Multitargeted combination effects of a triherbal formulation containing ELP against osteoporosis: in vitro evidence

J Pharm Pharmacol. 2016 Jun;68(6):826-33. doi: 10.1111/jphp.12542. Epub 2016 Mar 28.

Abstract

Objectives: An anti-osteoporotic herbal formula ELP containing Epimedii Herba (E), Ligustri Lucidi Fructus (L) and Psoraleae Fructus (P) was studied to investigate the herb-herb interaction (or the possible synergistic effect) among each component and to identify the principal herbs in different modes of action.

Methods: Rat osteoblast-like UMR-106 cells proliferation, rat MSCs-derived osteoblastogenesis and RANKL-induced RAW 264.7 osteoclastogenesis were adopted to investigate the bone-forming activity and bone-degrading activity of the herbal extracts. In the statistical aspect, a modified Tallarida's approach was employed to assess the synergistic effects in herbal combinations.

Key findings: Psoraleae Fructus is the active herb for stimulating osteoblast proliferation, and mild synergy was detected in the pairwise combinations EL, LP and formula ELP. In osteoblastogenesis assay, E and L are the principal herbs for promoting osteoblast differentiation and significant synergy was detected in the pairwise combination EL. For inhibiting osteoclast formation, L is the active herb and significant synergy was detected in the 3-way combination ELP.

Conclusions: The presence of E, L and P is essential for ELP formula as a whole to act against osteoporosis via enhancing bone formation and reducing bone reabsorption. An optimal dosage at 150 μg/ml was proposed for ELP based on our findings.

Keywords: Epimedii Herba; Ligustri Lucidi Fructus; Psoraleae Fructus; anti-osteoporotic herbal formula; combination effects; synergy.

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Bone Density Conservation Agents / isolation & purification
  • Bone Density Conservation Agents / pharmacology*
  • Bone Remodeling / drug effects*
  • Cell Differentiation / drug effects
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / isolation & purification
  • Drugs, Chinese Herbal / pharmacology*
  • Epimedium* / chemistry
  • Ligustrum* / chemistry
  • Male
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / pathology
  • Mice
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism
  • Osteoblasts / pathology
  • Osteoclasts / drug effects*
  • Osteoclasts / metabolism
  • Osteoclasts / pathology
  • Osteoporosis / drug therapy*
  • Osteoporosis / metabolism
  • Osteoporosis / pathology
  • Phytotherapy
  • Plant Components, Aerial
  • Plants, Medicinal
  • Psoralea* / chemistry
  • RANK Ligand / pharmacology
  • RAW 264.7 Cells
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Bone Density Conservation Agents
  • Drugs, Chinese Herbal
  • RANK Ligand
  • Tnfsf11 protein, mouse
  • Alkaline Phosphatase