鞣花酸及其代谢物对山羊卵巢颗粒细胞促增殖、抗氧化、抑凋亡的效果对比研究

doi:10.11843/j.issn.0366-6964.2025.12.024

畜牧兽医学报 ›› 2025, Vol. 56 ›› Issue (12): 6219-6231.doi: 10.11843/j.issn.0366-6964.2025.12.024

鞣花酸及其代谢物对山羊卵巢颗粒细胞促增殖、抗氧化、抑凋亡的效果对比研究

陈怡¹^,²(), 刘彬¹^,², 张习录¹^,², 陆情梅¹^,², 潘智仁¹^,², 施晓丽¹^,², 罗志军³, 赵佳福¹^,²^,*()

1. 贵州大学高原山地动物遗传育种与繁殖教育部重点实验室/贵州省动物遗传育种与繁殖重点实验室, 贵阳 550025
2. 贵州大学动物科学学院, 贵阳 550025
3. 贵阳倍隆生物科技有限公司, 贵阳 550214

收稿日期:2025-05-14 出版日期:2025-12-23 发布日期:2025-12-24
通讯作者: 赵佳福 E-mail:3330436407@qq.com;jfzhao@gzu.edu.cn
作者简介:陈怡(2000-)，女，浙江泰顺人，硕士，主要从事动物繁殖生理调控的研究，E-mail: 3330436407@qq.com
基金资助:
贵州省科技计划项目(黔科合支撑[2022]一般089)；贵州省“生物育种先导性研究”项目(黔科合支撑[2022]重点033)；贵州省科技创新团队项目(黔科合平台人才-CXTD[2023]025)

A Comparative Study on the Effects of Ellagic Acid and Its Metabolites on Proliferation Promotion, Antioxidation, Apoptosis Inhibition of Goat Ovarian Granulosa Cells

CHEN Yi¹^,²(), LIU Bin¹^,², ZHANG Xilu¹^,², LU Qingmei¹^,², PAN Zhiren¹^,², SHI Xiaoli¹^,², LUO Zhijun³, ZHAO Jiafu¹^,²^,*()

1. Key Laboratory of Genetic, Breeding and Reproduction of Highland Mountain Animals of Ministry of Education/Key Laboratory of Animal Genetic, Breeding and Reproduction of Guizhou Province, Guizhou University, Guiyang 550025, China
2. School of Animal Science, Guizhou University, Guiyang 550025, China
3. Guiyang Beilong Biotechnology Co., Ltd., Guiyang 550214, China

Received:2025-05-14 Online:2025-12-23 Published:2025-12-24
Contact: ZHAO Jiafu E-mail:3330436407@qq.com;jfzhao@gzu.edu.cn

摘要/Abstract

摘要：

旨在研究鞣花酸(EA)及其代谢物尿石素A(UA)、尿石素B(UB)和尿石素C(UC)对贵州黑山羊卵巢颗粒细胞(OGCs)促增殖、抗氧化、抑凋亡的效果对比，以期寻找相较于EA更优的选择。本研究通过采集健康且性成熟的羊卵巢组织，分离培养OGCs，经鉴定后用于后续研究。同时，基于课题组前人的研究发现，1 μmol·L^-1浓度的EA对OGCs具有最优的生物学效应。因此，试验分为5组：对照组(CON组)、EA组、UA组、UB组、UC组，处理组分别添加1 μmol·L^-1对应药物。随后，采用CCK-8检测添加各组药物0、24、36及48 h对OGCs细胞增殖的影响，采用细胞划痕试验检测其对OGCs细胞迁移的影响，采用ROS试剂盒检测其对OGCs的ROS水平影响，最后通过qRT-PCR检测其对抗凋亡基因Bcl-2，促凋亡基因Bax、Caspase-3、Caspase-9，炎症因子IL-1β、IL-6、TNF-α及繁殖相关基因GDF9、BMPR-1B、CYP19A1、FSHβ mRNA表达的影响。UA对OGCs的增殖效果最好，其次是EA与UB，最后是UC；细胞划痕试验发现UA显著促进了细胞迁移能力，UB显著抑制了细胞迁移，且EA与UA相比，两者之间并无显著性差异；ROS试验发现，UA与EA显著降低了细胞内ROS含量；qRT-PCR结果发现，与CON组相比，UA、UB、UC、EA组中促凋亡基因CASP3、CASP9、BAX的mRNA表达水平显著降低，而在抗凋亡方面，UA组中BCL-2的表达量显著高于其他组。对炎症因子mRNA表达水平的检测结果显示，UA、UC、EA组IL-1β相对表达量显著低于CON组，且UA组mRNA表达量最低；各组IL-6的表达量与CON组无显著差异，但TNF-α含量均显著降低。对繁殖相关基因的检测结果显示，UA、EA组GDF9、BMPR-1B、CYP19A1和FSHβ的表达量均显著高于CON组，其中UA组表达量最高。本研究发现，与EA及EA其他代谢物相比，UA在促进OGCs增殖、迁移、抗氧化、抗凋亡及调控生殖-炎症相关基因表达方面具有显著优势，可作为哺乳动物繁殖调控的重要添加剂进行深入研究。

关键词: 鞣花酸, 卵巢颗粒细胞, 代谢产物, 效果对比研究

Abstract:

This study aimed to compare the effects of ellagic acid (EA) and its metabolites urolithin A (UA), urolithin B (UB), and urolithin C (UC) on promoting proliferation, enhancing antioxidant activity, inhibiting apoptosis in Guizhou black goat ovarian granulosa cells (OGCs), in order to identify a superior alternative to EA.Ovarian tissues from healthy, sexually mature goats were collected to isolate and culture OGCs, which were validated for subsequent experiments. At the same time, based on previous research findings of the research group, 1 μmol·L^-1 concentration of EA had the optimal biological effect on OGCs. Therefore, cells were divided into 5 groups: control (CON), EA, UA, UB, and UC, with treatment groups supplemented with 1 μmol·L^-1 of the corresponding compounds. Proliferation was assessed via CCK-8 assay at 0, 24, 36, and 48 h. Cell migration was evaluated using a scratch assay. Intracellular ROS levels were measured using ROS detection kits. RT-qPCR was employed to analyze mRNA expression of anti-apoptotic (Bcl-2), pro-apoptotic (Bax, Caspase-3, Caspase-9), inflammatory factors (IL-1β, IL-6, TNF-α), and reproduction-related genes (GDF9, BMPR-1B, CYP19A1, FSHβ). UA exhibited the strongest pro-proliferative effect on OGCs, followed by EA and UB, with UC showing the weakest activity. The scratch assay revealed that UA significantly enhanced cell migration, whereas UB inhibited migration; no significant difference was observed between EA and UA. ROS levels were markedly reduced in UA and EA groups. qRT-PCR results demonstrated that UA, UB, UC, and EA significantly downregulated pro-apoptotic genes (CASP3, CASP9, BAX) compared to the CON group. UA upregulated BCL-2 expression most prominently. Among inflammatory factors, UA, UC, and EA significantly suppressed IL-1β expression (with UA being the lowest), there was no significant differences between CON group and other groups, while TNF-α levels decreased across all groups. UA and EA significantly enhanced the expression of reproduction-related genes (GDF9, BMPR-1B, CYP19A1, FSHβ), with UA showing the highest efficacy. In this study, compared to EA and other metabolites, UA demonstrated superior effects in promoting OGCs proliferation and migration, reducing oxidative stress and apoptosis, and modulating reproductive-inflammatory gene expression. These findings highlight UA as a promising candidate for further research as a reproductive regulatory additive in mammals.

Key words: ellagic acid, ovarian granulosa cells, metabolites, comparative study of effects

中图分类号:

S827.3

陈怡, 刘彬, 张习录, 陆情梅, 潘智仁, 施晓丽, 罗志军, 赵佳福. 鞣花酸及其代谢物对山羊卵巢颗粒细胞促增殖、抗氧化、抑凋亡的效果对比研究[J]. 畜牧兽医学报, 2025, 56(12): 6219-6231.

CHEN Yi, LIU Bin, ZHANG Xilu, LU Qingmei, PAN Zhiren, SHI Xiaoli, LUO Zhijun, ZHAO Jiafu. A Comparative Study on the Effects of Ellagic Acid and Its Metabolites on Proliferation Promotion, Antioxidation, Apoptosis Inhibition of Goat Ovarian Granulosa Cells[J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(12): 6219-6231.

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参考文献 62

1	周明帅. COL1A1调控卵巢颗粒细胞生物学功能影响贵州黑山羊产羔性状的研究[D]. 贵阳: 贵州大学, 2023.
	ZHOU M S, COL1A1 regulates the biological function ofovarian granulosa cells and affects the kiddingtraits of guizhou black goats Abstract[D]. Guiyang: Guizhou University, 2023. (in Chinese)
2	ZHANG F L , KONG L , ZHAO A H , et al. Inflammatory cytokines as key players of apoptosis induced by environmental estrogens in the ovary[J]. Environ Res, 2021, 198, 111225. doi: 10.1016/j.envres.2021.111225
3	YANG H , XIE Y , YANG D , et al. Oxidative stress-induced apoptosis in granulosa cells involves JNK, p53 and Puma[J]. Oncotarget, 2017, 8 (15): 25310- 25322. doi: 10.18632/oncotarget.15813
4	XUE H , HU Z , LIU S , et al. The mechanism of NF-kappaB-TERT feedback regulation of granulosa cell apoptosis in PCOS rats[J]. PLoS One, 2024, 19 (10): e312115.
5	LANDETE J M . Ellagitannins, ellagic acid and their derived metabolites: a review about source, metabolism, functions and health[J]. Food Res Int, 2011, 44, 1150- 1160. doi: 10.1016/j.foodres.2011.04.027
6	SHARIFI-RAD J , QUISPE C , CASTILLO C , et al. Ellagic acid: a review on its natural sources, chemical stability, and therapeutic potential[J]. Oxid Med Cell Longev, 2022, 2022, e848084.
7	WEN X , ZHOU M , LU Q , et al. Addition of ellagic acid improved the immune ability and delayed the apoptosis of ovarian granulosa cells of guizhou black goat[J]. Anim Prod Sci, 2024, 64 (1): 1- 11.
8	CECI C , GRAZIANI G , FARAONI I , et al. Strategies to improve ellagic acid bioavailability: from natural or semisynthetic derivatives to nanotechnological approaches based on innovative carriers[J]. Nanotechnology, 2020, 31 (38): 382001. doi: 10.1088/1361-6528/ab912c
9	GARCÍA-VILLALBA R , ESPÍN J C , TOMÁS-BARBERÁN F A . Chromatographic and spectroscopic characterization of urolithins for their determination in biological samples after the intake of foods containing ellagitannins and ellagic acid[J]. J Chromatogr A, 2016, 1428, 162- 175. doi: 10.1016/j.chroma.2015.08.044
10	LUDWIG I A , MENA P , CALANI L , et al. New insights into the bioavailability of red raspberry anthocyanins and ellagitannins[J]. Free Radic Biol Med, 2015, 89, 758- 769. doi: 10.1016/j.freeradbiomed.2015.10.400
11	XIAN W , YANG S , DENG Y , et al. Distribution of urolithins metabotypes in healthy chinese youth: difference in gut microbiota and predicted metabolic pathways[J]. J Agric Food Chem, 2021, 69 (44): 13055- 13065. doi: 10.1021/acs.jafc.1c04849
12	石莹, 杜凤, 王玥, 等. 尿石素A的药理作用及机制研究进展[J]. 中南药学, 2022, 20 (1): 113- 120.
	SHI Y , DU F , WANG Y , et al. Research progress in pharmacological effect and mechanism of urolithin A[J]. Central South Pharmacy, 2022, 20 (1): 113- 120.
13	ANDREUX P A , BLANCO-BOSE W , RYU D , et al. The mitophagy activator urolithin a is safe and induces a molecular signature of improved mitochondrial and cellular health in humans[J]. Nat Metab, 2019, 1 (6): 595- 603. doi: 10.1038/s42255-019-0073-4
14	ROGOVSKII V S , MATYUSHIN A I , SHIMANOVSKII N L . Influence of urolithin a on cytokine production by various cancer cell lines[J]. Pharm Chem J, 2023, 57, 481- 485. doi: 10.1007/s11094-023-02909-x
15	GARCÍA-VILLALBA R , GIMÉNEZ-BASTIDA J A , CORTÉS-MARTÍN A , et al. Urolithins: a comprehensive update on their metabolism, bioactivity, and associated gut microbiota[J]. Mol Nutr Food Res, 2022, 66 (21): e2101019. doi: 10.1002/mnfr.202101019
16	MA M , WANG Y , FAN S , et al. Urolithin a alleviates colitis in mice by improving gut microbiota dysbiosis, modulating microbial tryptophan metabolism, and triggering AhR activation[J]. J Agric Food Chem, 2023, 71 (20): 7710- 7722. doi: 10.1021/acs.jafc.3c00830
17	CHEN P , GUO Z , CHEN F , et al. Recent advances and perspectives on the health benefits of urolithin b, a bioactive natural product derived from ellagitannins[J]. Front Pharmacol, 2022, 13, 917266. doi: 10.3389/fphar.2022.917266
18	KANG I , KIM Y , TOMÁS-BARBERÁN F A , et al. Urolithin a, c, and d, but not iso-urolithin a and urolithin b, attenuate triglyceride accumulation in human cultures of adipocytes and hepatocytes[J]. Mol Nutr Food Res, 2016, 60 (5): 1129- 1138. doi: 10.1002/mnfr.201500796
19	SAVI M , BOCCHI L , MENA P , et al. In vivo administration of urolithin a and b prevents the occurrence of cardiac dysfunction in streptozotocin-induced diabetic rats[J]. Cardiovasc Diabetol, 2017, 16 (1): 80. doi: 10.1186/s12933-017-0561-3
20	HU J , MESNAGE R , TUOHY K , et al. (Poly)phenol-related gut metabotypes and human health: an update[J]. Food Funct, 2024, 15 (6): 2814- 2835. doi: 10.1039/D3FO04338J
21	ZHANG M , CUI S , MAO B , et al. Ellagic acid and intestinal microflora metabolite urolithin a: a review on its sources, metabolic distribution, health benefits, and biotransformation[J]. Crit Rev Food Sci Nutr, 2023, 63 (24): 6900- 6922. doi: 10.1080/10408398.2022.2036693
22	GARCÍA-VILLALBA R , GIMÉNEZ-BASTIDA J A , CORTÉS-MARTÍN A , et al. Urolithins: a comprehensive update on their metabolism, bioactivity, and associated gut microbiota[J]. Mol Nutr Food Res, 2022, 66 (21): e2101019. doi: 10.1002/mnfr.202101019
23	汪鸽, 韩延华. 早发性卵巢功能不全的颗粒细胞凋亡机制及中医药干预研究进展[J]. 中医药信息, 2022, 39 (2): 83- 88.
	WANG G , HAN Y H . Research progress in mechanism of granulosa cell apoptosis in POI and TCM intervention[J]. Information on Traditional Chinese Medicine, 2022, 39 (2): 83- 88.
24	徐保阳, 秦文峡, 晏向华. 母猪卵泡发育质量的营养调控研究进展[J]. 动物营养学报, 2022, 34 (10): 6334- 6342.
	XU B Y , QIN W X , YAN X H . Advances in nutritional regulation of follicular development quality of sows[J]. Chinese Journal of Animal Nutrition, 2022, 34 (10): 6334- 6342.
25	HE Y , DENG H , JIANG Z , et al. Effects of melatonin on follicular atresia and granulosa cell apoptosis in the porcine[J]. Mol Reprod Dev, 2016, 83 (8): 692- 700. doi: 10.1002/mrd.22676
26	GONZÁLEZ-SARRÍAS A , NÚÑEZ-SÁNCHEZ M Á , GARCÍA-VILLALBA R , et al. Antiproliferative activity of the ellagic acid-derived gut microbiota isourolithin A and comparison with its urolithin a isomer: the role of cell metabolism[J]. Eur J Nutr, 2017, 56 (2): 831- 841. doi: 10.1007/s00394-015-1131-7
27	CHEN H , BAI M , ZHANG T , et al. Ellagic acid induces cell cycle arrest and apoptosis through TGF-β/Smad3 signaling pathway in human breast cancer MCF-7 cells[J]. Int J Oncol, 2015, 46 (4): 1730- 1738. doi: 10.3892/ijo.2015.2870
28	MALIK A , AFAQ S , SHAHID M , et al. Influence of ellagic acid on prostate cancer cell proliferation: a caspase-dependent pathway[J]. Asian Pac J Trop Med, 2011, 4 (7): 550- 555. doi: 10.1016/S1995-7645(11)60144-2
29	张颖, 陈茜, 石华, 等. 尿石素A对肾癌786-O细胞的作用机制研究[J]. 湖南师范大学学报(医学版), 2024, 21 (1): 20- 25.
	ZHANG Y , CHEN Q , SHI H , et al. Biological effects of urolithin a on renal carcinoma 786-O cells[J]. Journal of Hunan Normal University(Medical Sciences), 2024, 21 (1): 20- 25.
30	陈婷婷, 吴宿慧, 李根林, 等. 鞣花酸类成分的肠道菌代谢过程及其药理作用变化研究进展[J]. 中国现代应用药学, 2024, 41 (21): 2982- 2989.
	CHEN T T , WU S H , LI G L , et al. Research progress on cut microbiota metabolism process and pharmacological effects of ellagic acid components[J]. Chinese Journal of Modern Applied Pharmacy, 2024, 41 (21): 2982- 2989.
31	ZHU H , YAN Y , JIANG Y , et al. Ellagic acid and its anti-aging effects on central nervous system[J]. Int J Mol Sci, 2022, 23 (18): 10937. doi: 10.3390/ijms231810937
32	UMESALMA S , SUDHANDIRAN G . Differential inhibitory effects of the polyphenol ellagic acid on inflammatory mediators NF-kappaB, iNOS, COX-2, TNF-alpha, and IL-6 in 1, 2-dimethylhydrazine-induced rat colon carcinogenesis[J]. Basic Clin Physiol Pharmacol, 2010, 107 (2): 650- 655. doi: 10.1111/j.1742-7843.2010.00565.x
33	张建伟. 板栗壳斗鞣花单宁及其代谢产物鞣花酸和尿石素的生物活性研究[D]. 北京: 北京林业大学, 2015.
	ZHANG J W. Studies on biological activities of euclidean tannins from burso of castanea mollissima. and their metabolic products ellagic acid and urolithin[D]. Beijing: Beijing Forestry University, 2015. (in Chinese)
34	温晓艳. 鞣花酸对玉米赤霉烯酮诱导贵州黑山羊卵巢颗粒细胞损伤的改善作用[D]. 贵阳: 贵州大学, 2024.
	WEN X Y. The improvement effect of ellagic acid on zearalenone-induced ovarian granulosa cell damage in guizhou black goats[D]. Guiyang: Guizhou University, 2024. (in Chinese)
35	ZHEN X , WU B , WANG J , et al. Increased incidence of mitochondrial cytochrome c oxidase 1 gene mutations in patients with primary ovarian insufficiency[J]. PLoS One, 2015, 10 (7): e132610.
36	DEVINE P J , PERREAULT S D , LUDERER U . Roles of reactive oxygen species and antioxidants in ovarian toxicity[J]. Biol Reprod, 2012, 86 (2): 27.
37	ESPÍN J C , LARROSA M , GARCÍA-CONESA M T , et al. Biological significance of urolithins, the gut microbial ellagic acid-derived metabolites: the evidence so far[J]. Evid Based Complement Alternat Med, 2013, 2013, 270418.
38	AHN D , PUTT D , KRESTY L , et al. The effects of dietary ellagic acid on rat hepatic and esophageal mucosal cytochromes P450 and phase Ⅱ enzymes[J]. Carcinogenesis, 1996, 17 (4): 821- 828. doi: 10.1093/carcin/17.4.821
39	GALANO A , FRANCISCO M M , PÉREZ-GONZÁLEZ A . Ellagic acid: an unusually versatile protector against oxidative stress[J]. Chem Res Toxicol, 2014, 27 (5): 904- 918. doi: 10.1021/tx500065y
40	SHAFIE B , POURAHMAD J , REZAEI M . N-acetylcysteine is more effective than ellagic acid in preventing acrolein induced dysfunction in mitochondria isolated from rat liver[J]. J Food Biochem, 2021, 45 (7): e13775.
41	XIAO Y , HUANG R , WANG N , et al. Ellagic acid alleviates oxidative stress by mediating Nrf2 signaling pathways and protects against paraquat-induced intestinal injury in piglets[J]. Antioxidants (Basel), 2022, 11 (2): 252. doi: 10.3390/antiox11020252
42	LARROSA M , GONZÁLEZ-SARRÍAS A , YÁÑEZ-GASCÓN M J , et al. Anti-inflammatory properties of a pomegranate extract and its metabolite urolithin-A in a colitis rat model and the effect of colon inflammation on phenolic metabolism[J]. J Nutr Biochem, 2010, 21 (8): 717- 725. doi: 10.1016/j.jnutbio.2009.04.012
43	HARPER P . A review of the dietary intake, bioavailability and health benefits of ellagic acid (EA) with a primary focus on its anti-cancer properties[J]. Cureus, 2023, 15 (8): e43156.
44	HOU Y , CHU X , PARK J , et al. Urolithin a improves alzheimer's disease cognition and restores mitophagy and lysosomal functions[J]. Alzheimers Dement, 2024, 20 (6): 4212- 4233. doi: 10.1002/alz.13847
45	CHEN P , WU L , LEI J , et al. The ellagitannin metabolite urolithin c attenuated cognitive impairment by inhibiting neuroinflammation via downregulation of MAPK/NF-kB signaling pathways in aging mice[J]. Int Immunopharmacol, 2024, 142 (Pt B): 113151.
46	贾晓燕, 胡朋朋, 王佩欣, 等. 覆盆子单宁富集组分消化稳定性及对肠道菌群的调节作用[J]. 食品科学, 2023, 44 (9): 104- 113.
	JIA X Y , HU P P , WANG P X , et al. Digestive stability of tannin-enriched fraction of rubus chingii hu fruits and its regulatory effect on the intestinal microflora[J]. Food Science, 2023, 44 (9): 104- 113.
47	HUO Y , LI Q , YANG L , et al. SDNOR, a Novel antioxidative lncRNA, is essential for maintaining the normal state and function of porcine follicular granulosa cells[J]. Antioxidants (Basel), 2023, 12 (4): 799. doi: 10.3390/antiox12040799
48	ELGEBALY M M , HAZAA A B M , AMER H A , et al. L-Cysteine improves bovine oocyte developmental competence in vitro via activation of oocyte-derived growth factors BMP-15 and GDF-9[J]. Reprod Domest Anim, 2022, 57 (7): 734- 742. doi: 10.1111/rda.14113
49	SHI X , JIN X , LIN J , et al. Idebenone relieves the damage of heat stress on the maturation and developmental competence of porcine oocytes[J]. Reprod Domest Anim, 2022, 57 (4): 418- 428. doi: 10.1111/rda.14080
50	AZAMI S H , NAZARIAN H , ABDOLLAHIFAR M A , et al. The antioxidant curcumin postpones ovarian aging in young and middle-aged mice[J]. Reprod Fertil Dev, 2020, 32 (3): 292- 303. doi: 10.1071/RD18472
51	SRI R , SASANGKA P , JANTJE S , et al. Luteinizing hormone effect on the GDF-9 and BMPR-1a expression of bovine granulosa cells culture[J]. IOP Conf Ser: Mater Sci Eng, 2019, 546 (6): 62021. doi: 10.1088/1757-899X/546/6/062021
52	CHRISTENSON L K , DEVOTO L . Cholesterol transport and steroidogenesis by the corpus luteum[J]. Reprod Biol Endocrinol, 2003, 1, 90. doi: 10.1186/1477-7827-1-90
53	MA X , YI H . BMP15 regulates FSHR through TGF-β receptor Ⅱ and SMAD4 signaling in prepubertal ovary of Rongchang pigs[J]. Res Vet Sci, 2022, 143, 66- 73. doi: 10.1016/j.rvsc.2021.12.013
54	BANG Y , KWON Y , KIM M , et al. Ursolic acid enhances autophagic clearance and ameliorates motor and non-motor symptoms in parkinson's disease mice model[J]. Acta Pharmacol Sin, 2023, 44 (4): 752- 765. doi: 10.1038/s41401-022-00988-2
55	WANG Y , REN F , LI B , et al. Ellagic acid exerts antitumor effects via the PI3K signaling pathway in endometrial cancer[J]. J Cancer, 2019, 10 (15): 3303- 3314. doi: 10.7150/jca.29738
56	SHEN M , LIU Z , LI B , et al. Involvement of FoxO1 in the effects of follicle-stimulating hormone on inhibition of apoptosis in mouse granulosa cells[J]. Cell Death Dis, 2014, 5 (10): e1475. doi: 10.1038/cddis.2014.400
57	HUNZICKER-DUNN M E , LOPEZ-BILADEAU B , LAW N C , et al. PKA and GAB2 play central roles in the FSH signaling pathway to PI3K and AKT in ovarian granulosa cells[J]. Proc Natl Acad Sci U S A, 2012, 109 (44): E2979- E2988.
58	CHO J , RHO O , JUNCO J , et al. Effect of combined treatment with ursolic acid and resveratrol on skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate[J]. Cancer Prev Res (Phila), 2015, 8 (9): 817- 825. doi: 10.1158/1940-6207.CAPR-15-0098
59	CASTREJON-JIMENEZ N S , LEYVA-PAREDES K , BALTIERRA-URIBE S L , et al. Ursolic and oleanolic acids induce mitophagy in A549 human lung cancer cells[J]. Molecules, 2019, 24 (19): 3444. doi: 10.3390/molecules24193444
60	LI L , ZHANG X , CUI L , et al. Ursolic acid promotes the neuroprotection by activating Nrf2 pathway after cerebral ischemia in mice[J]. Brain Res, 2013, 1497, 32- 39. doi: 10.1016/j.brainres.2012.12.032
61	GARCIA-VILLALBA R , GIMENEZ-BASTIDA J A , CORTES-MARTIN A , et al. Urolithins: a comprehensive update on their metabolism, bioactivity, and associated gut microbiota[J]. Mol Nutr Food Res, 2022, 66 (21): e2101019. doi: 10.1002/mnfr.202101019
62	SINGH R , CHANDRASHEKHARAPPA S , VEMULA P K , et al. Microbial metabolite urolithin b inhibits recombinant human monoamine oxidase a enzyme[J]. Metabolites, 2020, 10 (6): 258. doi: 10.3390/metabo10060258

基因 Gene	登录号 Accession number	引物序列(5′→3′) Primer sequence	片段大小/bp Products size
IL-1β	XM_013967700.2	F: ATGAGCCGAGAAGTGGTGTTC R: CAGGGTCGGTGTATCACCTT	135
IL-6	NM_001285640.1	F: AATCTGGGTTCAATCAGGCGA R: GCTCTGCAACTCCATGACAG	128
TNF-α	NM_001286442.1	F: GTGGAGCTGGCAGAGGAGGTG R: GGAGGAAGGAGAAGAGGCTGAGG	91
CYP19A1	NM_001285747.1	F: AAGTGCTGAACCCAAGGCAT R: TCCAGTGAGCAGCAGGATTG	89
BMPR-1B	XM_018049152.1	F: CCTGGAGAATCCCTGAGAGAC R: CCCCATAGCGACCTTTTCCA	143
GDF9	XM_013965446.2	F: CACCGCAGAGACCAGGAGAG R: TCCAGTTGTCCCACTTCAGC	135
FSHβ	XM_013969782.2	F: AGATGTCTGTGTGTACATGCG R: GGTTGGCTCTTCTCTTGAGG	122
BCL2	XM_018039337.1	F: TCTTTGAGTTCGGAGGGGTC R: TGGTGGAAGAGTGTGCTGTG	187
BAX	XM_013971446.2	F: CATCGGAGATGAATTGGACACTAA R: GGCCTTGAGCACCAGTTTGC	147
CASP3	NM_001286089.1	F: CCTGGACTGTCGTATTGAGA R: TAACCCGAGTAAGAATGTGC	218
CASP9	XM_005690814.3	F: TGAAGACCAGCAGACAAGC R: AGTGAATCCTCCAGAACCAA	167
β-actin	XM_013975437.2	F: GGTGCCCATCTACGAGG R: CTTGATGTCACGGACGATT	154

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A Comparative Study on the Effects of Ellagic Acid and Its Metabolites on Proliferation Promotion, Antioxidation, Apoptosis Inhibition of Goat Ovarian Granulosa Cells

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