Dendrophthoe pentandra (Mango Mistletoe) leaves modulate steroidogenic acute regulatory protein, aromatase, and estrogen receptor expression in aged mice
Main Article Content
Abstract
BACKGROUND
Ovarian aging is associated with impaired steroidogenesis and estrogen signaling, contributing to reproductive dysfunction. Dendrophthoe pentandra (Mango Mistletoe), a flavonoid-rich plant with antioxidant properties, has demonstrated anti-inflammatory and cytoprotective effects in experimental studies. However, its role in modulating the integration of ovarian steroidogenic and estrogen-responsive pathways during aging remains unclear. This study evaluated the effects of D. pentandra leaf extract on the expression of steroidogenic acute regulatory protein (StAR), aromatase (CYP19A1), estrogen receptor α (ERα), and ERβ in aged female mice.
METHODS
This experimental study included 25 female mice: 5 young (8–12 weeks) and 20 aged (18–20 months). Animals were allocated to five groups (n=5 per group): young controls, aged controls, and three aged treatment groups receiving D. pentandra leaf extract at doses of 150, 300, and 600 mg/kg BW, respectively, for 30 days. Protein expression was evaluated using immunohistochemistry and analyzed using one-way ANOVA followed by Tukey HSD post hoc test.
RESULTS
Aged mice exhibited significantly lower expression of StAR, aromatase, ERα, and ERβ compared with young controls. Administration of D. pentandra extract significantly increased expression of all evaluated markers in a dose-dependent manner (p<0.001). Post hoc analysis demonstrated significant restoration of steroidogenic and estrogen-signaling–related protein expression, particularly in the highest-dose group, where aromatase, ERα, and ERβ expression approached or exceeded levels observed in young controls.
CONCLUSION
D. pentandra leaf extract restored key components of ovarian steroidogenesis and estrogen signaling in aged mice, suggesting potential phytoendocrine modulatory activity against age-related ovarian endocrine decline.
Article Details
Section

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The journal allows the authors to hold the copyright without restrictions and allow the authors to retain publishing rights without restrictions.
How to Cite
References
1. Velarde MC. Mitochondrial and sex steroid hormone crosstalk during aging. Longev Heal 2014;3:2. doi:10.1186/2046-2395-3-2.
2. Wang X, Wang L, Xiang W. Mechanisms of ovarian aging in women: a review. J Ovarian Res 2023;16:67. doi:10.1186/s13048-023-01151-z.
3. Reiter RJ, Sharma R, Romero A, et al. Aging-related ovarian failure and infertility: melatonin to the rescue. Antioxidants 2023;12:695. doi:10.3390/antiox12030695.
4. Fuentes N, Silveyra P. Estrogen receptor signaling mechanisms. In: Advances in protein chemistry and structural biology. Elsevier; 2019.p.135–70. doi:10.1016/bs.apcsb.2019.01.001.
5. Manna PR, Stetson CL, Slominski AT, Pruitt K. Role of the steroidogenic acute regulatory protein in health and disease. Endocrine 2016;51:7–21. doi:10.1007/s12020-015-0715-6.
6. Chauvin S, Cohen-Tannoudji J, Guigon CJ. Estradiol signaling at the heart of folliculogenesis: its potential deregulation in human ovarian pathologies. Int J Mol Sci 2022;23:512. doi:10.3390/ijms23010512.
7. Camon C, Garratt M, Correa SM. Exploring the effects of estrogen deficiency and aging on organismal homeostasis during menopause. Nat Aging 2024;4:1731–44. doi:10.1038/s43587-024-00767-0.
8. Liu Y, Weng W, Gao R, Liu Y. New insights for cellular and molecular mechanisms of aging and aging-related diseases: herbal medicine as potential therapeutic approach. Oxid Med Cell Longev 2019;1–25. doi:10.1155/2019/4598167.
9. Silvia PA, Sjakoer NAA, Mubarakati NJ. Comparison of antioxidant activity of mistletoe mango leaves extract (Dendrophtoe pentandra (L.) Miq) using ethanol solution and methanol solution based on DPPH method. J Smart Bioprospecting Technol 2024;5:15–9. doi:10.21776/ub.jsmartech.2024.005.01.15.
10. Handono K, Pratama MZ, Yuniati MG, et al. The effect of mango mistletoes (Dendrophthoe pentandra) leaves extract toward immunosenescence on old BALB/c mice. The 4th International Conference on Life Science and Technology (ICoLiST); 2021. Malang, Indonesian. doi:10.1063/5.0117337.
11. Endharti AT, Wulandari A, Listyana A, Norahmawati E, Permana S. Dendrophthoe pentandra (L.) Miq extract effectively inhibits inflammation, proliferation and induces p53 expression on colitis-associated colon cancer. BMC Complement Altern Med 2016;16:374. doi:10.1186/s12906-016-1345-0.
12. Endharti AT, Sulastri E, Umanailo R, Yunialce, Nurseta T, Handono K. Mango mistletoe Dendrophthoe pentandra leaf extract acts synergistically with 5-fluorouracil to induce apoptosis and increase p21 expression in human cervical adenocarcinoma HeLa cells by reducing survivin expression. J Appl Pharm Sci 2018;8:10–5. doi:10.7324/JAPS.2018.8702.
13. Handono K, Pratama MZ, Sermoati IA, et al. The effect of Mango Mistletoes (Dendrophthoe pentandra) leaves extract on percentage of CD4+CD28+, CD8+CD28+, and interleukin-2 levels of aged BALB/c mice. Open Access Maced J Med Sci 2021;9:414–21. doi:10.3889/oamjms.2021.6182.
14. Awang MA, Nik Mat Daud NNN, Mohd Ismail NI, Abdullah FI, Benjamin MAZ. A review of Dendrophthoe pentandra (Mistletoe): phytomorphology, extraction techniques, phytochemicals, and biological activities. Processes 2023;11:2348. doi:10.3390/pr11082348.
15. Arifin WN, Zahiruddin WM. Sample size calculation in animal studies using resource equation approach. Malays J Med Sci 2017;24:101–5. https://doi.org/10.21315/mjms2017.24.5.11.
16. Hense JD, Isola JVV, Garcia DN, et al. The role of cellular senescence in ovarian aging. Npj Aging 2024;10:35. doi:10.1038/s41514-024-00157-1.
17. Ma S, Li G, Qin Y. Mitochondrial dysfunction in ovarian aging. Chin Med J (Engl) 2025;138:3069–82. doi:10.1097/CM9.0000000000003801.
18. Lliberos C, Liew SH, Zareie P, La Gruta NL, Mansell A, Hutt K. Evaluation of inflammation and follicle depletion during ovarian ageing in mice. Sci Rep 2021;11:278. doi:10.1038/s41598-020-79488-4.
19. Ju W, Yan B, Li D, Lian F, Xiang S. Mitochondria-driven inflammation: a new frontier in ovarian ageing. J Transl Med 2025;23:1005. doi:10.1186/s12967-025-06966-6.
20. Esencan E, Beroukhim G, Seifer DB. Age-related changes in folliculogenesis and potential modifiers to improve fertility outcomes - a narrative review. Reprod Biol Endocrinol 2022;20:156. doi:10.1186/s12958-022-01033-x.
21. Liu S, Jia Y, Meng S, Luo Y, Yang Q, Pan Z. Mechanisms of and potential medications for oxidative stress in ovarian granulosa cells: a review. Int J Mol Sci 2023;24:9205. doi:10.3390/ijms24119205.
22. Haryono SE, Aditiyarini D, Restiani R. Analysis of secondary metabolites and antioxidant activities of ethanol extract of Dendrophthoe pentandra (L.) Miq. in Sapuran, Central Java. Biog J Ilm Biol 2024;12:56–65. doi:10.24252/bio.v12i1.40323.
23. Inggrid AM, Aditiyarini D, Prakasita VC. Antibacterial activity of Dendrophthoe pentandra (L.) leaves extract against Staphylococcus aureus and Escherichia coli. J Biodjati 2024;9:280–93. doi:10.15575/biodjati.v9i2.3043.6.
24. Gong H, Zhang H, Liu Y, Mao X, Wang J. Role and mechanisms of plant polyphenols in ovarian aging. J Ovarian Res 2025;18:239. doi:10.1186/s13048-025-01799-9.
25. Desmawati D, Sulastri D. Phytoestrogens and their health effect. Open Access Maced J Med Sci 2019;7:495–9. doi:10.3889/oamjms.2019.086.