Ameliorative Effect of Citrus Lemon Peel Extract and Resveratrol on Premature Ovarian Failure Rat Model: Role of iNOS/Caspase-3 Pathway

Abstract

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-κB) levels, tumor necrosis factor-α (TNF-α), 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- κB pathways, evidenced by a considerable reduction in Casp3 & 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.

Network analysis and experimental approach to investigate the potential therapeutic mechanism of zishen yutai pills on premature ovarian insufficiency

“…Luan et al also found that administration of CTX resulted in the loss of primordial oocytes through apoptotic pathways [ 61 ]. Although our results indicated an upregulation in apoptosis after CTX exposure, there seemed to be no significant correlation with the caspase-3 pathway, which differs from the observations of other studies [ [39] , [62] ]. We surmise that this disparity might be ascribed to the method of determining caspase-3, as another study also found that cleaved caspase-3 staining can only be observed in primary, secondary, and pre-antral follicles (except PMF) [ 38 ].…”

Efficacy of natural products on premature ovarian failure: a systematic review and meta-analysis of preclinical studies

“…These natural products encompassed substances derived from plants to marine organisms. Among the phytochemicals, bioactive substances from plants were extensively investigated [ 27 , 30 , 32 – 37 , 39 – 43 , 46 , 47 , 49 – 52 , 63 ]. In addition, marine natural products such as tilapia skin peptides [ 38 ], oyster polypeptides [ 44 ], sea cucumber peptide [ 31 ], and coenzyme Q10 [ 45 ] were also explored.…”

Disease alleviating effects following prophylactic lemon and coriander essential oil treatment in mice with acute campylobacteriosis

“…The alleviated clinical signs in LEM-EO pretreated mice were paralleled by less distinct pathogen-induced colonic epithelial cell apoptosis. Although several investigations revealed pro-apoptotic effects of LEM in distinct cancer cells, two studies showed that the activation of caspase-3, which leads to apoptosis, is inhibited by LEM in the premature ovarian failure rat model ( Mobasher et al, 2023 ) and in human astrocytes CCF-STTG1 ( Koo et al, 2002 ), indicating that the pro- and anti-apoptotic effects of LEM are cell-type dependent. Furthermore, linalool derived from COR-EO has been shown to exert anti-apoptotic effects by the inhibition of caspase-3 and -9 attenuating ischemic injury in rodent PC12 cells ( Hosseini et al, 2022 ).…”