{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:18:24Z","timestamp":1790371104469,"version":"4.1.0"},"reference-count":44,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T00:00:00Z","timestamp":1685404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>It is evident that inflammation and metabolic syndrome instigated by diabetes mellitus can precipitate diabetes-induced neuropathy (DIN) and pain. In order to find an effective therapeutic method for diabetes-related problems, a multi-target-directed ligand model was used. 6-Hydroxyflavanone (6-HF) carrying anti-inflammatory and anti-neuropathic pain potential due to its quadruplicate mechanisms, targeting cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX), and opioid and GABA-A receptors was investigated. The anti-inflammatory potential of the test drug was confirmed utilizing in silico, in vitro, and in vivo tests. A molecular simulation approach was utilized to observe the interaction of 6-HF with the inflammatory enzyme COX-2 as well as opioid and GABA-A receptors. The same was confirmed via in vitro COX-2 and 5-LOX inhibitory assays. In vivo tests were performed to analyze the thermal anti-nociception in the hot-plate analgesiometer and anti-inflammatory action in the carrageenan-induced paw edema model in rodents. The potential anti-nociceptive effect of 6-HF was evaluated in the DIN model in rats. The Naloxone and Pentylenetetrazole (PTZ) antagonists were used to confirm the underlying mechanism of 6-HF. The molecular modeling studies revealed a favorable interaction of 6-HF with the identified protein molecules. In vitro inhibitory studies revealed that 6-HF inhibited the COX-2 and 5-LOX enzymes significantly. The 6-HF at dosages of 15, 30, and 60 mg\/kg substantially reduced heat nociception in a hot plate analgesiometer as well as carrageenan-induced paw edema in rodent models. The authors discovered that 6-HF had anti-nociception properties in a streptozotocin-induced diabetic neuropathy model. According to the findings of this study, 6-HF was demonstrated to diminish inflammation caused by diabetes as well as its anti-nociception effect in DIN.<\/jats:p>","DOI":"10.3390\/nu15112552","type":"journal-article","created":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T02:27:30Z","timestamp":1685500050000},"page":"2552","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Targeting Anti-Inflammatory Pathways to Treat Diabetes-Induced Neuropathy by 6-Hydroxyflavanone"],"prefix":"10.3390","volume":"15","author":[{"given":"Shehla","family":"Akbar","sequence":"first","affiliation":[{"name":"Department of Pharmacy, CECOS University of IT and Emerging Sciences, Peshawar 25000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fazal","family":"Subhan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, CECOS University of IT and Emerging Sciences, Peshawar 25000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aroosha","family":"Akbar","sequence":"additional","affiliation":[{"name":"North West Institute of Health Sciences, Peshawar 25000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faiza","family":"Habib","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Sciences, Khyber Medical University, Peshawar 25000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naila","family":"Shahbaz","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Sarhad University of Science and Technology, Peshawar 25000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashfaq","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Sarhad University of Science and Technology, Peshawar 25000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul","family":"Wadood","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Shankar Abdul Wali Khan University, Mardan 23200, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6592-9812","authenticated-orcid":false,"given":"Saad","family":"Salman","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, CECOS University of IT and Emerging Sciences, Peshawar 25000, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1002\/mus.27086","article-title":"Metabolic syndrome and peripheral neuropathy","volume":"63","author":"Kazamel","year":"2021","journal-title":"Muscle Nerve"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1002\/dmrr.2549","article-title":"Peroxynitrite and protein nitration in the pathogenesis of diabetic peripheral neuropathy","volume":"30","author":"Stavniichuk","year":"2014","journal-title":"Diabetes Metab. 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