Figure - available from: Frontiers in Neuroscience
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The molecular structure of BBR. The red structure in the figure represents the oxygen atom and the blue structure represents the hydrogen atom.
Source publication
Objective
To investigate the mechanism underlying the effects of berberine (BBR) in the treatment of Alzheimer’s disease (AD).
Methods
3 × Tg AD mice were treated with BBR for 3 months, then the open field test (OFT), the novel object recognition test (NOR) and the Morris water maze (MWM) test were performed to assess behavioral performance. Hemat...
Citations
... The association of DK with VEGFA in AD has not been studied to date, but it is possible that VEGFA is involved, based on previous findings that the compound crosses the BBB despite its relatively high molecular weight [32]. Wei et al. reported that Hsp90 encoded by HSP90AA is involved in the degradation of Aβ and tau through the proteasome system [33]. Other studies have shown that HSP90AA1 might be a key gene in the progression of inflammation, and Hsp90 inhibitors were considered to be potent inhibitors of the inflammatory response [34,35]. ...
Marine polyphenols, including eckol(EK), dieckol(DK), and 8,8’-bieckol(BK), have attracted attention as bioactive ingredients for preventing Alzheimer’s disease (AD). Since AD is a multifactorial disorder, the present study aims to provide an unbiased elucidation of unexplored targets of AD mechanisms and a systematic prediction of effective preventive combinations of marine polyphenols. Based on the omics data between each compound and AD, a protein–protein interaction (PPI) network was constructed to predict potential hub genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to provide further biological insights. In the PPI network of the top 10 hub genes, AKT1, SRC, EGFR, and ESR1 were common targets of EK and BK, whereas PTGS2 was a common target of DK and BK. GO and KEGG pathway analysis revealed that the overlapped genes between each compound and AD were mainly enriched in EGFR tyrosine kinase inhibitor resistance, the MAPK pathway, and the Rap1 and Ras pathways. Finally, docking validation showed stable binding between marine polyphenols and their top hub gene via the lowest binding energy and multiple interactions. The results expanded potential mechanisms and novel targets for AD, and also provided a system-level insight into the molecular targets of marine polyphenols against AD.
... Berberine regulates the GSK-3β/PGC-1α signaling pathway by inhibiting GSK-3β activity [199], showing potential neuroprotective effects against oxidation, neuroinflammation [200], Aβ pathology, and tau hyperphosphorylation [200,201]. It has also been suggested that berberine modulates the extracellular signal-regulated kinase and protein kinase B signaling pathways in a transgenic model of AD, thus regulating plasticity, as the activation of this signaling pathway is related to the mechanism of neuroplasticity [202]. Another signaling pathway that is altered in AD is phosphoinositide dependent kinase 1 (PDK1)/AKT, which is involved in AB production and tau phosphorylation, as well as in cell survival and synaptic health [199]. ...
... Therapeutic strategies attempting to activate this signaling pathway include Salvia officinalis [203], curcumin [204], and trypchloride [205]. All these compounds have been reported to produce a certain degree of cognitive enhancement in animal models of AD and reduce neuropathology [202,206]. However, safety factors and bioavailability need to be further investigated [207]. ...
Alzheimer disease (AD) is the most prevalent form of dementia among elderly people. Owing to its varied and multicausal etiopathology, intervention strategies have been highly diverse. Despite ongoing advances in the field, efficient therapies to mitigate AD symptoms or delay their progression are still of limited scope. Neuroplasticity, in broad terms the ability of the brain to modify its structure in response to external stimulation or damage, has received growing attention as a possible therapeutic target, since the disruption of plastic mechanisms in the brain appear to correlate with various forms of cognitive impairment present in AD patients. Several pre-clinical and clinical studies have attempted to enhance neuroplasticity via different mechanisms, for example , regulating glucose or lipid metabolism, targeting the activity of neurotransmitter systems, or addressing neuroinflammation. In this review, we first describe several structural and functional aspects of neuroplasticity. We then focus on the current status of pharmacological approaches to AD stemming from clinical trials targeting neuroplastic mechanisms in AD patients. This is followed by an analysis of analogous pharmacological interventions in animal models, according to their mechanisms of action.
To address the challenges posed by biofilm presence and achieve a substantial reduction in bacterial load within root canals during endodontic treatment, various irrigants, including nanoparticle suspensions, have been recommended. Berberine (BBR), a natural alkaloid derived from various plants, has demonstrated potential applications in dentistry treatments due to its prominent antimicrobial, anti-inflammatory, and antioxidant properties. This study aimed to produce and characterize a novel polymeric nanoparticle of poly (lactic-co-glycolic acid) (PLGA) loaded with berberine and evaluate its antimicrobial activity against relevant endodontic pathogens, Enterococcus faecalis, and Candida albicans. Additionally, its cytocompatibility using gingival fibroblasts was assessed. The polymeric nanoparticle was prepared by the nanoprecipitation method. Physicochemical characterization revealed spheric nanoparticles around 140 nm with ca, −6 mV of surface charge, which was unaffected by the presence of BBR. The alkaloid was successfully incorporated at an encapsulation efficiency of 77% and the designed nanoparticles were stable upon 20 weeks of storage at 4 °C and 25 °C. Free BBR reduced planktonic growth at ≥125 μg/mL. Upon incorporation into PLGA nanoparticles, 20 μg/mL of [BBR]-loaded nanoparticles lead to a significant reduction, after 1 h of contact, of both planktonic bacteria and yeast. Sessile cells within biofilms were also considered. At 30 and 40 μg/mL, [BBR]-loaded PLGA nanoparticles reduced the viability of the sessile endodontic bacteria, upon 24 h of exposure. The cytotoxicity of BBR-loaded nanoparticles to oral fibroblasts was negligible. The novel berberine-loaded polymeric nanoparticles hold potential as a promising supplementary approach in the treatment of endodontic infections.
The potential neurotoxic effects of propofol, an extensively utilized anesthetic, underline the urgency to comprehend its influence on neuronal health. Insights into the role of the RARα-Snhg1-Bdnf network can offer significant advancements in minimizing these effects. The study targets the exploration of the RARα and Snhg1 regulatory network's influence on Bdnf expression in the realm of propofol-induced neurotoxicity. Harnessing the GEO database and utilizing JASPAR and RPISeq for projections, the study embarks on an in-depth analysis employing both in vitro and in vivo models. The findings draw a clear link between propofol-induced neurotoxicity and the amplification of RAR signaling pathways, impacting hippocampal development and apoptosis and leading to increased RARα and Snhg1 and decreased Bdnf. Propofol is inferred to accentuate neurotoxicity by heightening RARα and Snhg1 interactions, culminating in Bdnf suppression.
Psychiatric and neurodegenerative disorders are amongst the most prevalent and debilitating diseases, but current treatments either have low success rates, greatly due to the low permeability of the blood– brain barrier, and/or are connected to severe side-effects. Hence, new strategies are extremely important, and here is where liposome-derived nanosystems come in. Niosomes, transfersomes and ethosomes are nanometric vesicular structures that allow drug encapsulation, protecting them from degradation, and increasing their solubility, permeability, and brain targeting and bioavailability. This review highlights the great potential of these nanosystems for the treatment of Alzheimer’s disease, Parkinson’s disease, schizophrenia, bipolar disorder, anxiety and depression. Studies regarding the encapsulation of synthetic and natural-derived molecules in these systems, for intravenous, oral, transdermal, or intranasal administration, have led to an increased brain bioavailability, when compared to conventional pharmaceutical forms. Moreover, the developed formulations proved to have neuroprotective, anti-inflammatory and antioxidant effects, including brain neurotransmitter levels restoration and brain oxidative status improvement, and improved locomotor activity or enhancement of recognition and working memories in animal models. Hence, albeit being relatively new technologies, niosomes, transfersomes and ethosomes have already proven to increase the brain bioavailability of psychoactive drugs, leading to increased effectiveness and decreased side-effects, showing promise as future therapeutics.
Inflammatory bowel diseases (IBDs) are characterized by chronic relapsing intestinal inflammation that causes digestive system dysfunction. For years, researchers have been working to find more effective and safer therapeutic strategies to treat these diseases. Silibinin (SIL), a flavonoid compound extracted from the seeds of milk thistle plants, possesses multiple biological activities and is traditionally applied to treat liver diseases. SIL is also widely used in the treatment of a variety of inflammatory diseases attributed to its excellent antioxidant and anti-inflammatory effects. However, the efficacy of SIL against IBDs and its mechanisms remain unclear. In this study, using Drosophila melanogaster as a model organism, we found that SIL can effectively relieve intestinal inflammation caused by dextran sulfate sodium (DSS). Our results suggested that SIL supplementation can inhibit the overproliferation of intestinal stem cells (ISCs) induced by DSS, protect intestinal barrier function, acid-base balance, and intestinal excretion function, reduce intestinal reactive oxygen species (ROS) levels and inflammatory stress, and extend the lifespan of Drosophila . Furthermore, our study demonstrated that SIL ameliorates intestinal inflammation via modulating the c-Jun N-terminal kinase (JNK) signaling pathway in Drosophila . Our research aims to provide new insight into the treatment of IBDs.
This study aimed to investigate the molecular mechanisms underlying spinal cord ischemia–reperfusion (SCI/R) injury. Through RNA-Seq high-throughput sequencing and bioinformatics analysis, we found that EGFR was downregulated in the spinal cord of SCI/R mice and may function via mediating the JAK2/STAT3 signaling pathway. In vitro cell experiments indicated that overexpression of EGFR activated the JAK2/STAT3 signaling pathway and reduced neuronal apoptosis levels. In vivo animal experiments further confirmed this conclusion, suggesting that EGFR inhibits SCI/R-induced neuronal apoptosis by activating the JAK2/STAT3 signaling pathway, thereby improving SCI/R-induced spinal cord injury in mice. This study revealed the molecular mechanisms of SCI/R injury and provided new therapeutic strategies for treating neuronal apoptosis.
