γ-Mangostin isolated from Garcinia mangostana L. suppresses inflammation and alleviates symptoms of osteoarthritis via modulating miR-124-3p/IL-6/NF-κB signaling

Aging (Albany NY). 2020 Apr 16;12(8):6630-6643. doi: 10.18632/aging.103003. Epub 2020 Apr 16.

Abstract

Osteoarthritis (OA) a disease associated with joints and become severe with age, due to softening, inflammation and degradation of cartilage in joints. The agents that can target OA is needed, specifically without any side effects. Garcinia mangostana L. (Mangosteen) a tropical fruit used to treat many skin and stomach associated ailments. γ- Mangostin (γ-MS) a key bioactive substance present in mangosteen. Here, we aimed to explore γ-MS potential in targeting the pro-inflammatory cytokine, factors and miRs in OA progression. Significantly, γ-MS suppresses the inflammatory cytokines (IL-6, TNF-α, and INF- γ) and factors (NF-κB, STAT3, and COX-2) which regulates/participate in the catabolic process of cartilage destruction. Result of Hematoxylin-eosin (H&E) staining of tissue sections of OA joints of γ-MS treated and non-treated mice confirm γ-MS improves the signs of injuries, and maintains the structural integrity of the articular cartilage (epiphyseal disk joints and bone marrow) and reduces inflammation. Mechanistically, γ-MS targets miR-98-5p and miR-124-3p which are found to suppress the expression IL-6 and NF-κB, respectively. But in OA these miRs are inhibited, especially miR-124-3p which regulates not only NF-κB but also TNF-α, IL-6 and MMP7. With a further investigation underway, γ-MS represents an important source for treating and managing OA.

Keywords: OA; inflammation; miR-124-3p; γ-MS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cartilage, Articular / pathology
  • Cell Line
  • Cyclooxygenase 2 / metabolism
  • Disease Models, Animal
  • Fibroblasts
  • Garcinia mangostana
  • Gene Expression / drug effects*
  • Humans
  • Interferon-gamma / genetics
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Mice
  • MicroRNAs / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Osteoarthritis / blood
  • Osteoarthritis / chemically induced
  • Osteoarthritis / drug therapy*
  • Osteoarthritis / pathology
  • Papain
  • Phytotherapy*
  • Plant Preparations
  • RNA, Messenger / blood
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Xanthones / pharmacology
  • Xanthones / therapeutic use*

Substances

  • IL6 protein, human
  • Interleukin-6
  • MIRN124 microRNA, human
  • MicroRNAs
  • NF-kappa B
  • Plant Preparations
  • RNA, Messenger
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Tumor Necrosis Factor-alpha
  • Xanthones
  • interleukin-6, mouse
  • Interferon-gamma
  • Cyclooxygenase 2
  • Papain
  • mangostin