Trigonelline insulates against oxidative stress, proinflammatory cytokines and restores BDNF levels in lipopolysaccharide induced cognitive impairment in adult mice

Abstract

Neuroinflammation is said to play a pivotal role in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). Trigonelline (TRG) is a naturally occurring alkaloid, commonly isolated from fenugreek and coffee beans. In the present study, we investigated whether TRG exerts neuroprotective action against LPS mediated cognitive impairment. Mice pretreated with TRG (50 and 100 mg/kg po) were administered with LPS (250 μg/kg ip) for 7 days. Memory was assessed in the Morris water maze (MWM) and Y maze. LPS administration caused poor memory retention in MWM and Y maze paradigms, and resulted in marked oxidative stress as evidenced by decrease in superoxide dismutase (SOD), reduced glutathione (GSH) levels and increased lipid peroxidation in the hippocampus and cortex. Cholinergic involvement during neuroinflammation was evaluated by measuring levels of acetylcholinesterase (AChE) enzyme. TRG treatment at both the doses reversed LPS induced behavioral and memory disturbances, significantly decreased the oxidative stress and AChE levels in both the hippocampus and cortex. LPS administration also elevated the tumour necrosis factor (TNF-α) and interleukin -6 (IL-6) levels, whereas brain derived neurotrophic factor (BDNF) levels were significantly depleted. TRG pretreatment led to decreased TNF-α and IL-6 levels and caused a significant upregulation of BDNF levels. In conclusion, present study highlights the promising neuroprotective role of TRG against LPS mediated cognitive impairment which could be attributed to reduced oxidative stress, inhibition of proinflammatory cytokines and restoration of BDNF levels.

Trigonelline through the Attenuation of Oxidative Stress Exerts Antidepressant- and Anxiolytic-Like Effects in a Mouse Model of Maternal Separation Stress

“…Literature searching showed that the TRG has various pharmacological effects including hypoglycemic, hypolipidemic, neuroprotective, antimigraine, sedative, and memory-improving activities [24,[58][59][60]. Recently, it has been determined that TRG through the attenuation of oxidative stress and mitigation of neuroinflammation exerted a neuroprotective effect against LPS-mediated cognitive impairment [27]. We showed that the administration of TRG significantly reversed depressive-and anxiety-like behaviors of MS. We observed that TRG significantly decreased immobility time in the FST, increased grooming activity time in the splash test, and increased both open arm time and open time entries in the EPM of the MS mice.…”

“…TRG is a pyridine alkaloid isolated from coffee beans, fenugreek seeds, and so on, [55]. TRG exerted a neuroprotective action in a rodent model of Parkinson's disease [56] and also reversed cognitive impairment in mice model of Alzheimer's disease [27]. Tohda et al [57], reported that TRG stimulates functional neurite outgrowth.…”

“…At the end of the study, blood samples were taken and the hippocampi were separated for biochemical assessments. Doses of TRG, fluoxetine, and vitamin E were chosen according to our pilot study and also previous studies [24,[27][28][29]. Each mouse was used only once in each test.…”

Trigonelline reduced diabetic nephropathy and insulin resistance in type�2 diabetic rats through peroxisome proliferator‑activated receptor‑γ

“…The results of the present study suggested that trigonelline significantly reduced BUN, creatinine and albumin levels, indicating reduced inflammation in T2DM rats. Furthermore, Chowdhury et al (15) demonstrated that trigonelline protects against oxidative stress and proinflammatory cytokines in lipopolysaccharide-induced cognitive impairment in adult mice.…”

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“…on mesenchymal stem cells to assess morphological changes that occur in response to the differentiation induction. Trigonelline has been known to exhibit medicinal properties like inhibition of adipocyte differentiation 9 , anticarcinogenic 10,11,12 , anti-hypercholesterolemia 13 , anti-diabetic and hypoglycemic 13,14,15 , antioxidant 10,16 , anti-apoptotic 17 activities and may help to prevent or at least increase the age when one suffers from obesity and associated effects.…”