Berberine modulates amyloid-β peptide generation by activating AMP-activated protein kinase

Zhang, Haijing; Zhao, Chunhui; Cao, Guoqiong; Guo, Limin; Zhang, Shuai; Liang, Yuexia; Qin, Chunxia; Su, Ping; Li, Hang; Zhang, Wensheng

doi:10.1016/j.neuropharm.2017.08.013

Cited by 41 publications

(29 citation statements)

References 46 publications

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“…313,314 Berberine (161) provided neuroprotection via inhibition of the mTOR signaling pathways and activation of cell survival and antioxidative signaling pathways, such as upregulated PI3K/AKT/Bcl-2 and Nrf2/HO-1 antioxidative signaling pathways. 245,315 Berberine reduced the accumulation of amyloid β (Aβ) and decreased the expression of β-site APP cleaving enzyme-1 by activating AMPK in N2a mouse neuroblastoma cells stably expressing human Swedish mutant APP695 (N2a/APP695sw), N2a cells, 315 and also inhibited Aβ-protein-induced apoptosis in primary cultured hippocampal neurons via the mitochondria-related caspase pathway. 316 Subsequently, Huang et al 317 suggested that berberine improves cognitive impairment by promoting autophagic clearance and inhibits production of Aβ in an APP/tau/PS1 mouse model of AD.…”

Section: Neuroprotective Effectsmentioning

confidence: 99%

Biologically active isoquinoline alkaloids covering 2014–2018

Shang

Yang

Morris‐Natschke

et al. 2020

Medicinal Research Reviews

139

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Isoquinoline alkaloids, an important class of N-based heterocyclic compounds, have attracted considerable attention from researchers worldwide since the early 19th century. Over the past 200 years, many compounds from this class were isolated, and most of them and their analogs possess various bioactivities. In this review, we survey the updated literature on bioactive alkaloids and highlight research achievements of this alkaloid class during the period of 2014-2018. We reviewed over 400 molecules with a broad range of bioactivities, including antitumor, antidiabetic and its complications, antibacterial, antifungal, antiviral, antiparasitic, insecticidal, anti-inflammatory, antioxidant, neuroprotective, and other activities. This review should provide new indications or directions for the discovery of new and better drugs from the original naturally occurring isoquinoline alkaloids.

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Section: Neuroprotective Effectsmentioning

confidence: 99%

Biologically active isoquinoline alkaloids covering 2014–2018

Shang

Yang

Morris‐Natschke

et al. 2020

Medicinal Research Reviews

139

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“…Metformin significantly increased the expression level of IDE, but not NEP, in the APP/PS1 mice. Previous studies have reported that the AMPK pathway is involved in metformin effect [24,[27][28][29][30].…”

Section: Metformin Activates Ampk and Increases Ide In Thementioning

confidence: 99%

“…AMPK is a crucial factor in the regulation of intracellular systems [30]. AMPK activation can enhance antiinflammatory effect, which might be regulated by AMPK/m-TOR and AMPK/NF-κB signaling pathways [24,[27][28][29][30]. Metformin was supposed to have a potential pharmacological effect, due to AMPK activation [35].…”

Section: Oxidative Medicine and Cellular Longevitymentioning

confidence: 99%

Metformin Ameliorates Aβ Pathology by Insulin-Degrading Enzyme in a Transgenic Mouse Model of Alzheimer’s Disease

Huang

Chen

et al. 2020

Oxidative Medicine and Cellular Longevity

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Alzheimer’s disease (AD) is the most common neurodegenerative disease. The accumulation of amyloid beta (Aβ) is the main pathology of AD. Metformin, a well-known antidiabetic drug, has been reported to have AD-protective effect. However, the mechanism is still unclear. In this study, we tried to figure out whether metformin could activate insulin-degrading enzyme (IDE) to ameliorate Aβ-induced pathology. Morris water maze and Y-maze results indicated that metformin could improve the learning and memory ability in APPswe/PS1dE9 (APP/PS1) transgenic mice. 18F-FDG PET-CT result showed that metformin could ameliorate the neural dysfunction in APP/PS1 transgenic mice. PCR analysis showed that metformin could effectively improve the mRNA expression level of nerve and synapse-related genes (Syp, Ngf, and Bdnf) in the brain. Metformin decreased oxidative stress (malondialdehyde and superoxide dismutase) and neuroinflammation (IL-1β and IL-6) in APP/PS1 mice. In addition, metformin obviously reduced the Aβ level in the brain of APP/PS1 mice. Metformin did not affect the enzyme activities and mRNA expression levels of Aβ-related secretases (ADAM10, BACE1, and PS1). Meanwhile, metformin also did not affect the mRNA expression levels of Aβ-related transporters (LRP1 and RAGE). Metformin increased the protein levels of p-AMPK and IDE in the brain of APP/PS1 mice, which might be the key mechanism of metformin on AD. In conclusion, the well-known antidiabetic drug, metformin, could be a promising drug for AD treatment.

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“…In another study, through surface plasmon resonance (SPR) binding analysis and docking studies, the direct binding of berberine and BACE-1 was illustrated [68]. Reports of berberine acting on the BACE1 expression levels are also available, hence, further studies are required for the identification of the potential mechanism of action of the compound [69]. No potential toxicity was shown by the compound in both the in vivo and in vitro studies conducted, but protoberberine alkaloids such as the epiberberine (12) groenlandicine (13) exhibit promising dose-dependent BACE1 noncompetitive inhibition with IC 50 values of 8.55 and 19.68 µM, respectively [67].…”

Section: Alkaloids Showing Inhibition Of Beta-site Amyloid Precursor mentioning

confidence: 99%

Natural Compounds with Anti-BACE1 Activity as Promising Therapeutic Drugs for Treating Alzheimerʼs Disease

et al. 2019

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Alzheimerʼs disease is a neurodegenerative disease that leads to irreversible neuronal damage. Senile plaques, composed of amyloid beta peptide, is the principal abnormal characteristic of the disease. Among the factors involved, the secretase enzymes, namely, α secretase, beta-site amyloid precursor protein-cleaving enzyme, β secretase, and γ secretase, hold consequential importance. Beta-site amyloid precursor protein-cleaving enzyme 1 is considered to be the rate-limiting factor in the production of amyloid beta peptide. Research supporting the concept of inhibition of beta-site amyloid precursor protein-cleaving enzyme activity as one of the effective therapeutic targets in the mitigation of Alzheimerʼs disease is well accepted. The identification of natural compounds, such as β-amyloid precursor protein-selective beta-site amyloid precursor protein-cleaving enzyme inhibitors, and the idea of compartmentalisation of the beta-site amyloid precursor protein-cleaving enzyme 1 action have caused a dire need to closely examine the natural compounds and their effectiveness in the disease mitigation. Many natural compounds have been reported to effectively modulate beta-site amyloid precursor protein-cleaving enzyme 1. At lower doses, compounds like 2,2′,4′-trihydroxychalcone acid, quercetin, and myricetin have been shown to effectively reduce beta-site amyloid precursor protein-cleaving enzyme 1 activity. The currently used five drugs that are marketed and used for the management of Alzheimerʼs disease have an increased risk of toxicity and restricted therapeutic efficiency, hence, the search for new anti-Alzheimerʼs disease drugs is of primary concern. A variety of natural compounds having pure pharmacological moieties showing multitargeting activity and others exhibiting specific beta-site amyloid precursor protein-cleaving enzyme 1 inhibition as discussed below have superior biosafety. Many of these compounds, which are isolated from medicinal herbs and marine flora, have been long used for the treatment of various ailments since ancient times in the Chinese and Ayurvedic medical systems. The aim of this article is to review the available data on the selected natural compounds, giving emphasis to the inhibition of beta-site amyloid precursor protein-cleaving enzyme 1 activity as a mode of Alzheimerʼs disease treatment.

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Berberine modulates amyloid-β peptide generation by activating AMP-activated protein kinase

Cited by 41 publications

References 46 publications

Biologically active isoquinoline alkaloids covering 2014–2018

Biologically active isoquinoline alkaloids covering 2014–2018

Metformin Ameliorates Aβ Pathology by Insulin-Degrading Enzyme in a Transgenic Mouse Model of Alzheimer’s Disease

Natural Compounds with Anti-BACE1 Activity as Promising Therapeutic Drugs for Treating Alzheimerʼs Disease

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