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Updated: Feb 10, 2026

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Ononin Mitigates Estrogen Deficiency-Induced Osteoporosis Through Activation of ALDH2 in Mice

Mingchuan Yu1, Dong Ruan1, Wentao Rao2,3

  • 1Department of Rehabilitation Medicine, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.

Phytotherapy Research : PTR
|February 9, 2026
PubMed

Insights

Ononin, a natural compound, combats postmenopausal osteoporosis by activating aldehyde dehydrogenase 2 (ALDH2). This enhances bone formation and reduces oxidative stress, offering a potential new therapy.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • Postmenopausal osteoporosis (PMOP) is linked to estrogen deficiency, oxidative stress, and reduced bone formation.
  • Current PMOP treatments have limitations, necessitating novel therapeutic strategies.

Purpose of the Study:

  • To identify ononin as a potential antiosteoporotic agent.
  • To elucidate the mechanism of ononin's action, focusing on aldehyde dehydrogenase 2 (ALDH2) activation.

Main Methods:

  • In vivo studies using ovariectomized (OVX) mice and in vitro studies with bone marrow-derived mesenchymal stem cells (BMSCs).
  • Integrated approach: network pharmacology, molecular docking, enzymatic assays, and ALDH2 knockout (Aldh2-/-) models.
  • Evaluation of bone parameters, osteogenic differentiation, reactive oxygen species (ROS), and lipid peroxidation markers.

Main Results:

  • Ononin significantly reduced OVX-induced bone loss and promoted BMSC osteogenic differentiation.
  • Network pharmacology and molecular docking identified ALDH2 as the primary target of ononin.
  • Ononin enhanced ALDH2 activity, decreased ROS and lipid peroxidation (4-HNE, MDA), and preserved mitochondrial function.
  • Beneficial effects were diminished in Aldh2-/- mice, confirming ALDH2 dependence.

Conclusions:

  • Ononin effectively mitigates PMOP by activating ALDH2, thereby promoting osteogenesis and restoring redox balance.
  • Ononin demonstrates significant potential as a natural therapeutic agent for postmenopausal osteoporosis.
Keywords:
ALDH2 enzymatic activitybone metabolismononinoxidative stresspostmenopausal osteoporosis

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