# Licochalcone B suppresses oxidative stress and apoptosis accompanied by upregulating Nrf2/HO-1 pathway to ameliorate diabetic nephropathy in mice

## TL;DR

Licochalcone B reduces kidney damage in diabetic mice by lowering oxidative stress and activating a protective pathway.

## Contribution

This study reveals Licochalcone B's novel therapeutic potential for diabetic nephropathy via the Nrf2/HO-1 pathway.

## Key findings

- LCB reduced blood glucose, kidney injury, and collagen accumulation in diabetic mice.
- LCB improved kidney function by lowering albumin, creatinine, and blood urea nitrogen levels.
- LCB suppressed oxidative stress and apoptosis in both mice and human kidney cells.

## Abstract

Diabetic nephropathy (DN), as a complication of diabetes, is one of the major causes of end-stage renal disease. Licochalcone B (LCB), a flavonoid active component derived from licorice, is well known for its anti-inflammatory and antioxidant properties. However, the influence of LCB on DN remains unclear. This research investigated the effect of LCB on DN and elucidated the regulatory mechanism.

We employed male C57BL/6 mice to construct a DN mouse model induced by a high-fat diet (HFD)/streptozotocin (STZ). In vitro, a high glucose (HG)-induced injury model in HK-2 (human renal tubular epithelial) cells was used to further confirm the protective effects of LCB.

LCB treatment (20 mg/kg and 40 mg/kg) decreased blood glucose levels, kidney injury, glycogen deposition, and collagen accumulation in the DN mice. Moreover, LCB at a dosage of 40 mg/kg reduced albumin, creatinine, and blood urea nitrogen levels by about 70.7%, 33.4%, and 45.6%, respectively, indicating an improvement in kidney function. In renal tissues, LCB suppressed oxidative stress and apoptosis in HFD/STZ-induced mice. Consistent with in vivo findings, LCB alleviated HG-induced oxidative stress and apoptosis in HK-2 cells. Transcriptome analysis revealed that LCB affects oxidative stress and renal function-related pathways to alleviate DN. Further mechanistic studies demonstrated that LCB treatment upregulates the expressions of heme oxygenase-1 (HO-1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2), suggesting activation of the Nrf2/HO-1 signaling pathway.

Taken together, this research demonstrates that LCB suppresses oxidative stress and apoptosis accompanied by modulating the Nrf2/HO-1 pathway to ameliorate DN, which provides a promising strategy for DN treatment.