Ginsenoside Rk1 mitigates type 2 diabetes mellitus by targeting signal transducer and activator of transcription 3 to alleviate adipocyte hypertrophy and adipose tissue inflammation in diabetic mice.

INTRODUCTION

Type 2 Diabetes Mellitus (T2DM) is a metabolic disease characterized by low-grade chronic inflammation in tissues such as white adipose tissue, which play a vital role in the development of insulin resistance. Ginsenoside Rk1, a minor ginsenoside derived from steamed or puffed ginseng, exhibits various pharmacological effects, including protection against endothelial dysfunction and β-cell apoptosis. However, its anti-diabetic effects remain largely unexplored.

OBJECTIVES

This study investigated the anti-inflammatory and anti-diabetic effects of Ginsenoside Rk1 in bone marrow-derived macrophages (BMDMs) and high-fat diet (HFD)-induced diabetic mice, with a focus on adipose tissue inflammation.

METHODS

In diabetic BMDMs and mice, we investigated whether Ginsenoside Rk1 possessed anti-diabetic and anti-inflammatory effects. We used different molecular biology techniques to study the underlying mechanisms of Ginsenoside Rk1 in mediating these effects. We also investigated the role of signal transducer and activator of transcription 3 (STAT3) in mediating the anti-inflammatory and anti-diabetic effects by using a specific STAT3 inhibitor Stattic.

RESULTS

Ginsenoside Rk1 exerted anti-diabetic effects in diabetic mice, evidenced by reduced fasting blood glucose levels and improved glucose tolerance and insulin resistance. These protective effects were mediated by the suppression of adipose tissue inflammation, characterized by increased interleukin-10 (IL-10) levels, decreased pro-inflammatory cytokine levels, and M2 polarization induction. These effects were also confirmed in diabetic BMDMs. The IL-10/STAT3 pathway was shown to be crucial for the alleviation of adipose tissue inflammation by Ginsenoside Rk1, with STAT3 identified as a potential direct target of Ginsenoside Rk1. STAT3 inhibition reversed the protective effects of Ginsenoside Rk1 in diabetic mice.

CONCLUSION

Our findings unveiled the remarkable anti-diabetic effects of Ginsenoside Rk1 in diabetic mice, emphasizing the pivotal role of STAT3 in alleviating adipocyte hypertrophy, adipose tissue inflammation and T2DM.