Related Experiment Video
Updated: Aug 26, 2025
Author Spotlight: Exploring the Impact of Lingnan Fire-Needle Therapy in Osteoporosis Intervention
Published on: April 26, 2024
A molecular phenotypic screen reveals that lobetyolin alleviates cardiac dysfunction in 5/6 nephrectomized mice by
Shi-Hao Ni1, Xiao-Lu OuYang1, Xin Liu1
1The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510407, China; Key Laboratory of Chronic Heart Failure, Guangzhou University of Chinese Medicine, Guangzhou 510407, China.
Insights
Lobetyolin (LBT) treats cardiorenal syndrome (CRS) by reducing cardiac dysfunction and fibrosis. It works by inhibiting Osteopontin (OPN) via the c-Jun N-terminal kinase (JNK) pathway, offering new therapeutic insights.
Area of Science:
- Nephrology
- Cardiology
- Pharmacology
Background:
- Cardiovascular diseases are a leading cause of mortality in advanced chronic kidney disease (CKD).
- Cardiac dysfunction, characterized by hypertrophy and fibrosis, is prevalent in end-stage renal disease (ESRD).
- Effective therapies are needed to preserve cardiac function in ESRD patients.
Purpose of the Study:
- To identify novel therapeutic compounds and their molecular targets for cardiorenal syndrome type 4 (CRS).
- To investigate the effects of identified compounds using molecular phenotyping and experimental models.
Main Methods:
- Utilized bioinformatics and gene expression analysis in 5/6 nephrectomized mice (NPM) models.
- Employed molecular phenotyping, including Picrosirius red staining, echocardiography, and qPCR, to assess compound efficacy.
- Investigated compound effects on cardiac cells and identified targets using RNA-Seq and Western blotting, with Osteopontin (OPN) modulation assessed.
Main Results:
- Osteopontin (OPN) expression was significantly elevated in uremic cardiomyopathy.
- Lobetyolin (LBT) demonstrated efficacy in improving cardiac function and reducing cardiac remodeling in NPM mice.
- LBT suppressed OPN expression through the c-Jun N-terminal kinase (JNK) signaling pathway, impacting cardiac dysfunction.
Conclusions:
- Lobetyolin (LBT) ameliorates cardiorenal syndrome (CRS) by inhibiting Osteopontin (OPN) via the JNK pathway.
- This study highlights LBT's cardioprotective effects and its potential in CRS drug discovery.
Background:
Cardiovascular diseases are the major cause of mortality in patients with advanced chronic kidney diseases. The predominant abnormality observed among this population is cardiac dysfunction secondary to myocardial remodelings, such as hypertrophy and fibrosis, emphasizing the need to develop potent therapies that maintain cardiac function in patients with end-stage renal disease.
Aims:
To identify potential compounds and their targets as treatments for cardiorenal syndrome type 4 (CRS) using molecular phenotyping and in vivo/in vitro experiments.
Methods:
Gene expression was assessed using bioinformatics and verified in animal experiments using 5/6 nephrectomized mice (NPM). Based on this information, a molecular phenotyping strategy was pursued to screen potential compounds. Picrosirius red staining, wheat germ agglutinin staining, Echocardiography, immunofluorescence staining, and real-time quantitative PCR (qPCR) were utilized to evaluate the effects of compounds on CRS in vivo. Furthermore, qPCR, immunofluorescence staining and flow cytometry were applied to assess the effects of these compounds on macrophages/cardiac fibroblasts/cardiomyocytes. RNA-Seq analysis was performed to locate the targets of the selected compounds. Western blotting was performed to validate the targets and mechanisms. The reversibility of these effects was tested by overexpressing Osteopontin (OPN).
Results:
OPN expression increased more remarkably in individuals with uremia-induced cardiac dysfunction than in other cardiomyopathies. Lobetyolin (LBT) was identified in the compound screen, and it improved cardiac dysfunction and suppressed remodeling in NPM mice. Additionally, OPN modulated the effect of LBT on cardiac dysfunction in vivo and in vitro. Further experiments revealed that LBT suppressed OPN expression via the phosphorylation of c-Jun N-terminal protein kinase (JNK) signaling pathway.
Conclusions:
LBT improved CRS by inhibiting OPN expression through the JNK pathway. This study is the first to describe a cardioprotective effect of LBT and provides new insights into CRS drug discovery.
