{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:22:47Z","timestamp":1787062967592,"version":"build-2736575974"},"reference-count":37,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2019,10,12]],"date-time":"2019-10-12T00:00:00Z","timestamp":1570838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>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-\u03baB), tumor necrosis factor alpha (TNF-\u03b1), 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.<\/jats:p>","DOI":"10.3390\/antiox8100482","type":"journal-article","created":{"date-parts":[[2019,10,14]],"date-time":"2019-10-14T03:54:13Z","timestamp":1571025253000},"page":"482","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Salix tetrasperma Roxb. Extract Alleviates Neuropathic Pain in Rats via Modulation of the NF-\u03baB\/TNF-\u03b1\/NOX\/iNOS Pathway"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2719-8534","authenticated-orcid":false,"given":"Mansour","family":"Sobeh","sequence":"first","affiliation":[{"name":"Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, 69120 Heidelberg, Germany"},{"name":"AgroBioSciences Research Division, Mohammed VI Polytechnic University, Lot 660\u2013Hay MoulayRachid, Ben-Guerir 43150, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5312-2066","authenticated-orcid":false,"given":"Mona F.","family":"Mahmoud","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4421-0686","authenticated-orcid":false,"given":"Samar","family":"Rezq","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amira E.","family":"Alsemeh","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Embryology, Faculty of Medicine, Zagazig University, Zagazig 44519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar M.","family":"Sabry","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, College of Pharmacy, Cairo University, Cairo 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6437-5528","authenticated-orcid":false,"given":"Islam","family":"Mostafa","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed A. O.","family":"Abdelfattah","sequence":"additional","affiliation":[{"name":"College of Engineering and Technology, American University of the Middle East, Egaila 54200, Kuwait"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khadija","family":"Ait El-Allem","sequence":"additional","affiliation":[{"name":"AgroBioSciences Research Division, Mohammed VI Polytechnic University, Lot 660\u2013Hay MoulayRachid, Ben-Guerir 43150, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Assem M.","family":"El-Shazly","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7513-9037","authenticated-orcid":false,"given":"Aziz","family":"Yasri","sequence":"additional","affiliation":[{"name":"AgroBioSciences Research Division, Mohammed VI Polytechnic University, Lot 660\u2013Hay MoulayRachid, Ben-Guerir 43150, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7875-4510","authenticated-orcid":false,"given":"Michael","family":"Wink","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0014-2999(01)01303-6","article-title":"Pathobiology of neuropathic pain","volume":"429","author":"Zimmermann","year":"2001","journal-title":"Eur. 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