Attenuation of Aluminum Chloride-Induced Neuroinflammation and Caspase Activation Through the AKT/GSK-3β Pathway by Hesperidin in Wistar Rats

Arokiasamy Justin-Thenmozhi, Mathiyazahan Dhivya Bharathi, Ramaraj Kiruthika, Thamilarasan Manivasagam, Anupom Borah, Musthafa Mohamed Essa

Research output: Contribution to journalArticle

7 Citations (Scopus)


Hesperidin, a flavanoglycone abundantly present in citrus fruits, is reported to have antioxidant, anti-inflammatory, and neuroprotective properties. Previous reports from our laboratory indicated the neuroprotective effect of hesperidin against aluminum chloride (AlCl3)-induced memory loss, acetylcholine esterase hyperactivity, oxidative stress, and enhanced expression of amyloid β protein biosynthesis-related markers. However, their role on AlCl3-induced inflammation, caspase activation, Tau pathology, altered Akt/GSK 3β signaling pathway, and Aβ clearance marker has not yet been fully elucidated. Intraperitonial injection of AlCl3 (100 mg/kg body weight) for 60 days significantly elevated the expressions of insulin-degrading enzyme (IDE), cyclin-dependent kinase 5 (CDK 5), and phosphoTau (pTau); inflammatory markers such as glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1 (Iba-1), NF-kB, cyclooxygenase-2 (COX-2), interleukin (IL)-1β, IL-4, IL-6, tumor necrosis factor-alpha (TNF-α), inducible nitric oxide synthase (iNOS); and apoptotic markers including cytosolic cytochrome c (cyto c), caspase-3, caspase-8, and caspase-9, and lowered expressions of mitochondrial cyto c, phospho-Akt (pAkt) and phospho-glycogen synthase kinase-3β (pGSK-3β) in the hippocampus and cortex. Co-administration of hesperidin to AlCl3 rats for 60 days significantly ameliorated the aluminum-induced pathological changes. The behavioral studies also supported the above findings. Our results imply that treatment with hesperidin might be a potent option for treating the symptoms of cognitive impairment in Alzheimer’s disease by targeting its most prominent hallmarks.

Original languageEnglish
Pages (from-to)1-14
Number of pages14
JournalNeurotoxicity Research
Publication statusAccepted/In press - Apr 23 2018



  • Akt/GSK 3β signaling pathway
  • Aluminum
  • Alzheimer’s disease
  • Hesperidin
  • Inflammation
  • Tau pathology

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

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