Single‐cell spatial transcriptomics reveals potential molecular mechanisms of <i>Abelmoschus manihot</i> (L.) medic in treating diabetic kidney disease

A clinical study reported that <i>Abelmoschus manihot</i> (L.) Medic (<i>A. manihot</i>), in the form of Huangkui capsule (HKC), combined with irbesartan (IRB) is an effective therapy for patients with diabetic kidney disease (DKD). The bioactive components of HKC are total flavones extracted from <i>A. manihot</i> (TFA). To explore the pharmaceutical molecular mechanisms underlying the efficacy of <i>A. manihot</i> in the treatment of DKD, we have combined SpaTial Enhanced REsolution Omics-sequencing (at 0.25 μm resolution) with single-cell full-length RNA sequencing. We employed the db/db mouse model of type 2 diabetes and DKD. These experimental methods generated the first single-cell resolution pharmacopathological spatial atlas in kidneys of db/db mice that were treated with TFA or IRB. TFA exhibited therapeutic effects on DKD comparable to those of TFA combined with IRB. Following genome-wide gene screening and molecular docking simulation, we have identified the key renal receptors (<i>Itga3</i>, <i>Itga5</i>, <i>Tgfbr1</i>, etc.) and regulators (<i>Jun</i>, <i>Junb</i>, <i>Stat1</i>, etc.) underlying the therapeutic action of TFA in DKD. This study provides novel insights into the pharmaceutical mechanisms of <i>A. manihot</i> in the treatment of DKD.