PMID- 29277879 OWN - NLM STAT- MEDLINE DCOM- 20190205 LR - 20190215 IS - 1573-7365 (Electronic) IS - 0885-7490 (Linking) VI - 33 IP - 3 DP - 2018 Jun TI - Trigonelline insulates against oxidative stress, proinflammatory cytokines and restores BDNF levels in lipopolysaccharide induced cognitive impairment in adult mice. PG - 681-691 LID - 10.1007/s11011-017-0147-5 [doi] AB - 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 mug/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-alpha) and interleukin -6 (IL-6) levels, whereas brain derived neurotrophic factor (BDNF) levels were significantly depleted. TRG pretreatment led to decreased TNF-alpha 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. FAU - Chowdhury, Amrita A AU - Chowdhury AA AD - Department of Pharmaceutical Sciences and Technology (DPST), Institute of Chemical Technology (ICT), N. P. Marg, Matunga (E), Mumbai, -400019, India. FAU - Gawali, Nitin B AU - Gawali NB AD - Department of Pharmaceutical Sciences and Technology (DPST), Institute of Chemical Technology (ICT), N. P. Marg, Matunga (E), Mumbai, -400019, India. FAU - Munshi, Renuka AU - Munshi R AD - Department of Clinical Pharmacology, B. Y. L. Nair Charitable Hospital and Topiwala National Medical College, Dr. A. L. Nair Road, Mumbai, 400008, India. FAU - Juvekar, Archana R AU - Juvekar AR AD - Department of Pharmaceutical Sciences and Technology (DPST), Institute of Chemical Technology (ICT), N. P. Marg, Matunga (E), Mumbai, -400019, India. juvekar.archana@gmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20171226 PL - United States TA - Metab Brain Dis JT - Metabolic brain disease JID - 8610370 RN - 0 (Alkaloids) RN - 0 (Antioxidants) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Cytokines) RN - 0 (Lipopolysaccharides) RN - 3NQ9N60I00 (trigonelline) SB - IM MH - Alkaloids/*pharmacology MH - Animals MH - Antioxidants/pharmacology MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Cognitive Dysfunction/chemically induced/*metabolism MH - Cytokines/*metabolism MH - Disease Models, Animal MH - Hippocampus/drug effects/metabolism MH - Lipopolysaccharides/pharmacology MH - Male MH - Memory Disorders/drug therapy MH - Mice MH - Oxidative Stress/*drug effects OTO - NOTNLM OT - Brain derived neurotrophic factor OT - Lipopolysaccharide OT - Neuroinflammation OT - Oxidative stress OT - Trigonelline EDAT- 2017/12/27 06:00 MHDA- 2019/02/06 06:00 CRDT- 2017/12/27 06:00 PHST- 2017/08/02 00:00 [received] PHST- 2017/11/07 00:00 [accepted] PHST- 2017/12/27 06:00 [pubmed] PHST- 2019/02/06 06:00 [medline] PHST- 2017/12/27 06:00 [entrez] AID - 10.1007/s11011-017-0147-5 [pii] AID - 10.1007/s11011-017-0147-5 [doi] PST - ppublish SO - Metab Brain Dis. 2018 Jun;33(3):681-691. doi: 10.1007/s11011-017-0147-5. Epub 2017 Dec 26.