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

This study utilized db/db mice and MPC5 cells induced by high glucose as experimental models to examine the protective mechanisms of the traditional Chinese medicine formula TangNaikang (TNK) in mitigating podocyte injury in diabetic nephropathy (DN).

The chemical constituents of TNK and TNK-containing serum were identified through UPLC-Q-TOF/MS. The underlying mechanism of TNK in treating DN was analyzed using network pharmacology. In vivo, following an 8-week intervention, db/db mice's serum biomarkers (TC, TG, HDL, LDL, AGEs, BUN, Scr, and β2-MG) were compared. H&E, PAS staining, and electron microscopy were used to perform a histopathological investigation on kidney sections. High glucose-induced MPC5 cells were treated with TNK-containing serum. Cellular viability was measured through a CCK-8 assay. The expression levels of podocyte-associated and PI3K/AKT pathway proteins in kidney tissues and MPC5 cells were determined by immunofluorescence, western blotting, and RT-qPCR analysis.

The UPLC-Q-TOF/MS results showed that the TNK formula consisted of 69 compounds, including flavonoids, triterpenoids, and lignans. TNK-containing serum was identified with 34 compounds including 9 TNK prototype components and 25 metabolites. TNK was found to be substantially linked with the PI3K/AKT pathway using network pharmacology. When compared to the model group, the TNK-H group mice had significantly improved serum lipid profiles as well as renal structural and functional profiles. Immunofluorescence and western blotting analyses indicated that TNK regulated the expression levels of the podocyte-associated (SYNPO, nephrin, CD2AP, and podocin) as well as PI3K/AKT pathway proteins (PI3K, AKT, SHIP2, IRS2, and GLUT4). These data were confirmed by RT-qPCR results. TNK-containing serum enhanced MPC5 cell viability via modulating the PI3K/AKT pathway and inhibiting SHIP2.

TNK ameliorates podocyte injury in DN and high glucose-induced MPC5 cells by modulating the SHIP2/PI3K/AKT pathway.