Extract from Polygala fallax Hemsl. Protects Kidneys in db/db Mice by Inhibiting the TLR4/MyD88/NF-κB Signaling Pathway

Abstract

ABSTRACTDiabetic nephropathy (DN) is a chronic kidney disease caused by the loss of renal function. The extract of Polygala fallax Hemsl (EPF) possesses anti-inflammatory a nd other pharmacological effects. Objective: To investigate the effect and potenti al mechanism of EPF in the treatment of diabetic nephropathy-associated inflammati on. Materials and methods: Db/db mice were administered varying doses of EPF (15, 30, 60 mg/kg), after which the kidney organ index and glucose tolerance were calcu lated. Urine microalbumin was detected in urine collected over 24 hours. Serum FBG, Cr, and BUN levels were measured, and H&E and PAS staining were used to observe pathological changes in the kidney. The expression of TLR4, MyD88, NF-κB, and MMP −9 in kidney tissue was measured using immunohistochemistry, quantitative real-tim e PCR, and western blotting. Additionally, the expression of TNF-α, MCP-1, IL-6, IL-18, and IL-1βinflammatory factors in the serum was measured by ELISA. Results : EPF significantly decreased the renal organ index and ameliorated glucose intole rance symptoms in db/db mice, reduced 24-hour mALB, FBG, Cr, and BUN serum levels, and mitigated renal pathological changes. Moreover, EPF significantly inhibited th e expression of TLR4, MyD88, NF-κB, MMP-9, and related inflammatory factors TNF-α, MCP-1, IL-6, IL-18, and IL-1βin kidney tissue. Discussion and conclusions: E PF from P. fallax exhibits low toxicity and is safe for use. For the first time, it was discovered that EPF might reduce renal inflammation by inhibiting the TLR4/M yD88/NF-κB signaling pathway in vivo, thereby protecting the kidneys of db/db mic e from damage.