Hederagenin may promote functional recovery following spinal cord injury by modulating microglial polarization through the PPAR-γ signaling pathway

spinal cord injury (SCI) is a debilitating condition that can lead to severe motor deficits. This study aimed to evaluate the therapeutic effects of hederagenin, a Chinese herbal medicinal ingredient, on motor recovery and the inflammatory response in rat models of SCI.
We used the Allen weight-drop technique to create a Sprague–Dawley rat model of spinal cord injury. We then administered hederagenin (10 mg/kg) via intraperitoneal injection for 28 consecutive days.
Third-class first-class hospital.
The Basso-Beattie-Bresnahan (BBB) scores were evaluated. Histological analyses were performed via hematoxylin and eosin staining. The levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in SCI rat spinal cord tissues were evaluated by immumohistochemical staining. Microglial activation markers (Iba-1) and M2 phenotypic markers (CD206) were assessed by Immunofluorescence staining. PPAR-γ in rats were assessed by western blotting (WB).
The Basso-Beattie-Bresnahan (BBB) scoring system assessed locomotor function, and revealed significant improvements in BBB score in hederagenin-treated rats starting from the fifth day post-surgery. We also found elevated levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in the spinal cord tissues of SCI rats, which significantly decreased after hederagenin Treatment. We also analyzed Microglial activation markers were analyzed, including Iba-1. Our results showed increased expression of CD206 in response to hederagenin, indicating that it promotes M2 polarization and reduces microglial activation. Additionally, hederagenin increased the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) in rats with SCI. However, the PPAR-γ inhibitor GW966 reversed the above roles of hederagenin.
Our results indicate that hederagenin not only aids in the recovery of motor function in SCI rats but also diminishes inflammation while fostering neuroprotection via the modulation of microglial activity. This effect may be linked to the activation of the PPAR-γ signaling pathway. These results provide compelling evidence for the potential of hederagenin as a therapeutic agent for SCI and warrant further investigation into its clinical applications in neuroregeneration and inflammation modulation.