Pycnogenol attenuates oxidative stress and neuroinflammation, enhancing structural and functional recovery after sciatic nerve crush injury in rats.

Abstract

<p>BACKGROUND: Peripheral nerve injuries frequently lead to incomplete functional recovery, largely due to secondary oxidative stress and neuroinflammation that impede regeneration. Pycnogenol®, a standardized French maritime pine bark extract rich in procyanidins, exhibits potent antioxidant and anti-inflammatory activities, suggesting potential neuroregenerative benefits. This study aimed to comprehensively evaluate the neuroregenerative potential of Pycnogenol® in a rat sciatic nerve crush model using an integrated assessment of histopathological, biochemical, and functional electrophysiological outcomes. METHODS: In a randomized, blinded, controlled study, 20 male Wistar rats underwent sciatic nerve crush injury. Animals were allocated to receive either intraperitoneal Pycnogenol® (20&nbsp;mg/kg/day) or an equivalent volume of saline vehicle for 28 days. Functional recovery was assessed by measuring the motor threshold current (MTC) at baseline and day 28. Histopathological evaluation of nerve sections (H&amp;E and Masson's trichrome) was performed using a semi-quantitative 0-3 scale for axonal integrity, myelin integrity, Schwann cell response, fibrosis, inflammatory infiltration, and vascular alterations. Nerve homogenates were analyzed for pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) via ELISA and for redox balance using total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI). RESULTS: Pycnogenol® treatment significantly improved all histopathological scores versus controls (total score: 7.20 ± 0.79 vs. 11.70 ± 2.63; p&nbsp;&lt;&nbsp;0.001). Pro-inflammatory cytokines were markedly reduced in the Pycnogenol® group (IL-1β: 17.74 ± 3.55 vs. 34.38 ± 3.04&nbsp;pg/mg protein; IL-6: 14.49 ± 2.52 vs. 25.45 ± 2.72; TNF-α: 12.94 ± 1.90 vs. 24.24 ± 3.18; all p&nbsp;&lt;&nbsp;0.001). Redox balance shifted favorably, with higher TAS (0.149 ± 0.016 vs. 0.106 ± 0.020&nbsp;mmol Trolox/mg protein) and lower TOS and OSI (p&nbsp;&lt;&nbsp;0.001). Electrophysiologically, Pycnogenol®-treated rats showed superior recovery, with a significantly lower ΔMTC (0.268 ± 0.035 vs. 0.534 ± 0.053&nbsp;mA; p&nbsp;&lt;&nbsp;0.001). CONCLUSION: Systemic Pycnogenol® administration enhances multi-dimensional recovery after sciatic nerve crush injury by concurrently attenuating oxidative stress and inflammation, preserving nerve structure, improving the local molecular milieu, and improving functional electrophysiological recovery, as reflected by reduced motor threshold currents. These findings support its potential as an adjuvant therapy for peripheral nerve repair.</p>