Salvianolic Acid A Alleviates Sciatic Nerve Injury in Rats Via Inhibiting NLRP3 Inflammasome Through the Activation of Schwann Cells Autophagy

被引：0
作者：
Mingfu Fu [1 ]
Fenghua Zhang [1 ]
Yanli Song [1 ]
Jianhang Wang [1 ]
机构：
[1] Department of Orthopedic Surgery, Yantaishan Hospital, 10087 Keji Avenue, Laishan District, Shandong, Yantai
来源：
Neurochemical Research | 2025年 / 50卷 / 3期
关键词：
Autophagy; NLRP3; inflammasome; Salvianolic acid A; Schwann cell; Sciatic nerve injury;
D O I：
10.1007/s11064-025-04402-1
中图分类号：
学科分类号：
摘要：
Salvianolic acid A (SalA) is a phenolic acid of Salvia miltiorrhiza with the effects of anti-oxidant and immunoenhancing medicinal properties. In this study, we investigated the activities of SalA on the neurorestorative function and the autophagy-regulated NLRP3 inflammasome in sciatic nerve injury (SNI) rats and schwann cells. Sciatic nerve compression model rats were constructed, the sciatic nerve function index and gastrocnemius muscle mass ratio were used to detect the recovery of motor function. The effect of SalA on repairing pathological injured nerves was evaluated by H&E staining and masson staining, toluidine blue staining and TEM were used to analyze the myelin removal ability. Western blotting and immunohistochemistry were used to identify the expression of NLRP3 inflammasome, autophagy-related proteins and myelin proteins in the injured area. Moreover, the modulatory effects of SalA on cellular antioxidant capacity and damage were investigated by appending the autophagy inhibitor 3-MA based on LPS-treated RSC96 cells. SalA promoted the recovery of motor nerve function after injury, increased the number of myelinated nerve regeneration and improved the damaged myelin sheath structure. SalA administration could increase MBP, NF200 and Beclin-1 expression, reduce the NLRP3/pro-caspase1/ASC signaling pathway in SNI rats, up-regulate LC3 level in RSC96 cells. SalA increased cell survival and decreased inflammatory factors production, which was reversed by 3-MA. SalA restores neuromotor function after nerve crush injury by accelerating early myelin degradation and promoting proliferation. In addition, SalA inhibits neuroinflammation and apoptosis by reducing the activation of NLRP3 inflammasome, and autophagy-related signaling pathways may be potential regulatory targets ( © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.
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  • [1] North R.B., Kidd D.H., Zahurak M., Piantadosi S., Specificity of diagnostic nerve blocks: a prospective, randomized study of sciatica due to lumbosacral spine disease, Pain, pp. 77-85, (1996)
  • [2] Sunter G., Uluc K., Salcini C., Temucin C.M., Yilmaz O., Tanridag T., Us O., Padua L., Motor nerve impairment in diabetic patients with symmetrical distal sensory polyneuropathy: a single nerve fiber conduction velocity study, Muscle Nerve, pp. 84-89, (2014)
  • [3] Kaya Y., Savas K., Sarikcioglu L., Yaras N., Angelov D.N., Melatonin leads to axonal regeneration, reduction in oxidative stress, and improved functional recovery following sciatic nerve injury, Curr. Neurovasc. Res, pp. 53-62, (2015)
  • [4] Uslusoy F., Naziroglu M., Cig B., Inhibition of the TRPM2 and TRPV1 channels through Hypericum perforatum in sciatic nerve Injury-induced rats demonstrates their key role in apoptosis and mitochondrial oxidative stress of sciatic nerve and dorsal root ganglion, Front Physiol, 2017, (2017)
  • [5] Salzer J.L., Schwann cell myelination, Cold Spring Harbor Perspect. Biol a, (2015)
  • [6] Namgung U., The role of Schwann cell-axon interaction in peripheral nerve regeneration, Cells Tissues Organs, pp. 6-12, (2014)
  • [7] Gordon T., Peripheral nerve regeneration and muscle reinnervation, Int J Mol Sci, (2020)
  • [8] Cuervo A.M., Bergamini E., Brunk U.T., Droge W., Ffrench M., Terman A., Autophagy and aging: the importance of maintaining clean cells, Autophagy, pp. 131-140, (2005)
  • [9] Zhong Z., Sanchez-Lopez E., Karin M., Autophagy, NLRP3 inflammasome and auto-inflammatory/immune diseases, Clin. Exp. Rheumatol, 12, (2016)
  • [10] Gupta S., Cassel S.L., Sutterwala F.S., Dagvadorj J., Regulation of the NLRP3 inflammasome by autophagy and mitophagy, Immunol Rev, (2024)
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