The effect of phloretin on synaptic proteins and adult hippocampal neurogenesis in Aβ (1-42)-injected male Wistar rats

Ghumatkar, Priya; Peshattiwar, Vaibhavi; Patil, Sachin; Muke, Suraj; Whitfield, David; Howlett, David; Francis, Paul T.; Sathaye, Sadhana

doi:10.1111/jphp.12925

Cited by 12 publications

(3 citation statements)

References 40 publications

(98 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This phytopolyphenol has been shown to have significant antioxidant properties and might, therefore, be useful in treating pathogenic conditions that have oxidative stress as a common mechanism (de Oliveira, 2016; Jiang et al, 2010). Indeed, some evidence suggests that Phl is a pharmacotherapeutic approach to cardiovascular disease (Stangl et al, 2005), cancer (Ma et al, 2016), ischemia-reperfusion injury (Liu et al, 2015) and neurodegeneration (Ghumatkar et al, 2018). In this regard, we have previously shown that Phl prevented electrophile (e.g., acrolein)-induced nerve terminal toxicity (LoPachin et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Phloretin cytoprotection and toxicity

Geohagen

Korsharskyy

Vydyanatha

et al. 2018

Chemico-Biological Interactions

View full text Add to dashboard Cite

Phloretin (Phl) is a dihydrochalcone flavonoid with significant cytoprotective properties; e.g., free radical trapping, electrophile scavenging. Based on this, it has been suggested that Phl might be useful in the treatment of pathogenic processes and prevention of drug toxicities. Therefore, we determined the ability of Phl to provide route- and dose-dependent hepatoprotection in a mouse model of acetaminophen (APAP) overdose. Intraperitoneal (i.p.) administration of Phl produced a bimodal effect; i.e., the highest dose (2.40 mmol/kg) did not prevent APAP-induced lethality, whereas lower doses (0.2 – 0.4 mmol/kg) afforded modest hepatoprotection. When given alone, the highest i.p. Phl dose was lethal within 24 hrs, whereas the lower doses were not toxic. Oral Phl (0.40 – 2.40 mmol/kg) did not prevent APAP-induced hepatotoxicity. The highest oral dose given alone (2.4 mmol/kg) produced 64% lethality, whereas lower doses were not lethal. This toxicity profile was reflected in a study using APAP-exposed isolated mouse hepatocytes, which showed that the Phl pharmacophores, 1,3,5-trihydroxyacetophenone (PG) and 2’,4’,6’-trihydroxyacetophenone (THA) where protective. Corroborative cell free studies showed that polyphenol protectants prevented glutathione loss mediated by the APAP metabolite, N-acetyl-p-benzoquinone imine (NAPQI). Thus, in spite of possesing cytoprotective attributes, Phl was generally toxic in our APAP models. These and earlier findings suggest that Phl is not a candidate for drug design. In contrast, we have found that the enol-forming pharmacophores, THA and PG, are potential platforms for pharmacotherapeutic development.

show abstract

Section: Introductionmentioning

confidence: 99%

Phloretin cytoprotection and toxicity

Geohagen

Korsharskyy

Vydyanatha

et al. 2018

Chemico-Biological Interactions

View full text Add to dashboard Cite

show abstract

“…Quercetin (40 mg/kg/day) recovered the learning and memory performance in Alzheimer animal model by promoting neural stem/progenitor proliferation 10 . Similarly, phloretin significantly increased the proliferation of DCX‐positive neuron in the DG in β‐amyloid induced Alzheimer mice 35 . Our results showed that NLPE and NLWE increased DCX‐positive neuron, nestin‐positive neural progenitor cells, and NeuN‐positive matured neuron cells in the DG, CA3, and CA1 regions, suggesting NLPE and NLWE promoted AHN in scopolamine‐treated mice.…”

Section: Discussionmentioning

confidence: 98%

“…10 Similarly, phloretin significantly increased the proliferation of DCX-positive neuron in the DG in β-amyloid induced Alzheimer mice. 35 Upon binding to their receptors, neurotrophic factors, such as BDNF, nerve growth factor-activated downstream targets to trigger neuron differentiation, neural proliferation, and synapse formation. 28,36 BDNF abundantly expressed in the hippocampus and front cortex plays a pivotal role in memory and learning.…”

Section: Nlwe and Q3g Recovered Neurogenesis And Bdnf Downstream Sign...mentioning

confidence: 99%

Nelumbo nucifera leaves extract ameliorated scopolamine‐induced cognition impairment via enhanced adult hippocampus neurogenesis

Lee,

Lin,

Chang

et al. 2024

Environmental Toxicology

View full text Add to dashboard Cite

In this presentation, we explored the molecular mechanisms of N. nucifera leaf water extracts (NLWEs) and polyphenol extract (NLPE) on scopolamine‐induced cell apoptosis and cognition defects. The administration of NLWE and NLPE did not alter the body weight and serum biomarker rs and significantly ameliorated scopolamine‐induced cognition impairment according to Y‐maze test analysis. In mice, treatment with scopolamine disrupted normal histoarchitecture in the hippocampus, whereas the administration of NLWE and NLPE reversed the phenomenon. Western blot analysis revealed that scopolamine mitigated the expression of doublecortin (DCX), nestin, and NeuN, and cotreatment with NLWE or NLPE significantly recovered the expression of these proteins. NLWE and NLPE upregulated DCX and NeuN expression in the hippocampus region, as evidenced by immunohistochemical staining analysis of scopolamine‐treated mice. NLWE and NLPE obviously elevated brain‐derived neurotrophic factor (BDNF) and enhanced its downstream proteins activity. NLWE and NLPE attenuated scopolamine‐induced apoptosis by reducing Bax and increased Bcl‐2 expression. In addition, scopolamine also triggered apoptosis in human neuroblastoma SH‐SY5Y cells whereas co‐treatment with NLWE or quercetin‐3‐glucuronide (Q3G) reversed the phenomenon. NLWE or Q3G enhanced Bcl‐2 and reduced Bax expression in the presence of scopolamine in SH‐SY5Y cells. NLWE or Q3G recovered the inhibitory effects of scopolamine on neurogenesis and BDNF signals in SH‐SY5Y cells. Overall, our results revealed that N. nucifera leaf extracts and Q3G promoted adult hippocampus neurogenesis and prevented apoptosis to mitigate scopolamine‐induced cognition dysfunction through the regulation of BDNF signaling pathway.

show abstract

Phloretin: Advances on Resources, Biosynthesis Pathway, Bioavailability, Bioactivity, and Pharmacology

Trifan,

Luca

2023

Handbook of Dietary Flavonoids

View full text Add to dashboard Cite

The effect of phloretin on synaptic proteins and adult hippocampal neurogenesis in Aβ (1-42)-injected male Wistar rats

Cited by 12 publications

References 40 publications

Phloretin cytoprotection and toxicity

Phloretin cytoprotection and toxicity

Nelumbo nucifera leaves extract ameliorated scopolamine‐induced cognition impairment via enhanced adult hippocampus neurogenesis

Phloretin: Advances on Resources, Biosynthesis Pathway, Bioavailability, Bioactivity, and Pharmacology

Contact Info

Product

Resources

About