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Liu-Shen-Wan 通过抑制 PI3K/Akt 和 TRPV1 信号通路缓解大鼠骨癌痛。

Liu-Shen-Wan inhibits PI3K/Akt and TRPV1 signaling alleviating bone cancer pain in rats.

机构信息

Department of Oncology, Guangdong Provincial Hospital of Traditional Chinese Medicine, Hainan Hospital, Haikou, Hainan, China.

Department of Oncology, Affiliated Hainan Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Haikou, Hainan, China.

出版信息

Cancer Biol Ther. 2024 Dec 31;25(1):2432098. doi: 10.1080/15384047.2024.2432098. Epub 2024 Nov 25.

DOI:10.1080/15384047.2024.2432098
PMID:39587385
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11601056/
Abstract

Patients with advanced-stage cancers often suffer from severe pain caused by bone metastasis and destruction, for which effective treatment options are limited. Liu-Shen-Wan (LSW) is a widely recognized herbal formula utilized for pain relief. This study aims to elucidate the effects of LSW on bone cancer pain (BCP). In this study, the pharmacology of LSW on BCP was screened by network pharmacology. A BCP model was conducted using Walker 256 cells. Paw withdrawal threshold and paw withdrawal latency were employed as measures to assess the pain threshold in rats. The pathways and cell types of LSW against BCP were explored. Next, the impact of LSW on Walker 256 cells was evaluated, and UPLC-MS was utilized to identify the active ingredients of LSW. Furthermore, the effects of the key active ingredient, Bufalin, on the BCP rats were evaluated. There were 275 shared targets between LSW and BCP, which were enriched in neural tissue ligand-receptor interaction pathway. LSW increased pain threshold and decreased inflammatory cytokines levels in BCP rats by inhibiting PI3K/Akt and transient receptor potential vanilloid 1 (TRPV1) signaling through astrocytes and microglia. LY294002 further alleviated BCP in rats, while the effects were reversed after treatment with insulin-like growth factor 1 (IGF-1). Both LSW and its active ingredient Bufalin were shown to inhibit the viability and migration of Walker 256 cells and induce apoptosis. Bufalin appears to be the key active ingredient of LSW and exerts its pain-relieving effects by suppressing PI3K/Akt and TRPV1 signaling in BCP.

摘要

晚期癌症患者常因骨转移和破坏而遭受严重疼痛，而有效的治疗选择有限。Liu-Shen-Wan（LSW）是一种广泛认可的用于缓解疼痛的草药配方。本研究旨在阐明 LSW 对骨癌痛（BCP）的影响。在这项研究中，通过网络药理学筛选了 LSW 对 BCP 的药理学作用。使用 Walker 256 细胞建立 BCP 模型。使用大鼠的爪退缩阈值和爪退缩潜伏期来评估疼痛阈值。探讨了 LSW 针对 BCP 的途径和细胞类型。接下来，评估了 LSW 对 Walker 256 细胞的影响，并使用 UPLC-MS 鉴定 LSW 的活性成分。此外，评估了关键活性成分Bufalin 对 BCP 大鼠的影响。LSW 和 BCP 之间有 275 个共享靶点，这些靶点富集在神经组织配体-受体相互作用途径中。LSW 通过星形胶质细胞和小胶质细胞抑制 PI3K/Akt 和瞬时受体电位香草素 1（TRPV1）信号通路来提高 BCP 大鼠的疼痛阈值并降低炎症细胞因子水平。LY294002 进一步缓解了 BCP 大鼠的病情，但在用胰岛素样生长因子 1（IGF-1）治疗后，效果逆转。LSW 及其活性成分 Bufalin 均显示抑制 Walker 256 细胞的活力和迁移并诱导细胞凋亡。Bufalin 似乎是 LSW 的关键活性成分，通过抑制 BCP 中的 PI3K/Akt 和 TRPV1 信号通路发挥其止痛作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b57d/11601056/950208d58936/KCBT_A_2432098_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b57d/11601056/fd9466f3afb8/KCBT_A_2432098_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b57d/11601056/2cdaefdd4981/KCBT_A_2432098_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b57d/11601056/cb720567d740/KCBT_A_2432098_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b57d/11601056/ea3f813d3f79/KCBT_A_2432098_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b57d/11601056/8d6dad57ef21/KCBT_A_2432098_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b57d/11601056/015c79042fe6/KCBT_A_2432098_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b57d/11601056/950208d58936/KCBT_A_2432098_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b57d/11601056/fd9466f3afb8/KCBT_A_2432098_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b57d/11601056/2cdaefdd4981/KCBT_A_2432098_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b57d/11601056/cb720567d740/KCBT_A_2432098_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b57d/11601056/ea3f813d3f79/KCBT_A_2432098_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b57d/11601056/8d6dad57ef21/KCBT_A_2432098_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b57d/11601056/015c79042fe6/KCBT_A_2432098_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b57d/11601056/950208d58936/KCBT_A_2432098_F0007_OC.jpg

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