Zuogui Pills alleviate cyclophosphamide-induced ovarian aging by reducing oxidative stress and restoring the stemness of oogonial stem cells through the Nrf2/HO-1 signaling pathway
Zuogui Pill (ZGP) is a traditional herbal formula of Chinese Medicine with a long history of use in alleviating ovarian aging. To examine the impact of ZGP on oxidative stress and the stemness of oogonial stem cells (OSCs) in cyclophosphamide (CTX)-induced ovarian aging, as well as its molecular mec...
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| creator | Li, Zuang Liang, Yunyi Wang, Yixuan Lin, Yuewei Zeng, Lihua Zhang, Yuying Zhu, Ling |
| description | Zuogui Pill (ZGP) is a traditional herbal formula of Chinese Medicine with a long history of use in alleviating ovarian aging.
To examine the impact of ZGP on oxidative stress and the stemness of oogonial stem cells (OSCs) in cyclophosphamide (CTX)-induced ovarian aging, as well as its molecular mechanisms involving the nuclear factor erythroid 2-related factor 2 (Nrf2, NFE2L2)/heme oxygenase-1 (HO-1, Hmox1) pathway.
Female Sprague-Dawley (SD) rats were randomly divided into seven groups: control, model (CTX), estradiol valerate (EV, 0.103 mg/kg), ZGP-L (low dose Zuogui Pill, 1.851 g/kg), ZGP-H (high dose Zuogui Pill, 3.702 g/kg), ML385 (30 mg/kg), and ML385+ZGP-L. After CTX modeling, the EV, ZGP-L, ZGP-H, and ML385+ZGP-L groups were treated by gavage for 8 weeks, while the ML385 and ML385+ZGP-L groups were administered the Nrf2 antagonist ML385 twice a week. OSCs were isolated after modeling and then treated with drug serum containing 10% ZGP or 10 μM ML385. The general conditions of the rats, including body weight, ovarian weight/body weight ratio, and estrous cycle, were observed. Ovarian ultrastructure, follicle and corpus luteum counts were assessed via hematoxylin and eosin (H&E) staining. Serum hormone levels were measured using enzyme-linked immunosorbent assay (ELISA). Nrf2/HO-1 pathway, stem cell, germ cell, and cell cycle biomarkers were analyzed by qPCR and Western blot. Cell viability was assessed by cell counting kit-8 (CCK-8) assay. Oxidative stress biomarkers were evaluated using flow cytometry and assay kits. Immunofluorescence was employed to detect and locate OSCs in the ovary, quantify the average fluorescence intensity, and identify OSCs.
After ZGP treatment, rats with CTX-induced ovarian aging exhibited improved general condition, increased body weight, higher total ovarian weight to body weight ratio, and a restoration of the estrous cycle similar to the control group. Serum levels of estradiol (E2) and follicle stimulating hormone (FSH), two sex hormones, were also improved. Ovarian ultrastructure and follicle count at all stages showed improvement. Moreover, the viability and proliferation capacity of OSCs were enhanced following ZGP intervention.
The Nrf2/HO-1 pathway was found to be down-regulated in CTX-induced aging ovarian OSCs. However, ZGP reversed this effect by activating the expression of Nrf2, HO-1, and NAD(P)H oxidoreductase 1 (NQO1), increasing the activity of antioxidant enzymes superoxide dismutase (SOD) and glutathi |
| doi_str_mv | 10.1016/j.jep.2024.118505 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_3074133628</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0378874124008043</els_id><sourcerecordid>3074133628</sourcerecordid><originalsourceid>FETCH-LOGICAL-c235t-3fb432ec71ec1ae7b698adc346376029d4ff75618cc661f258474efe05677ce43</originalsourceid><addsrcrecordid>eNp9kc1u1DAUhS0EokPhAdggL9lk6r_YGbFCVaFIFWUBGzaWx7lJPErsYCcD8148IHansGTlK59zj33vh9BrSraUUHl12B5g3jLCxJbSpib1E7ShjWKVqhV_ijaEq6ZqlKAX6EVKB0KIooI8Rxe82YlaSLlBv7-voV8d_uLGMWEzjnB0ZgFsT3YM8xDSPJjJtVA5364WWhyOJjrjsemd7_H-hCNkodThl2vN4o6A0xIh5TTfZjUtIRZ5GYoAky9S6HAIffDOjA-X2EJ5fxliWPvhwfs5duzq9r6iOLnem7FkzGYZfprTS_SsM2OCV4_nJfr24ebr9W11d__x0_X7u8oyXi8V7_aCM7CKgqUG1F7uGtNaLiRXkrBdK7pO1ZI21kpJO1Y3QgnogNRSKQuCX6K359w5hh9rnkRPLpWfGg9hTZqTvFvOJWuylZ6tNoaUInR6jm4y8aQp0QWWPugMSxdY-gwr97x5jF_3E7T_Ov7SyYZ3ZwPkIY8Ook7Wgc8YXAS76Da4_8T_AadGqQs</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3074133628</pqid></control><display><type>article</type><title>Zuogui Pills alleviate cyclophosphamide-induced ovarian aging by reducing oxidative stress and restoring the stemness of oogonial stem cells through the Nrf2/HO-1 signaling pathway</title><source>MEDLINE</source><source>Access via ScienceDirect (Elsevier)</source><creator>Li, Zuang ; Liang, Yunyi ; Wang, Yixuan ; Lin, Yuewei ; Zeng, Lihua ; Zhang, Yuying ; Zhu, Ling</creator><creatorcontrib>Li, Zuang ; Liang, Yunyi ; Wang, Yixuan ; Lin, Yuewei ; Zeng, Lihua ; Zhang, Yuying ; Zhu, Ling</creatorcontrib><description>Zuogui Pill (ZGP) is a traditional herbal formula of Chinese Medicine with a long history of use in alleviating ovarian aging.
To examine the impact of ZGP on oxidative stress and the stemness of oogonial stem cells (OSCs) in cyclophosphamide (CTX)-induced ovarian aging, as well as its molecular mechanisms involving the nuclear factor erythroid 2-related factor 2 (Nrf2, NFE2L2)/heme oxygenase-1 (HO-1, Hmox1) pathway.
Female Sprague-Dawley (SD) rats were randomly divided into seven groups: control, model (CTX), estradiol valerate (EV, 0.103 mg/kg), ZGP-L (low dose Zuogui Pill, 1.851 g/kg), ZGP-H (high dose Zuogui Pill, 3.702 g/kg), ML385 (30 mg/kg), and ML385+ZGP-L. After CTX modeling, the EV, ZGP-L, ZGP-H, and ML385+ZGP-L groups were treated by gavage for 8 weeks, while the ML385 and ML385+ZGP-L groups were administered the Nrf2 antagonist ML385 twice a week. OSCs were isolated after modeling and then treated with drug serum containing 10% ZGP or 10 μM ML385. The general conditions of the rats, including body weight, ovarian weight/body weight ratio, and estrous cycle, were observed. Ovarian ultrastructure, follicle and corpus luteum counts were assessed via hematoxylin and eosin (H&E) staining. Serum hormone levels were measured using enzyme-linked immunosorbent assay (ELISA). Nrf2/HO-1 pathway, stem cell, germ cell, and cell cycle biomarkers were analyzed by qPCR and Western blot. Cell viability was assessed by cell counting kit-8 (CCK-8) assay. Oxidative stress biomarkers were evaluated using flow cytometry and assay kits. Immunofluorescence was employed to detect and locate OSCs in the ovary, quantify the average fluorescence intensity, and identify OSCs.
After ZGP treatment, rats with CTX-induced ovarian aging exhibited improved general condition, increased body weight, higher total ovarian weight to body weight ratio, and a restoration of the estrous cycle similar to the control group. Serum levels of estradiol (E2) and follicle stimulating hormone (FSH), two sex hormones, were also improved. Ovarian ultrastructure and follicle count at all stages showed improvement. Moreover, the viability and proliferation capacity of OSCs were enhanced following ZGP intervention.
The Nrf2/HO-1 pathway was found to be down-regulated in CTX-induced aging ovarian OSCs. However, ZGP reversed this effect by activating the expression of Nrf2, HO-1, and NAD(P)H oxidoreductase 1 (NQO1), increasing the activity of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), and reducing the accumulation of malonaldehyde (MDA) and reactive oxygen species (ROS), thus restoring resistance to oxidative stress.
Additionally, ZGP improved the cell cycle of OSCs, up-regulated the expression of Cyclin D1 and Cyclin E1, restored cell stemness, promoted proliferation, enhanced the expression of cell stemness markers octamer-binding transcription factor 4 (Oct4) and mouse VASA homolog (MVH), and down-regulated the expression of P21, thereby inhibiting apoptosis.
The therapeutic effects of ZGP against oxidative stress and restoration of cell stemness were attenuated following inhibition of the Nrf2 signaling pathway using ML385.
ZGP protected against CTX-induced ovarian aging by restoring normal ovarian function, alleviating oxidative stress in aging OSCs, promoting OSCs proliferation, and restoring their stemness in rats, possibly through regulating the Nrf2/HO-1 pathway.
[Display omitted]
•ZGP restores ovarian function impaired by cyclophosphamide-induced ovarian aging.•ZGP mitigates oxidative stress in aging ovaries via Nrf2/HO-1.•ZGP reduces oxidative stress and restores stemness in aging OSCs via Nrf2/HO-1.</description><identifier>ISSN: 0378-8741</identifier><identifier>ISSN: 1872-7573</identifier><identifier>EISSN: 1872-7573</identifier><identifier>DOI: 10.1016/j.jep.2024.118505</identifier><identifier>PMID: 38945466</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Aging - drug effects ; Animals ; Cyclophosphamide ; Drugs, Chinese Herbal - pharmacology ; Female ; Heme Oxygenase (Decyclizing) - metabolism ; Heme Oxygenase-1 - metabolism ; NF-E2-Related Factor 2 - metabolism ; Nrf2/HO-1 ; Oogonial Stem Cells - drug effects ; OSCs ; Ovarian aging ; Ovary - drug effects ; Ovary - metabolism ; Ovary - pathology ; Oxidative stress ; Oxidative Stress - drug effects ; Rats ; Rats, Sprague-Dawley ; Signal Transduction - drug effects ; Stemness ; Zuogui pill</subject><ispartof>Journal of ethnopharmacology, 2024-10, Vol.333, p.118505, Article 118505</ispartof><rights>2024 Elsevier B.V.</rights><rights>Copyright © 2024 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c235t-3fb432ec71ec1ae7b698adc346376029d4ff75618cc661f258474efe05677ce43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jep.2024.118505$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38945466$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Zuang</creatorcontrib><creatorcontrib>Liang, Yunyi</creatorcontrib><creatorcontrib>Wang, Yixuan</creatorcontrib><creatorcontrib>Lin, Yuewei</creatorcontrib><creatorcontrib>Zeng, Lihua</creatorcontrib><creatorcontrib>Zhang, Yuying</creatorcontrib><creatorcontrib>Zhu, Ling</creatorcontrib><title>Zuogui Pills alleviate cyclophosphamide-induced ovarian aging by reducing oxidative stress and restoring the stemness of oogonial stem cells through the Nrf2/HO-1 signaling pathway</title><title>Journal of ethnopharmacology</title><addtitle>J Ethnopharmacol</addtitle><description>Zuogui Pill (ZGP) is a traditional herbal formula of Chinese Medicine with a long history of use in alleviating ovarian aging.
To examine the impact of ZGP on oxidative stress and the stemness of oogonial stem cells (OSCs) in cyclophosphamide (CTX)-induced ovarian aging, as well as its molecular mechanisms involving the nuclear factor erythroid 2-related factor 2 (Nrf2, NFE2L2)/heme oxygenase-1 (HO-1, Hmox1) pathway.
Female Sprague-Dawley (SD) rats were randomly divided into seven groups: control, model (CTX), estradiol valerate (EV, 0.103 mg/kg), ZGP-L (low dose Zuogui Pill, 1.851 g/kg), ZGP-H (high dose Zuogui Pill, 3.702 g/kg), ML385 (30 mg/kg), and ML385+ZGP-L. After CTX modeling, the EV, ZGP-L, ZGP-H, and ML385+ZGP-L groups were treated by gavage for 8 weeks, while the ML385 and ML385+ZGP-L groups were administered the Nrf2 antagonist ML385 twice a week. OSCs were isolated after modeling and then treated with drug serum containing 10% ZGP or 10 μM ML385. The general conditions of the rats, including body weight, ovarian weight/body weight ratio, and estrous cycle, were observed. Ovarian ultrastructure, follicle and corpus luteum counts were assessed via hematoxylin and eosin (H&E) staining. Serum hormone levels were measured using enzyme-linked immunosorbent assay (ELISA). Nrf2/HO-1 pathway, stem cell, germ cell, and cell cycle biomarkers were analyzed by qPCR and Western blot. Cell viability was assessed by cell counting kit-8 (CCK-8) assay. Oxidative stress biomarkers were evaluated using flow cytometry and assay kits. Immunofluorescence was employed to detect and locate OSCs in the ovary, quantify the average fluorescence intensity, and identify OSCs.
After ZGP treatment, rats with CTX-induced ovarian aging exhibited improved general condition, increased body weight, higher total ovarian weight to body weight ratio, and a restoration of the estrous cycle similar to the control group. Serum levels of estradiol (E2) and follicle stimulating hormone (FSH), two sex hormones, were also improved. Ovarian ultrastructure and follicle count at all stages showed improvement. Moreover, the viability and proliferation capacity of OSCs were enhanced following ZGP intervention.
The Nrf2/HO-1 pathway was found to be down-regulated in CTX-induced aging ovarian OSCs. However, ZGP reversed this effect by activating the expression of Nrf2, HO-1, and NAD(P)H oxidoreductase 1 (NQO1), increasing the activity of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), and reducing the accumulation of malonaldehyde (MDA) and reactive oxygen species (ROS), thus restoring resistance to oxidative stress.
Additionally, ZGP improved the cell cycle of OSCs, up-regulated the expression of Cyclin D1 and Cyclin E1, restored cell stemness, promoted proliferation, enhanced the expression of cell stemness markers octamer-binding transcription factor 4 (Oct4) and mouse VASA homolog (MVH), and down-regulated the expression of P21, thereby inhibiting apoptosis.
The therapeutic effects of ZGP against oxidative stress and restoration of cell stemness were attenuated following inhibition of the Nrf2 signaling pathway using ML385.
ZGP protected against CTX-induced ovarian aging by restoring normal ovarian function, alleviating oxidative stress in aging OSCs, promoting OSCs proliferation, and restoring their stemness in rats, possibly through regulating the Nrf2/HO-1 pathway.
[Display omitted]
•ZGP restores ovarian function impaired by cyclophosphamide-induced ovarian aging.•ZGP mitigates oxidative stress in aging ovaries via Nrf2/HO-1.•ZGP reduces oxidative stress and restores stemness in aging OSCs via Nrf2/HO-1.</description><subject>Aging - drug effects</subject><subject>Animals</subject><subject>Cyclophosphamide</subject><subject>Drugs, Chinese Herbal - pharmacology</subject><subject>Female</subject><subject>Heme Oxygenase (Decyclizing) - metabolism</subject><subject>Heme Oxygenase-1 - metabolism</subject><subject>NF-E2-Related Factor 2 - metabolism</subject><subject>Nrf2/HO-1</subject><subject>Oogonial Stem Cells - drug effects</subject><subject>OSCs</subject><subject>Ovarian aging</subject><subject>Ovary - drug effects</subject><subject>Ovary - metabolism</subject><subject>Ovary - pathology</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Signal Transduction - drug effects</subject><subject>Stemness</subject><subject>Zuogui pill</subject><issn>0378-8741</issn><issn>1872-7573</issn><issn>1872-7573</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1u1DAUhS0EokPhAdggL9lk6r_YGbFCVaFIFWUBGzaWx7lJPErsYCcD8148IHansGTlK59zj33vh9BrSraUUHl12B5g3jLCxJbSpib1E7ShjWKVqhV_ijaEq6ZqlKAX6EVKB0KIooI8Rxe82YlaSLlBv7-voV8d_uLGMWEzjnB0ZgFsT3YM8xDSPJjJtVA5364WWhyOJjrjsemd7_H-hCNkodThl2vN4o6A0xIh5TTfZjUtIRZ5GYoAky9S6HAIffDOjA-X2EJ5fxliWPvhwfs5duzq9r6iOLnem7FkzGYZfprTS_SsM2OCV4_nJfr24ebr9W11d__x0_X7u8oyXi8V7_aCM7CKgqUG1F7uGtNaLiRXkrBdK7pO1ZI21kpJO1Y3QgnogNRSKQuCX6K359w5hh9rnkRPLpWfGg9hTZqTvFvOJWuylZ6tNoaUInR6jm4y8aQp0QWWPugMSxdY-gwr97x5jF_3E7T_Ov7SyYZ3ZwPkIY8Ook7Wgc8YXAS76Da4_8T_AadGqQs</recordid><startdate>20241028</startdate><enddate>20241028</enddate><creator>Li, Zuang</creator><creator>Liang, Yunyi</creator><creator>Wang, Yixuan</creator><creator>Lin, Yuewei</creator><creator>Zeng, Lihua</creator><creator>Zhang, Yuying</creator><creator>Zhu, Ling</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20241028</creationdate><title>Zuogui Pills alleviate cyclophosphamide-induced ovarian aging by reducing oxidative stress and restoring the stemness of oogonial stem cells through the Nrf2/HO-1 signaling pathway</title><author>Li, Zuang ; Liang, Yunyi ; Wang, Yixuan ; Lin, Yuewei ; Zeng, Lihua ; Zhang, Yuying ; Zhu, Ling</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c235t-3fb432ec71ec1ae7b698adc346376029d4ff75618cc661f258474efe05677ce43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Aging - drug effects</topic><topic>Animals</topic><topic>Cyclophosphamide</topic><topic>Drugs, Chinese Herbal - pharmacology</topic><topic>Female</topic><topic>Heme Oxygenase (Decyclizing) - metabolism</topic><topic>Heme Oxygenase-1 - metabolism</topic><topic>NF-E2-Related Factor 2 - metabolism</topic><topic>Nrf2/HO-1</topic><topic>Oogonial Stem Cells - drug effects</topic><topic>OSCs</topic><topic>Ovarian aging</topic><topic>Ovary - drug effects</topic><topic>Ovary - metabolism</topic><topic>Ovary - pathology</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Signal Transduction - drug effects</topic><topic>Stemness</topic><topic>Zuogui pill</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Zuang</creatorcontrib><creatorcontrib>Liang, Yunyi</creatorcontrib><creatorcontrib>Wang, Yixuan</creatorcontrib><creatorcontrib>Lin, Yuewei</creatorcontrib><creatorcontrib>Zeng, Lihua</creatorcontrib><creatorcontrib>Zhang, Yuying</creatorcontrib><creatorcontrib>Zhu, Ling</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of ethnopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Zuang</au><au>Liang, Yunyi</au><au>Wang, Yixuan</au><au>Lin, Yuewei</au><au>Zeng, Lihua</au><au>Zhang, Yuying</au><au>Zhu, Ling</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Zuogui Pills alleviate cyclophosphamide-induced ovarian aging by reducing oxidative stress and restoring the stemness of oogonial stem cells through the Nrf2/HO-1 signaling pathway</atitle><jtitle>Journal of ethnopharmacology</jtitle><addtitle>J Ethnopharmacol</addtitle><date>2024-10-28</date><risdate>2024</risdate><volume>333</volume><spage>118505</spage><pages>118505-</pages><artnum>118505</artnum><issn>0378-8741</issn><issn>1872-7573</issn><eissn>1872-7573</eissn><abstract>Zuogui Pill (ZGP) is a traditional herbal formula of Chinese Medicine with a long history of use in alleviating ovarian aging.
To examine the impact of ZGP on oxidative stress and the stemness of oogonial stem cells (OSCs) in cyclophosphamide (CTX)-induced ovarian aging, as well as its molecular mechanisms involving the nuclear factor erythroid 2-related factor 2 (Nrf2, NFE2L2)/heme oxygenase-1 (HO-1, Hmox1) pathway.
Female Sprague-Dawley (SD) rats were randomly divided into seven groups: control, model (CTX), estradiol valerate (EV, 0.103 mg/kg), ZGP-L (low dose Zuogui Pill, 1.851 g/kg), ZGP-H (high dose Zuogui Pill, 3.702 g/kg), ML385 (30 mg/kg), and ML385+ZGP-L. After CTX modeling, the EV, ZGP-L, ZGP-H, and ML385+ZGP-L groups were treated by gavage for 8 weeks, while the ML385 and ML385+ZGP-L groups were administered the Nrf2 antagonist ML385 twice a week. OSCs were isolated after modeling and then treated with drug serum containing 10% ZGP or 10 μM ML385. The general conditions of the rats, including body weight, ovarian weight/body weight ratio, and estrous cycle, were observed. Ovarian ultrastructure, follicle and corpus luteum counts were assessed via hematoxylin and eosin (H&E) staining. Serum hormone levels were measured using enzyme-linked immunosorbent assay (ELISA). Nrf2/HO-1 pathway, stem cell, germ cell, and cell cycle biomarkers were analyzed by qPCR and Western blot. Cell viability was assessed by cell counting kit-8 (CCK-8) assay. Oxidative stress biomarkers were evaluated using flow cytometry and assay kits. Immunofluorescence was employed to detect and locate OSCs in the ovary, quantify the average fluorescence intensity, and identify OSCs.
After ZGP treatment, rats with CTX-induced ovarian aging exhibited improved general condition, increased body weight, higher total ovarian weight to body weight ratio, and a restoration of the estrous cycle similar to the control group. Serum levels of estradiol (E2) and follicle stimulating hormone (FSH), two sex hormones, were also improved. Ovarian ultrastructure and follicle count at all stages showed improvement. Moreover, the viability and proliferation capacity of OSCs were enhanced following ZGP intervention.
The Nrf2/HO-1 pathway was found to be down-regulated in CTX-induced aging ovarian OSCs. However, ZGP reversed this effect by activating the expression of Nrf2, HO-1, and NAD(P)H oxidoreductase 1 (NQO1), increasing the activity of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), and reducing the accumulation of malonaldehyde (MDA) and reactive oxygen species (ROS), thus restoring resistance to oxidative stress.
Additionally, ZGP improved the cell cycle of OSCs, up-regulated the expression of Cyclin D1 and Cyclin E1, restored cell stemness, promoted proliferation, enhanced the expression of cell stemness markers octamer-binding transcription factor 4 (Oct4) and mouse VASA homolog (MVH), and down-regulated the expression of P21, thereby inhibiting apoptosis.
The therapeutic effects of ZGP against oxidative stress and restoration of cell stemness were attenuated following inhibition of the Nrf2 signaling pathway using ML385.
ZGP protected against CTX-induced ovarian aging by restoring normal ovarian function, alleviating oxidative stress in aging OSCs, promoting OSCs proliferation, and restoring their stemness in rats, possibly through regulating the Nrf2/HO-1 pathway.
[Display omitted]
•ZGP restores ovarian function impaired by cyclophosphamide-induced ovarian aging.•ZGP mitigates oxidative stress in aging ovaries via Nrf2/HO-1.•ZGP reduces oxidative stress and restores stemness in aging OSCs via Nrf2/HO-1.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>38945466</pmid><doi>10.1016/j.jep.2024.118505</doi></addata></record> |
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| ispartof | Journal of ethnopharmacology, 2024-10, Vol.333, p.118505, Article 118505 |
| issn | 0378-8741 1872-7573 1872-7573 |
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| source | MEDLINE; Access via ScienceDirect (Elsevier) |
| subjects | Aging - drug effects Animals Cyclophosphamide Drugs, Chinese Herbal - pharmacology Female Heme Oxygenase (Decyclizing) - metabolism Heme Oxygenase-1 - metabolism NF-E2-Related Factor 2 - metabolism Nrf2/HO-1 Oogonial Stem Cells - drug effects OSCs Ovarian aging Ovary - drug effects Ovary - metabolism Ovary - pathology Oxidative stress Oxidative Stress - drug effects Rats Rats, Sprague-Dawley Signal Transduction - drug effects Stemness Zuogui pill |
| title | Zuogui Pills alleviate cyclophosphamide-induced ovarian aging by reducing oxidative stress and restoring the stemness of oogonial stem cells through the Nrf2/HO-1 signaling pathway |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-20T18%3A34%3A35IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Zuogui%20Pills%20alleviate%20cyclophosphamide-induced%20ovarian%20aging%20by%20reducing%20oxidative%20stress%20and%20restoring%20the%20stemness%20of%20oogonial%20stem%20cells%20through%20the%20Nrf2/HO-1%20signaling%20pathway&rft.jtitle=Journal%20of%20ethnopharmacology&rft.au=Li,%20Zuang&rft.date=2024-10-28&rft.volume=333&rft.spage=118505&rft.pages=118505-&rft.artnum=118505&rft.issn=0378-8741&rft.eissn=1872-7573&rft_id=info:doi/10.1016/j.jep.2024.118505&rft_dat=%3Cproquest_cross%3E3074133628%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3074133628&rft_id=info:pmid/38945466&rft_els_id=S0378874124008043&rfr_iscdi=true |