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调节免疫作用及天芪西洋参颗粒通过 TLR4/MAPKs 和 PI3K/AKT/FOXO3a 信号通路对环磷酰胺诱导免疫抑制的机制。

Immunomodulatory effects and mechanisms of Tiepishihu Xiyangshen granules on cyclophosphamide induced immuno-suppression via TLR4/MAPKs and PI3K/AKT/FOXO3a signal pathways.

机构信息

Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.

Department of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.

出版信息

J Ethnopharmacol. 2023 May 10;307:116192. doi: 10.1016/j.jep.2023.116192. Epub 2023 Jan 25.

DOI:10.1016/j.jep.2023.116192
PMID:36706933
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Tiepishihu Xiyangshen granules (TXG) is a traditional Chinese medicine formula composed of Panax quinquefolius L, Dendrobium officinale Kimura & Migo and Ganoderma lucidum (Curtis) P. Karst. It has long been used as a nutritional supplement and an immune enhancer in China. However, the immunomodulatory effects and the underlying mechanisms of TXG have not been clarified.

AIM OF THE STUDY

This study aims to investigate the immunomodulatory effects of TXG and clarify the underlying mechanism.

MATERIALS AND METHOD

TXG was administered by gavage for 18 days. From the 15th day, the immunosuppression model was induced by intraperitoneally injecting 80 mg/kg CTX for 3 days. The immune regulatory effects of TXG on immune organs were verified by calculating the organ index and observing the spleen tissue structure through HE staining. The effects of TXG on immune cells were examined by recording the PBWC, the proliferation rate of lymphocyte and the T lymphocyte phenotype. The effects of TXG on immune molecules were measured by detecting serum hemolysin and the content of cytokines. In parallel, kit was utilized to detect its antioxidant capacity. RNA seq and Western blot were used to analyze the possible immune regulation mechanism of TXG. HPLC and UPLC-Q-TOF-MS were used to identify the chemical components in TXG.

RESULTS

At the level of immune organs, TXG effectively reduced the adverse reaction to the body and the substantial damage to the spleen after chemotherapy by improving the spleen damage. At the level of immune molecules, TXG upregulated the expression of cytokines and antibodies. At the level of immune cells, TXG antagonized bone marrow suppression by increasing the PBWC of immunosuppressed mice. Meanwhile, TXG upregulated the ratio of CD4/CD8 lymphocytes and ameliorated the proliferation of T and B lymphocytes. And the mechanism of TXG to improve immunity might be through TLR4/MAPKs and PI3K/AKT/FOXO3a signaling pathways.

CONCLUSION

The results of this study confirmed that TXG has prominent immunomodulatory activities, and the immunity regulations of TXG may be achieved by regulating TLR4/MAPKs and PI3K/AKT/FOXO3a signal pathways.

摘要

民族药理学相关性

天芪西洋参颗粒(TXG)是一种中药配方,由西洋参、铁皮石斛和灵芝组成。它在中国长期以来一直被用作营养补充剂和免疫增强剂。然而,TXG 的免疫调节作用及其潜在机制尚未得到阐明。

研究目的

本研究旨在探讨 TXG 的免疫调节作用,并阐明其潜在机制。

材料和方法

通过灌胃给药 TXG 18 天。从第 15 天开始,通过腹腔注射 80mg/kgCTX 连续 3 天诱导免疫抑制模型。通过计算器官指数和观察 HE 染色后的脾脏组织结构来验证 TXG 对免疫器官的免疫调节作用。通过记录 PBWC、淋巴细胞增殖率和 T 淋巴细胞表型来检测 TXG 对免疫细胞的影响。通过检测血清溶血素和细胞因子含量来测量 TXG 对免疫分子的影响。同时,试剂盒用于检测其抗氧化能力。RNA 测序和 Western blot 用于分析 TXG 可能的免疫调节机制。HPLC 和 UPLC-Q-TOF-MS 用于鉴定 TXG 中的化学物质。

结果

在免疫器官水平上,TXG 通过改善脾损伤,有效减轻了化疗后对机体的不良反应和对脾脏的实质性损伤。在免疫分子水平上,TXG 上调了细胞因子和抗体的表达。在免疫细胞水平上,TXG 通过增加免疫抑制小鼠的 PBWC 来拮抗骨髓抑制。同时,TXG 上调了 CD4/CD8 淋巴细胞的比值,并改善了 T 和 B 淋巴细胞的增殖。TXG 改善免疫的机制可能是通过 TLR4/MAPKs 和 PI3K/AKT/FOXO3a 信号通路。

结论

本研究结果证实,TXG 具有显著的免疫调节活性,其免疫调节作用可能是通过调节 TLR4/MAPKs 和 PI3K/AKT/FOXO3a 信号通路来实现的。

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