<i>Salix tetrasperma</i> Roxb. Extract Alleviates Neuropathic Pain in Rats via Modulation of the NF-κB/TNF-α/NOX/iNOS Pathway

Patients with neuropathic pain experience chronic painful tingling, burning, and prickling sensations accompanied with hyperalgesia and/or allodynia. In this study, 38 secondary metabolites of a methanol extract from <i>Salix tetrasperma</i> flowers were identified by liquid chromatograp...

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Main Authors: Mansour Sobeh, Mona F. Mahmoud, Samar Rezq, Amira E. Alsemeh, Omar M. Sabry, Islam Mostafa, Mohamed A. O. Abdelfattah, Khadija Ait El-Allem, Assem M. El-Shazly, Aziz Yasri, Michael Wink
Format: Article
Language:English
Published: MDPI AG 2019-10-01
Series:Antioxidants
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Online Access:https://www.mdpi.com/2076-3921/8/10/482
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author Mansour Sobeh
Mona F. Mahmoud
Samar Rezq
Amira E. Alsemeh
Omar M. Sabry
Islam Mostafa
Mohamed A. O. Abdelfattah
Khadija Ait El-Allem
Assem M. El-Shazly
Aziz Yasri
Michael Wink
author_facet Mansour Sobeh
Mona F. Mahmoud
Samar Rezq
Amira E. Alsemeh
Omar M. Sabry
Islam Mostafa
Mohamed A. O. Abdelfattah
Khadija Ait El-Allem
Assem M. El-Shazly
Aziz Yasri
Michael Wink
author_sort Mansour Sobeh
collection DOAJ
description Patients with neuropathic pain experience chronic painful tingling, burning, and prickling sensations accompanied with hyperalgesia and/or allodynia. In this study, 38 secondary metabolites of a methanol extract from <i>Salix tetrasperma</i> flowers were identified by liquid chromatography-mass spectrometry (HPLC-MS/MS). The extract showed substantial anti-inflammatory, central and peripheral anti-nociceptive, antipyretic, and antioxidant activities in vitro and in different animal models. In the chronic constriction injury (CCI) rat model, the extract was able to attenuate and significantly relieve hyperalgesia and allodynia responses in a dose dependent manner and restore the myelin sheath integrity and Schwann cells average number in the sciatic nerve. The enzyme-linked immunosorbent assay (ELISA) showed that the extract significantly reduced the expression of various pro-inflammatory biomarkers including nuclear factor kabba B (NF-&#954;B), tumor necrosis factor alpha (TNF-&#945;), prostaglandin E2 (PGE2), 5-lipoxygenase (5-LOX), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and the oxidative stress biomarker NADPH oxidase 1 (NOX1), in brain stem and sciatic nerve tissues. These findings were supported by in vitro enzyme inhibition assays (COX-1, COX-2 and 5-LOX). Moreover, the extract significantly reduced p53 expression in the brain stem tissue. These findings support the use of <i>S. tetrasperma</i> in folk medicine to alleviate pain. It could be a promising natural product for further clinical investigations to treat inflammation, nociceptive pain and chronic neuropathic pain.
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spelling doaj.art-d2092667099c473793ed1babc2cb84642023-09-02T04:20:50ZengMDPI AGAntioxidants2076-39212019-10-0181048210.3390/antiox8100482antiox8100482<i>Salix tetrasperma</i> Roxb. Extract Alleviates Neuropathic Pain in Rats via Modulation of the NF-κB/TNF-α/NOX/iNOS PathwayMansour Sobeh0Mona F. Mahmoud1Samar Rezq2Amira E. Alsemeh3Omar M. Sabry4Islam Mostafa5Mohamed A. O. Abdelfattah6Khadija Ait El-Allem7Assem M. El-Shazly8Aziz Yasri9Michael Wink10Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, 69120 Heidelberg, GermanyDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, EgyptDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, EgyptDepartment of Anatomy and Embryology, Faculty of Medicine, Zagazig University, Zagazig 44519, EgyptDepartment of Pharmacognosy, College of Pharmacy, Cairo University, Cairo 11562, EgyptDepartment of Pharmacognosy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, EgyptCollege of Engineering and Technology, American University of the Middle East, Egaila 54200, KuwaitAgroBioSciences Research Division, Mohammed VI Polytechnic University, Lot 660–Hay MoulayRachid, Ben-Guerir 43150, MoroccoDepartment of Pharmacognosy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, EgyptAgroBioSciences Research Division, Mohammed VI Polytechnic University, Lot 660–Hay MoulayRachid, Ben-Guerir 43150, MoroccoInstitute of Pharmacy and Molecular Biotechnology, Heidelberg University, 69120 Heidelberg, GermanyPatients with neuropathic pain experience chronic painful tingling, burning, and prickling sensations accompanied with hyperalgesia and/or allodynia. In this study, 38 secondary metabolites of a methanol extract from <i>Salix tetrasperma</i> flowers were identified by liquid chromatography-mass spectrometry (HPLC-MS/MS). The extract showed substantial anti-inflammatory, central and peripheral anti-nociceptive, antipyretic, and antioxidant activities in vitro and in different animal models. In the chronic constriction injury (CCI) rat model, the extract was able to attenuate and significantly relieve hyperalgesia and allodynia responses in a dose dependent manner and restore the myelin sheath integrity and Schwann cells average number in the sciatic nerve. The enzyme-linked immunosorbent assay (ELISA) showed that the extract significantly reduced the expression of various pro-inflammatory biomarkers including nuclear factor kabba B (NF-&#954;B), tumor necrosis factor alpha (TNF-&#945;), prostaglandin E2 (PGE2), 5-lipoxygenase (5-LOX), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and the oxidative stress biomarker NADPH oxidase 1 (NOX1), in brain stem and sciatic nerve tissues. These findings were supported by in vitro enzyme inhibition assays (COX-1, COX-2 and 5-LOX). Moreover, the extract significantly reduced p53 expression in the brain stem tissue. These findings support the use of <i>S. tetrasperma</i> in folk medicine to alleviate pain. It could be a promising natural product for further clinical investigations to treat inflammation, nociceptive pain and chronic neuropathic pain.https://www.mdpi.com/2076-3921/8/10/482<i>salix tetrasperma</i>polyphenolsneuropathynf-κb/tnf-α/nox/inos pathwaychronic constriction injuryp53
spellingShingle Mansour Sobeh
Mona F. Mahmoud
Samar Rezq
Amira E. Alsemeh
Omar M. Sabry
Islam Mostafa
Mohamed A. O. Abdelfattah
Khadija Ait El-Allem
Assem M. El-Shazly
Aziz Yasri
Michael Wink
<i>Salix tetrasperma</i> Roxb. Extract Alleviates Neuropathic Pain in Rats via Modulation of the NF-κB/TNF-α/NOX/iNOS Pathway
Antioxidants
<i>salix tetrasperma</i>
polyphenols
neuropathy
nf-κb/tnf-α/nox/inos pathway
chronic constriction injury
p53
title <i>Salix tetrasperma</i> Roxb. Extract Alleviates Neuropathic Pain in Rats via Modulation of the NF-κB/TNF-α/NOX/iNOS Pathway
title_full <i>Salix tetrasperma</i> Roxb. Extract Alleviates Neuropathic Pain in Rats via Modulation of the NF-κB/TNF-α/NOX/iNOS Pathway
title_fullStr <i>Salix tetrasperma</i> Roxb. Extract Alleviates Neuropathic Pain in Rats via Modulation of the NF-κB/TNF-α/NOX/iNOS Pathway
title_full_unstemmed <i>Salix tetrasperma</i> Roxb. Extract Alleviates Neuropathic Pain in Rats via Modulation of the NF-κB/TNF-α/NOX/iNOS Pathway
title_short <i>Salix tetrasperma</i> Roxb. Extract Alleviates Neuropathic Pain in Rats via Modulation of the NF-κB/TNF-α/NOX/iNOS Pathway
title_sort i salix tetrasperma i roxb extract alleviates neuropathic pain in rats via modulation of the nf κb tnf α nox inos pathway
topic <i>salix tetrasperma</i>
polyphenols
neuropathy
nf-κb/tnf-α/nox/inos pathway
chronic constriction injury
p53
url https://www.mdpi.com/2076-3921/8/10/482
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