TangNaikang Formula Alleviates Podocyte Injury in Diabetic Nephropathy by Modulating the SHIP2/PI3K/AKT Pathway

Area of Science:

• Pharmacology
• Nephrology
• Traditional Chinese Medicine

Background:

• Diabetic nephropathy (DN) is a major complication of diabetes, characterized by podocyte injury.
• Traditional Chinese Medicine (TCM) formulas are explored for potential therapeutic benefits in managing DN.
• TangNaikang (TNK) is a TCM formula investigated for its protective effects against DN.

Purpose of the Study:

• To investigate the protective mechanisms of TangNaikang (TNK) in mitigating podocyte injury in diabetic nephropathy (DN).
• To elucidate the molecular pathways involved in TNK's therapeutic effects using both in vivo and in vitro models.

Main Methods:

• Chemical constituents of TNK and TNK-containing serum were identified using UPLC-Q-TOF/MS.
• Network pharmacology was employed to analyze TNK's mechanism in treating DN.
• db/db mice and high glucose-induced MPC5 cells were used as experimental models to assess TNK's effects on renal function, histopathology, and protein expression related to podocyte injury and the PI3K/AKT pathway.

Main Results:

• TNK consists of 69 compounds, with TNK-containing serum containing 34 identified compounds.
• TNK treatment significantly improved serum lipid profiles and renal structure/function in db/db mice.
• TNK modulated the expression of podocyte-associated proteins (SYNPO, nephrin, CD2AP, podocin) and PI3K/AKT pathway proteins (PI3K, AKT, SHIP2, IRS2, GLUT4) in kidney tissues and MPC5 cells.

Conclusions:

• TangNaikang (TNK) ameliorates podocyte injury in diabetic nephropathy (DN) and high glucose-induced podocyte damage.
• The protective effects of TNK are mediated through the modulation of the SHIP2/PI3K/AKT signaling pathway.