Objective To investigate the therapeutic effect and mechanism of tanshinone IIA on motor function recovery after brachial plexus root avulsion (BPA) using a rat brachial plexus root avulsion (BPA)-replantation model and an hydrogen peroxide (H2O2)-induced oxidative damage model in NSC-34 cells. Methods A total of 60 SD rats were randomly divided into sham group, model group, tanshinone IIA low- and high-dose (10, 30 mg/kg) groups, with 15 rats in each group. After modeling, continuous administration was performed for eight weeks. Motor function recovery was evaluated using Terzis grooming test (TGT). The biceps brachii muscle was weighed and processed for hematoxylin-eosin (HE) staining to assess morphological changes. Motor neuron survival in the spinal cord was determined by neutral red staining. Axonal regeneration was assessed by Fluoro-Gold retrograde labeling and immunofluorescence staining for choline acetyltransferase (ChAT) and neurofilament 200 (NF200) in the musculocutaneous nerve. Immunofluorescence was performed to detect ionized calcium-binding adapter molecule 1 (Iba1), glial fibrillary acidic protein (GFAP) and neuronal nitric oxide synthase (nNOS) expressions. Level of malondialdehyde (MDA) and activity of superoxide dismutase in the injured spinal cord were measured. The protein expressions of Ras-related C3 botulinum toxin substrate l (Rac1), cell division control protein 42 (Cdc42), c-Jun N-terminal kinase (JNK) and c-Jun in the injured spinal cord were detected by Western blotting. In vitro, control group, model group, tanshinone IIA group and Rac1 inhibitor group were established. NSC-34 cells were induced with 400 μmol/L H2O2 to cause oxidative damage. After intervention with tanshinone IIA or NSC 23766, cell viability was assessed using CCK-8 assay. Levels of MDA, reactive oxygen species (ROS) and activity of SOD were measured, and the expressions of Rac1/JNK pathway-related proteins was analyzed by Western blotting. Results The BPA model was successfully established as evidenced by consistently 0 TGT scores in model group at 1 week post-surgery. Compared with model group, tanshinone IIA significantly improved the TGT scores (P < 0.05, 0.01), enhanced axonal regeneration (P < 0.01), increased motor neuron count (P < 0.01), mitigated muscle atrophy (P < 0.05, 0.01), and reduced the expressions of Iba1 and GFAP (P < 0.05, 0.01). Meanwhile, tanshinone IIA improved oxidative stress damage, including decreased nNOS positive motor neurons (P < 0.05, 0.01), reduced MDA level (P < 0.001), elevated SOD activity (P < 0.01), while up-regulating Rac1, Cdc42, JNK and c-Jun expressions in spinal cord tissue (P < 0.01, 0.001). In vitro, tanshinone IIA significantly increased viability of H2O2-injured NSC-34 cells (P < 0.01), elevated SOD activity (P < 0.01), decreased MDA and ROS levels (P < 0.01), up-regulated Rac1, Cdc42, JNK and c-Jun protein expressions (P < 0.05, 0.01, 0.001). Notably, these protective effects of tanshinone IIA were partially attenuated by co-administration of Rac1 inhibitor NSC 23766 (P < 0.05, 0.01). Conclusion Tanshinone IIA promotes motor function recovery following brachial plexus root avulsion by activating Rac1/JNK signaling pathway, which attenuates oxidative stress and neuroinflammation, thereby enhancing motor neuron survival and axonal regeneration.
ZHANG Qin, CHENG Xiaomin, CHEN Manni, HU Xianghang, PAN Qiyang, JIA Caiju, LIU Yuhong, ZHANG Xie.
Tanshinone IIA facilitates motor function recovery following brachial plexus root avulsion by modulating Rac1/JNK pathway[J].
Chinese Traditional and Herbal Drugs,
2026
, 57
(3)
: 935
-948
.
DOI: 10.7501/j.issn.0253-2670.2026.03.013
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