Curcumin Targets the Spleen–Brain Axis in Diabetes: A Comparative Study with Liraglutide via JAK2/STAT3 Signaling

Abstract

Diabetes mellitus causes damage to most body organs owing to induced inflammation and immune dysregulation. The spleen and brain are two significant organs affected in diabetes. Curcumin is a natural polyphenol known for its anti-inflammatory, anti-oxidant, and neuroprotective effects. The current research aims to compare the effects of curcumin to liraglutide in alloxan-induced diabetic rats. While the anti-diabetic, anti-inflammatory, and neuroprotective effects of curcumin and liraglutide are well recognized, this study is the first one comparing them on the spleen–brain axis in diabetes. A common mechanistic target, the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway, was investigated. Unprecedented insights that have not previously been detected can be obtained from this comparative framework and pathway. The aim of the current quest is to investigate and compare the anti-oxidative, anti-inflammatory, and neuroprotective potential of curcumin and liraglutide within the spleen–brain axis in an alloxan-induced diabetic rat model, emphasizing the modulation of the JAK2/STAT3 signaling pathway. Male Wistar rats were used in the study, where there were four groups, each contained 10 animals. The four groups were as follows: normal control, diabetic control, a group treated with curcumin (250 mg/kg), and a group treated with liraglutide (1 mg/kg). For diabetes induction, alloxan (150 mg/kg) was used. Biochemical and histological analyses were conducted accordingly. Curcumin enhanced glucose homeostasis, increased serum insulin and glucagon-like peptide-1 levels, as well as anti-oxidant activity, while reducing inflammation. In the meantime, it increased the levels of dopamine, brain-derived neurotrophic factor, tropomyosin receptor kinase B, and cyclic AMP response element-binding protein while lowering amyloid-beta levels. Both treatments modulated the JAK2/STAT3 pathway and kept the histopathological architecture of the tissue. From the current findings, curcumin has multiple therapeutic targets as an alternative to liraglutide and may possess the capacity to modulate neuroimmune dysfunction in diabetes by protecting the spleen–brain axis through JAK2/STAT3 modulation. Curcumin demonstrates therapeutic potential comparable to liraglutide in safeguarding against diabetes-induced splenic and cerebral damage.