Rostellularia procumbens (L) Nees. extract attenuates adriamycin-induced nephropathy by maintaining mitochondrial dynamics balance via SIRT1/ PGC-1α signaling pathway activation

Ethnopharmacological relevance: Rostellularia procumbens (L) Nees. (R. procumbens) is a classical Chinese herbal medicine that has been used for effective treatment of kidney disease for nearly a thousand years in China. Recently, significant progress has been achieved in understanding the abnormal mitochondrial structure and function from chronic kidney disease (CKD). However, the regulatory mechanisms underlying R. procumbens treatment for CKD and its association with dysfunctional mitochondrial function remain elusive. Aim of the study: To study the protective effect of N-butanol extract from R. procumbens (J-NE) on chronic glomerulonephritis (CGN) mice using a mice model and mitochondrial function-related experiments. Materials and methods: A renal injury mouse model was developed using a single tail vein injection of adriamycin (9 mg/kg). Renal pathology was analyzed through hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM). Cell apoptosis in kidney tissues was analyzed using TUNEL staining. Protein levels were measured via immunohistochemistry (HIF-1 alpha, FN, alpha-SMA, and Collagen I) and Western blot (Mn-SOD, p-DrpS637, MFN1, MFN2, OPA1, TFAM, Nrf1, ATP6, SIRT1, and PGC-1 alpha) analysis. UHPLC-MS/MS was used to analyze the presence of bioactive phytocompounds in J-NE. Results: The results reported that the levels of kidney injury markers (urinary protein, glomerular atrophy, and renal cell apoptosis), mitochondrial dysfunction markers (mitochondrial ultrastructure, Mn-SOD, HIF-1 alpha, FN and alpha-SMA),mitochondrial dynamic imbalance markers (p-Drp-S637, MFN1, MFN2 and OPA1) and SIRT1/PGC-1 alpha signaling pathway markers (TFAM, Nrf1, ATP6, SIRT1, and PGC-1 alpha) were settled to a significant improvement by the oral administration of J-NE. Conclusions: In conclusion, R. procumbens could be able to protect the kidneys from podocyte injury caused mitochondrial dynamics and energy metabolism dysregulation by modulating the SIRT1/PGC-1 alpha signaling pathway.