Effect of Justicia gendarussa Leaf Extract on Bone Homeostasis through the Regulation of RANKL, OPG, and Osteoclast/Osteoblast Ratio in Hypoestrogenic Rats

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Sri Dinengsih, Happy Kurnia Permatasari, Sutrisno Sutrisno, Agustina Tri Endharti

2026 Advanced Journal of Chemistry, Section A Vol. 9 Issue 2 Article Cited by 0 Quartile

Abstract

This study aimed to evaluate the effects of Justicia gendarussa leaf ethanol extract on bone homeostasis in a hypoestrogenic rat model by analyzing the regulation of key bone remodeling markers such as RANKL, OPG, and the osteoclast/osteoblast ratio. Thirty female rats were divided into five groups, including a healthy control (KN), an ovariectomized group without treatment (KP), and three treatment groups (OVX 1, OVX 2, and OVX 3) that received the extract at doses of 125, 250, and 500 mg/kg body weight for 21 days. The results demonstrated a dose-dependent decrease in EGFR and RANKL expression, accompanied by a significant increase in OPG levels in the treated groups. These molecular changes were reflected in a reduced osteoclast ratio and an increased osteoblast ratio, indicating improved bone remodeling. Histological and immunohistochemical analyses confirmed the extract's ability to modulate bone turnover. The highest dose (500 mg/kg body weight) showed the most optimal effect, approaching the physiological conditions observed in the healthy control group. These findings suggest that the bioactive flavonoid compounds in J. gendarussa may contribute to bone preservation by modulating the RANKL/OPG axis and EGFR-associated signaling pathways, offering potential as a safe and effective alternative therapy for postmenopausal osteoporosis. © 2026 by SPC (Sami Publishing Company).

Affiliations

Doctoral Program of Medical Sciences, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia; Midwifery Program, Faculty of Health Sciences, Universitas Nasional, Jakarta, Indonesia; Department of Biochemistry and Biomolecular, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia; Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia; Department of Parasitology, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia