Fenugreek seed extract combined with acellular nerve allografts promotes peripheral nerve regeneration and neovascularization in sciatic nerve defects

Background: Acellular nerve allografts (ANAs) have been confirmed to improve the repair and reconstruction of long peripheral nerve defects. However, its efficacy is not comparable to that of autologous nerve grafts, which are used as the gold standard for treating peripheral nerve defects. Our study investigated whether fenugreek seed extract (FSE) exhibits neuroprotective potential and enhances the therapeutic outcomes of ANA repair in peripheral nerve defects. Methods: Rat Schwann cells were treated with FSE to assess the effects of FSE on cell proliferation and their secretion function of neurotrophic factors in vitro. Sprague-Dawley rats with a unilateral 15-mm sciatic nerve defect were randomized into the ANA group (the 15-mm defect was replaced by an 18-mm ANA), the ANA & thorn; FSE group (the 15-mm defect was repaired with an 18-mm ANA with FSE administration for four weeks), and the Auto group (the 15-mm defect was repaired with an autologous graft). After four weeks post-surgery, various behavioral tests and electrophysiological assays were performed to evaluate the motor and sensory behavior as well as nerve conduction of rats. Then, rats were sacrificed, and the nerve grafts were collected for toluidine blue staining, RT-qPCR, immunofluorescence staining, immunohistochemical staining to evaluate nerve regeneration, neovascularization, and neuroinflammation. Their gastrocnemius was harvested for Masson's trichrome staining to examine gastrocnemius muscle recovery. Results: FSE treatment promoted Schwann cell proliferation and its secretion of neurotrophic factors in vitro. Compared with ANAs alone, FSE treatment combined with ANAs enhanced axonal regeneration, upregulated S100, NF200, P0, MBP, and GAP43 expression, facilitated angiogenesis, and elevated neurotrophic factor expression in regenerating nerves of rats with sciatic nerve defects. In addition, FSE treatment promoted gastrocnemius muscle recovery, stimulated motor and sensory functional recovery and nerve conduction, and mitigated neuroinflammation in rats with sciatic nerve defects after repair with ANAs. Conclusion: FSE treatment improves the beneficial effects of ANA repair on sciatic nerve defects. (c) 2024 The Author(s). Published by Elsevier BV on behalf of The Japanese Society for Regenerative Medicine. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/lice nses/by-nc-nd/4.0/).