Puerarin Attenuates Complete Freund's Adjuvant-Induced Trigeminal Neuralgia and Inflammation in a Mouse Model via Sirt1-Mediated TGF-β1/Smad3 Inhibition

葛根素通过 Sirt1 介导的 TGF-β1/Smad3 抑制减轻小鼠模型中完全弗氏佐剂诱发的三叉神经痛和炎症

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作者:Kairong Du #, Wei Wu #, Xiaobo Feng, Jianjuan Ke, Hengtao Xie, Yingying Chen

Background

Puerarin, an active compound of radix puerariae, is a major compound used in Chinese herbal medicines and it has been well known for its pharmacological effects, including antioxidant, anti‑inflammatory, neuroprotective and cardioprotective properties. The

Conclusion

The findings suggested that Pue functioned as a potential Sirt1 activator to improve neuroinflammation-induced TN and neuronal apoptosis via the suppression of TGF-β1/Smad3 activity. The pharmacological activity of Pue provides a new perspective for the effective prevention and treatment of TN.

Methods

Mice were injected with CFA on the unilateral face to induce TN. A cell model of inflammation-associated TN was established by interleukin-1β (IL-1β; 10 ng/mL) and tumor necrosis factor-α (TNF-α; 50 ng/mL) stimulation of neurons. Reverse transcription-quantitative PCR and Western blot analyses were performed to analyze mRNA and protein expression levels in trigeminal ganglion and nerve cells. Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining was used to determine nerve cell apoptosis following IL-1β/TNF-α or Pue treatment.

Results

Pue is a conceivable Sirtuin1 (Sirt1) activator used for the prevention of trigeminal nerve injury that attenuates CFA-induced TN and inflammatory cytokine-evoked overactivation of neuronal inflammation and apoptosis. Treatment of mice with inflammatory cytokines induced upregulation of cleaved caspase-3 protein expression, which was neutralized by Pue supplementation. Both in vivo and in vitro experiments led to the

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