The modulatory role of phloretin in Aβ25–35 induced sporadic Alzheimer’s disease in rat model

Ghumatkar, Priya; Patil, Sachin; Peshattiwar, Vaibhavi; Vijaykumar, Tushara; Dighe, Vikas; Vanage, Geeta; Sathaye, Sadhana

doi:10.1007/s00210-018-1588-z

Cited by 25 publications

(9 citation statements)

References 50 publications

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“…It can reflect the changes of morphological structure and function of neurons. 47 In this study, the obvious histological changes of neurons in rats with trigeminal neuralgia were observed by Nissl staining, which is another direct and strong evidence that trigeminal neuralgia causes neurodegeneration in rats.…”

Section: Discussionsupporting

confidence: 55%

Trigeminal neuralgia causes neurodegeneration in rats associated with upregulation of the CD95/CD95L pathway

et al. 2020

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Objectives: To explore the effects of trigeminal neuralgia on neurodegeneration in rats and the underlining mechanism. Methods: Sixty adult male Sprague Dawley rats were divided randomly into Chronic Constriction Injury of the Rat's Infraorbital Nerve (ION-CCI) group and sham group (n ¼ 30). Right suborbital nerve was ligated in ION-CCI group to establish a trigeminal neuralgia model. In sham group, suborbital nerve was exposed without ligation. Pain thresholds were measured before surgery and 1, 7, 15, and 30 days after surgery (n ¼ 10). Morris water maze tests (n ¼ 10) were conducted at 1, 15, and 30 days after surgery to evaluate the changes in learning and memory ability of rats. At 5, 19, and 34 days after surgery, serum S100b protein concentration and hippocampal Ab1-42 protein expression were detected by enzyme-linked immunosorbent assay; total tau protein expression was detected by Western blotting; changes of neurons in hippocampus were observed by Nissl staining; and the expression of ser404 p-tau, cluster of differentiation (CD)95, CD95L, and cleaved caspase-3 proteins was detected by immunofluorescence and Western blotting. Results: Hyperalgesia occurred in ION-CCI group, and mechanical pain threshold decreased significantly (P < 0.05). On the 15th and 30th days after surgery, ION-CCI group showed lower learning and memory ability than sham group (P < 0.05). Serum S100b protein concentration, hippocampal A b1-42, and ser404 p-tau protein expression increased in the ION-CCI group 19 and 34 days after surgery (P < 0.05), hippocampal CD95 expression increased in the ION-CCI group after surgery (P < 0.05), hippocampal CD95L expression increased at 19 and 34 days after surgery (P < 0.05), and cleaved caspase-3 expression increased at 5 and 19 days after surgery (P < 0.05). Nissl bodies in ION-CCI group decreased significantly at 15 days after surgery. The expression of cleaved caspase-3 protein in ION-CCI group was positively correlated with the expression of CD95 and CD95L (P < 0.05). Conclusions: Trigeminal neuralgia may lead to neuronal inflammation and neuronal apoptosis associated with upregulation of CD95/CD95L expression, thus causing neurodegeneration.

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Section: Discussionsupporting

confidence: 55%

Trigeminal neuralgia causes neurodegeneration in rats associated with upregulation of the CD95/CD95L pathway

et al. 2020

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“…It is likely that the neuroprotective effect of ormosanine is attributable to its antioxidant property. Oxidative stress enhances the synthesis and release of inflammatory cytokines, which in turn cause neuronal cell injury and apoptosis [18]. The results of this study showed that ormosanine reduces the levels of cytokines, an indication that the crude drug may possess anti-inflammatory effect.…”

Section: Discussionmentioning

confidence: 58%

“…There are several pathogenic factors involved in the development of AD including cytokine and oxidative stress [18]. Neuronal injury occurs due to imbalance between levels of antioxidant molecules and reactive oxygen species.…”

Section: Discussionmentioning

confidence: 99%

Ormosanine confers protection on neuronal function via regulation of inflammatory cytokine levels and oxidative stress

Liang¹,

Dong²,

Yang³

2022

Trop. J. Pharm Res

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Purpose: To investigate the neuroprotective effect of ormosanine on rat model of Alzheimer’s disease (AD), and the mechanism(s) of action involved. Methods: Rats were randomly assigned to 4 groups (10 rats/group): control group, AD group, 25 mg ormosanine/kg group, and 50 mg ormosanine/kg group. Alzheimer’s disease (AD) was induced in the rats via intracerebroventricular (ICV) injection of amyloid-β (Aβ)25-35 at a concentration of 1 mg/mL. Cognitive function was determined by Morris water maze test (MWMT), while lipid profile, oxidative stress parameters and cytokine level were assayed using their respective assay kits. The levels of monoamines were determined in brain tissues using high-performance liquid chromatography (HPLC), while terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to determine apoptosis in neuronal cells. Results: Cognitive function was significantly improved (p < 0.05) in ormosanine treated group than AD group of rats. Ormosanine significantly and dose-dependently reduced lipid and cytokines levels as well as activities of AST and ALT, but it significantly increased the level of HDL-C in a dose-dependent fashion (p < 0.05). Moreover, ormosanine significantly and dose-dependently increased SOD activity, but reduced MDA level and neuronal cell apoptosis in brain tissues of AD rats (p < 0.05). Treatment of AD rats with ormosanine led to significant and dose-dependent increase in the levels of monoamines and BDNF in rat brain tissues (p < 0.05). Conclusion: These results show that ormosanine confers protection on neuronal function via regulation of inflammatory cytokine levels and oxidative stress, and therefore, could potentially be developed for the management of Alzheimer’s disease.

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“…In other disease models, phloretin was also reported to exert neuroprotective and immune-modulatory features. In particular, phloretin was found to activate the Nrf2 pathway in the brain upon cerebral ischemia and decrease amyloid beta accumulation in the rat Alzheimer’s disease model [ 80 – 84 ]. Phloretin might also affect other immune cells in vivo, as this compound has been found to inhibit T cell and dendritic cell activation in vitro [ 85 , 86 ].…”

Section: Discussionmentioning

confidence: 99%

Phloretin suppresses neuroinflammation by autophagy-mediated Nrf2 activation in macrophages

Dierckx

Haidar

Grajchen

et al. 2021

J Neuroinflammation

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Background Macrophages play a dual role in neuroinflammatory disorders such as multiple sclerosis (MS). They are involved in lesion onset and progression but can also promote the resolution of inflammation and repair of damaged tissue. In this study, we investigate if and how phloretin, a flavonoid abundantly present in apples and strawberries, lowers the inflammatory phenotype of macrophages and suppresses neuroinflammation. Methods Transcriptional changes in mouse bone marrow-derived macrophages upon phloretin exposure were assessed by bulk RNA sequencing. Underlying pathways related to inflammation, oxidative stress response and autophagy were validated by quantitative PCR, fluorescent and absorbance assays, nuclear factor erythroid 2–related factor 2 (Nrf2) knockout mice, western blot, and immunofluorescence. The experimental autoimmune encephalomyelitis (EAE) model was used to study the impact of phloretin on neuroinflammation in vivo and confirm underlying mechanisms. Results We show that phloretin reduces the inflammatory phenotype of macrophages and markedly suppresses neuroinflammation in EAE. Phloretin mediates its effect by activating the Nrf2 signaling pathway. Nrf2 activation was attributed to 5′ AMP-activated protein kinase (AMPK)-dependent activation of autophagy and subsequent kelch-like ECH-associated protein 1 (Keap1) degradation. Conclusions This study opens future perspectives for phloretin as a therapeutic strategy for neuroinflammatory disorders such as MS. Trial registration Not applicable.

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The modulatory role of phloretin in Aβ25–35 induced sporadic Alzheimer’s disease in rat model

Cited by 25 publications

References 50 publications

Trigeminal neuralgia causes neurodegeneration in rats associated with upregulation of the CD95/CD95L pathway

Trigeminal neuralgia causes neurodegeneration in rats associated with upregulation of the CD95/CD95L pathway

Ormosanine confers protection on neuronal function via regulation of inflammatory cytokine levels and oxidative stress

Phloretin suppresses neuroinflammation by autophagy-mediated Nrf2 activation in macrophages

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