Butterbur Leaves Attenuate Memory Impairment and Neuronal Cell Damage in Amyloid Beta-Induced Alzheimer’s Disease Models

Kim, Namkwon; Choi, Jin Gyu; Park, Sangsu; Lee, Jong Kil; Oh, Myung Sook

doi:10.3390/ijms19061644

Cited by 13 publications

(12 citation statements)

References 43 publications

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“…Studies have shown in both cellular and animal models that oxidative stress upregulates the expression and activity of BACE1 through the activation of the c-Jun N-terminal kinase/activator protein1 pathway [58,59,60,61]. Kim et al reported that treating SK-N-MC cells with palmitic acid conjugated with bovine serum albumin (PA-BSA) results in an increased expression of BACE1 and Aβ production through the G protein-coupled receptor 40 (GPCR40) [62].…”

Section: Discussionmentioning

confidence: 99%

MST1 Regulates Neuronal Cell Death via JNK/Casp3 Signaling Pathway in HFD Mouse Brain and HT22 Cells

Khan

Rutten

Kim

2019

IJMS

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Oxidative stress has been considered as the main mediator in neurodegenerative diseases. A high-fat diet (HFD) and metabolic diseases result in oxidative stress generation, leading to various neurodegenerative diseases via molecular mechanisms that remain largely unknown. Protein kinases play an important role in the homeostasis between cell survival and cell apoptosis. The mammalian sterile 20-like kinase-1 (MST1) protein kinase plays an important role in cellular apoptosis in different organ systems, including the central nervous system. In this study, we evaluated the MST1/c-Jun N-terminal kinase (JNK) dependent oxidative damage mediated cognitive dysfunction in HFD-fed mice and stress-induced hippocampal HT22 (mice hippocampal) cells. Our Western blot and immunofluorescence results indicate that HFD and stress-induced hippocampal HT22 cells activate MST1/JNK/Caspase-3 (Casp-3) signaling, which regulates neuronal cell apoptosis and beta-amyloid-cleaving enzyme (BACE1) expression and leads to impaired cognition. Moreover, MST1 expression inhibition by shRNA significantly reduced JNK/Casp-3 signaling. Our in vivo and in vitro experiments mimicking metabolic stress, such as a high-fat diet, hyperglycemia, and an inflammatory response, determined that MST1 plays a key regulatory role in neuronal cell death and cognition, suggesting that MST1 could be a potential therapeutic target for numerous neurodegenerative diseases.

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Section: Discussionmentioning

confidence: 99%

MST1 Regulates Neuronal Cell Death via JNK/Casp3 Signaling Pathway in HFD Mouse Brain and HT22 Cells

Khan

Rutten

Kim

2019

IJMS

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“…Safety evaluations are critical when new compounds/foods are introduced to the marketplace [24,25]. In our preliminary studies, we elucidated two new lignans and isolated six known compounds from KP-1 that showed neuroprotective and anti-inflammatory effects [9,10]. PL extracts are used as medicines in the West.…”

Section: Resultsmentioning

confidence: 99%

“…Our previous study demonstrated the neuroprotective effects of hot water extracts of P. japonicus leaves (KP-1) in Aβ 25-35 -plaque-induced Alzheimer's disease models. KP-1 protects hippocampal cells against Aβ 25-35 plaque toxicity by regulating intracellular reactive oxygen species (ROS) levels and in vitro activation of cAMP response element-binding protein (CREB)induced antioxidant enzymes [10]. Development of and research on pharmaceutical and functional foods using natural products are actively progressing, which reinforces the need for safety assessments.…”

Section: Introductionmentioning

confidence: 99%

Single and Repeated Oral Dose Toxicity and Genotoxicity of the Leaves of Butterbur

Park

Lim²,

Lee

et al. 2021

Foods

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Butterbur (Petasites japonicus (Siebold & Zucc.) Maxim) leaves are available to consumers in the marketplace, but there is no guarantee that they are safe for human consumption. Previously, we demonstrated that hot water extracts of P. japonicus leaves (KP-1) had anti-inflammatory properties and attenuated memory impairment. However, data regarding KP-1 toxicity are lacking. This study assessed the safety of KP-1 by examining oral and genotoxic effects using in vivo and in vitro tests, respectively. In a single oral dose toxicity and two-week repeated oral dose toxicity study, we observed no toxicologically significant clinical signs or changes in hematology, blood chemistry, and organ weights at any dose during the experiment. Following a thirteen-week repeated oral dose, toxicity, hyperkeratosis, and squamous cell hyperplasia of the limiting ridge in the stomach were observed. The no observable adverse effect level (NOAEL) was found to be 1250 mg/kg/day in male and female rats. However, hyperkeratosis and hyperplasia were not considered to be of toxicological significance when extrapolating the NOAEL to humans because the limiting ridge in the stomach is species-specific to rats. Therefore, in our study, the NOAEL was considered to be 5000 mg/kg/day when the changes in the stomach’s limiting ridge were discounted. Moreover, in vitro bacterial reverse mutations and chromosomal aberrations in Chinese hamster lung (CHL) cells and the in vivo micronucleus in Institute of cancer research (ICR) mice assays showed that KP-1 possessed no mutagenicity. Although additional research is required, these toxicological evaluations suggest that KP-1 could be safe for human consumption.

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“…Mouse anti-synaptophysin (SYP) and the other reagents were purchased from Sigma-Aldrich (St. Louis, MO, USA) unless noted. Aβ 25–35 was purchased from AnaSpec (Fremont, CA, USA) and reconstituted in sterile water at a concentration of 500 μM and incubated at 37 °C for 72 hours to form amyloid plaque as previously described [23].…”

Section: Methodsmentioning

confidence: 99%

Cuscutae Japonicae Semen Ameliorates Memory Dysfunction by Rescuing Synaptic Damage in Alzheimer’s Disease Models

Kim

Choi

et al. 2019

Nutrients

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Alzheimer’s disease (AD) is the most common type of dementia in the elderly. It is characterized by the accumulation of amyloid-beta (Aβ) and progressive cognitive impairment. To alleviate the symptoms of AD, functional foods and nutrients have been used for centuries. In this study, we investigated whether Cuscutae Japonicae Semen (CJS), a medicinal food traditionally used in East Asia, has effects on memory improvement and synapse protection in AD. We orally administered CJS to 5x familiar AD (5xFAD) transgenic mice and performed the Morris water maze test. The results showed that CJS treatment ameliorated the decline of memory function. Then, we demonstrated that CJS attenuated the degeneration of pre- and post-synaptic proteins in the hippocampi of 5xFAD mice. To demonstrate the effects of CJS in vitro, we treated Aβ in primary neuronal culture with CJS and observed that CJS rescued the loss of functional synapses. The protective effects of CJS on the synapse were due to the inhibition of activated caspase-3 expression. Additionally, CJS inhibited the phosphorylation of glycogen synthase kinase-3β and tau proteins, which contribute to synaptic dysfunction. Taken together, our results suggest that CJS is efficient in alleviating memory loss by rescuing caspase-3-mediated synaptic damage in AD treatment.

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Butterbur Leaves Attenuate Memory Impairment and Neuronal Cell Damage in Amyloid Beta-Induced Alzheimer’s Disease Models

Cited by 13 publications

References 43 publications

MST1 Regulates Neuronal Cell Death via JNK/Casp3 Signaling Pathway in HFD Mouse Brain and HT22 Cells

MST1 Regulates Neuronal Cell Death via JNK/Casp3 Signaling Pathway in HFD Mouse Brain and HT22 Cells

Single and Repeated Oral Dose Toxicity and Genotoxicity of the Leaves of Butterbur

Cuscutae Japonicae Semen Ameliorates Memory Dysfunction by Rescuing Synaptic Damage in Alzheimer’s Disease Models

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