Department of Oncology, Xiangya Hospital, Central South University, Changsha, People's Republic of China.
Department of Stomatology, Third Xiangya Hospital, Central South University, Changsha, People's Republic of China.
Drug Des Devel Ther. 2022 Jun 30;16:2067-2081. doi: 10.2147/DDDT.S357638. eCollection 2022.
Paclitaxel-induced peripheral neuropathy (PIPN) is increasingly becoming one of the most widespread adverse effects in the treatment of cancer patients, and further precipitate neuroinflammation in the nervous system. Interestingly, Shaoyao Gancao Decoction (SGD), a traditional Chinese analgesic prescription, has emerged as a primary adjuvant to chemotherapy in relieving side effects, especially in the case of PIPN. However, the underlying mechanism of SGD functioning in PIPN remains elusive. Accordingly, the current study set out to explore the potential axis implicated in the functioning of SGD in PIPN.
First, network pharmacology was adopted to predict the role of the transient receptor potential vanilloid type 1 (TRPV1) protein in treating PIPN with SGD. Subsequently, the effects of SGD treatment on mechanical allodynia and thermal hyperalgesia were evaluated in rat PIPN models. Based on the bioinformatics information and current literature, paclitaxel activates toll-like receptor 4 (TLR4) induces the sensitization of TRPV1 mechanistically. Thereafter, TLR4-myeloid-differentiation response gene 88 (MyD88) signaling and TRPV1 expression patterns in dorsal root ganglias (DRGs) were measured by means of Western blotting, qPCR and immunofluorescence.
Initial bioinformatics reared a total of 105 bioactive compounds and 1075 target genes from SGD. In addition, 40 target genes intersected with PIPN were considered as potential therapeutic genes. Based on the network analysis, SGD was found to exert its analgesic effect by reducing the expression of TRPV1. Further experimentation validated that SGD exerted an analgesic effect on thermal hyperalgesia in PIPN models, such that this protective effect was associated with the suppression of TRPV1 and TLR4-MyD88 Signaling over-expression.
Collectively, our findings indicated that SGD ameliorates PIPN by inhibiting the over-expression of TLR4-MyD88 Signaling and TRPV1, and further highlights the use of SGD as a potential alternative treatment for PIPN.
紫杉醇诱导的周围神经病变（PIPN）日益成为癌症患者治疗中最广泛的不良反应之一，并进一步在神经系统中引发神经炎症。有趣的是，芍药甘草汤（SGD），一种传统的中药止痛处方，已成为化疗缓解副作用的主要辅助药物，特别是在 PIPN 的情况下。然而，SGD 在 PIPN 中发挥作用的潜在机制仍不清楚。因此，本研究旨在探讨 SGD 在 PIPN 中发挥作用的潜在机制。
首先，采用网络药理学预测 TRPV1 蛋白在 SGD 治疗 PIPN 中的作用。随后，在大鼠 PIPN 模型中评价 SGD 治疗对机械性痛觉过敏和热痛觉过敏的影响。基于生物信息学信息和现有文献，紫杉醇通过激活 Toll 样受体 4（TLR4）激活 TRPV1，从而引起 TRPV1 敏化。此后，通过 Western blot、qPCR 和免疫荧光测定 TLR4-髓样分化反应基因 88（MyD88）信号和背根神经节（DRG）中 TRPV1 的表达模式。
最初的生物信息学从 SGD 中总共培养了 105 种生物活性化合物和 1075 个靶基因。此外，与 PIPN 交叉的 40 个靶基因被认为是潜在的治疗基因。基于网络分析，SGD 通过降低 TRPV1 的表达发挥其镇痛作用。进一步的实验验证了 SGD 对 PIPN 模型中的热痛觉过敏具有镇痛作用，这种保护作用与抑制 TRPV1 和 TLR4-MyD88 信号过度表达有关。
总的来说，我们的研究结果表明，SGD 通过抑制 TLR4-MyD88 信号和 TRPV1 的过度表达来改善 PIPN，并进一步强调了 SGD 作为 PIPN 潜在治疗方法的应用。
