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

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

Original languageEnglish
Pages (from-to)1022-1030
Number of pages9
JournalJournal of Pharmacy and Pharmacology
Issue number8
Publication statusPublished - Aug 2018

King's Authors


Objectives: Considering the deleterious effect of Aβ1-42, a study was designed to evaluate the effect of phloretin on altered synaptic proteins and adult hippocampal neurogenesis in Aβ1-42-injected Wistar rats. Methods: The rats were pretreated with 5 mg/kg p.o dose of phloretin and donepezil (positive control) for 28 days, followed by intrahippocampal injections of aggregated Aβ1-42. After termination, perfused brains were isolated and subjected to Western blot and immunohistochemistry (IHC) analysis. Key findings: The Western blot revealed that Aβ1-42-injected rats had significantly low levels of synaptophysin as compared to sham control. Phloretin pretreatment significantly protected the presynaptic protein synaptophysin against the effects of Aβ1-42. There were no significant changes in the levels of PSD95 between different groups. The IHC findings showed that Aβ1-42 significantly reduced the Ki67 and DCX in the dentate gyrus as compared to sham control. However, phloretin significantly improved the number of Ki67- and DCX-positive neurons in the dentate gyrus region as compared to Aβ1-42 group. Conclusions: This study demonstrated the protective effect of phloretin on synaptophysin and adult neuronal proliferating cells in Aβ1-42-injected rats. The encouraging findings highlight the potential of phloretin as a dietary supplement targeting key therapeutic mechanisms in neurodegenerative disorders such as AD.

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