Corosolic Acid Applications in Diabetes and Cancer Therapeutics

Corosolic acid is a naturally occurring pentacyclic triterpenoid predominantly extracted from the leaves of Eriobotrya japonica and Lagerstroemia speciosa. It has attracted sustained interest for its dual potential in the management of metabolic diseases and various malignancies. In diabetes research, corosolic acid enhances insulin sensitivity, promotes glucose uptake and glycogen storage, and downregulates key gluconeogenic enzymes, thereby counteracting hyperglycaemia and dyslipidaemia. Its mechanisms of action encompass modulation of insulin receptor signalling, suppression of phosphoenolpyruvate carboxykinase expression and attenuation of inflammatory mediators. In oncology, corosolic acid exerts cytotoxic effects across a spectrum of tumour types by triggering non-apoptotic cell death through lipid peroxidation, inhibiting metastatic pathways such as the ERK1/2–matrix metalloproteinase axis and synergising with chemotherapeutic agents to overcome drug resistance. Preclinical models also suggest that corosolic acid may impede the progression of non-alcoholic fatty liver disease to hepatocellular carcinoma via antioxidant and anti-inflammatory activities. Together, these findings underscore corosolic acid as a multitargeted agent with considerable promise for translation into therapeutic regimens addressing both metabolic dysfunction and cancer.

Research from Nature Portfolio

Recent studies have elucidated the hypoglycaemic actions of corosolic acid in cellular and whole-organism models. In hepatocyte-based assays, corosolic acid potentiated glucose consumption and glycogen accumulation by suppressing the expression of phosphoenolpyruvate carboxykinase and regulating key glycolytic and gluconeogenic enzymes. In zebrafish and rodent models of type 2 diabetes, administration of corosolic acid reduced blood glucose levels, improved insulin resistance indices and alleviated oxidative stress and inflammatory biomarkers. These investigations demonstrated engagement of insulin receptor signalling pathways alongside attenuation of pro-inflammatory cytokines, thereby confirming corosolic acid’s capacity to restore metabolic homeostasis in hyperglycaemic states.

Corosolic Acid Applications in Diabetes and Cancer Therapeutics publication trend

The graph below shows the total number of articles in corosolic acid applications in diabetes and cancer therapeutics across all publications each year (not limited to Nature Index journals).

Technical terms

Phosphoenolpyruvate carboxykinase (PEPCK): A key gluconeogenic enzyme that catalyses the conversion of oxaloacetate to phosphoenolpyruvate.

Reactive oxygen species (ROS): Chemically reactive molecules containing oxygen that can damage cellular components.

Lipid peroxidation: Oxidative degradation of lipids leading to cell membrane damage and non-apoptotic cell death.

Matrix metalloproteinase (MMP): A family of enzymes that degrade extracellular matrix components and facilitate tumour invasion.

ERK1/2 pathway: A mitogen-activated protein kinase cascade involved in cell proliferation, differentiation and survival.

Non-alcoholic fatty liver disease (NAFLD): A metabolic disorder characterised by excess lipid accumulation in the liver, which can progress to hepatocellular carcinoma.

References

1. Corosolic acid isolated from Eriobotrya japonica leaves reduces glucose level in human hepatocellular carcinoma cells, zebrafish and rats. Scientific Reports (2019).
2. Corosolic Acid Induces Non-Apoptotic Cell Death through Generation of Lipid Reactive Oxygen Species Production in Human Renal Carcinoma Caki Cells. International Journal of Molecular Sciences (2018).
3. Biological effects of corosolic acid as an anti-inflammatory, anti-metabolic syndrome and anti-neoplasic natural compound. Oncology Letters (2020).
4. Modulating the ERK1/2–MMP1 Axis through Corosolic Acid Inhibits Metastasis of Human Oral Squamous Cell Carcinoma Cells. International Journal of Molecular Sciences (2021).