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

Yukun Bao, Zeyue Wang, Qing Xu, Lixin Wang, Yi Wen, Peng Deng, Qin Xu.

Diabetic Nephropathy (DN) is a chronic kidney disease caused by the loss of renal function. The Extract of Polygala Fallax Hemsl (EPF) possesses anti-inflammatory and other pharmacological effects.

Objective: To investigate the effect and potential mechanism of Extract of Polygala Fallax Hemsl (EPF) in the treatment of diabetic nephropathy-associated inflammation.

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 calculated. Urine micro albumin 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-time PCR, and western blotting. Additionally, the expression of TNF-α, MCP-1, IL-6, IL-18, and IL-1β inflammatory factors in the serum was measured by EnzymeLinked Immuno Sorbent Assay (ELISA).

Results: EPF significantly decreased the renal organ index and ameliorated glucose intolerance symptoms in db/ db mice, reduced 24-hour mALB, FBG, Cr, and BUN serum levels, and mitigated renal pathological changes. Moreover, EPF significantly inhibited the expression of TLR4, MyD88, NF-κB, MMP-9, and related inflammatory factors TNF-α, MCP-1, IL-6, IL-18, and IL-1β in kidney tissue.

Conclusion: EPF 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/MyD88/NF-κB signaling pathway in vivo, thereby protecting the kidneys of db/db mice from damage.