Cinnamaldehyde protects against oxidative stress and inhibits the TNF‑α‑induced inflammatory response in human umbilical vein endothelial cells

Abstract

Oxidative stress and inflammation play critical roles in the development of cardiovascular diseases. Cinnamaldehyde (CA) is a natural compound from Cinnamomum cassia, and its anticancer, antimicrobial and anti-inflammatory activities have been widely investigated. In the present study, the cytoprotective and anti-inflammatory effects of CA on H 2 O 2-or tumor necrosis factor (TNF)-α-exposed human umbilical vein endothelial cells (HUVECs) were examined. CA and its natural derivative, 2-methoxycinnamaldehyde (MCA), markedly increased the cellular protein level of heme oxygenase-1 (HO-1) and promoted the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus. CA-mediated Nrf2/HO-1 activation protected the HUVECs from H 2 O 2-induced oxidative stress, which promotes apoptosis. HO-1 depletion by siRNA attenuated the CA-mediated cell protective effects against oxidative stress. Additionally, CA markedly inhibited the adhesion of U937 monocytic cells to HUVECs by decreasing the expression level of vascular cell adhesion protein 1 (VCAM-1). An in vivo experiment confirmed the anti-inflammatory effects of CA, as lipopolysaccharide (LPS)-induced inflammatory cell infiltration was effectively inhibited by the compound. Overall, these observations suggest that CA may be used as a therapeutic agent for oxidative stress-mediated cardiovascular diseases, such as atherosclerosis.

Activation of Nrf2/HO-1 signaling: An important molecular mechanism of herbal medicine in the treatment of atherosclerosis via the protection of vascular endothelial cells from oxidative stress

“…In addition, CINM also activates Nrf2, and this effect could be blocked by siRNA against Nrf2. These results suggest that CINM exerts protective effects on H 2 O 2 -induced HUVECs through the Nrf2/HO-1 signaling pathway [87] . Ferulic acid and caffeic acid are two other classical and simple phenylpropanoids that comprehensively exist in natural plants, and the two compounds possess similar structures.…”

Beneficial effects of cinnamon and its extracts in the management of cardiovascular diseases and diabetes

“…109 Cinnamaldehyde elevated the cellular protein level of HO-1 and facilitated the translocation of Nrf2 to the nucleus in HUVECs, which indicated that Nrf2/HO-1 may be the pathway by which cinnamaldehyde protects against oxidative stress. 17 In mouse aortas under high glucose conditions, cinnamaldehyde exerts antioxidant effects mediated through Nrf2 activation and the upregulation of downstream target proteins, including HO-1, NQO1, CAT, and glutathione peroxidase 1 (Gpx-1). 74 In short, the anti-atherosclerotic effects of cinnamon can also be explained by its antioxidative properties.…”

“…Numerous studies have revealed that cinnamon has neuroprotective, lipid-lowering, antioxidant, anti-inflammatory, and hypoglycaemic effects, some of which are closely related to the development of diabetes and CVDs. [13][14][15][16][17][18] In this review, we provide a comprehensive overview of the therapeutic potential and possible mechanisms of cinnamon in treating diabetes and CVDs.…”

Research Progress on Targeted Antioxidant Therapy and Vitiligo

“…Uchi et al found that cinnamaldehyde can activate Nrf2 and induce its nuclear translocation, resulting in the upregulation of HO-1 gene expression [ 38 ]. Cinnamaldehyde also activates the Nrf2/HO-1 antioxidant system and was found to alleviate benzopyrene-induced ROS production in keratinocytes [ 39 , 40 ]. More than a hundred Kampo formulations, including cinnamaldehyde, have been approved by the Japanese Ministry of Health as prescription drugs for the treatment of various chronic diseases; cinnamaldehyde, in particular, may have the potential to treat vitiligo and other diseases caused by oxidative stress [ 38 , 41 ].…”