Amygdalin inhibits endometrial stromal cell proliferation, migration, and invasion in endometriosis mice via inhibiting Wnt/β-catenin signaling

To explore the impact of amygdalin on the proliferation, migration, and invasion of human endometrial stromal cells (HESCs) and the possible underlying mechanism. HESCs were incubated with 50, 100, and 200 µg/mL of amygdalin. The malignant activities of HESCs were analyzed by functional experiments. The activation of the Wnt/β-catenin signaling was tested using TOP/FOPFlash. The mRNA expressions of genes were validated by qRT-PCR. The endometriosis (EMS) mouse model was induced and the impact of amygdalin on the growth of ectopic endometrial lesions were assessed. It was observed that amygdalin markedly lessened the malignant activities of HESCs in a dose-dependent way (p < 0.05). Amygdalin dose-dependently declined the activation of TOPFlash and mRNA levels of β-catenin, cyclinD1 and c-Myc in HESCs (p < 0.05). Additionally, the increasing dose of amygdalin progressively inhibited the growth of ectopic endometrial lesions in EMS mouse model (p < 0.05). We reached a conclusion that amygdalin could inhibit the malignant activities of HESCs and alleviate EMS, which was related to Wnt/β-catenin signaling activation. Similar content being viewed by others Data availability No datasets were generated or analysed during the current study.

Al-Khafaji K, Taskin Tok T (2021) Amygdalin as multi-target anticancer drug against targets of cell division cycle: double docking and molecular dynamics simulation. J Biomol Struct Dyn 39(6):1965–1974 Albogami S, Alnefaie A (2021) Role of Amygdalin in blocking DNA replication in breast Cancer in Vitro. Curr Pharm Biotechnol 22(12):1612–1627 Attia AA, Salama AF, Eldiasty JG, Mosallam SAE, El-Naggar SA, El-Magd MA, Nasser HM, Elmetwalli A (2022) Amygdalin potentiates the anti-cancer effect of Sorafenib on Ehrlich ascites carcinoma and ameliorates the associated liver damage. Sci Rep 12(1):6494 Brichant G, Laraki I, Henry L, Munaut C, Nisolle M (2021) New therapeutics in endometriosis: a review of Hormonal, Non-hormonal, and non-coding RNA treatments. Int J Mol Sci 22(19) Chen J, Hu Y, Mou X, Wang H, Xie Z (2021) Amygdalin alleviates renal injury by suppressing inflammation, oxidative stress and fibrosis in streptozotocin-induced diabetic rats. Life Sci 265:118835 Cui L, Xu F, Jiang Z, Wang S, Li X, Ding Y, Zhang Y, Du M (2021) Melatonin regulates proliferation and apoptosis of endometrial stromal cells via MT1. Acta Biochim Biophys Sin (Shanghai) 53(10):1333–1341 Dai Y, Luo H, Zhu L, Yang W, Xiang H, Shi Q, Jin P (2024) Dysmenorrhea pattern in adolescences informing adult endometriosis. BMC Public Health 24(1):373 Doumpas N, Lampart F, Robinson MD, Lentini A, Nestor CE, Cantu C, Basler K (2019) TCF/LEF dependent and independent transcriptional regulation of Wnt/beta-catenin target genes. EMBO J 38(2) Hu F, Hu Y, Peng F (2019) Synergistic and protective effect of atorvastatin and amygdalin against histopathological and biochemical alterations in Sprague-Dawley rats with experimental endometriosis. AMB Express 9(1):37 Jaszczak-Wilke E, Polkowska Z, Koprowski M, Owsianik K, Mitchell AE, Balczewski P (2021) Amygdalin: toxicity, Anticancer Activity and Analytical procedures for its determination in Plant seeds. Molecules 26(8) Jin Z, Zhang Y, Li J, Lv S, Zhang L, Feng Y (2021) Endometriosis stem cell sources and potential therapeutic targets: literature review and bioinformatics analysis. Regen Med 16(10):949–962 Lin Y, Kojima S, Ishikawa A, Matsushita H, Takeuchi Y, Mori Y, Ma J, Takeuchi K, Umezawa K, Wakatsuki A (2023) Inhibition of MLCK–mediated migration and invasion in human endometriosis stromal cells by NF–kappaB inhibitor DHMEQ. Mol Med Rep 28(2) Liu J, Xiao Q, Xiao J, Niu C, Li Y, Zhang X, Zhou Z, Shu G, Yin G (2022) Wnt/beta-catenin signalling: function, biological mechanisms, and therapeutic opportunities. Signal Transduct Target Ther 7(1):3 Liu Y, Zhang W, Jin L, Ren J, Liu Z, Lu D (2023) The role of long noncoding RNAs in endometriosis progression. Front Biosci (Landmark Ed) 28(6):109 Mani J, Neuschafer J, Resch C, Rutz J, Maxeiner S, Roos F, Chun FK, Juengel E, Blaheta RA (2020) Amygdalin modulates prostate Cancer Cell Adhesion and Migration in Vitro. Nutr Cancer 72(3):528–537 Qian L, Xie B, Wang Y, Qian J (2015) Amygdalin-mediated inhibition of non-small cell lung cancer cell invasion in vitro. Int J Clin Exp Pathol 8(5):5363–5370 Saati S, Dehghan P, Azizi-Soleiman F, Mobasseri M (2023) The effect of bitter almond (Amygdalus communis L. var. Amara) gum as a functional food on metabolic profile, inflammatory markers, and mental health in type 2 diabetes women: a blinded randomized controlled trial protocol. Trials 24(1):35 Schunk SJ, Floege J, Fliser D, Speer T (2021) WNT-beta-catenin signalling - a versatile player in kidney injury and repair. Nat Rev Nephrol 17(3):172–184 Shi L, Xue X, Tian H, Ye H, Wang H, Wang R, Liu Y, Zhang C, Chen Q, Sun L (2021) WEE1 promotes endometriosis via the Wnt/beta-catenin signaling pathway. Reprod Biol Endocrinol 19(1):161 Tassinari V, Smeriglio A, Stillittano V, Trombetta D, Zilli R, Tassinari R, Maranghi F, Frank G, Marcoccia D, Di Renzo L (2023) Endometriosis treatment: role of natural polyphenols as anti-inflammatory agents. Nutrients 15(13) Vannuccini S, Clemenza S, Rossi M, Petraglia F (2022) Hormonal treatments for endometriosis: the endocrine background. Rev Endocr Metab Disord 23(3):333–355 Wang W, Xiao XZ, Xu XQ, Li ZJ, Zhang JM (2021) Variation in Amygdalin Content in Kernels of six almond species (Prunus Spp. L.) distributed in China. Front Plant Sci 12:753151 Xu Y, Hu J, Lv Q, Shi C, Qiu M, Xie L, Liu W, Yang B, Shan W, Cheng Y et al (2023) Endometrium-derived mesenchymal stem cells suppress progression of endometrial cancer via the DKK1-Wnt/beta-catenin signaling pathway. Stem Cell Res Ther 14(1):159 Yang Q, Wang Y, Cai H, Zhou Q, Zeng L, Li S, Du H, Wei W, Zhang W, Dai W et al (2023) Translocation of vaginal and cervical low-abundance non-lactobacillus bacteria notably associate with endometriosis: a pilot study. Microb Pathog 183:106309 Zhang C, Zhang Y, Pan H, Tan Y, Wei Q, Dai X, Wei J, Chen Y (2021) Combination of Ferulic Acid, Ligustrazine and Tetrahydropalmatine attenuates epithelial-mesenchymal Transformation via Wnt/beta-catenin pathway in endometriosis. Int J Biol Sci 17(10):2449–2460 Zhang L, Li Y, Dong YC, Guan CY, Tian S, Lv XD, Li JH, Su X, Xia HF, Ma X (2022a) Transplantation of umbilical cord-derived mesenchymal stem cells promotes the recovery of thin endometrium in rats. Sci Rep 12(1):412 Zhang T, Yang S, Zhang B, Yang D, Lu Y, Du G (2022b) Insights into the properties of Amygdalin Solvatomorphs: X-ray structures, Intermolecular Interactions, and transformations. ACS Omega 7(10):8906–8918 Zhang G, Li H, Sun L, Liu Y, Cao Y, Ren X, Liu Y (2023) Study on the correlation between the appearance traits and intrinsic chemical quality of bitter almonds based on fingerprint-chemometrics. J Chromatogr Sci 61(2):110–118 Zhang Y, Sun X, Li Z, Han X, Wang W, Xu P, Liu Y, Xue Y, Wang Z, Xu S et al (2024) Interactions between miRNAs and the Wnt/beta-catenin signaling pathway in endometriosis. Biomed Pharmacother 171:116182 Zhao H, Ming T, Tang S, Ren S, Yang H, Liu M, Tao Q, Xu H (2022) Wnt signaling in colorectal cancer: pathogenic role and therapeutic target. Mol Cancer 21(1):144 Zhou Y, Xu J, Luo H, Meng X, Chen M, Zhu D (2022) Wnt signaling pathway in cancer immunotherapy. Cancer Lett 525:84–96 Author information Authors and Affiliations Contributions Miao Miao Yu and Lu Yang were responsible for conception and design. Miao Miao Yu was responsible for manuscript writing. Miao Miao Yu, Lu Yang and Yong Hong Pei were responsible for collection and assembly of data. Miao Miao Yu, Lu Yang and Mei Xu were responsible for data analysis and interpretation. All authors were responsible for the final approval of the manuscript. Corresponding author Ethics declarations Competing interests The authors declare no competing interests. Additional information Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Yu, M., Yang, L., Pei, Y. et al. Amygdalin inhibits endometrial stromal cell proliferation, migration, and invasion in endometriosis mice via inhibiting Wnt/β-catenin signaling. J Mol Histol 56, 11 (2025). https://doi.org/10.1007/s10735-024-10301-6 Received: Accepted: Published: Version of record: DOI: https://doi.org/10.1007/s10735-024-10301-6