Immunomodulatory activities of isolated compounds from the root-bark of Cussonia arborea

Pharm Biol. 2017 Dec;55(1):2240-2247. doi: 10.1080/13880209.2017.1400078.

Abstract

Context: Cussonia arborea Hochst. ex A. Rich (Araliaceae) is a folk medicine used to treat various diseases. However, there is no report of the root phytochemistry.

Objective: This study isolates and identifies the immunomodulatory compounds from root-bark of C. arborea.

Materials and methods: The methanol extract (18 g) was subjected to repeated column chromatography resulting in isolation of five compounds (1-5). Structure determination was achieved by analysis of their 1 D and 2 D NMR, and mass spectroscopy. The compounds (100-1.0 μg/mL) were examined immunomodulatory for effect on production of reactive oxygen species (ROS) from whole blood phagocytes and on proliferation of T-cells. The compounds cytotoxicity (100-1.0 μg/mL) was evaluated on NIH-3T3 normal fibroblast cells.

Results: Three pentacyclic triterpenoids [3, 23-dihydroxy-12-oleanen-28-oic acid (1), 3β-hydroxylolean-12-en-28-oic (2) and 23-hydoxy-oxo-urs-12-en-28-oic acid (5)], two phytosterols: [stigmasterol (3)] and [3-O-β-d-glucopyranosyl stigmasterol (4)] were all isolated from the methanol soluble extract. All the tested compounds (1-4) were found to be nontoxic on NIH-3T3 cells. Compound 1 and 2 moderately inhibited the production of ROS (IC50 = 24.4 ± 4.3 and 37.5 ± 0.1 μg/mL, respectively) whereas compound 2 exhibited the highest inhibitory effect (IC50 = 12.6 ± 0.4 μg/mL) on proliferation of phytoheamagglutinin (PHA) activated T-cells.

Conclusions: The isolated compounds (1-5) are reported for the first time from this species. In addition, compound 2 with suppressive potential on production of intracellular ROS and proliferation of T-cells could be of immense value in control of autoimmune diseases as well as in immune compromised patients.

Keywords: Araliaceae; NMR spectroscopy; T-cell proliferation assay; hederagenin; oleanolic acid; reactive oxygen species; steroid; stigmasterol; triterpenoids.

MeSH terms

  • Animals
  • Araliaceae / chemistry*
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Humans
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / isolation & purification
  • Immunologic Factors / pharmacology*
  • Inhibitory Concentration 50
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Medicine, Traditional / methods
  • Mice
  • NIH 3T3 Cells
  • Plant Bark
  • Plant Extracts / administration & dosage
  • Plant Extracts / pharmacology*
  • Reactive Oxygen Species / metabolism*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism

Substances

  • Immunologic Factors
  • Plant Extracts
  • Reactive Oxygen Species