Nyctanthes arbor-tristis bioactive extract ameliorates LPS-induced inflammation through the inhibition of NF-κB signalling pathway

J Ethnopharmacol. 2024 Feb 10:320:117382. doi: 10.1016/j.jep.2023.117382. Epub 2023 Nov 2.

Abstract

Ethnopharmacological relevance: Nyctanthes arbor-tristis L. is a mythical plant used in traditional Indian medicinal systems for the treatment of inflammation, rheumatoid arthritis, and pain-related responses. However, its bioactive compounds and underlying mechanism of action have not been fully elucidated.

Aim of the study: This investigation aimed to study the anti-inflammatory and anti-nociceptive effects of the bioactive extract of N. arbor-tristis (NATE), both in vitro and in vivo, elucidate the possible mechanism of action, and determine its chemicals.

Materials and methods: We studied the anti-inflammatory and anti-nociceptive activities of NATE on lipopolysaccharide-stimulated RAW264.7 macrophages, paw-ear edema, and acetic acid-induced pain in rats and analysed its chemical components using Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometric (LC-ESI-MS).

Results: NATE efficiently reduced the production of various inflammatory mediators and factors, such as free radicals, lipid peroxidation, nitrous oxide (NO), reactive oxygen species (ROS), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNFα), interleukin-6 (IL-6), interleukin-1beta (IL-1β), and IL-10, as well as their corresponding mRNA expression in LPS-induced RAW264.7 cells (p < 0.001). Furthermore, NATE inhibited the activation of a key signaling pathway, nuclear factor-kappa B (NF-kB), as it caused a decrease in the degradation of inhibitor of kB alpha (IkBa). Administration of NATE significantly inhibited carrageenan-induced paw edema (p < 0.001), TPA-induced ear edema, and the production of inflammatory factors (p < 0.01). NATE revealed anti-nociceptive impacts in acetic acid-induced writhing and tail immersion experiments (p < 0.001) as well as no toxicity signs. A total of six compounds, namely iridoid glycoside (6,7-di-O-benzonylnyctanthoside), arborsides A, arborsides C, betulinic acid, kaempferol 3-O-glucoside, and kaempferol 3-O-rutinoside, were characterized through the examination of their mass spectra in correlation with those documented in a database of mass spectra.

Conclusions: The present study furnishes scientific corroboration of the inhibitory potency of N. arbor-tristis as a promising herbal treatment for inflammation and pain responses without toxicity, offering a scientific basis for future drug development strategies aimed at ameliorating inflammatory diseases.

Keywords: Anti-inflammation; LC-ESI-MS; Lipopolysaccharide; NF-κB signalling; Nyctanthes arbor-tristis.

MeSH terms

  • Acetates / pharmacology
  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Cyclooxygenase 2 / metabolism
  • Edema / chemically induced
  • Edema / drug therapy
  • Edema / metabolism
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Kaempferols / pharmacology
  • Lipopolysaccharides* / toxicity
  • NF-kappa B* / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Pain / chemically induced
  • Pain / drug therapy
  • Plant Extracts / adverse effects
  • Rats
  • Signal Transduction

Substances

  • NF-kappa B
  • Lipopolysaccharides
  • Plant Extracts
  • Kaempferols
  • Anti-Inflammatory Agents
  • Acetates
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2