Protopanaxadiol improves lupus nephritis by regulating the PTX3/MAPK/ERK1/2 pathway

IF 2.5 4区医学 Q3 CHEMISTRY, MEDICINAL

Journal of Natural Medicines Pub Date : 2024-03-03 DOI:10.1007/s11418-023-01777-9

Zhenyuan Li, Hailin Gan, Kai Ji, Mingyan Yang, Tao Pan, Xiangting Meng, Teng Liu, Zhixia Wang, Baifang Gong, Ke Liu, Dong Qi, Huaying Fan

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Abstract

Lupus nephritis (LN) is a kidney disease that occurs after systemic lupus erythematosus (SLE) affects the kidneys. Pentraxin 3 (PTX3) is highly expressed in the serum of patients with LN. Renal PTX3 deposition is directly related to clinical symptoms such as proteinuria and inflammation. The excessive proliferation of mesangial cells (MCs) is one of the representative pathological changes in the progression of LN, which is closely related to its pathogenesis. Protopanaxadiol (PPD) is the main component of ginsenoside metabolism and has not been reported in LN. The aim of this study was to investigate the relationship between PTX3 and mesangial cell proliferation and to evaluate the potential role and mechanism of PPD in improving LN. PTX3 is highly expressed in the kidneys of LN patients and LN mice and is positively correlated with renal pathological indicators, including proteinuria and PCNA. The excessive expression of PTX3 facilitated the proliferation of MCs, facilitated the activation of the MAPK/ERK1/2 signaling pathway, and increased the expression of HIF-1α. Further studies showed that PPD can effectively inhibit the abnormal proliferation of MCs with high expression of PTX3 and significantly improve LN symptoms such as proteinuria in MRL/lpr mice. The mechanism may be related to the inhibition of the PTX3/MAPK/ERK1/2 pathway. In this study, both in vitro, in vivo, and clinical sample results show that PTX3 is involved in the regulation of MCs proliferation and the early occurrence of LN. Natural active compound PPD can improve LN by regulating the PTX3/MAPK/ERK1/2 pathway.

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原人参酚通过调节 PTX3/MAPK/ERK1/2 通路改善狼疮肾炎

摘要狼疮性肾炎（LN）是系统性红斑狼疮（SLE）影响肾脏后出现的一种肾脏疾病。五毒素 3（PTX3）在狼疮肾炎患者的血清中高度表达。肾脏 PTX3 沉积与蛋白尿和炎症等临床症状直接相关。间质细胞（MCs）过度增殖是 LN 进展过程中具有代表性的病理变化之一，与 LN 的发病机制密切相关。原人参皂苷（PPD）是人参皂苷代谢的主要成分，在 LN 中尚未见报道。本研究旨在探讨 PTX3 与间质细胞增殖之间的关系，并评估 PPD 在改善 LN 中的潜在作用和机制。PTX3 在 LN 患者和 LN 小鼠的肾脏中高表达，并与蛋白尿和 PCNA 等肾脏病理指标呈正相关。PTX3 的过度表达促进了 MCs 的增殖，促进了 MAPK/ERK1/2 信号通路的激活，并增加了 HIF-1α 的表达。进一步的研究表明，PPD能有效抑制PTX3高表达的MCs的异常增殖，明显改善MRL/lpr小鼠的蛋白尿等LN症状。其机制可能与抑制PTX3/MAPK/ERK1/2通路有关。本研究的体外、体内和临床样本结果均表明，PTX3参与了MCs增殖和LN早期发生的调控。天然活性化合物PPD可通过调节PTX3/MAPK/ERK1/2通路改善LN。图表摘要

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来源期刊

Journal of Natural Medicines 医学-药学

CiteScore

6.90

自引率

3.00%

发文量

审稿时长

1.7 months

期刊介绍： The Journal of Natural Medicines is an international journal publishing original research in naturally occurring medicines and their related foods and cosmetics. It covers: -chemistry of natural products -biochemistry of medicinal plants -pharmacology of natural products and herbs, including Kampo formulas and traditional herbs -botanical anatomy -cultivation of medicinal plants. The journal accepts Original Papers, Notes, Rapid Communications and Natural Resource Letters. Reviews and Mini-Reviews are generally invited.