Research Article | Volume: 16, Issue: 8, August, 2026

Protective Effects of Physalis angulata Leaf Extract on Busulfan-induced Ovarian Dysfunction: In Vivo, Network Pharmacology, and Molecular Dynamics Insights

Yanti Sulistyana,  Damiana Rita Ekastuti,  Wahono Esthi Prasetyaningtyas,  Aryani Sismin Satyaningtijas,  I Ketut Mudite Adnyane,  Ronald Tarigan,  Kusdiantoro Mohamad   

Yanti Sulistyana1, Damiana Rita Ekastuti2, Wahono Esthi Prasetyaningtyas3, Aryani Sismin Satyaningtijas2, I Ketut Mudite Adnyane3, Ronald Tarigan2, Kusdiantoro Mohamad3

1Study Program of Animal Biomedical Sciences, School of Veterinary Medicine and Biomedical Sciences, IPB University, Bogor, West Java, Indonesia.

2Division of Physiology, School of Veterinary Medicine and Biomedical Sciences, IPB University, Bogor, West Java, Indonesia.

3Division of Anatomy, Histology, and Embryology, School of Veterinary Medicine and Biomedical Sciences, IPB University, Bogor, West Java, Indonesia.

Open Access   

Published:  Jun 18, 2026

DOI: 10.1177/22313354261453147
PDF [ 8.6 MB]
Request Permission
Share
Download Citation
Print
Download PDF
Abstract

Cancer is a major cause of mortality worldwide, including in Indonesia. Busulfan, a chemotherapeutic agent for hematopoietic malignancies, is known to impair female reproductive function and induce ovarian failure. Physalis angulata L. contains phytosteroids with the potential to restore hormonal homeostasis. This study evaluated the effects of P. angulata leaf extract on estrous cycles and pregnancy outcomes in female rats exposed to busulfan. Antioxidant activity, phytosteroid, phenolic, and flavonoid contents were analyzed in vitro. In vivo experiments employed a randomized design with five groups: control, busulfan (40 mg/kgBW), P. angulata (300 mg/kgBW for 28 days), sequential busulfan—P. angulata, and simultaneous busulfan— P. angulata. Metabolite profiling was performed using LC-HRMS, while in silico analyses applied network pharmacology, molecular docking, and molecular dynamics simulations. The results showed moderate antioxidant activity attributed to phytosteroids, phenolics, and flavonoids. P. angulata extract improved busulfan-induced estrous cycle and ovarian histology disruption but paradoxically reduced pregnancy rates. Seventy-seven metabolites were identified, with Physalin F acting as an estrogen receptor 1 (ESR1) antagonist and Albanol A as an ESR1 agonist; Albanol A demonstrated superior stability in molecular dynamics simulations. In conclusion, P. angulata leaf extract exerts dual mechanisms: ameliorating reproductive cycle impairment while reducing pregnancy rates in busulfan-treated female rats.


Keyword:     Estrus cycle flavonoids ovarian histology Physalis angulata phytosteroids pregnancy success

Citation:

Sulistyana Y, Ekastuti DR, Prasetyaningtyas WE, Satyaningtijas AS, Adnyane IKM, Tarigan R, Mohamad K. Protective Effects of Physalis angulata Leaf Extract on Busulfan-induced Ovarian Dysfunction: In Vivo, Network Pharmacology, and Molecular Dynamics Insights. J Appl Pharm Sci. 2026;16(8):687–709. https://doi.org/10.1177/22313354261453147

Copyright: © The Author(s). This open-access article is distributed under the Creative Commons Attribution-NonCommercial 4.0 International License, which permits non-commercial use, sharing, adaptation, distribution, and reproduction in any medium or format, provided appropriate credit is given, a link to the license is included, and any changes are indicated.
HTML Full Text

Reference

Article Metrics
54 Views 24 Downloads 78 Total

Year

Month

Related Search

By author names