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

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

doi:10.1016/j.phymed.2025.156430

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

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

Authors

Ke Li¹, Ya-Jun Wang², Chen Chen³, Xiao-Jie Wang⁴, Wei Li⁵

Affiliations

¹ 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.
² 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.
³ Endocrinology and Metabolism, School of Biomedical Sciences, University of Queensland, Brisbane 4072, Australia.
⁴ College of Life Sciences, Engineering Research Center of the Chinese Ministry of Education for Bioreactor and Pharmaceutical Development, Jilin Agricultural University, Changchun 130118, China; School of Pharmacy, Wenzhou Medical University, Chashan University Park, Wenzhou 325035, China.
⁵ 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. Electronic address: liwei7727@126.com.

PMID: 39892311
DOI: 10.1016/j.phymed.2025.156430

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.

Keywords: Active ingredients; Diabetes; Diabetic chronic complication; Ginseng; Pyroptosis.

Publication types

Systematic Review

MeSH terms

Animals
Diabetes Complications* / drug therapy
Diabetes Mellitus* / drug therapy
Endoplasmic Reticulum Stress / drug effects
Ginsenosides / pharmacology
Humans
Oxidative Stress / drug effects
Panax* / chemistry
Plant Extracts* / pharmacology
Pyroptosis* / drug effects

Substances

Ginsenosides
Plant Extracts