{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:14:33Z","timestamp":1792588473109,"version":"4.5.0"},"reference-count":102,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T00:00:00Z","timestamp":1671753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007614","name":"Deanship of Scientific Research at Jouf University","doi-asserted-by":"publisher","award":["DSR-2021-01-03147"],"award-info":[{"award-number":["DSR-2021-01-03147"]}],"id":[{"id":"10.13039\/501100007614","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Premature ovarian failure (POF) is described as a loss of oocytes and the absence of folliculogenesis and is considered an adverse effect of chemotherapeutic drugs, which leads to infertility. Subsequently, the existing inquiry was achieved by exploring the potential suspicious influences of lemon peel extract (LPE), and resveratrol (RES) on cyclophosphamide (CPA) induced-POF. The results showed that CPA-induced POF significantly decreased serum estradiol (E2) and progesterone levels, along with a considerable rise in serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels. Moreover, CPA administration to rats significantly increased the serum level of Malondialdehyde (MDA) and significantly lowered the levels of reduced glutathione (GSH) and superoxide dismutase (SOD); in addition, it increased nuclear factor kappa B (NF-\u03baB) levels, tumor necrosis factor-\u03b1 (TNF-\u03b1), as well as cyclooxygenase 2 (COX-2) with the spread expression of inducible nitric oxide synthase (iNOS) mRNA levels and caspase-3 (Casp3) levels in ovarian tissues versus the control rats. However, treatment with LPE and RES suppressed the triggering of NF- \u03baB pathways, evidenced by a considerable reduction in Casp3 &amp; iNOS mRNA expression level and significant ameliorative effects in all evaluated parameters, as confirmed by the histological and immunohistochemical investigation when comparing the model group. In overall findings, both lemon peel extract and resveratrol can mitigate the adverse effects of CPA-induced POF. Most crucially, its combination therapy is a promising pharmacological agent for this disease.<\/jats:p>","DOI":"10.3390\/molecules28010122","type":"journal-article","created":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T02:53:11Z","timestamp":1672109591000},"page":"122","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Ameliorative Effect of Citrus Lemon Peel Extract and Resveratrol on Premature Ovarian Failure Rat Model: Role of iNOS\/Caspase-3 Pathway"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2987-0387","authenticated-orcid":false,"given":"Maysa A.","family":"Mobasher","sequence":"first","affiliation":[{"name":"Department of Pathology, Biochemistry Division, College of Medicine, Jouf University, Sakaka 72388, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa T.","family":"Hassen","sequence":"additional","affiliation":[{"name":"Department of Zoology, Faculty of Women for Arts, Science and Education, Ain Shams University, Cairo 11757, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5814-4475","authenticated-orcid":false,"given":"Rasha A.","family":"Ebiya","sequence":"additional","affiliation":[{"name":"Department of Zoology, Faculty of Women for Arts, Science and Education, Ain Shams University, Cairo 11757, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0608-4797","authenticated-orcid":false,"given":"Norah A.","family":"Alturki","sequence":"additional","affiliation":[{"name":"Clinical Laboratory Science Department, College of Applied Medical Science, King Saud University, Riyadh 11433, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7134-663X","authenticated-orcid":false,"given":"Ahmad","family":"Alzamami","sequence":"additional","affiliation":[{"name":"Clinical Laboratory Science Department, College of Applied Medical Science, Shaqra University, Al Quwaiiyah 11961, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6749-4103","authenticated-orcid":false,"given":"Hanaa K.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Zoology, Faculty of Women for Arts, Science and Education, Ain Shams University, Cairo 11757, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3006-8570","authenticated-orcid":false,"given":"Nabil S.","family":"Awad","sequence":"additional","affiliation":[{"name":"Department of Genetics, Faculty of Agriculture and Natural Resources, Aswan University, Aswan 81528, Egypt"},{"name":"College of Biotechnology, Misr University for Science and Technology, Giza 12563, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3412-4138","authenticated-orcid":false,"given":"Dina","family":"Khodeer","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4722-7953","authenticated-orcid":false,"given":"Bosy A.","family":"Abd El-Motelp","sequence":"additional","affiliation":[{"name":"Department of Zoology, Faculty of Women for Arts, Science and Education, Ain Shams University, Cairo 11757, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101600","DOI":"10.1016\/j.beem.2021.101600","article-title":"Diagnosis and Management of Premature Ovarian Insufficiency","volume":"35","author":"Rahman","year":"2021","journal-title":"Best Pract. 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