Work

Huangkui capsule, an extract from Abelmoschus manihot (L.) medic, inhibits adrenal aldosterone synthesis and renal ERK/EGR1 pathway in the treatment of diabetic kidney disease

Year: 2025

Type: article

Abstract: ETHNOPHARMACOLOGICAL RELEVANCE: Huangkui capsule (HKC) is prepared with the extract of the flower of Abelmoschus manihot (L.) medic and has been used as a traditional Chinese medicine in the treatment of kidney diseases, including diabetic kidney disease (DKD). AIM OF THE STUDY: Our recent single-cell profile study has implicated that HKC regulates Hsd11b2 expression in renal principal cells of collecting duct, a gene crucial for glucocorticoids inactivation and mineralocorticoid receptor (MR) specificity in the kidney. The goal of this study is to further investigate the effects of HKC on adrenal steroid hormone production, renal aldosterone-MR signaling in the treatment of DKD. MATERIALS AND METHODS: Adrenal zones in db/db mice with and without HKC treatment were histologically observed. Adrenal RNA sequencing and adrenal steroid profiling were performed to analyze the expression of steroidogenesis genes and the levels of steroid hormones. Serum steroid hormone levels were measured with ELISA kits. The activity of the genes involved in renal ERK/EGR1 and MR signaling pathways were detected with Western blotting. RESULTS: HKC treatment reduced the adrenal aldosterone synthesis, and diminished the Cyp11b2 expression. Consequently, the expression of phosphorylated ERK1/2, EGR1 and fibrosis and inflammation markers, including TGFβ1, ICAM1, and Collagen IV was decreased. HKC treatment led to a decrease in cortisol levels and alleviated renal MR overactivation reflected by reduced expression of SGK1. HKC treatment elevated the expression of HSD11B2, suggesting a reduced MR activation by cortisol after HKC treatment. HKC treatment reduced high blood pressures and restored serum K+ content and the Na+/K+ ratio in db/db mice. CONCLUSION: The present study reveals a novel pharmaceutical role of A. manihot (L.) in the treatment of DKD via suppressing the aldosterone-ERK/EGR1 pathway, and MR activation, thereby reducing the fibrosis and kidney dysfunction.

Source: Journal of Ethnopharmacology

DOI: 10.1016/j.jep.2025.119936

Authors: Rengui Saxu, Haitao Tang, Hongmei Yu, Haitao Ge, Harvest F. Gu

Institutions: China Pharmaceutical University, Taizhou University, Taizhou University, Qilu Medical University, Nanjing University of Chinese Medicine

Language: English

Topic: Hormonal Regulation and Hypertension

Subfield: Endocrinology, Diabetes and Metabolism

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,740