Validation of Active Compound of Terminalia catappa L. Extract and Its Anti-Inflammatory and Antioxidant Properties by Regulating Mitochondrial Dysfunction and Cellular Signaling Pathways

J Microbiol Biotechnol. 2024 Oct 28;34(10):2118-2131. doi: 10.4014/jmb.2407.07044. Epub 2024 Sep 2.

Abstract

As chronic inflammation and oxidative stress cause various diseases in the human body, this study aimed to develop functional materials to prevent inflammation and oxidative stress. This study investigated the biological function and components of Terminalia catappa L. extract prepared using its leaves and branches (TCE). TCE was determined using ultraperformance liquid chromatography-quadrupole-time-of-flight mass spectrometry. Using RAW 264.7 mouse macrophages, inhibitory effects of the identified compounds on nitric oxide (NO) and reactive oxygen species (ROS) generation were analyzed. Therefore, α-punicalagin was selected as an active compound with the highest content (986.6 ± 68.4 μg/g) and physiological activity. TCE exhibited an inhibitory effect on lipopolysaccharide (LPS)-induced inflammatory markers, including NO, inducible nitric oxide synthase, and inflammatory cytokines without exerting cytotoxicity. Moreover, TCE prevented excessive ROS production mediated by LPS and upregulated hemeoxygenase-1 expression via the nuclear translocation of nuclear factor erythroid 2-related factor 2. Interestingly, TCE prevented LPS-induced mitochondrial membrane potential loss, mitochondrial ROS production, and dynamin-related protein 1 phosphorylation (serine 616), a marker of abnormal mitochondrial fission. Furthermore, TCE considerably repressed the activation of LPS-induced mitogen-activated protein kinase pathway. Thus, TCE is a promising anti-inflammatory and antioxidant pharmaceutical or nutraceutical, as demonstrated via mitochondrial dysfunction and cellular signaling pathway regulation.

Keywords: Terminalia catappa L.; functional food; inflammation; mitochondria; signaling pathway; ultraperformance liquid chromatography-quadrupole-time-of-flight mass spectrometry.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents* / pharmacology
  • Antioxidants* / pharmacology
  • Cytokines / metabolism
  • Heme Oxygenase-1 / metabolism
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Lipopolysaccharides*
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Mitochondria* / drug effects
  • Mitochondria* / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Nitric Oxide* / metabolism
  • Oxidative Stress / drug effects
  • Plant Extracts* / chemistry
  • Plant Extracts* / pharmacology
  • Plant Leaves / chemistry
  • RAW 264.7 Cells
  • Reactive Oxygen Species* / metabolism
  • Signal Transduction* / drug effects
  • Terminalia* / chemistry

Substances

  • Anti-Inflammatory Agents
  • Plant Extracts
  • Antioxidants
  • Reactive Oxygen Species
  • Lipopolysaccharides
  • Nitric Oxide
  • Cytokines
  • Heme Oxygenase-1
  • Nitric Oxide Synthase Type II