Aloperine treatment attenuates acute spinal cord injury by reducing oxidative, inflammatory, and apoptotic responses via PI3K/AKT/NF-κB signaling in a rat contusion model

Spinal cord injury (SCI) is a severe condition that can result in nerve damage, impaired motor or sensory function, and ultimately a high mortality rate for injured individuals. High oxidative and inflammatory responses are closely linked to poor prognosis and can influence the recovery of neurological functions. Therefore, overcoming these processes early is a valuable therapy approach for SCI. Aloperine (ALO) is a quinolizidine-type alkaloid with numerous pharmacological activities, including antioxidant, anti-inflammatory, and neuroprotective effects. However, the role of ALO in SCI recovery remains unclear. Herein, we investigated its therapeutic impact on a contusion model of moderate SCI. ALO (100 mg/kg/day) was intraperitoneally administered to adult Sprague-Dawley rats for a week following surgery/SCI. Basso-Beattie-Bresnahan locomotor score was used to assess neural function after post-SCI (day-1/4/7), showing that ALO modestly improved hind-limb locomotor recovery. HE-staining showed that ALO attenuated the increased tissue sparseness and liquefactive necrosis due to the contusion injury. ALO treatments reduced the injury-induced apoptosis (Bax/Bcl-2, cleaved-caspase3), oxidative (4HNE, MDA), and inflammatory (NF-κB, TNF-α) responses, and increased antioxidant enzymes SOD1 and GPx1 levels. The network pharmacology and immunoblot analyses revealed that the molecular targets of ALO and SCI include the PI3K/AKT pathway. Our findings, for the first time, clearly demonstrated that a natural compound, aloperine, has a neuroprotective effect on SCI by reducing apoptosis, inducing the antioxidant defense system, and modulating PI3K/AKT and NF-κB signaling. These results suggest that aloperine administration might improve the total antioxidant status and significantly promote functional recovery following traumatic SCI.