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Open AccessArticle

Zingerone Targets Status Epilepticus by Blocking Hippocampal Neurodegeneration via Regulation of Redox Imbalance, Inflammation and Apoptosis

1
Department of Pharmacology & Toxicology, College of Pharmacy Girls Section, Prince Sattam Bin Abdulaziz University, P.O. Box-173, Al-Kharj 11942, Saudi Arabia
2
Department of Pharmaceutical Chemistry, RAK College of Pharmaceutical Sciences, RAK Medical and Health Sciences University, Ras Al Khaimah P.O. Box 11172, United Arab Emirates
3
Division of Veterinary Biochemistry, Faculty of Veterinary Science and Animal Husbandry, SKUAST-Kashmir, Alustang, Shuhama 190006, India
4
Department of Clinical Pharmacy, College of Pharmacy, King Saud University, P.O. Box-2457, Riyadh 11451, Saudi Arabia
5
Department of Zoology, College of Science, King Saud University, P.O. Box-2457, Riyadh 11451, Saudi Arabia
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Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, P.O. Box-2457, Riyadh 11451, Saudi Arabia
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Antoni Camins Espuny
Pharmaceuticals 2021, 14(2), 146; https://doi.org/10.3390/ph14020146
Received: 19 December 2020 / Revised: 4 February 2021 / Accepted: 5 February 2021 / Published: 11 February 2021
(This article belongs to the Special Issue Epilepsy and Neurodegeneration: Current Therapeutic Implications 2021)
Epilepsy is an intricate neurological disease where the neurons are severely affected, leading to the mortality of millions worldwide. Status epilepticus (SE), induced by lithium chloride (LiCl) and pilocarpine, is the most accepted model for epilepsy. The current work aims to unravel the mechanisms underlying the anti-epileptic efficacy of zingerone (an active ingredient of ginger), which has beneficial pharmacological activities on seizure-induced behavioral, histological, neurochemical, and molecular patterns in mice. Zingerone restored cognitive function by diminishing seizure activity, escape latency, and subsequent hippocampal damage manifested in histology. Seizures are associated with local inflammation, redox imbalance, and neural loss, confirmed by the present study of SE, and was attenuated by zingerone treatment. Nuclear factor-kappa B and its downstream signaling molecules (TNF-α, IL-1β, IL-6, NO, MPO) were activated in the LiCl-and-pilocarpine-induced group leading to inflammatory signaling, which was substantially ameliorated by zingerone treatment. The intrinsic apoptotic process was triggered subsequent to SE, as demonstrated by augmentation of cleaved caspase-3, downregulation of Bcl-2. However, zingerone treatment downregulated caspase-3 and upregulated Bcl-2, increasing cell survival and decreasing hippocampal neural death, deciphering involvement of apoptosis in SE. Therefore, zingerone plays an essential role in neuroprotection, probably by precluding oxidative stress, inflammation, and obstructing the mitochondrial pathway of apoptosis. View Full-Text
Keywords: status epilepticus; zingerone; inflammation; apoptosis; caspase-3; Bcl-2; redox status; histology; cognition; NF-κB status epilepticus; zingerone; inflammation; apoptosis; caspase-3; Bcl-2; redox status; histology; cognition; NF-κB
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MDPI and ACS Style

Rashid, S.; Wali, A.F.; Rashid, S.M.; Alsaffar, R.M.; Ahmad, A.; Jan, B.L.; Paray, B.A.; Alqahtani, S.M.A.; Arafah, A.; Rehman, M.U. Zingerone Targets Status Epilepticus by Blocking Hippocampal Neurodegeneration via Regulation of Redox Imbalance, Inflammation and Apoptosis. Pharmaceuticals 2021, 14, 146. https://doi.org/10.3390/ph14020146

AMA Style

Rashid S, Wali AF, Rashid SM, Alsaffar RM, Ahmad A, Jan BL, Paray BA, Alqahtani SMA, Arafah A, Rehman MU. Zingerone Targets Status Epilepticus by Blocking Hippocampal Neurodegeneration via Regulation of Redox Imbalance, Inflammation and Apoptosis. Pharmaceuticals. 2021; 14(2):146. https://doi.org/10.3390/ph14020146

Chicago/Turabian Style

Rashid, Summya; Wali, Adil F.; Rashid, Shahzada M.; Alsaffar, Rana M.; Ahmad, Ajaz; Jan, Basit L.; Paray, Bilal A.; Alqahtani, Saeed M.A.; Arafah, Azher; Rehman, Muneeb U. 2021. "Zingerone Targets Status Epilepticus by Blocking Hippocampal Neurodegeneration via Regulation of Redox Imbalance, Inflammation and Apoptosis" Pharmaceuticals 14, no. 2: 146. https://doi.org/10.3390/ph14020146

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