Unlock the Power of Ginsenoside Rg3: Defend Against DKD with miR-216a-5p

Unlock the Power of Ginsenoside Rg3: Defend Against DKD with miR-216a-5p


Diabetic kidney disease (DKD) has emerged as one of the primary cause of mortality among the patients with end-stage renal disease such as renal failure, accounting for 30-50% of chronic renal failure cases. Recent studies have shed light on the potential of ginsenoside Rg3 in hindering the progression of DKD by enhancing antioxidant activity as well as repressing the renal inflammation and apoptosis. Intriguingly, the molecular underpinnings of Rg3's impact have been traced to its ability to downregulate miR-216a-5p level, offering a novel clue for therapeutic intervention in DKD management.

About DKD

DKD is one of the major microvascular complications of diabetes, impairing the ability of kidneys to eliminate waste and excess fluids. The clinical manifestations of DKD chiefly include hypertension, proteinuria, edema, and renal insufficiency. In traditional Chinese medicine (TCM), DKD can be classified into the categories of edema, deficiency, and Guange, which is mainly caused by spleen and kidney deficiency, dampness, and blood stasis block and can be treated by invigorating the spleen and kidney as well as eliminating the turbid by purgation.

The benefit of Chinese herbs in treating DKD

Chinese herbs (astragalus, ginseng, and coptidis rhizome) have good hypoglycemic efficacy, and exhibit unique advantages in blood glucose control, such as multi-function, multi-target, low toxicity and side effects, safety and reliability, mild and long-lasting effects, which can effectively slow down the occurrence of DKD. Among them, ginseng is a precious herb with a long history in TCM. Its essence for medical use is initially contained in Shen Nong Ben Cao Jing (Shennong's Classic of Materia Medica). It is said that ginseng, sweet in taste and slightly cold in property, is the main tonic for the five viscera, with the functions of enriching yin and nourishing kidney, invigorating spleen for benefiting lung, calming mind and enhancing intelligence. Strikingly, Rg3, a saponin compound in the TCM ginseng, has a potential therapeutic effect on DKD.

Therapeutic effect of Rg3 on DKD and underlying molecular mechanisms

After treatment with Rg3 or a miR-216a-5p inhibitor, typical histopathological phenotypes of DKD, such as glomerulosclerosis, cellular vacuolization, and inflammatory cell infiltration, are notably improved, and basement membrane hyperplasia is also repaired to some extent, as revealed by H&E staining. Additionally, there is a significant decrease in fasting blood glucose, blood urea nitrogen, and creatinine levels in kidney tissues of diabetic model mice, indicating an overall improvement in renal function. Moreover, Rg3 induces the proliferation, yet suppresses apoptosis in high glucose (HG)-induced mouse mesangial cells SV40 MES 13. Mechanically, Rg3 activates MAPK pathway by downregulating miR-216a-5p level to attenuate renal injury, thereby hampering the progression of DKD.



Rg3 could repress the development of DKD by downregulating miR-216a-5p and activating MAPK pathway. The discovery underscores the potential of traditional medicine to offer innovative solutions to modern health challenges, paving the way for integrative medical strategies that merges ancient healing knowledge with modern scientific methods.


[1] Chen Y, Peng Y, Li P, Jiang Y, Song D. Ginsenoside Rg3 induces mesangial cells proliferation and attenuates apoptosis by miR-216a-5p/MAPK pathway in diabetic kidney disease. Aging (Albany NY). Published online June 7, 2024. doi:10.18632/aging.205907
[2] Li Y, Hou JG, Liu Z, et al. Alleviative effects of 20(R)-Rg3 on HFD/STZ-induced diabetic nephropathy via MAPK/NF-κB signaling pathways in C57BL/6 mice. J Ethnopharmacol. 2021;267:113500. doi:10.1016/j.jep.2020.113500
[3] Zhou T, Sun L, Yang S, et al. 20(S)-Ginsenoside Rg3 Protects Kidney from Diabetic Kidney Disease via Renal Inflammation Depression in Diabetic Rats. J Diabetes Res. 2020;2020:7152176. Published 2020 Mar 18. doi:10.1155/2020/7152176

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