Abstract
The antioxidant effects of the ethyl acetate fraction of Dillenia indica bark (DIBEt) and the underlying mechanisms were investigated in tert-butyl hydroperoxide (t-BHP)-stimulated oxidative stress in RAW 264.7 cells. Paper spray ionization-mass spectroscopy with positive-ion mode tentatively revealed 27 secondary metabolites in D. indica bark extract; predominant among them were alkaloids, phenolic acids, and flavonoids. A new triterpenoid (nutriacholic acid) was confirmed in DIBEt for the first time. DIBEt had strong free radical-scavenging capabilities and was also able to reduce t-BHP-induced cellular reactive oxygen species (ROS) generation in RAW 264.7 cells. DIBEt was found to prevent oxidative stress by boosting the levels of heme oxygenase-1 (HO-1) through the up-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) via the regulation of extracellular signal-regulated kinase (ERK) phosphorylation in RAW 264.7 cells. These results support the potential of DIBEt for defense against oxidative stress-stimulated diseases.
Highlights
Among the various signaling molecules, reactive oxygen species (ROS) and reactive nitrogen species (RNS) play critical roles in maintaining cellular homeostasis
Macrophage cells serve as the first line of defense in infected cells, and activated macrophages are a major source of ROS and RNS triggers epigenetic modifications, leading to the pathogenesis of chronic diseases [2]
The identification and characterization of the related compounds from DIBEt were performed in two steps
Summary
Among the various signaling molecules, reactive oxygen species (ROS) and reactive nitrogen species (RNS) play critical roles in maintaining cellular homeostasis. Redox imbalance precisely participates in the pathogenesis and pathophysiology of numerous chronic diseases [1]. Macrophage cells serve as the first line of defense in infected cells, and activated macrophages are a major source of ROS and RNS triggers epigenetic modifications, leading to the pathogenesis of chronic diseases [2]. Natural medicinal products have been exploited in medical practice for centuries. It is essential to understand and validate the bioactivities of natural compounds and their molecular mechanisms to form concrete scientific evidence for their clinical use and effectiveness and to meet regulatory challenges
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