Postmenopausal women are at increased risk for both osteoporosis and depression, but their common biological basis remains poorly understood and there is no single treatment that effectively addresses both conditions. In a recent study, researchers discovered that a traditional plant extract used in traditional Chinese medicine may act on a common molecular pathway underlying both bone loss and mood disorders, paving the way for treatments that target both conditions simultaneously.
For many women, menopause brings more than hormonal changes. Postmenopausal women often face two seemingly unrelated health challenges at the same time: osteoporosis and depression. Both of these symptoms are related to estrogen levels, so they tend to occur together. Specifically, the loss of estrogen increases oxidative stress (a condition in which highly reactive molecules accumulate and damage cells) and impairs mitochondria, the organelles that power cells. These disruptions not only damage bone-forming cells, but also affect areas of the brain that regulate mood.
Despite the overlap of these symptoms, modern medicine still treats them separately. Simply put, osteoporosis drugs strengthen bones but have little effect on mood, and antidepressants do not prevent bone loss. Hormone replacement therapy can address both, but long-term use increases the risk of cardiovascular disease and certain estrogen-related cancers, so it is not suitable for many women. An even more serious problem is that scientists have struggled to identify common molecular mechanisms associated with bone and brain health in postmenopausal women.
Recently, a research team led by Dr. Xu Wei, Dr. Kai Sun (China Academy of Chinese Medical Sciences), Professor Weiwei Tao (Nanjing University of Traditional Chinese Medicine), and Dr. Zhiwen Luo (Fudan University) sought to address this knowledge gap. Their study investigated whether well-known plant extracts can act on common biological pathways that affect both bones and the brain.
The plant extract in question is Drinaria Fortuni (TFDF), widely used in traditional Chinese medicine for its bone regeneration and strengthening effects. The research team sought to test its effects in an animal model designed to simultaneously mimic both postmenopausal osteoporosis and depression. To do this, the researchers used mice that had their ovaries removed (to mimic menopause) and were exposed to chronic stress (to induce depression-like behavior). In this way, they were able to study bone deterioration and behavioral changes together. Alongside experiments on cultured bone cells and neurons, the research team conducted detailed molecular analyzes of the animals’ bone tissue and the hippocampus, a brain region important for mood regulation and stress responses.
The results were surprisingly consistent across these systems: TFDF improved bone density and restored the fine internal structure of bones, while also reducing behaviors associated with depression, such as loss of interest in rewarding stimuli. Mice treated with TFDF also had better preservation of neurons in the hippocampus. Additionally, at the cellular level, TFDF helped restore mitochondrial function and autophagy, a process cells use to recycle damaged components.
Central to these effects was a signaling pathway involving three key molecules: SIRT1, FOXO3, and DEPP1. SIRT1 is a protein that helps cells respond to stress and maintain proper energy balance. This study revealed that TFDF activates SIRT1, which restores FOXO3 function. This decreased the levels of DEPP1, a stress-responsive protein involved in autophagy regulation and cell damage under oxidative conditions. This cascade ultimately helped normalize both mitochondrial function and cellular recycling in bone cells and brain cells. ”To our knowledge, this is the first study to investigate TFDF in an integrated comorbidity model, allowing the simultaneous assessment of skeletal and neurological outcomes within one framework.” emphasizes Dr. Wei Xu. Most importantly, this integrated approach allowed researchers to identify common biological pathways underlying both conditions, rather than studying both conditions separately.
Overall, the findings suggest new ways of thinking about postmenopausal health. Rather than treating bone loss and depression as separate diseases, they may partially reflect different outcomes of a common cellular stress response. Therefore, by targeting that common mechanism, it may be possible to treat both conditions at once. ”Our results suggest that TFDF may provide a practical “single-drug, two-organ” strategy for the treatment of postmenopausal osteoporosis with depression, and merits further comparative evaluation with other SIRT1 activators and autophagy regulators.” added Dr. Wei Shu.
If these findings hold up in future human studies, they could help inform new therapeutic approaches that simultaneously address bone and brain health in postmenopausal women with a single plant extract.
sauce:
Science and Technology Review Publishing
Reference magazines:
Zhang Yu Others. (2026). Targeting shared mitophagy regulators: the SIRT1–FOXO3–DEPP1 axis underpins the dual benefits of total flavonoids to bone and brain. Drinaria Fortuni. the study. DOI: 10.34133/research.1125. https://spj.science.org/doi/10.34133/research.1125
