Aloe-emodin inhibits osteogenic differentiation and calcification of mouse vascular smooth muscle cells.

Abstract

Vascular calcification increases the risk of morbidity and mortality in patients with cardiovascular diseases, chronic kidney diseases, and diabetes. However, viable therapeutic methods to target vascular calcification are limited. Aloe-emodin (AE), an anthraquinone is a natural compound found in the leaves of Aloe-vera. In this study, we investigated the underlying mechanism of AE in the calcification of vascular smooth muscle cells (VSMCs) and murine thoracic aorta. We demonstrate that AE repressed not only the phenotypes of Ca2+ induced calcification but also level of calcium in VSMCs. AE has no effect on cell viability in VSMC cells. Alizarin red, von Kossa stainings and calcium quantification showed that Ca2+ induced vascular calcification is significantly decreased by AE in a concentration-dependent manner. In contrast, AE attenuated Ca2+ induced calcification through inhibiting osteoblast differentiation genes such as SMAD4, collagen 1α, osteopontin (OPN), Runt-related transcription factor (RUNX-2) and Osterix. AE also suppressed Ca2+ induced osteoblast-related protein expression including collagen 1α, bone morphogenic protein 2 (BMP-2), RUNX-2 and smooth muscle actin (SMA). Furthermore, Alizarin red, von Kossa stainings and calcium quantification showed that AE significantly inhibited the calcification of ex vivo ring formation in murine thoracic aorta, and markedly inhibited vitamin D3 induced medial aorta calcification in vivo. Taken together, our findings suggest that AE may have therapeutic potential for the prevention of vascular calcification program.

• Authors: Mahesh Sapkota, Saroj Kumar Shrestha, Ming Yang, Young Ran Park, Yunjo Soh
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 865 Pg. 172772 (Dec 15 2019) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 31697934 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• Anthraquinones
• Bmp2 protein, mouse
• Bone Morphogenetic Protein 2
• Smad4 Protein
• Smad4 protein, mouse
• aloe emodin
• Calcium

Topics

• Animals
• Anthraquinones (pharmacology)
• Aorta, Thoracic (cytology)
• Bone Morphogenetic Protein 2 (metabolism)
• Calcification, Physiologic (drug effects)
• Calcium (metabolism)
• Male
• Mice, Inbred ICR
• Muscle, Smooth, Vascular (cytology)
• Myocytes, Smooth Muscle (drug effects, physiology)
• Osteogenesis (drug effects)
• Smad4 Protein (genetics)