Berberine alleviates tendinopathy by suppressing the cGAS-STING pathway and Relieving ferroptosis

Berberine, a key bioactive component of Coptis rhizome, has been extensively studied for its therapeutic effects on various diseases. This research aimed to investigate the potential benefits of berberine in treating tendinopathy and to elucidate the underlying mechanisms through animal and laboratory studies. Our findings indicated that berberine effectively treated type I collagenase-induced tendinopathy in rats, confirmed by cellular-level validation. At the molecular level, berberine reduced the activation of the cGAS-STING signaling pathway and decreased the accumulation of malondialdehyde (MDA) and reactive oxygen species (ROS) in both animal models and cell cultures. Additionally, berberine upregulated the expression of glutathione (GSH) and glutathione peroxidase 4 (GPX4) in tissues. These results suggested that berberine alleviated ferroptosis via the cGAS-STING pathway, thus exerting therapeutic effects on tendinopathy. To validate these findings further, we administered the ferroptosis inducer Imidazole Ketone Erastin (IKE) to evaluate the effects of berberine. IKE significantly diminished the therapeutic effects of berberine on tendinopathy, as indicated by the previously mentioned markers. Thus, berberine mitigated ferroptosis by inhibiting the cGAS-STING pathway, highlighting its potential in managing tendinopathy.