Inhibition of DPP-4 activity and neuronal atrophy with genistein attenuates neurological deficits induced by transient global cerebral ischemia and reperfusion in streptozotocin-induced diabetic mice

Rajput, Mithun Singh, Sarkar, Purnima Dey and Nirmal, Nilesh Prakash (2017) Inhibition of DPP-4 activity and neuronal atrophy with genistein attenuates neurological deficits induced by transient global cerebral ischemia and reperfusion in streptozotocin-induced diabetic mice. Inflammation, 40 2: 1-13. doi:10.1007/s10753-017-0509-5


Author Rajput, Mithun Singh
Sarkar, Purnima Dey
Nirmal, Nilesh Prakash
Title Inhibition of DPP-4 activity and neuronal atrophy with genistein attenuates neurological deficits induced by transient global cerebral ischemia and reperfusion in streptozotocin-induced diabetic mice
Journal name Inflammation   Check publisher's open access policy
ISSN 1573-2576
0360-3997
Publication date 2017-01-16
Year available 2017
Sub-type Article (original research)
DOI 10.1007/s10753-017-0509-5
Open Access Status Not yet assessed
Volume 40
Issue 2
Start page 1
End page 13
Total pages 13
Place of publication New York, NY, United States
Publisher Springer New York LLC
Language eng
Subject 2723 Immunology and Allergy
2403 Immunology
Abstract Genistein, an isoflavonoid phytoestrogen, has been known for its potential pharmacological properties especially for neuroprotection and treating diabetes. The present study aims to determine the neuroprotective efficacy of genistein against global cerebral ischemia-reperfusion-induced neuronal injury in streptozotocin-induced diabetic mice and explore the underlying mechanisms. Streptozotocin-induced diabetic mice were subjected to transient cerebral ischemia by occluding both common carotid arteries for 30 min followed by 24 h reperfusion to induce neuronal injury. Effect of genistein (2.5, 5.0, and 10.0 mg/kg, i.p., o.d.) treatment on ischemia-reperfusion-induced neuronal injury in diabetic mice was evaluated in terms of cerebral infarct size, oxidative damage, mitochondrial activity in terms of neuronal apoptosis and cellular viability, dipeptidyl peptidase-4 activity and active glucagon-like peptide-1 concentration, and neurological functions measured as short-term memory and motor performance. Genistein administration following transient cerebral ischemia significantly (p ˂ 0.0001) counteracted cognitive impairment and re-established (p ˂ 0.001) motor performance in diabetic mice. Ischemia-reperfusion increased the infarct size, genistein administration prevented the increase in cerebral infarct size (p ˂ 0.0001) and significantly suppressed (p ˂ 0.001) the increase in cerebral oxidative stress in transient cerebral ischemia-reperfusion subjected diabetic mice. Genistein treatment significantly (p ˂ 0.001) reduced neuronal apoptosis and increased cellular viability (p ˂ 0.0001), almost completely suppressed (p ˂ 0.0001) the circulating dipeptidyl peptidase-4 activity, and enhanced (p ˂ 0.0001) glucagon-like peptide-1 concentration in diabetic mice with cerebral ischemia-reperfusion. This study suggests that genistein has potent neuroprotective activity against global cerebral ischemia-reperfusion-induced neuronal injury and consequent neurological deficits in streptozotocin-induced diabetic mice.
Formatted abstract
Genistein, an isoflavonoid phytoestrogen, has been known for its potential pharmacological properties especially for neuroprotection and treating diabetes. The present study aims to determine the neuroprotective efficacy of genistein against global cerebral ischemia-reperfusion-induced neuronal injury in streptozotocin-induced diabetic mice and explore the underlying mechanisms. Streptozotocin-induced diabetic mice were subjected to transient cerebral ischemia by occluding both common carotid arteries for 30 min followed by 24 h reperfusion to induce neuronal injury. Effect of genistein (2.5, 5.0, and 10.0 mg/kg, i.p., o.d.) treatment on ischemia-reperfusion-induced neuronal injury in diabetic mice was evaluated in terms of cerebral infarct size, oxidative damage, mitochondrial activity in terms of neuronal apoptosis and cellular viability, dipeptidyl peptidase-4 activity and active glucagon-like peptide-1 concentration, and neurological functions measured as short-term memory and motor performance. Genistein administration following transient cerebral ischemia significantly (p ˂ 0.0001) counteracted cognitive impairment and re-established (p ˂ 0.001) motor performance in diabetic mice. Ischemia-reperfusion increased the infarct size, genistein administration prevented the increase in cerebral infarct size (p ˂ 0.0001) and significantly suppressed (p ˂ 0.001) the increase in cerebral oxidative stress in transient cerebral ischemia-reperfusion subjected diabetic mice. Genistein treatment significantly (p ˂ 0.001) reduced neuronal apoptosis and increased cellular viability (p ˂ 0.0001), almost completely suppressed (p ˂ 0.0001) the circulating dipeptidyl peptidase-4 activity, and enhanced (p ˂ 0.0001) glucagon-like peptide-1 concentration in diabetic mice with cerebral ischemia-reperfusion. This study suggests that genistein has potent neuroprotective activity against global cerebral ischemia-reperfusion-induced neuronal injury and consequent neurological deficits in streptozotocin-induced diabetic mice.
Keyword Brain atrophy
Cerebral ischemia
DPP-4
Genistein
GLP-1
Mitochondrial function
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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