<i>Hypericum perforatum</i> L. Nanoemulsion Mitigates Cisplatin-Induced Chemobrain via Reducing Neurobehavioral Alterations, Oxidative Stress, Neuroinflammation, and Apoptosis in Adult Rats

Cisplatin (Cis) is a potent chemotherapeutic agent; however, it is linked with oxidative stress, inflammation, and apoptosis, which may harmfully affect the brain. <i>Hypericum perforatum</i> L. (HP L.) is a strong medicinal plant, but its hydrophobic polyphenolic compounds limit its act...

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Main Authors: Heba M. A. Khalil, Hanan M. A. El Henafy, Islam A. Khalil, Alaa F. Bakr, Mohamed I. Fahmy, Nancy S. Younis, Riham A. El-Shiekh
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:Toxics
Subjects:
Online Access:https://www.mdpi.com/2305-6304/11/2/159
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author Heba M. A. Khalil
Hanan M. A. El Henafy
Islam A. Khalil
Alaa F. Bakr
Mohamed I. Fahmy
Nancy S. Younis
Riham A. El-Shiekh
author_facet Heba M. A. Khalil
Hanan M. A. El Henafy
Islam A. Khalil
Alaa F. Bakr
Mohamed I. Fahmy
Nancy S. Younis
Riham A. El-Shiekh
author_sort Heba M. A. Khalil
collection DOAJ
description Cisplatin (Cis) is a potent chemotherapeutic agent; however, it is linked with oxidative stress, inflammation, and apoptosis, which may harmfully affect the brain. <i>Hypericum perforatum</i> L. (HP L.) is a strong medicinal plant, but its hydrophobic polyphenolic compounds limit its activity. Therefore, our study aimed to investigate the neuroprotective action of HP L. and its nanoemulsion (NE) against Cis-induced neurotoxicity. The prepared HP.NE was subjected to characterization. The droplet size distribution, surface charge, and morphology were evaluated. In addition, an in vitro dissolution study was conducted. Compared to Cis-intoxicated rats, HP L. and HP.NE-treated rats displayed improved motor activity and spatial working memory. They also showed an increase in their antioxidant defense system and a reduction in the levels of pro-inflammatory cytokines in the brain. Moreover, they showed an increase in the expression levels of the PON-3 and GPX genes, which are associated with a reduction in the brain levels of COX-2 and TP-53. These findings were confirmed by reducing the immunohistochemical expression of nuclear factor kappa (NF-ƘB) and enhanced Ki-67 levels. In conclusion, HP L. is a promising herb and could be used as an adjuvant candidate to ameliorate chemotherapeutic-induced neurotoxicity. Moreover, HP.NE has superior activity in lessening Cis-induced oxidative stress, inflammation, and apoptosis in brain tissue.
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spelling doaj.art-d367271d9b6c4bc694e20f2e0c7965ce2023-11-16T23:37:45ZengMDPI AGToxics2305-63042023-02-0111215910.3390/toxics11020159<i>Hypericum perforatum</i> L. Nanoemulsion Mitigates Cisplatin-Induced Chemobrain via Reducing Neurobehavioral Alterations, Oxidative Stress, Neuroinflammation, and Apoptosis in Adult RatsHeba M. A. Khalil0Hanan M. A. El Henafy1Islam A. Khalil2Alaa F. Bakr3Mohamed I. Fahmy4Nancy S. Younis5Riham A. El-Shiekh6Department of Veterinary Hygiene and Management, Faculty of Veterinary Medicine, Cairo University, Giza 12211, EgyptMedical Laboratory Department, Faculty of Applied Medical Sciences, October 6 University, Giza 3230911, EgyptDepartment of Pharmaceutics, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University of Science and Technology (MUST), Giza 12582, EgyptDepartment of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza 12211, EgyptDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Heliopolis University, Cairo 2834, EgyptDepartment of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi ArabiaDepartment of Pharmacognosy, Faculty of Pharmacy, Cairo University, Kasr el Aini St., Cairo 11562, EgyptCisplatin (Cis) is a potent chemotherapeutic agent; however, it is linked with oxidative stress, inflammation, and apoptosis, which may harmfully affect the brain. <i>Hypericum perforatum</i> L. (HP L.) is a strong medicinal plant, but its hydrophobic polyphenolic compounds limit its activity. Therefore, our study aimed to investigate the neuroprotective action of HP L. and its nanoemulsion (NE) against Cis-induced neurotoxicity. The prepared HP.NE was subjected to characterization. The droplet size distribution, surface charge, and morphology were evaluated. In addition, an in vitro dissolution study was conducted. Compared to Cis-intoxicated rats, HP L. and HP.NE-treated rats displayed improved motor activity and spatial working memory. They also showed an increase in their antioxidant defense system and a reduction in the levels of pro-inflammatory cytokines in the brain. Moreover, they showed an increase in the expression levels of the PON-3 and GPX genes, which are associated with a reduction in the brain levels of COX-2 and TP-53. These findings were confirmed by reducing the immunohistochemical expression of nuclear factor kappa (NF-ƘB) and enhanced Ki-67 levels. In conclusion, HP L. is a promising herb and could be used as an adjuvant candidate to ameliorate chemotherapeutic-induced neurotoxicity. Moreover, HP.NE has superior activity in lessening Cis-induced oxidative stress, inflammation, and apoptosis in brain tissue.https://www.mdpi.com/2305-6304/11/2/159cisplatin<i>Hypericum perforatum</i> L.neuroprotectiveoxidative stressinflammationapoptosis
spellingShingle Heba M. A. Khalil
Hanan M. A. El Henafy
Islam A. Khalil
Alaa F. Bakr
Mohamed I. Fahmy
Nancy S. Younis
Riham A. El-Shiekh
<i>Hypericum perforatum</i> L. Nanoemulsion Mitigates Cisplatin-Induced Chemobrain via Reducing Neurobehavioral Alterations, Oxidative Stress, Neuroinflammation, and Apoptosis in Adult Rats
Toxics
cisplatin
<i>Hypericum perforatum</i> L.
neuroprotective
oxidative stress
inflammation
apoptosis
title <i>Hypericum perforatum</i> L. Nanoemulsion Mitigates Cisplatin-Induced Chemobrain via Reducing Neurobehavioral Alterations, Oxidative Stress, Neuroinflammation, and Apoptosis in Adult Rats
title_full <i>Hypericum perforatum</i> L. Nanoemulsion Mitigates Cisplatin-Induced Chemobrain via Reducing Neurobehavioral Alterations, Oxidative Stress, Neuroinflammation, and Apoptosis in Adult Rats
title_fullStr <i>Hypericum perforatum</i> L. Nanoemulsion Mitigates Cisplatin-Induced Chemobrain via Reducing Neurobehavioral Alterations, Oxidative Stress, Neuroinflammation, and Apoptosis in Adult Rats
title_full_unstemmed <i>Hypericum perforatum</i> L. Nanoemulsion Mitigates Cisplatin-Induced Chemobrain via Reducing Neurobehavioral Alterations, Oxidative Stress, Neuroinflammation, and Apoptosis in Adult Rats
title_short <i>Hypericum perforatum</i> L. Nanoemulsion Mitigates Cisplatin-Induced Chemobrain via Reducing Neurobehavioral Alterations, Oxidative Stress, Neuroinflammation, and Apoptosis in Adult Rats
title_sort i hypericum perforatum i l nanoemulsion mitigates cisplatin induced chemobrain via reducing neurobehavioral alterations oxidative stress neuroinflammation and apoptosis in adult rats
topic cisplatin
<i>Hypericum perforatum</i> L.
neuroprotective
oxidative stress
inflammation
apoptosis
url https://www.mdpi.com/2305-6304/11/2/159
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