The Potential Health Benefit of Cowpea Estrogen-like Activity to Restore Vaginal Epithelial Cells Thinning Due to Menopausal Syndrome


  • An Nisa Fithri Doctoral Program of Medical Sciences, Faculty of Medicine, Universitas Brawijaya, Indonesia
  • Yuyun Yueniwati Department of Radiology, Saiful Anwar Hospital, Faculty of Medicine, Universitas Brawijaya, Indonesia
  • I Wayan Arsana Department of Fertility, Endocrinology and Reproduction, Obstetrics and Gynecology, Saiful Anwar Hospital, Faculty of Medicine, Universitas Brawijaya, Indonesia
  • Husnul Khotimah Department of Pharmacology, Faculty of Medicine, Universitas Brawijaya, Indonesia
  • Wiwit Nurwidyaningtyas Center for Biomedical Research, Research Organization for Health, BRIN, Cibinong Science Center, Bogor, West Java, Indonesia



Vigna unguiculata, vaginal atrophy, genistein, estrogen receptor


Vigna unguiculata, cowpea, contains genistein, a compound with a structure similar to estrogen. However, the genistein content of cowpea and its potential for addressing menopause-related vaginal epithelial cell atrophy remains uncharted. This research aims to examine the interaction mode and estrogenic effect of Indonesian cowpea seeds' genistein on the estrogen receptor (ER) both in silico and in vivo. Through the application of liquid chromatography-tandem mass spectrometry (LC-MS/MS), the genistein content of dry pasta cowpea seeds KT4 and KT6 was examined. Autodock 4.0, an integral component of the PyRx 0.9.5 software, was utilized to establish a virtual interaction between genistein molecules from cowpea compounds and the ERα and ERβ proteins. An immunohistochemistry assay was employed to characterize the estrogen receptor expression profile of vaginal tissue in 36 female Sprague-Dawley rats subjected to treatment-dependent doses of cowpea. Genistein was 15.64 µg/g higher in cowpea KT4 than in KT6. Moreover, genistein docking in cowpeas revealed a significant interaction with ERα and ERβ at -9.03 and 10.8 kcal/mol, respectively. Expression of ERα and ERβ significantly increased in vaginal menopausal rat models treated with 4-ethanolic extract of cowpea seed varieties at a dose of 5 mg/kgBB compared to a lower dose (p=0.004). In sum, cowpea ethanol extract exhibited to have an estrogenic effect on vaginal tissue in menopausal models. Accordingly, future applications of the cowpea as a complementary therapy for vaginal dryness due to menopausal syndrome will enhance the quality of life for postmenopausal women.


Ambikairajah A, Walsh E, Cherbuin N. A review of menopause nomenclature. Reprod Health. 2022; 19(1):1-15.

Bleibel B, Nguyen H. Vaginal Atrophy [Internet]. StatPearls Publishing; 2023 [cited 2024 Mar 10]. Available from:

Li S, Herrera GG, Tam KK, Lizarraga JS, Beedle M-T, Winuthayanon W. Estrogen action in the epithelial cells of the mouse vagina regulates neutrophil infiltration and vaginal tissue integrity. Sci Rep. 2018; 8(1):1-13.

Liu ZM, Zhang D, Li G, Ho SC, Chen YM, Ma J, Huang Q, Li S, Ling WH. The 6‐month effect of whole soy and purified isoflavones daidzein on thyroid function—A double‐blind, randomized, placebo-controlled trial among Chinese equol‐producing postmenopausal women. Phytother Res. 2021; 35(10): 5838-46.

Cho L, Kaunitz AM, Faubion SS, Hayes SN, Lau ES, Pristera N, Scott N, Shifren JL, Shufelt CL, Stuenkel CA, Lindley KJ. Rethinking menopausal hormone therapy: For whom, what, when, and how long? Circulation. 2023; 147(7): 597-610.

Hodis HN, Mack WJ. Menopausal hormone replacement therapy and reduction of all-cause mortality and cardiovascular disease: It is about time and timing. Cancer J. 2022; 28(3): 208-23.

Rasheed S, Rehman K, Shahid M, Suhail S, Akash MSH. Therapeutic potentials of genistein: New insights and perspectives. J Food Biochem. 2022; 46(9): 1-13.

Nikolić Lj I, Savić-Gajić M I, Tačić D A, Savić M I. Classification and biological activity of phytoestrogens: A review. Adv Technol. 2017; 6(2): 96-106.

Sureda A, Sanches Silva A, Sánchez-Machado DI, López-Cervantes J, Daglia M, Nabavi SF, Nabavi SM. Hypotensive effects of genistein: From chemistry to medicine. Chem Biol Interact. 2017; 268: 37-46.

Li M, Yu Y, Xue K, Li J, Son G, Wang J, Qian W, Wang S, Zheng Z, Yang C, Ge J. Genistein mitigates senescence of bone marrow mesenchymal stem cells via ERRα-mediated mitochondrial biogenesis and mitophagy in ovariectomized rats. Redox Biol. 2023; 61(102649): 1-15.

Sharifi-Rad J, Quispe C, Imran M, Rauf A, Nadeem M, Gondal TA, Ahmad B, Atif M, Mubarak MS,Sytar O, Zhilina OM, Garsiya ER, Smeriglio A, Trombetta D, Pons DG, Matorell M, Cardoso SM, Razis AFA, Sunusi U,Kamal RM, Rotariu LS, Butnariu M, Docea AO, Calina D. Genistein: An integrative overview of its mode of action, pharmacological properties, and health benefits. Oxid Med Cell Longev. 2021; 2021: 1-36.

Fithri An, Yueniwati Y, Arsana I.W, Khotimah.H, Nurwidyaningtyas.W. Targeted proteins for vaginal epithelial repair. J Pharm Pharmacogn Res 2023; 11(1): 110-6.

Pourhadi N, Mørch LS, Holm EA, Torp-Pedersen C, Meaidi A. Menopausal hormone therapy and dementia: nationwide, nested case-control study. Brit Med J. 2023; 381: 1-15.

Lega IC, Fine A, Antoniades ML, Jacobson M. A pragmatic approach to the management of menopause. Can Med Assoc J. 2023; 195(19):E677-82.

Andrea R Genazzani, Patrizia Monteleone, Andrea Giannini, Tommaso Simoncini. Hormone therapy in the postmenopausal years: considering benefits and risks in clinical practice. Hum Reprod Update. 2021; 27(6): 1111-1115.

Gonçalves A, Goufo P, Barros A, Domínguez-Perles R, Trindade H, Rosa EAS, Ferreira L, Rodrigues M. Cowpea (Vigna unguiculata L. Walp), a renewed multipurpose crop for a more sustainable agri‐food system: nutritional advantages and constraints. J Sci Food Agric. 2016; 96(9): 2941-51.

Lonardi S, Muñoz-Amatriaín M, Liang Q, Shu S, Wanamaker SI, Lo S, Tanskanen J, Schulman AH, Zhu T, Luo CM, Alhakami H, Ounit R, Hasan MA, Verdier J, Roberts PA, Santoso JRP, Ndeve A, Dolezel Z, Vrana J, Hokin SA, Farmer AD, Cannon SB, Close TJ. The genome of cowpea (Vigna unguiculata [L.] Walp.). Plant J. 2019; 98(5): 767-82.

Martins TF, Souza PFN, Alves MS, Silva FDA, Arantes MR, Vasconcelos IM, Oliveira JTA. Identification, characterization, and expression analysis of cowpea (Vigna unguiculata [L.] Walp.) miRNAs in response to cowpea severe mosaic virus (CPSMV) challenge. Plant Cell Rep. 2020; 39(8): 1061-78.

Souza VR, Mendes E, Casaro M, Antiorio ATFB, Oliveira FA, Ferreira CM. Description of ovariectomy protocol in mice. In: Methods in Molecular Biology. New York, NY: Springer New York; 2019. 303-309 p.

Adel M, Sadegh AB, Arizza V, Abbasi H, Inguglia L, Saravi HN. Anesthetic efficacy of ketamine-diazepam, ketamine-xylazine, and ketamine-acepromazine in Caspian Pond turtles (Mauremys caspica). Indian J Pharmacol. 2017; 4 9(1): 93-97.

Křížová L, Dadáková K, Kašparovská J, Kašparovský T. Isoflavones. Molecules. 2019; 24(6):1076-1089.

Du Z-R, Feng X-Q, Li N, Qu J-X, Feng L, Chen L, Chen Weng-Fang. G protein-coupled estrogen receptor is involved in the anti-inflammatory effects of genistein in microglia. Phytomedicine. 2018; 43:11-20.

Yoriki K, Mori T, Aoyama K, Tarumi Y, Kataoka H, Kokabu T, Kitawaki J. Genistein induces long-term expression of progesterone receptor regardless of estrogen receptor status and improves the prognosis of endometrial cancer patients. Sci Rep. 2022; 12(1): 1-18.

Agarwal S, Alzahrani F, Ahmed A. Hormone Replacement Therapy: Would it be Possible to Replicate a Functional Ovary? Int J Mol Sci. 2018; 19(10): 3160-3172.

Paciuc J. Hormone Therapy in Menopause. In: Advances in Experimental Medicine and Biology. Cham: Springer International Publishing; 2020; 89-120 p.

Vigneswaran K, Hamoda H. Hormone replacement therapy – Current recommendations. Best Pract Res Clin Obstet Gynaecol. 2022; 81:8-21.

Sun Y, Wang L, Wang B, Meng Y, Wang W. Genistein up-regulates the expression of EGF and E-cadherin in the treatment of senile vaginitis. Molecules. 2022; 27(8): 1-18.

Ding C, Zou Q, Wang F, Wu H, Chen R, Lv J, Ling M, Wang W, Li H, Huang B. Human amniotic mesenchymal stem cells improve ovarian function in natural aging through secreting hepatocyte growth factor and epidermal growth factor. Stem Cell Res Ther. 2018; 9(1): 1-11.

Naumova I, Castelo-Branco C. Current treatment options for postmenopausal vaginal atrophy. Int J Womens Health. 2018; 10: 387-95.

Chen L-R, Chen K-H. Utilization of isoflavones in soybeans for women with menopausal syndrome: An overview. Int J Mol Sci. 2021; 22(6): 3212-3225.

Ghazanfarpour M, Sadeghi R, Roudsari RL. The application of soy isoflavones for subjective symptoms and objective signs of vaginal atrophy in menopause: A systematic review of randomised controlled trials. J Obstet Gynaecol. 2016; 36(2):160-71.

Dizavandi FR, Ghazanfarpour M, Roozbeh N, Kargarfard L, Khadivzadeh T, Dashti S. An overview of the phytoestrogen effect on vaginal health and dyspareunia in peri- and post-menopausal women. Post Reprod Health. 2019; 25(1): 11-20.

Khuleshwari K, Vijay P. Genistein enhances expression of extracellular regulated kinases (ERK) 1/2, and learning and memory of mouse. IBRO Neurosci Rep. 2021; 10: 90-95.

Smolińska E, Moskot M, Jakóbkiewicz-Banecka J, Węgrzyn G, Banecki B, Szczerkowska-Dobosz A, Bohdan DP, Ciminska GM. Molecular action of isoflavone genistein in the human epithelial cell line HaCaT. PLoS One. 2018; 13(2): 1-27.

Ishola AO, Ogundola FA, Liasu OM, Sunday OA, Adeeyo OA. View of the effect of inoculation with Glomus mosseae on early growth and pattern of root exudates in potted Cowpea [Vigna unguiculata (L.) Walp]. Trop J. Nat Prod Res. 2022; 6(1): 76-79.

Oboh G, Akerele GP, Adedayo BC, Ademiluyi AO. Comparative studies of the effects of five indigenous Cowpea (Vigna unguiculata) varieties on enzymes linked to type 2 diabetes and their glycemic indices. Trop J. Nat Prod Res. 2021; 970-976.




How to Cite

Fithri, A. N., Yueniwati, Y., Arsana, I. W., Khotimah, H., & Nurwidyaningtyas, W. (2024). The Potential Health Benefit of Cowpea Estrogen-like Activity to Restore Vaginal Epithelial Cells Thinning Due to Menopausal Syndrome. Tropical Journal of Natural Product Research (TJNPR), 8(3), 6624–6630.