T assays were carried out according to a previous report [ 6 ]. Briefly, 80 μL of phosphate buffer containing 50 mM NaCl at pH 7.4 was added to a 500 μL test tube, followed by the addition of 10 μL of DMSO containing test sample to the phosphate buffer solution.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of Aβ aggregation by naphtho-γ-pyrone derivatives from a marine-derived fungus, Aspergillus sp. MPUC239

et al. 2023

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Alzheimer’s disease (AD) is an important human disease that mainly causes cognitive impairments. Growing evidence has shown that amyloid-β (Aβ) peptide plays a key role in AD pathogenesis in what is known as the Aβ cascade hypothesis. This hypothesis suggests the importance of suppressing Aβ aggregation and Aβ production. The latter process is governed by β-site APP Cleaving Enzyme1 (BACE1) and γ-secretase. We, therefore, focused on Aβ aggregation inhibitory activity, initially assessing numerous extracts derived from our marine-derived fungus collections. One EtOAc extract derived from an Aspergillus sp. exhibited Aβ aggregation inhibitory activity. Eleven known compounds ( 1 – 11 ) were isolated from CHCl 3 and EtOAc extracts derived from the fungus, and the structures were identified based on MS, NMR, and ECD spectra. Compounds 2 , 6 , and 10 inhibited Aβ aggregation with IC 50 values of 2.8, 3.9, and 8.1 μM, respectively. The protective effect on SH-SY5Y cells against Aβ toxicity was also evaluated, and compounds 6 and 10 significantly alleviated Aβ toxicity. BACE1 inhibitory activity was also examined, and compounds 4 , 5 , 7 , 10 , and 11 inhibited BACE1 activity with IC 50 values of 14.9, 70.0, 36.5, 28.0, and 72.8 μM, respectively. These data suggest that compound 10 could be useful in AD treatment. Supplementary Information The online version contains supplementary material available at 10.1007/s11418-023-01696-9.

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“…Several triterpene saponins were isolated from the methanolic extract of Stenocereus pruinosus , and thioflavin-T assay revealed the significant inhibitory power of triterpenes against Aβ aggregation [ 95 ]. Various flavonoids, isoflavonoids, and coumestan are widely distributed in Pueraria lobata .…”

Section: Plants and Their Bioactive Compounds In Averting The Pathoge...mentioning

confidence: 99%

Plant-Derived Bioactive Compounds in the Management of Neurodegenerative Disorders: Challenges, Future Directions and Molecular Mechanisms Involved in Neuroprotection

et al. 2023

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Neurodegenerative disorders encompass a wide range of pathological conditions caused by progressive damage to the neuronal cells and nervous-system connections, which primarily target neuronal dysfunction and result in problems with mobility, cognition, coordination, sensation, and strength. Molecular insights have revealed that stress-related biochemical alterations such as abnormal protein aggregation, extensive generation of reactive oxygen and nitrogen species, mitochondrial dysfunction, and neuroinflammation may lead to damage to neuronal cells. Currently, no neurodegenerative disease is curable, and the available standard therapies can only provide symptomatic treatment and delay the progression of the disease. Interestingly, plant-derived bioactive compounds have drawn considerable attention due to their well-established medicinal properties, including anti-apoptotic, antioxidant, anti-inflammatory, anticancer, and antimicrobial properties, as well as neuroprotective, hepatoprotective, cardioprotective, and other health benefits. Plant-derived bioactive compounds have received far more attention in recent decades than synthetic bioactive compounds in the treatment of many diseases, including neurodegeneration. By selecting suitable plant-derived bioactive compounds and/or plant formulations, we can fine tune the standard therapies because the therapeutic efficacy of the drugs is greatly enhanced by combinations. A plethora of in vitro and in vivo studies have demonstrated plant-derived bioactive compounds’ immense potential, as proven by their capacity to influence the expression and activity of numerous proteins implicated in oxidative stress, neuroinflammation, apoptosis, and aggregation. Thus, this review mostly focuses on the antioxidant, anti-inflammatory, anti-aggregation, anti-cholinesterase, and anti-apoptotic properties of several plant formulations and plant-derived bioactive compounds and their molecular mechanisms against neurodegenerative disorders.

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Amyloid β aggregation inhibitory activity of triterpene saponins from the cactus Stenocereus pruinosus

Cited by 11 publications

References 48 publications

Neurorescue Effects of Frondoside A and Ginsenoside Rg3 in C. elegans Model of Parkinson’s Disease

Neurorescue Effects of Frondoside A and Ginsenoside Rg3 in C. elegans Model of Parkinson’s Disease

Inhibition of Aβ aggregation by naphtho-γ-pyrone derivatives from a marine-derived fungus, Aspergillus sp. MPUC239

Plant-Derived Bioactive Compounds in the Management of Neurodegenerative Disorders: Challenges, Future Directions and Molecular Mechanisms Involved in Neuroprotection

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