Baicalein reduces disuse-driven skeletal senescence and alters gut microbes in rats
Oral treatment restored bone density and mechanical strength while suppressing inflammatory markers and rebalancing intestinal bacteria in a disuse model.
In a hind limb unloading rat model simulating disuse, researchers administered baicalein by gavage at 30 mg per kilogram daily for four weeks. The treatment mitigated skeletal aging, increasing bone mineral density by 1.20-fold, trabecular number by 38.04 percent, bone mineral apposition rate by 42.76 percent, and biomechanical ultimate load by 31.64 percent. Baicalein also lowered tibial senescence markers p16, p21, and p53, while attenuating high bone turnover markers in serum. In addition, the flavonoid decreased pro-inflammatory cytokines, raised anti-inflammatory factors, and shifted the gut microbiota by reducing Proteobacteria and increasing Actinobacteria and Firmicutes.
Why it matters
Mechanical disuse accelerates skeletal senescence and bone deterioration, presenting challenges in long-term immobility and spaceflight. Linking microbiome remodeling to lower bone senescence and inflammation supports the gut-bone axis as a target for protecting skeletal homeostasis.
Caveats
The findings are limited to a rodent model of mechanical unloading, meaning efficacy and safety cannot yet be assumed in humans. Additionally, the data do not establish whether gut microbiota alterations directly caused the observed improvements in bone tissue.
- Baicalein
- Cellular senescence
- Chronic inflammation
- Dysbiosis
- p16INK4a–RB pathway
- p53–p21 pathway
- Cdkn1a
- Cdkn2a
- Cxcl8
- Ifng
- Il10
- Il4
The paper
Baicalein Attenuates Disuse-Driven Skeletal Senescence in Association with Gut Microbiota Modulation
Zhao X, Ren T, Bai W et al.
Molecules · 20 Sep 2026