Glaucocalyxin A inhibits hydrogen peroxide-induced oxidative stress and inflammatory response in coronary artery smooth muscle cells.

Abstract

Atherosclerosis is a complex chronic inflammatory disease that remains one of the leading causes of death and disability worldwide. A previous study reported that glaucocalyxin A (GLA), a natural ent-Kaurane diterpenoid triptolide, exhibits anti-atherosclerotic activity. However, the underlying molecular mechanism has not yet been explored. In the present study, we evaluated the anti-atherosclerotic effect of GLA and the underlying mechanism in vitro. Human coronary artery smooth muscle cells (HCASMCs) were stimulated by hydrogen peroxide (H2 O2 ) to induce oxidative stress and inflammation. The results showed that GLA pretreatment improved the viability of H2 O2 -induced HCASMCs. The increased reactive oxygen species production and decreased superoxide dismutase and glutathione peroxidase activities in H2 O2 -induced HCASMCs were reversed by GLA pretreatment. In addition, GLA treatment suppressed the H2 O2 -induced expression of inducible nitric oxide synthase, NADPH oxidase (NOX) 2, and NOX4 in HCASMCs. Moreover, treatment with GLA reduced the production of several inflammatory cytokines, including tumour necrosis factor-alpha, interleukin (IL)-6, and IL-1β in H2 O2 -induced HCASMCs. Furthermore, GLA treatment suppressed the phosphorylation of p38, as well as inactivating the NF-κB signalling pathway. These findings suggested that GLA protected against H2 O2 -induced oxidative stress and inflammation via inhibition of p38 phosphorylation and NF-κB activation in HCASMCs.

• Authors: Shunming Zhu, Junbo Zhang, Ying Lv
• Journal: Clinical and experimental pharmacology & physiology (Clin Exp Pharmacol Physiol) Vol. 47 Issue 5 Pg. 765-770 (05 2020) ISSN: 1440-1681 [Electronic] Australia
• PMID: 31912910 (Publication Type: Journal Article)
• Copyright: © 2020 John Wiley & Sons Australia, Ltd.

Chemical References

• Anti-Inflammatory Agents
• Antioxidants
• Diterpenes, Kaurane
• Inflammation Mediators
• NF-kappa B
• Reactive Oxygen Species
• glaucocalyxin A
• Hydrogen Peroxide
• p38 Mitogen-Activated Protein Kinases

Topics

• Anti-Inflammatory Agents (pharmacology)
• Antioxidants (pharmacology)
• Coronary Artery Disease (drug therapy, metabolism)
• Coronary Vessels (drug effects, metabolism)
• Diterpenes, Kaurane (pharmacology)
• Humans
• Hydrogen Peroxide (toxicity)
• Inflammation (drug therapy, metabolism)
• Inflammation Mediators (metabolism)
• Muscle, Smooth, Vascular (drug effects, metabolism)
• Myocytes, Smooth Muscle (drug effects, metabolism)
• NF-kappa B (metabolism)
• Oxidative Stress (drug effects)
• Phosphorylation
• Reactive Oxygen Species (metabolism)
• Signal Transduction
• p38 Mitogen-Activated Protein Kinases (metabolism)