Fischer Dietmar
Center of Pharmacology, Institute for Pharmacology 2, Medical Faculty and University of Cologne, Cologne, Germany.
Front Cell Dev Biol. 2025 Apr 17;13:1558525. doi: 10.3389/fcell.2025.1558525. eCollection 2025.
Traumatic peripheral nerve injuries frequently result in irreversible functional deficits. While neurons possess an intrinsic capacity for axonal regeneration, the temporal constraints and the slow pace of neurite outgrowth often impede the complete restoration of sensory and motor capabilities. This impairment, often culminating in chronic disability, represents a significant clinical challenge, as there are currently no approved pharmacological interventions available to accelerate axon regeneration and improve functional recovery. This perspective focuses on recent scientific advancements that have identified sesquiterpene lactones, a family of naturally derived plant metabolites, as potential therapeutic candidates for treating peripheral nerve trauma. Preclinical investigations employing parthenolide and cnicin have revealed that these compounds can substantially augment axonal extension and functional recovery in diverse animal paradigms and primary human neuronal cultures. The favorable bioavailability of cnicin following oral administration, coupled with its notable tolerability at dosages considerably largely surpassing the therapeutic range, underscores its substantial potential as an effective pharmacological treatment for addressing the challenges associated with nerve regeneration and restoring sensory and motor functions.
创伤性周围神经损伤常常导致不可逆的功能缺陷。虽然神经元具有轴突再生的内在能力，但时间限制和神经突生长的缓慢速度常常阻碍感觉和运动能力的完全恢复。这种损伤往往最终导致慢性残疾，这是一个重大的临床挑战，因为目前尚无批准的药物干预措施可加速轴突再生并改善功能恢复。这篇综述聚焦于最近的科学进展，这些进展已确定倍半萜内酯（一类天然衍生的植物代谢产物）为治疗周围神经创伤的潜在治疗候选物。使用小白菊内酯和土木香内酯的临床前研究表明，这些化合物可在多种动物模型和原代人神经元培养物中显著增强轴突延伸和功能恢复。土木香内酯口服后的良好生物利用度，以及其在大大超过治疗范围的剂量下具有显著的耐受性，突出了其作为有效药物治疗的巨大潜力，可应对与神经再生相关的挑战并恢复感觉和运动功能。
