Boldine Ameliorates Vascular Oxidative Stress and Endothelial Dysfunction

Abstract

Abstract:Epidemiological and clinical studies have demonstrated that a growing list of natural products, as components of the daily diet or phytomedical preparations, are a rich source of antioxidants. Boldine [(S)-2,9-dihydroxy-1,10-dimethoxy-aporphine], an aporphine alkaloid, is a potent antioxidant found in the leaves and bark of the Chilean boldo tree. Boldine has been extensively reported as a potent “natural” antioxidant and possesses several health-promoting properties like anti-inflammatory, antitumor promoting, antidiabetic, and cytoprotective. Boldine exhibited significant endothelial protective effect in animal models of hypertension and diabetes mellitus. In isolated thoracic aorta of spontaneously hypertensive rats, streptozotocin-induced diabetic rats, and db/db mice, repeated treatment of boldine significantly improved the attenuated acetylcholine-induced endothelium-dependent relaxations. The endothelial protective role of boldine correlated with increased nitric oxide levels and reduction of vascular reactive oxygen species via inhibition of the nicotinamide adenine dinucleotide phosphate oxidase subunits, p47phox and nicotinamide adenine dinucleotide phosphate oxidase 2, and angiotensin II–induced bone morphogenetic protein-4 oxidative stress cascade with downregulation of angiotensin II type 1 receptor and bone morphogenetic protein-4 expression. Taken together, it seems that boldine may exert protective effects on the endothelium via several mechanisms, including protecting nitric oxide from degradation by reactive oxygen species as in oxidative stress–related diseases. The present review supports a complimentary therapeutic role of the phytochemical, boldine, against endothelial dysfunctions associated with hypertension and diabetes mellitus by interfering with the oxidative stress–mediated signaling pathway.

Inhibition of glial hemichannels by boldine treatment reduces neuronal suffering in a murine model of Alzheimer's disease

“…However, we observed that the progression of the amyloid deposition is not modified by boldine treatment suggesting that if boldine has an effect on BBB, it is only marginal and likely not essential in its neuroprotective action. Second, boldine was also reported to have anti‐inflammatory effects (Lau et al, ), In agreement with this, we have shown that the level of TNFα was slightly but significantly reduced in APP/PS1 mice treated with boldine while IL‐1ß level was not significantly affected. We previously showed that inflammation is involved in Panx1 HC activitation in astrocytes close to amyloid plaques in APP/PS1 mice (Yi et al, ).…”

“…In this context, we have selected boldine, an alkaloid extracted from a Chilean tree, termed boldo. This molecule is known for its cytoprotective effects mostly mediated by its potent antioxidant properties reported in diverse i n vitro preparations as well as in animal models of diabetes, hypertension and atherosclerosis (Lau, Ling, Murugan, & Mustafa, ; O'Brien, Carrasco‐Pozo, & Speisky, ; Santanam Penumetcha, Speisky, & Parthasarathy, ). However, it was recently reported to block HCs and not gap junctions in mesangial cells in culture by a mechanism yet unknown but independent of its antioxidant property (Hernández‐Salinas et al, ).…”

Low molecular weight fucoidan ameliorates streptozotocin-induced hyper-responsiveness of aortic smooth muscles in type 1 diabetes rats

“…Many studies have shown that hyperglycemia produces damaging effects through the overproduction of ROS or the impaired elimination by antioxidant enzymes, and are known to alter vascular functions (Johansen et al, 2005;Lau et al, 2014;Wong et al, 2013). To explore the protective mechanism of LMWF, the level of ROS, lipid peroxides Figure 3d,e).…”

Alterations of voltage‐dependent K+ channels in the mesenteric artery during the early and chronic phases of diabetes

“…Many previous studies have reported that DM is closely associated with vascular dysfunction via both endothelium‐dependent and ‐independent mechanisms . However, most studies of vascular dysfunction in diabetes have focused on the formation of reactive oxygen species (ROS), impairment of vasorelaxation, and abnormalities in vascular smooth muscle . Although several reports have revealed alterations in ion channel function during diabetes, studies of alterations in vascular voltage‐dependent K + (Kv) channel functions are limited …”