The effect of icariin on autoimmune premature ovarian insufficiency via modulation of Nrf2/HO-1/Sirt1 pathway in mice

Chen, Haoran; Song, Linjiang; Xu, Xinglian; Han, Zhongyu; Peng, Fang; Zhang, Qinxiu; Liu, Chi; Liang, Xin

doi:10.1016/j.repbio.2022.100638

Cited by 12 publications

(5 citation statements)

References 42 publications

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“…In both animal models and patients, iron overload plays a pathogenic role in ovarian toxicity in several ovarian disorders, such as endometriosis-related infertility and polycystic ovary syndrome (PCOS) [ 33 , 34 ]. Paradoxically, HO-1 is considered to have a cytoprotective role in ovarian function in several studies, as HO-1 deficiency causes deficient ovulation in mice [ 11 , 12 , 35 ]. On the other hand, HO-1-deficient mice developed an anemia associated with abnormally low serum iron levels [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

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Cyclophosphamide induces ovarian granulosa cell ferroptosis via a mechanism associated with HO-1 and ROS-mediated mitochondrial dysfunction

Chen,

Nie,

et al. 2024

J Ovarian Res

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Abnormal granulosa cell (GC) death contributes to cyclophosphamide (CTX) induced primary ovarian insufficiency (POI). To investigate the contribution of GCs to POI, gene profiles of GCs exposed to CTX were assessed using RNA-Seq and bioinformatics analysis. The results showed the differentially expressed genes (DEGs) were enriched in the ferroptosis-related pathway, which is correlated with upregulated heme oxygenase 1 (HO-1) and downregulated glutathione peroxidase-4 (GPX4). Using CTX-induced cell culture (COV434 and KGN cells), the levels of iron, reactive oxygen species (ROS), lipid peroxide, mitochondrial superoxide, mitochondrial morphology and mitochondrial membrane potential (MMP) were detected by DCFDA, MitoSOX, C11-BODIPY, MitoTracker, Nonylacridine Orange (NAO), JC-1 and transmission electron microscopy respectively. The results showed iron overload and disrupted ROS, including cytoROS, mtROS and lipROS homeostasis, were associated with upregulation of HO-1 and could induce ferroptosis via mitochondrial dysfunction in CTX-induced GCs. Moreover, HO-1 inhibition could suppress ferroptosis induced GPX4 depletion. This implies a role for ROS in CTX-induced ferroptosis and highlights the effect of HO-1 modulators in improving CTX-induced ovarian damage, which may provide a theoretical basis for preventing or restoring GC and ovarian function in patients with POI.

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Section: Discussionmentioning

confidence: 99%

“…HO-1 is mainly expressed in GCs in ovaries and HO-1-deficient mice showed deficient ovulation [ 11 ]. In autoimmune POI mice, HO-1-mediated immunodeficiency has been found to improve ovarian reserve capacity through the HO-1 pathway [ 12 ]. This evidence revealed HO-1 counteracts immune-mediated inflammation mechanism in POI.…”

Section: Introductionmentioning

confidence: 99%

Cyclophosphamide induces ovarian granulosa cell ferroptosis via a mechanism associated with HO-1 and ROS-mediated mitochondrial dysfunction

Chen,

Nie,

et al. 2024

J Ovarian Res

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“…The beneficial effects of ICI on the estrous cycle, which was accompanied by alleviated POI, have been attributed to affecting the Nrf2/HO-1/Sirt1 pathway in the mice ovary [53]. More importantly, the administration of ICI to the induced aging led to increased pregnancy rate, improved average litter sizes, elevated average litter birth weight, average weaning weight of litters, and weaning rate revealing the beneficial effects of ICI on female fertility and newborn health [33].…”

Section: Discussionmentioning

confidence: 99%

Icariin, A Novel Promising Complementary Therapeutic Strategy In The Management Of Female Infertility: A Literature Review

Mosavi

Rostami

Pooladi

et al. 2023

GMJ

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The prevalence of pre-menopausal female infertility is increasing considerably due to various causes such as environmental pollutants, increased administration of chemotherapeutics and radiation exposure, microbial infections, and genetic/epigenetic alterations. However, the current therapeutical strategies remain unfavorite as the disadvantages are strongly challenging. Icariin (ICI) is a phytoestrogen that exerts some promising properties in order to alleviate female infertility. Therefore, the current literature review aimed to evaluate the conducted studies regarding the beneficial impacts of ICI on the female reproductive system and female fecundity. The findings of the present study revealed that ICI is able to modulate the levels of reproductive hormones as it causes a significant decrement in the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) while increasing the levels of estrogen and progesterone. Furthermore, the administration of ICI results in a dramatic alteration in the expression of sex steroids’ receptors, particularly in female reproductive tissues. In addition, preserving ovarian follicular reserve, improving the ovarian and uterine histoarchitecture, elongating the estrous cycle duration, and eventually advancing the female fecundity are other major effects of ICI on the female reproductive system. Despite these desired beneficial properties, the current knowledge appears to be insufficient, hence further investigations, particularly on humans, are encouraged. To the best of our knowledge, this review provides a comprehensive information regarding the beneficial effects of Icariin on female infertility for the firs time

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“…Icariin has demonstrated its involvement in the pathogenesis of several autoimmune disorders. It alleviated the injury of ovarian structure and endocrine function in autoimmune POI mice by upregulating the expression of Nrf2 and HO-1 [120].…”

Section: Natural Plant and Animal Extractsmentioning

confidence: 98%

Role of the Nrf2 Signaling Pathway in Ovarian Aging: Potential Mechanism and Protective Strategies

Gao,

Wang,

Huang

et al. 2023

IJMS

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The ovary holds a significant role as a reproductive endocrine organ in women, and its aging process bears implications such as menopause, decreased fertility, and long-term health risks including osteoporosis, cardiovascular disorders, and cognitive decline. The phenomenon of oxidative stress is tightly linked to the aging metabolic processes. More and more studies have demonstrated that oxidative stress impacts both physiologic and pathologic ovarian aging, and the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway plays a crucial role in regulating the antioxidant response. Furthermore, various therapeutic approaches have been identified to ameliorate ovarian aging by modulating the Nrf2 pathway. This review summarizes the important role of the Nrf2/ Kelch-like ECH-associated protein 1 (Keap1) signaling pathway in regulating oxidative stress and influencing ovarian aging. Additionally, it highlights the therapeutic strategies aimed at targeting the Nrf2/Keap1 pathway.

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The effect of icariin on autoimmune premature ovarian insufficiency via modulation of Nrf2/HO-1/Sirt1 pathway in mice

Cited by 12 publications

References 42 publications

Cyclophosphamide induces ovarian granulosa cell ferroptosis via a mechanism associated with HO-1 and ROS-mediated mitochondrial dysfunction

Cyclophosphamide induces ovarian granulosa cell ferroptosis via a mechanism associated with HO-1 and ROS-mediated mitochondrial dysfunction

Icariin, A Novel Promising Complementary Therapeutic Strategy In The Management Of Female Infertility: A Literature Review

Role of the Nrf2 Signaling Pathway in Ovarian Aging: Potential Mechanism and Protective Strategies

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