Berberine inhibits NLRP3 inflammasome activation and proinflammatory macrophage M1 polarization to accelerate peripheral nerve regeneration

Jun Sun; Qiuhua Zeng; Zhimin Wu; Lixin Huang; Tao Sun; Cong Ling; Baoyu Zhang; Chuan Chen; Hui Wang

doi:10.1016/j.neurot.2024.e00347

Berberine inhibits NLRP3 inflammasome activation and proinflammatory macrophage M1 polarization to accelerate peripheral nerve regeneration

Neurotherapeutics. 2024 Apr 3;21(4):e00347. doi: 10.1016/j.neurot.2024.e00347. Online ahead of print.

Authors

Jun Sun¹, Qiuhua Zeng², Zhimin Wu³, Lixin Huang³, Tao Sun³, Cong Ling³, Baoyu Zhang³, Chuan Chen⁴, Hui Wang⁵

Affiliations

¹ Department of Neurosurgery, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, 510630, Guangdong, PR China. Electronic address: sunj69@mail2.sysu.edu.cn.
² Department of Radiology, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510120, Guangdong, PR China.
³ Department of Neurosurgery, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, 510630, Guangdong, PR China.
⁴ Department of Neurosurgery, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, 510630, Guangdong, PR China. Electronic address: chenchn6@mail.sysu.edu.cn.
⁵ Department of Neurosurgery, The Third Affiliated Hospital of Sun Yat-sen University, No. 600 Tianhe Road, Guangzhou, 510630, Guangdong, PR China. Electronic address: wangh22@mail.sysu.edu.cn.

PMID: 38570276
DOI: 10.1016/j.neurot.2024.e00347

Abstract

Berberine (BBR) has demonstrated potent anti-inflammatory effects by modulating macrophage polarization. Nevertheless, the precise mechanisms through which berberine regulates post-injury inflammation within the peripheral nerve system remain elusive. This study seeks to elucidate the role of BBR and its underlying mechanisms in inflammation following peripheral nerve injury (PNI). Adult male C57BL/6J mice subjected to PNI were administered daily doses of berberine (0, 60, 120, 180, 240 mg/kg) via gavage from day 1 through day 28. Evaluation of the sciatic function index (SFI) and paw withdrawal threshold revealed that BBR dose-dependently enhanced both motor and sensory functions. Immunofluorescent staining for anti-myelin basic protein (anti-MBP) and anti-neurofilament-200 (anti-NF-200), along with histological staining comprising hematoxylin-eosin (HE), luxol fast blue (LFB), and Masson staining, demonstrated that BBR dose-dependently promoted structural regeneration. Molecular analyses including qRT-PCR, Western blotting, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence confirmed that inactivation of the NLRP3 inflammasome by MCC950 shifted macrophages from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, while also impeding macrophage infiltration. Furthermore, BBR significantly downregulated the expression of the NLRP3 inflammasome and its associated molecules in macrophages, thereby mitigating NLRP3 inflammasome activation-induced macrophage M1 polarization and inflammation. In summary, BBR's neuroprotective effects were concomitant with the suppression of inflammation after PNI, achieved through the inhibition of NLRP3 inflammasome activation-induced macrophage M1 polarization.

Keywords: Berberine; Inflammation; Macrophage polarization; NLRP3 inflammasome; Peripheral nerve injury.