靶向细胞焦亡：人参治疗糖尿病及其慢性并发症的新策略。

Targeting pyroptosis: A novel strategy of ginseng for the treatment of diabetes and its chronic complications.

作者信息

Li Ke, Wang Ya-Jun, Chen Chen, Wang Xiao-Jie, Li Wei

机构信息

College of Life Sciences, Engineering Research Center of the Chinese Ministry of Education for Bioreactor and Pharmaceutical Development, Jilin Agricultural University, Changchun 130118, China; College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun 130118, China; Jilin Provincial International Joint Research Center for the Development and Utilization of Authentic Medicinal Materials, Changchun 130118, China.

出版信息

Phytomedicine. 2025 Mar;138:156430. doi: 10.1016/j.phymed.2025.156430. Epub 2025 Jan 26.

DOI:10.1016/j.phymed.2025.156430

PMID:39892311

Abstract

BACKGROUND

Pyroptosis is a recently identified form of programmed cell death that plays a crucial role in the pathogenesis and progression of diabetes and associated chronic complications, while the occurrence mechanism remains unclear. Ginseng (Panax Ginseng C. A. Mey.) is a valuable traditional medicinal material with proved therapeutic effects on prevention and treatment of diabetes and diabetic complications. Targeting pyroptosis pathway has become a focus of study for ginseng in improvement of diabetes and related chronic complications.

PURPOSE

The review aims to elucidate the happening mechanism of pyroptosis in diabetes and diabetic chronic complications, evaluate the effects of ginseng and its active components on diabetes and its chronic complications via pyroptosis-related pathways, and provide a new perspective for the management of diabetes.

METHODS

We conducted the literature retrieval with PubMed, Web of Science, and ScienceDirect databases in a systematic manner (up to August 2024). The keywords included pyroptosis, diabetes, diabetic nephropathy, diabetic retinopathy, diabetic cardiomyopathy, diabetic neuropathy, ginseng, ginseng extract, and ginsenoside. The obtained literatures were comprehensively sorted out.

RESULTS

Oxidative stress, endoplasmic reticulum stress (ERS), and inflammatory responses were primary contributors to pyroptosis in diabetes and associated chronic complications. In addition, some RNA molecules (miRNAs, circRNAs, and lncRNAs) also contributed to pyroptosis under hyperglycemia. The signaling pathways mainly included Nrf2/HO-1, IκB/NF-κB/NLRP3, NOX1/NOX4/TXNIP, and P2X7R/TXNIP/NLRP3. Ginseng extracts, some ginsenosides and flavonoid (Quercetin) could exert anti-diabetic effect by regulating pyroptosis-related pathways. We also discussed the toxicity, side effects and clinical applications of ginseng.

CONCLUSION

In summary, this review elucidates the happening mechanisms of pyroptosis in diabetes and associated chronic complications, and summarizes published studies about ginseng and its active ingredients in improving diabetes by regulating pyroptosis-related pathways. However, almost all researches are limited to animal and cell experiments, and more clinical trials are required to prove the therapeutic effect of ginseng on diabetes by targeting pyroptosis.

摘要

背景

细胞焦亡是一种最近被发现的程序性细胞死亡形式，在糖尿病及其相关慢性并发症的发病机制和进展中起关键作用，但其发生机制仍不清楚。人参是一种珍贵的传统药材，对糖尿病及糖尿病并发症的防治具有确切疗效。靶向细胞焦亡途径已成为人参改善糖尿病及相关慢性并发症的研究热点。

目的

本综述旨在阐明糖尿病及糖尿病慢性并发症中细胞焦亡的发生机制，评估人参及其活性成分通过细胞焦亡相关途径对糖尿病及其慢性并发症的影响，为糖尿病的治疗提供新视角。

方法

我们系统检索了PubMed、Web of Science和ScienceDirect数据库（截至2024年8月）。关键词包括细胞焦亡、糖尿病、糖尿病肾病、糖尿病视网膜病变、糖尿病心肌病、糖尿病神经病变、人参、人参提取物和人参皂苷。对获取的文献进行了全面梳理。

结果

氧化应激、内质网应激（ERS）和炎症反应是糖尿病及相关慢性并发症中细胞焦亡的主要促成因素。此外，一些RNA分子（微小RNA、环状RNA和长链非编码RNA）在高血糖状态下也促成细胞焦亡。信号通路主要包括Nrf2/HO-1、IκB/NF-κB/NLRP3、NOX1/NOX4/TXNIP和P2X7R/TXNIP/NLRP3。人参提取物、一些人参皂苷和黄酮类化合物（槲皮素）可通过调节细胞焦亡相关途径发挥抗糖尿病作用。我们还讨论了人参的毒性、副作用及临床应用。