<em>Hedysarum polybotrys</em> polysaccharide attenuates renal inflammatory infiltration and fibrosis in diabetic mice by inhibiting the HMGB1/RAGE/TLR4 pathway

Xu,Changqing; Chen,Yanxu; Liu,Zongmei; Fu,Xiaoyan

doi:10.3892/etm.2023.12192

Hedysarum polybotrys polysaccharide attenuates renal inflammatory infiltration and fibrosis in diabetic mice by inhibiting the HMGB1/RAGE/TLR4 pathway

Authors:
- Changqing Xu
- Yanxu Chen
- Zongmei Liu
- Xiaoyan Fu
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Affiliations: Clinical College of Traditional Chinese Medicine, Gansu University of Traditional Chinese Medicine, Lanzhou, Gansu 730000, P.R. China, The First Clinical Medical College, Shaanxi University of Chinese Medicine, Xi'an, Shaanxi 710077, P.R. China, Hyperbaric Oxygen Chamber, The Second Affiliated Hospital of Shaanxi University of Chinese Medicine, Xi'an, Shaanxi 710077, P.R. China
Published online on: September 6, 2023 https://doi.org/10.3892/etm.2023.12192
Article Number: 493

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Abstract

Diabetic kidney disease (DKD) is a leading cause of kidney failure. Previous studies demonstrated the therapeutic potential of Astragalus polysaccharide in treating diabetic nephropathy. Astragalus and Hongqi both come from the leguminous plant Astragalus, but their species and genera are different, belonging to the same family and different genera of traditional Chinese medicinal plants. However, the effects of Hedysarum polybotrys polysaccharide (HPS), a polysaccharide compound from Hongqi, on DKD, including its components and efficacy, have remained elusive. The present study utilized db/db mice as a DKD animal model administered with low (30 mg/kg) and high doses (60 mg/kg) of HPS, in addition to glyburide (7.2 mg/kg). Blood and urine samples were collected from mice and blood glucose, serum creatinine, urinary albumin excretion and urinary β2‑microglobulin were measured. In addition, apoptosis and histological changes in kidney tissue were observed using TUNEL and HE staining, respectively, and the secretion and expression of inflammatory factors in kidney tissue were detected using EILSA and reverse transcription‑quantitative PCR. Furthermore, we the expression of fibrosis‑related proteins and NF‑κB signaling pathway proteins was determined using western blot analysis. HPS was found to reduce the blood glucose concentration, serum creatinine levels, urinary albumin excretion rates and urinary β2‑microglobulin in a dose‑dependent manner. In addition, HPS treatment mitigated apoptosis and pathological damage in the kidney tissues of DKD mice. The expression levels of fibrosis‑related proteins fibronectin, α‑smooth muscle actin and TGF‑β1 were observed to be decreased in kidney tissues of DKD mice following HPS treatment. The secretion levels of inflammatory factors (IL‑6, TNF‑α and IL‑1β) were also reduced in kidney tissues, with high‑dose HPS treatment found to be more effective, similar to the effects mediated by the glyburide. Further mechanistic analysis revealed that the therapeutic effects of HPS on DKD mice may be mediated by inhibiting the high mobility group box 1/receptor for advanced glycation end‑products/toll‑like receptor 4 pathway. In conclusion, the present findings could provide insight for the treatment of DKD.

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