Maslinic Acid Ameliorates Inflammation via the Downregulation of NF-κB and STAT-1

Abstract

Maslinic acid (MA), a natural compound of the triterpenoid group derived from olive, prevents the generation of pro-inflammatory cytokines and oxidative stress. In human umbilical vein endothelial cells (HUVECs) treated with lipopolysaccharide (LPS), we characterized the effects of MA on the regulation of heme oxygenase (HO)-1, cyclooxygenase (COX-)2, and inducible nitric oxide synthase (iNOS). MA was tested in the lung tissues of LPS-treated mice, to determine its effect on levels of iNOS expression and representative inflammatory mediators such as interleukin (IL)-1α and tumor necrosis factor (TNF)-α. We show that MA induced the expression of HO-1, reduced LPS-induced NF-κB-luciferase activity, and inhibited iNOS/NO and COX-2/PGE2, resulting in the downregulation of STAT-1 phosphorylation. Furthermore, our data show that MA induced the nuclear translocation of Nrf2, increased the binding of Nrf2 to ARE, and decreased IL-1α production in LPS-treated HUVECs. The MA-induced reduction in iNOS/NO expression was reversed by RNAi suppression of HO-1. In mice treated with LPS, MA significantly downregulated levels of iNOS in lung tissue and TNF-α in the bronchoalveolar lavage fluid. Taken together, our findings indicate that MA exerts a critical anti-inflammatory effect by modulating iNOS via the downregulation of NF-κB and p-STAT-1. Thus, we propose that MA may be an ideal substance to treat inflammatory diseases.

Retinoprotective Effect of Wild Olive (Acebuche) Oil-Enriched Diet against Ocular Oxidative Stress Induced by Arterial Hypertension

“…Additionally, Ampofo et al [ 92 ] described a maslinic acid-dependent downregulation of NF-κB in endothelial cells, paralleled by increased eNOS expression and reduced oxidative DNA damage. Experiments carried out in human umbilical vein endothelial cells (HUVEC) also demonstrated NF-κB downregulation by maslinic acid [ 93 ]. Furthermore, ursolic and oleanolic acids have also been described as promising anti-inflammatory compounds via NF-κB inactivation [ 94 ].…”

“…Several authors have attributed to OO the ability to modulate Nrf-2 [ 99 ], where polyphenols such as secoiridoids seem to be positively implicated in this effect [ 62 ], as these are also associated with a reduction in NF-κB levels [ 100 ]. In the same way, maslinic [ 93 ] and ursolic acids [ 101 ] are also positive modulators of Nrf-2 with beneficial effects against oxidative/inflammatory damage in different situations.…”

Terpenoids as Potential Geroprotectors

“…At the same time, ursolic acid in combination with leucine can stimulate myoblast differentiation and muscle mass increase through the induction of the mTOR pathway [ 278 ]. In addition, triterpenoid compounds exert anti-inflammatory action inhibiting NF-κB, COX-2, iNOS, TNF-α [ 260 , 289 , 290 , 291 , 292 , 293 , 294 , 295 ].…”

“…In addition, oleanolic acid has bone anti-resorption activity in aged female rats and can be applied in osteoporosis prevention [ 330 ]. Due to anti-inflammatory activity, triterpenoids, such as maslinic acid, can prevent related diseases, particularly arthritis [ 294 , 295 ]. Squalene and ginsenosides can be used for the protection against skin photoaging [ 242 , 273 ].…”

Maslinic acid prevents IL‐1β‐induced inflammatory response in osteoarthritis via PI3K/AKT/NF‐κB pathways

“…Recent studies suggest that maslinic acid inhibits PI3K/AKT signaling in human aortic endothelial cells (F. Li, Li, Shi, & Guo, 2017). It has also been reported that maslinic acid exerts anti-inflammatory effect by downregulating NF-κB (Lee, Kim, Park, & Bae, 2020). Although the anti-inflammatory effects of MA have been extensively studied, the mechanism of regulation of inflammatory cells in OA remains unclear.…”