Repurposing Nano‐Dimensions of a Small Phytomolecule, Rhein, Into Nano‐Rhein to Unveil Its Efficacy on Hypercalciuria‐Induced Nephropathies on a SERS‐Based Calcification Profiling Platform

Renal disorders induced by calcium oxalate (CaOx) crystals potentiate a complex pathophysiological landscape devoid of effective pharmacological interventions. Herein, a bioactive herbal compound, rhein, isolated from Cassia fistula Linn is known for its well-documented anti-inflammatory and anti-cancer properties. It's role as a CaOx inhibitor has received inadequate scrutiny. The clinical viability of rhein is hampered bypoor aqueous solubility and low bioavailability. To surmount these challenges, a simple and rapid sonochemical self-assembly technique is engineered to transform rhein into nano-rhein, aiming to augment its inhibitory efficacy toward CaOx. The anti-calcification properties of both rhein and nano-rhein were assessed through an in vitro model employing human embryonic kidney cells HEK-293. Through surface-enhanced Raman scattering (SERS), we established a Raman imaging platform to monitor calcification processes. To deepen the understanding of cellular responses to CaOx we conducted an RNA sequencing experiment to evaluate the the transcriptomic modification exerted by nano-rhein. In addition, in vivo studies further demonstrated that nano-rhein significantly reduced renal CaOx crystal deposition and alleviated kidney injury and dysfunction in a C57BL/6 mouse model. This exploration offers intricate insights into the potential of rhein, particularly in its nano form, as a promising therapeutic agent for CaOx-induced nephropathies.