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

1
Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg 69120, Germany
2
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, 44519 Zagazig, Egypt
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Department of Anatomy and Embryology, Faculty of Medicine, Zagazig University, 44519 Zagazig, Egypt
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Department of Pharmacognosy, College of Pharmacy, Cairo University, Cairo 11562, Egypt
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Department of Pharmacognosy, Faculty of Pharmacy, Zagazig University, 44519 Zagazig, Egypt
6
College of Engineering and Technology, American University of the Middle East, Egaila 54200, Kuwait
7
AgroBioSciences Research Division, Mohammed VI Polytechnic University, Lot 660–Hay MoulayRachid, 43150 Ben-Guerir, Morocco
*
Authors to whom correspondence should be addressed.
Antioxidants 2019, 8(10), 482; https://doi.org/10.3390/antiox8100482
Received: 3 September 2019 / Revised: 9 October 2019 / Accepted: 10 October 2019 / Published: 12 October 2019
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 Salix tetrasperma 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-κB), tumor necrosis factor alpha (TNF-α), 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 S. tetrasperma 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.
Keywords: Salix tetrasperma; polyphenols; neuropathy; NF-κB/TNF-α/NOX/iNOS pathway; chronic constriction injury; p53 Salix tetrasperma; polyphenols; neuropathy; NF-κB/TNF-α/NOX/iNOS pathway; chronic constriction injury; p53
MDPI and ACS Style

Sobeh, M.; Mahmoud, M.F.; Rezq, S.; Alsemeh, A.E.; Sabry, O.M.; Mostafa, I.; Abdelfattah, M.A.; El-Allem, K.A.; El-Shazly, A.M.; Yasri, A.; Wink, M. Salix tetrasperma Roxb. Extract Alleviates Neuropathic Pain in Rats via Modulation of the NF-κB/TNF-α/NOX/iNOS Pathway. Antioxidants 2019, 8, 482.

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