Berberine Alleviates Amyloid-Beta Pathology in the Brain of APP/PS1 Transgenic Mice via Inhibiting β/γ-Secretases Activity and Enhancing α-Secretases

Cai, Zhiyou; Wang, Chuanling; He, Wenbo; Chen, Yi

doi:10.2174/1567205015666180702105740

Cited by 51 publications

(45 citation statements)

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“…BACE-1 is the major β-secretase that determines Aβ production. This result is consistent with the animal experiment of Cai [103] in male APP/ PS1 transgenic mice. Zhu found that BBR inhibited the expression of BACE by activating the ERK1/2 pathway in HEK293 cells, reducing the production of Aβ40/42 [104].…”

Section: Berberinesupporting

confidence: 92%

Traditional Chinese medicine for anti-Alzheimer’s disease: berberine and evodiamine from Evodia rutaecarpa

et al. 2020

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Alzheimer's disease (AD) is one of the most common diseases in elderly people with a high incidence of dementia at approximately 60-80%. The pathogenesis of AD was quite complicated and currently there is no unified conclusion in the academic community, so no efficiently clinical treatment is available. In recent years, with the development of traditional Chinese medicine (TCM), researchers have proposed the idea of relying on TCM to prevent and treat AD based on the characteristic of multiple targets of TCM. This study reviewed the pathological hypothesis of AD and the potential biomarkers found in the current researches. And the potential targets of berberine and evodiamine from Evodia rutaecarpa in AD were summarized and further analyzed. A compound-targets-pathway network was carried out to clarify the mechanism of action of berberine and evodiamine for AD. Furthermore, the limitations of current researches on the TCM and AD were discussed. It is hoped that this review will provide some references for development of TCM in the prevention and treatment of AD.

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Section: Berberinesupporting

confidence: 92%

Traditional Chinese medicine for anti-Alzheimer’s disease: berberine and evodiamine from Evodia rutaecarpa

et al. 2020

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“…α -, β -, and γ -secretases are considered to be the main enzymes that cause proteolytic cleavage of APP and produce A β peptides [8–10]. Accumulative evidence implicated that A β secretion resulted from α - and β -secretase cleavage of APP, respectively, to induce sAPP- α and sAPP- β [7, 11, 12]. However, sAPP- α has low expression and derives from the nonamyloidogenic pathway.…”

Section: Introductionmentioning

confidence: 99%

“…Over the last decade, numerous BACE1 inhibitors have been tested in clinical trials. The administration of BACE1 inhibitor could dramatically decrease the A β level and attenuate behavioral deficits in APP transgenic mice [12, 19], yet their brains naturally possess high concentrations of soluble A β . The deletion of BACE1 gene decreased A β secretion and improved learning and memory in AD mouse models [20].…”

Section: Introductionmentioning

confidence: 99%

Electroacupuncture Mitigates Hippocampal Cognitive Impairments by Reducing BACE1 Deposition and Activating PKA in APP/PS1 Double Transgenic Mice

et al. 2019

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Increased amyloid-β (Aβ) plaque deposition is thought to be the main cause of Alzheimer’s disease (AD). β-Site amyloid precursor protein cleaving enzyme 1 (BACE1) is the key protein involved in Aβ peptide generation. Excessive expression of BACE1 might cause overproduction of neurotoxins in the central nervous system. Previous studies indicated that BACE1 initially cleaves the amyloid precursor protein (APP) and may subsequently interfere with physiological functions of proteins such as PKA, which is recognized to be closely associated with long-term potentiation (LTP) level and can effectively ameliorate cognitive impairments. Therefore, revealing the underlying mechanism of BACE1 in the pathogenesis of AD might have a significant impact on the future development of therapeutic agents targeting dementia. This study examined the effects of electroacupuncture (EA) stimulation on BACE1, APP, and p-PKA protein levels in hippocampal tissue samples. Memory and learning abilities were assessed using the Morris water maze test after EA intervention. Immunofluorescence, immunohistochemistry, and western blot were employed to assess the distribution patterns and expression levels of BACE1, APP, and p-PKA, respectively. The results showed the downregulation of BACE1 and APP and the activation of PKA by EA. In summary, EA treatment might reduce BACE1 deposition in APP/PS1 transgenic mice and regulate PKA and its associated substrates, such as LTP to change memory and learning abilities.

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“…AChE can also have noncholinergic effect, i.e., inducing Aβ oligomerization via the PAS active site (TRP 279 ), or regulating inflammation by CAP. The main alkaloids in STR, CR, and PCC could alleviate Aβ-induced injury or have an antineuroinflammatory effect [12,47,48]. The alkaloids in STR, CR, and PCC can affect other factors related with AD: fangchinoline has a protective effect on cyanide-induced neurotoxicity [49,50]; coptisine ameliorates cognitive impairment by inhibiting indoleamine 2,3-dioxygenase [51]; and berberine shows multiple activities to relieve symptoms of AD [52].…”

Section: Discussionmentioning

confidence: 99%

Synergistic Inhibition of Acetylcholinesterase by Alkaloids Derived from Stephaniae Tetrandrae Radix, Coptidis Rhizoma and Phellodendri Chinensis Cortex

et al. 2019

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Alkaloids having acetylcholinesterase (AChE) inhibitory activity are commonly found in traditional Chinese medicine (TCM); for example, berberine from Coptis chinensis, galantamine from Lycoris radiata, and huperzine A from Huperzia serrata. In practice of TCM, Stephaniae Tetrandrae Radix (STR) is often combined with Coptidis Rhizoma (CR) or Phellodendri Chinensis Cortex (PCC) as paired herbs during clinical application. Fangchinoline from STR and coptisine and/or berberine from CR and/or PCC are active alkaloids in inhibiting AChE. The traditional usage of paired herbs suggests the synergistic effect of fangchinoline-coptisine or fangchinoline-berberine pairing in AChE inhibition. HPLC was applied to identify the main components in herbal extracts of STR, CR, and PCC, and the AChE inhibition of their main components was determined by Ellman assay. The synergism of herb combination and active component combination was calculated by median-effect principle. Molecular docking was applied to investigate the underlying binding mechanisms of the active components with the AChE protein. It was found that fangchinoline showed AChE inhibitory potency; furthermore, fangchinoline-coptisine/berberine pairs (at ratios of 1:5, 1:2, 1:1, and 2:1) synergistically inhibited AChE; the combination index (CI) at different ratios was less than one when Fa = 0.5, suggesting synergistic inhibition of AChE. Furthermore, the molecular docking simulation supported this enzymatic inhibition. Therefore, fangchinoline-coptisine/berberine pairs, or their parental herbal mixtures, may potentially be developed as a possible therapeutic strategy for Alzheimer's patients.

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Berberine Alleviates Amyloid-Beta Pathology in the Brain of APP/PS1 Transgenic Mice via Inhibiting β/γ-Secretases Activity and Enhancing α-Secretases

Abstract: BBR inhibits the activity of β/γ-secretases, enhances α-secretases, and lowers the Aβ level in the hippocampus of AD mice, and improves Alzheimer's-like cognitive impairment.

Cited by 51 publications

References 0 publications

Traditional Chinese medicine for anti-Alzheimer’s disease: berberine and evodiamine from Evodia rutaecarpa

Traditional Chinese medicine for anti-Alzheimer’s disease: berberine and evodiamine from Evodia rutaecarpa

Electroacupuncture Mitigates Hippocampal Cognitive Impairments by Reducing BACE1 Deposition and Activating PKA in APP/PS1 Double Transgenic Mice

Synergistic Inhibition of Acetylcholinesterase by Alkaloids Derived from Stephaniae Tetrandrae Radix, Coptidis Rhizoma and Phellodendri Chinensis Cortex

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