黄精是一种中草药，中国古代医家认为具有滋阴润肺的功效。临床上用于治疗肺部系统疾病，包括非小细胞肺癌。然而，黄精治疗非小细胞肺癌的确切活性成分和潜在机制仍不清楚。本研究旨在通过数据挖掘、网络药理学、体外和体外实验等手段探讨黄精治疗非小细胞肺癌的活性成分和机制。体内实验。首先，通过网络药理学预测了黄精的主要活性成分和关键靶点。使用 Pymol 将黄精的潜在关键靶点与主要活性化合物进行分子对接。在体内，我们验证了化精及其主要活性化合物是否具有抗肺癌作用。通过 PCR 和免疫组织化学验证了关键靶标。在体外，我们通过CCK-8、集落形成、伤口愈合实验和流式细胞术验证了黄精主要活性化合物对A549细胞增殖、凋亡和迁移的影响。通过PCR和Western blot验证关键靶点和信号通路。网络药理学结果表明β-谷甾醇是主要活性物质。 TP53、JUN、AKT1、MAPK14、ESR1、RELA、HIF1A 和 RXRA 是黄精的潜在靶点。分子对接结果表明MAPK14、HIF-1α和RXRA与β-谷甾醇对接良好。体内试验也证实黄精能显着抑制肺癌肿瘤的生长，同时PCR和免疫组化结果提示HIF-1α的表达显着降低。关键的是，KEGG分析表明PI3K/Akt/HIF-1α信号通路被推荐为黄精抗NSCLC作用的主要通路之一。我们进行了体外实验来证实β-谷甾醇对A549细胞的增殖、凋亡、迁移和集落形成的显着影响。此外，我们的研究结果表明，高剂量的β-谷甾醇可以有效降低A549细胞中HIF-1α、AKT1、JUN和RELA的表达。同样，体外实验也发现，高剂量的β-谷甾醇可以抑制PI3K/Akt/HIF-1α信号通路。我们发现黄精及其主要活性成分β-谷甾醇可以降低HIF-1α、AKT1、JUN和RELA 表达并通过 PI3K/Akt/HIF-1α 信号通路减少非小细胞肺癌生长。版权所有 © 2024。由 Elsevier B.V. 出版。

Polygonatum cyrtonema Hua (Huangjing) is a Chinese herb that is considered by ancient Chinese healers to have the effect of nourishing yin and moisturizing the lungs. It is clinically used to treat diseases of the pulmonary system, including non-small cell lung cancer. However, the precise active components and underlying mechanisms of Huangjing in the context of treating NSCLC remain uncertain.This study aimed to explore the active components and mechanisms of Huangjing for the treatment of NSCLC by means of data mining, network pharmacology, and in vitro and vivo experiments.First, the main active compounds and key targets of Huangjing were predicted by network pharmacology. The potential key targets of Huangjing were molecularly docked with the main active compounds using Pymol. In vivo, we verified whether Huajing and its main active compound have anti-lung cancer effects. Key targets were verified by PCR and immunohistochemistry. In vitro, we verified the effects of Huangjing's main active compound on the proliferation, apoptosis, and migration of A549 cells by CCK-8, colony formation, wound healing assay, and flow cytometry. Key targets and signaling pathway were validated by PCR and Western blot.The network pharmacology results suggested that β-sitosterol was the main active substance. TP53, JUN, AKT1, MAPK14, ESR1, RELA, HIF1A, and RXRA were potential targets of Huangjing. Molecular docking results suggested that MAPK14, HIF-1α, and RXRA docked well with β-sitosterol. In vivo tests also confirmed that Huangjing could significantly inhibit the growth of lung cancer tumors, while PCR and immunohistochemistry results suggested that the expression of HIF-1α was significantly decreased. Critically, KEGG analysis indicated that the PI3K/Akt/HIF-1α signaling pathway was recommended as one of the main pathways related to the anti-NSCLC effect of Huangjing. We conducted in vitro experiments to confirm the significant impact of β-sitosterol on the proliferation, apoptosis, migration, and colony formation of A549 cells. Furthermore, our findings indicate that a high dosage of β-sitosterol may effectively decrease the expression of HIF-1α, AKT1, JUN and RELA in A549 cells. Similarly, in vitro experiments also revealed that high doses of β-sitosterol could inhibit the PI3K/Akt/HIF-1α signaling pathway.We discovered Huangjing and its main active ingredient, β-sitosterol, can reduce HIF-1α, AKT1, JUN and RELA expression and decrease non-small cell lung cancer growth through the PI3K/Akt/HIF-1α signaling pathway.Copyright © 2024. Published by Elsevier B.V.