PMID- 37209564 OWN - NLM STAT- MEDLINE DCOM- 20230606 LR - 20240210 IS - 1090-2104 (Electronic) IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 667 DP - 2023 Jul 30 TI - Neuroprotective effect of herbal extracts inhibiting soluble epoxide hydrolase (sEH) and cyclooxygenase (COX) against chemotherapy-induced cognitive impairment in mice. PG - 64-72 LID - S0006-291X(23)00564-8 [pii] LID - 10.1016/j.bbrc.2023.05.008 [doi] AB - Chemotherapy-induced cognitive impairment (CICI) is a novel clinical condition characterized by memory, learning, and motor function deficits. Oxidative stress and inflammation are potential factors contributing to chemotherapy's adverse effects on the brain. Inhibition of soluble epoxide hydrolase (sEH) has been proven effective in neuroinflammation and reversal of memory impairment. The research aims to evaluate the memory protective effect of sEH inhibitor and dual inhibitor of sEH and COX and compare its impact with herbal extracts with known nootropic activity in an animal model of CICI. In vitro sEH, the inhibitory activity of hydroalcoholic extracts of Sizygium aromaticum, Nigella sativa, and Mesua ferrea was tested on murine and human sEH enzyme as per the protocol, and IC(50) was determined. Cyclophosphamide (50 mg/kg), methotrexate (5 mg/kg), and fluorouracil (5 mg/kg) combination (CMF) were administered intraperitoneally to induce CICI. The known herbal sEH inhibitor, Lepidium meyenii and the dual inhibitor of COX and sEH (PTUPB) were tested for their protective effect in the CICI model. The herbal formulation with known nootropic activity viz Bacopa monnieri and commercial formulation (Mentat) were also used to compare the efficacy in the CICI model. Behavioral parameter such as cognitive function was assessed by Morris Water Maze besides investigating oxidative stress (GSH and LPO) and inflammatory (TNFalpha, IL-6, BDNF and COX-2) markers in the brain. CMF-induced CICI, which was associated with increased oxidative stress and inflammation in the brain. However, treatment with PTUPB or herbal extracts inhibiting sEH preserved spatial memory via ameliorating oxidative stress and inflammation. S. aromaticum and N. sativa inhibited COX2, but M. Ferrea did not affect COX2 activity. Lepidium meyenii was the least effective, and mentat showed superior activity over Bacopa monnieri in preserving memory. Compared to untreated animals, the mice treated with PTUPB or hydroalcoholic extracts showed a discernible improvement in cognitive function in CICI. CI - Copyright (c) 2023. Published by Elsevier Inc. FAU - Kulkarni, Rachana AU - Kulkarni R AD - Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru, 570015, India. FAU - Mehta, Richa AU - Mehta R AD - Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru, 570015, India. FAU - Goswami, Sumanta Kumar AU - Goswami SK AD - Department of Entomology and Nematology, UC Davis Comprehensive Cancer Center, University of California Davis, Davis, CA, United States. FAU - Hammock, Bruce D AU - Hammock BD AD - Department of Entomology and Nematology, UC Davis Comprehensive Cancer Center, University of California Davis, Davis, CA, United States. FAU - Morisseau, Christophe AU - Morisseau C AD - Department of Entomology and Nematology, UC Davis Comprehensive Cancer Center, University of California Davis, Davis, CA, United States. FAU - Hwang, Sung Hee AU - Hwang SH AD - Department of Entomology and Nematology, UC Davis Comprehensive Cancer Center, University of California Davis, Davis, CA, United States. FAU - Mallappa, Onkaramurthy AU - Mallappa O AD - Discovery Sciences Group, R&D Centre, Himalaya Wellness Company, Makali, Bengaluru, 562162, India. FAU - Azeemuddin, Mohammed Mukhram AU - Azeemuddin MM AD - Discovery Sciences Group, R&D Centre, Himalaya Wellness Company, Makali, Bengaluru, 562162, India. FAU - Rafiq, Mohamed AU - Rafiq M AD - Discovery Sciences Group, R&D Centre, Himalaya Wellness Company, Makali, Bengaluru, 562162, India. FAU - S N, Manjula AU - S N M AD - Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Mysuru, 570015, India. Electronic address: snmanjula@jssuni.edu.in. LA - eng GR - P42 ES004699/ES/NIEHS NIH HHS/United States GR - R35 ES030443/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20230503 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - 0 (Neuroprotective Agents) RN - EC 3.3.2.- (Epoxide Hydrolases) RN - 0 (Nootropic Agents) SB - IM MH - Humans MH - Mice MH - Animals MH - Cyclooxygenase 2 MH - *Neuroprotective Agents/pharmacology/therapeutic use MH - Epoxide Hydrolases MH - *Chemotherapy-Related Cognitive Impairment MH - *Nootropic Agents MH - Inflammation PMC - PMC10849156 MID - NIHMS1960598 OTO - NOTNLM OT - Chemotherapy-induced cognitive impairments OT - Lepidium meyenii OT - Mesua ferrea OT - Nigella sativa OT - Sizygium aromaticum OT - sEH COIS- Declaration of competing interest Bruce D. Hammock, SungHee Hwang and Christophe Morisseau have patents regarding use of sEH inhibitors. EDAT- 2023/05/21 01:05 MHDA- 2023/06/06 06:42 PMCR- 2024/07/30 CRDT- 2023/05/20 18:06 PHST- 2023/04/15 00:00 [received] PHST- 2023/04/18 00:00 [revised] PHST- 2023/05/02 00:00 [accepted] PHST- 2024/07/30 00:00 [pmc-release] PHST- 2023/06/06 06:42 [medline] PHST- 2023/05/21 01:05 [pubmed] PHST- 2023/05/20 18:06 [entrez] AID - S0006-291X(23)00564-8 [pii] AID - 10.1016/j.bbrc.2023.05.008 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2023 Jul 30;667:64-72. doi: 10.1016/j.bbrc.2023.05.008. Epub 2023 May 3.