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Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Research Article

Acupuncture Combined with Bushen-Jianpi Decoction Ameliorates the Ovarian Function of Diminished Ovarian Reserve Rats by Regulating Phosphoinositide 3-Kinase/AKT Signaling

Author(s): Jianting Lao, Panwei Hu, Jia Li, Jiahui Li, Xiaole Zhang, Hong Yang* and Cong Qi*

Volume 27, Issue 16, 2024

Published on: 03 January, 2024

Page: [2402 - 2418] Pages: 17

DOI: 10.2174/0113862073264971231113061204

Price: $65

Abstract

Objective: This study aimed to explore the therapeutic efficiency as well as mechanism of acupuncture combined with Bushen-Jianpi decoction (BJD) to treat rats with diminished ovarian reserve (DOR).

Methods: A DOR rat model was constructed using zona pellucida 3 peptide, and acupuncture, BJD, and their combination were administered as therapeutic interventions. We measured changes in the ovarian indexes, the number of follicles at all levels, the serum levels of sex hormones and immune factors, the expression levels of phosphoinositide 3-kinase (PI3K), AKT, p-AKT, and caspase-3, and the changes in the proportions of splenic T cell subtypes, including T-helper 17 (Th17), Tc17, regulatory T (Treg), CD4+, and CD8+ cells.

Results: Acupuncture combined with BJD induced a decrease in the levels of follicle-stimulating and luteinizing hormones, and the effect was greater than that elicited by BJD or acupuncture alone (P < 0.05). Additionally, this combination treatment effectively abrogated the increase in the levels of interleukin-2 (IL-2), IL-17, anti-zona pellucida antibody, and cleaved caspase-3 (P < 0.05), while promoting the regulation of IL-6 and p-AKT (P < 0.01). Furthermore, treatment with acupuncture combined with BJD restored the proportions of CD4+ cells and the CD4+ / CD8+ T cell ratio (P < 0.01), decreased the proportion of CD8+ T and Th17 cells (P < 0.01), and increased the proportions of Tc17 and Treg cells (P < 0.01).

Conclusion: Combining acupuncture with BJD can enhance ovarian function in DOR rats. The regulation of sex hormone levels and immune function in rats may be attributed to the adjustment of the mRNA and proteins levels of PI3K, AKT, and caspase-3 in the PI3K/AKT signaling pathway, which leads to an improvement in the immune function of DOR rats.

[1]
Kesharwani, D.K.; Mohammad, S.; Acharya, N.; Joshi, K.S. Fertility with early reduction of ovarian reserve. Cureus, 2022, 14(10), e30326.
[http://dx.doi.org/10.7759/cureus.30326] [PMID: 36407155]
[2]
Ata, B.; Seyhan, A.; Seli, E. Diminished ovarian reserve versus ovarian aging: overlaps and differences. Curr. Opin. Obstet. Gynecol., 2019, 31(3), 139-147.
[http://dx.doi.org/10.1097/GCO.0000000000000536] [PMID: 30870184]
[3]
Luo, J.; Sun, Z. MicroRNAs in POI, DOR and POR. Arch. Gynecol. Obstet., 2023, 308(5), 1419-1430.
[http://dx.doi.org/10.1007/s00404-023-06922-z] [PMID: 36840768]
[4]
Park, S.U.; Walsh, L.; Berkowitz, K.M. Mechanisms of ovarian aging. Reproduction, 2021, 162(2), R19-R33.
[http://dx.doi.org/10.1530/REP-21-0022] [PMID: 33999842]
[5]
Zhao, N.; Zhang, C.; Ding, J.; Wu, H.; Cheng, W.; Li, M.; Zhu, R.; Li, H. Altered T lymphocyte subtypes and cytokine profiles in follicular fluid associated with diminished ovary reserve. Am. J. Reprod. Immunol., 2022, 87(4), e13522.
[http://dx.doi.org/10.1111/aji.13522] [PMID: 35006631]
[6]
Jiang, X.; Tai, H.; Xiao, X.; Zhang, S.; Cui, S.; Qi, S.; Hu, D.; Zhang, L.; Kuang, J.; Meng, X.; Li, S. Cangfudaotan decoction inhibits mitochondria-dependent apoptosis of granulosa cells in rats with polycystic ovarian syndrome. Front. Endocrinol., 2022, 13, 962154.
[http://dx.doi.org/10.3389/fendo.2022.962154] [PMID: 36465612]
[7]
Yin, N.; Wu, C.; Qiu, J.; Zhang, Y.; Bo, L.; Xu, Y.; Shi, M.; Zhu, S.; Yang, G.; Mao, C. Protective properties of heme oxygenase-1 expressed in umbilical cord mesenchymal stem cells help restore the ovarian function of premature ovarian failure mice through activating the JNK/Bcl-2 signal pathway-regulated autophagy and upregulating the circulating of CD8+CD28− T cells. Stem Cell Res. Ther., 2020, 11(1), 49.
[http://dx.doi.org/10.1186/s13287-019-1537-x] [PMID: 32019599]
[8]
Han, Y.; Wang, S.; Wang, Y.; Zeng, S. IGF-1 inhibits apoptosis of porcine primary granulosa cell by targeting degradation of BimEL. Int. J. Mol. Sci., 2019, 20(21), 5356.
[http://dx.doi.org/10.3390/ijms20215356] [PMID: 31661816]
[9]
Jiao, Y.; Zhu, S.; Li, J.; Jam Zaheer, A.; Li, M.; Huang, B. PS48 promotes in vitro maturation and developmental competence of porcine oocytes through activating PI3K/Akt signalling pathway. Reprod. Domest. Anim., 2020, 55(12), 1678-1687.
[http://dx.doi.org/10.1111/rda.13818] [PMID: 32946622]
[10]
Artini, P.G.; Tatone, C.; Sperduti, S.; D’Aurora, M.; Franchi, S.; Di Emidio, G.; Ciriminna, R.; Vento, M.; Di Pietro, C.; Stuppia, L.; Gatta, V. Cumulus cells surrounding oocytes with high developmental competence exhibit down-regulation of phosphoinositol 1,3 kinase/protein kinase B (PI3K/AKT) signalling genes involved in proliferation and survival. Hum. Reprod., 2017, 32(12), 2474-2484.
[http://dx.doi.org/10.1093/humrep/dex320] [PMID: 29087515]
[11]
Gong, Y.; Luo, S.; Fan, P.; Zhu, H.; Li, Y.; Huang, W. Growth hormone activates PI3K/Akt signaling and inhibits ROS accumulation and apoptosis in granulosa cells of patients with polycystic ovary syndrome. Reprod. Biol. Endocrinol., 2020, 18(1), 121.
[http://dx.doi.org/10.1186/s12958-020-00677-x] [PMID: 33287836]
[12]
Wang, Y.; Teng, X.; Liu, J. Research progress on the effect of traditional chinese medicine on signal pathway related to premature ovarian insufficiency. Evid. Based Complement. Alternat. Med., 2022, 2022, 1-13.
[http://dx.doi.org/10.1155/2022/7012978] [PMID: 36159578]
[13]
Fu, Y.; Ding, D.N.; Shen, Y.; Jia, L.Y.; Yan, M.Y.; Wei, W.; Song, C.H.; Han, F.J. Complementary and alternative medicine for premature ovarian insufficiency: A review of utilization and mechanisms. Evid. Based Complement. Alternat. Med., 2022, 2022, 1-15.
[http://dx.doi.org/10.1155/2022/9053930] [PMID: 35399635]
[14]
Nair, A.; Jacob, S. A simple practice guide for dose conversion between animals and human. J. Basic Clin. Pharm., 2016, 7(2), 27-31.
[http://dx.doi.org/10.4103/0976-0105.177703] [PMID: 27057123]
[15]
Xu, D.S.; Zhao, S.; Cui, J.J.; Ma, T.M.; Xu, B.; Yu, X.C.; Zhu, B.; Jing, X.H.; Bai, W.Z. [A new attempt of re-mapping acupoint atlas in the rat. Zhen Ci Yan Jiu, 2019, 44(1), 62-65.
[PMID: 30773865]
[16]
Yin, N.; Zhao, W.; Luo, Q.; Yuan, W.; Luan, X.; Zhang, H. Restoring ovarian function with human placenta-derived mesenchymal stem cells in autoimmune-induced premature ovarian failure mice mediated by treg cells and associated cytokines. Reprod. Sci., 2018, 25(7), 1073-1082.
[http://dx.doi.org/10.1177/1933719117732156] [PMID: 28954601]
[17]
Yin, N.; Wang, Y.; Lu, X.; Liu, R.; Zhang, L.; Zhao, W.; Yuan, W.; Luo, Q.; Wu, H.; Luan, X.; Zhang, H. Retraction note: hPMSC transplantation restoring ovarian function in premature ovarian failure mice is associated with change of Th17/Tc17 and Th17/Treg cell ratios through the PI3K/Akt signal pathway. Stem Cell Res. Ther., 2022, 13(1), 471.
[http://dx.doi.org/10.1186/s13287-022-03173-8] [PMID: 36104765]
[18]
Li, S.; Hu, L.; Zhang, C. Effect of chronological age of patients with diminished ovarian reserve on in vitro fertilization outcome. J. Obstet. Gynaecol., 2022, 42(4), 654-657.
[http://dx.doi.org/10.1080/01443615.2021.1922996] [PMID: 34384322]
[19]
Ke, H.; Hu, J.; Zhao, L.; Ding, L.; Jiao, X.; Qin, Y. Impact of thyroid autoimmunity on ovarian reserve, pregnancy outcomes, and offspring health in euthyroid women following in vitro fertilization/intracytoplasmic sperm injection. Thyroid, 2020, 30(4), 588-597.
[http://dx.doi.org/10.1089/thy.2018.0657] [PMID: 31928166]
[20]
Serin, A.N.; Birge, Ö.; Uysal, A.; Görar, S.; Tekeli, F. Hashimoto’s thyroiditis worsens ovaries in polycystic ovary syndrome patients compared to Anti-Müllerian hormone levels. BMC Endocr. Disord., 2021, 21(1), 44.
[http://dx.doi.org/10.1186/s12902-021-00706-9] [PMID: 33750377]
[21]
Deng, J.; Yang, C.; Wang, Y.; Yang, M.; Chen, H.; Ning, H.; Wang, C.; Liu, Y.; Zhang, Z.; Hu, T. Inositol pyrophosphates mediated the apoptosis induced by hypoxic injury in bone marrow-derived mesenchymal stem cells by autophagy. Stem Cell Res. Ther., 2019, 10(1), 159.
[http://dx.doi.org/10.1186/s13287-019-1256-3] [PMID: 31159888]
[22]
Wang, S.; Lin, S.; Zhu, M.; Li, C.; Chen, S.; Pu, L.; Lin, J.; Cao, L.; Zhang, Y. Acupuncture reduces apoptosis of granulosa cells in rats with premature ovarian failure via restoring the PI3K/Akt signaling pathway. Int. J. Mol. Sci., 2019, 20(24), 6311.
[http://dx.doi.org/10.3390/ijms20246311] [PMID: 31847241]
[23]
Zhang, H.; Qin, F.; Liu, A.; Sun, Q.; Wang, Q.; Xie, S.; Lu, S.; Zhang, D.; Lu, Z. Electro-acupuncture attenuates the mice premature ovarian failure via mediating PI3K/AKT/mTOR pathway. Life Sci., 2019, 217, 169-175.
[http://dx.doi.org/10.1016/j.lfs.2018.11.059] [PMID: 30521869]
[24]
Wu, H.; Zhang, J.; Sun, Z.; Xiang, S.; Qiao, Y.; Lian, F. Effects of electroacupuncture on expression of pi3k/akt/foxo3a in granulosa cells from women with shen (kidney) deficiency syndrome undergoing in vitro fertilization-embryo transfer. Chin. J. Integr. Med., 2019, 25(4), 252-258.
[http://dx.doi.org/10.1007/s11655-019-2948-3] [PMID: 31236889]
[25]
Liu, H.; Yang, H.; Qin, Z.; Chen, Y.; Yu, H.; Li, W.; Zhu, X.; Cai, J.; Chen, J.; Zhang, M. Exploration of the danggui buxue decoction mechanism regulating the balance of ESR and AR in the TP53-AKT signaling pathway in the prevention and treatment of POF. Evid. Based Complement. Alternat. Med., 2021, 2021, 1-16.
[http://dx.doi.org/10.1155/2021/4862164] [PMID: 35003302]
[26]
Dou, X.; Jin, X.; Chen, X.; Zhou, Q.; Chen, H.; Wen, M.; Chen, W. Bu-Shen-Ning-Xin decoction alleviates premature ovarian insufficiency (POI) by regulating autophagy of granule cells through activating PI3K/AKT/mTOR pathway. Gynecol. Endocrinol., 2022, 38(9), 754-764.
[http://dx.doi.org/10.1080/09513590.2022.2112941] [PMID: 35989579]
[27]
Hu, Y.; Zhong, R.; Guo, X.; Li, G.; Zhou, J.; Yang, W.; Ren, B.; Zhu, Y. Jinfeng pills ameliorate premature ovarian insufficiency induced by cyclophosphamide in rats and correlate to modulating IL-17A/IL-6 axis and MEK/ERK signals. J. Ethnopharmacol., 2023, 307, 116242.
[http://dx.doi.org/10.1016/j.jep.2023.116242] [PMID: 36775079]
[28]
Li, L.; Shi, X.; Shi, Y.; Wang, Z. The signaling pathways involved in ovarian follicle development. Front. Physiol., 2021, 12, 730196.
[http://dx.doi.org/10.3389/fphys.2021.730196] [PMID: 34646156]
[29]
Maidarti, M.; Anderson, R.A.; Telfer, E.E. Crosstalk between PTEN/PI3K/Akt signalling and DNA damage in the Oocyte: Implications for primordial follicle activation, oocyte quality and ageing. Cells, 2020, 9(1), 200.
[http://dx.doi.org/10.3390/cells9010200] [PMID: 31947601]
[30]
Qu, Q.; Liu, L.; Cui, Y.; Liu, H.; Yi, J.; Bing, W.; Liu, C.; Jiang, D.; Bi, Y. miR-126-3p containing exosomes derived from human umbilical cord mesenchymal stem cells promote angiogenesis and attenuate ovarian granulosa cell apoptosis in a preclinical rat model of premature ovarian failure. Stem Cell Res. Ther., 2022, 13(1), 352.
[http://dx.doi.org/10.1186/s13287-022-03056-y] [PMID: 35883161]
[31]
Zheng, K.; Lv, B.; Wu, L.; Wang, C.; Xu, H.; Li, X.; Wu, Z.; Zhao, Y.; Zheng, Z. Protecting effect of emodin in experimental autoimmune encephalomyelitis mice by inhibiting microglia activation and inflammation via Myd88/PI3K/Akt/NF-κB signalling pathway. Bioengineered, 2022, 13(4), 9322-9344.
[http://dx.doi.org/10.1080/21655979.2022.2052671] [PMID: 35287559]
[32]
Esparvarinha, M.; Madadi, S.; Aslanian-Kalkhoran, L.; Nickho, H.; Dolati, S.; Pia, H.; Danaii, S.; Taghavi, S.; Yousefi, M. Dominant immune cells in pregnancy and pregnancy complications: T helper cells (TH1/TH2, TH17/Treg cells), NK cells, MDSCs, and the immune checkpoints. Cell Biol. Int., 2023, 47(3), 507-519.
[http://dx.doi.org/10.1002/cbin.11955] [PMID: 36335635]
[33]
Gong, P.; Wang, D.; Cui, D.; Yang, Q.; Wang, P.; Yang, W.; Chen, F. Anti-aging function and molecular mechanism of radix astragali and radix astragali preparata via network pharmacology and PI3K/Akt signaling pathway. Phytomedicine, 2021, 84, 153509.
[http://dx.doi.org/10.1016/j.phymed.2021.153509] [PMID: 33636579]
[34]
Yuan, Y.; Zhang, Y.; Zheng, R.; Yuan, H.; Zhou, R.; Jia, S.; Liu, J. Elucidating the anti-aging mechanism of Si Jun Zi Tang by integrating network pharmacology and experimental validation in vivo. Aging (Albany NY), 2022, 14(9), 3941-3955.
[http://dx.doi.org/10.18632/aging.204055] [PMID: 35537009]

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