Natural Compounds for Bone Remodeling: A Computational and Experimental Approach Targeting Bone Metabolism-Related Proteins

Int J Mol Sci. 2024 May 6;25(9):5047. doi: 10.3390/ijms25095047.

Abstract

Osteoporosis, characterized by reduced bone density and increased fracture risk, affects over 200 million people worldwide, predominantly older adults and postmenopausal women. The disruption of the balance between bone-forming osteoblasts and bone-resorbing osteoclasts underlies osteoporosis pathophysiology. Standard treatment includes lifestyle modifications, calcium and vitamin D supplementation and specific drugs that either inhibit osteoclasts or stimulate osteoblasts. However, these treatments have limitations, including side effects and compliance issues. Natural products have emerged as potential osteoporosis therapeutics, but their mechanisms of action remain poorly understood. In this study, we investigate the efficacy of natural compounds in modulating molecular targets relevant to osteoporosis, focusing on the Mitogen-Activated Protein Kinase (MAPK) pathway and the gut microbiome's influence on bone homeostasis. Using an in silico and in vitro methodology, we have identified quercetin as a promising candidate in modulating MAPK activity, offering a potential therapeutic perspective for osteoporosis treatment.

Keywords: MAPKs; bone metabolism; molecular docking; molecular dynamics simulations; natural compounds; osteoporosis; quercetin.

MeSH terms

  • Animals
  • Biological Products* / pharmacology
  • Biological Products* / therapeutic use
  • Bone Remodeling* / drug effects
  • Bone and Bones / drug effects
  • Bone and Bones / metabolism
  • Gastrointestinal Microbiome / drug effects
  • Humans
  • MAP Kinase Signaling System / drug effects
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism
  • Osteoclasts / drug effects
  • Osteoclasts / metabolism
  • Osteoporosis* / drug therapy
  • Osteoporosis* / metabolism
  • Quercetin / pharmacology
  • Quercetin / therapeutic use

Substances

  • Biological Products
  • Quercetin