Biomolecule from Trigonella stellata from Saudi Flora to Suppress Osteoporosis via Osteostromal Regulations.

Hairul-Islam Mohamed Ibrahim,Hany Ezzat Khalil,Hossam M Darrag,Mohammed Refdan Alhajhoj

doi:10.3390/plants9111610

Hairul-Islam Mohamed Ibrahim, Hany Ezzat Khalil + Show 2 more

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https://doi.org/10.3390/plants9111610

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Abstract

Trigonella stellata has used in folk medicine as palatable and nutraceutical herb. It also regulates hypocholesterolemia, hypoglycemia, and has showed anti-inflammatory activities as well as antioxidants efficacy. Osteoporosis is a one of bone metabolic disorders and is continuously increasing worldwide. In the present study, caffeic acid was isolated from Trigonella stellata and identified using 1 D- and 2 D-NMR spectroscopic data. Caffeic acid was investigated on osteoblast and osteoclast in vitro using mice bone marrow-derived mesenchymal cells. Caffeic acid played reciprocal proliferation between osteoblast and osteoclast cells and accelerated the bone mineralization. It was confirmed by cytotoxicity, alkaline phosphatase (ALP), alizarin red S (ARS), and Tartrate resistant acid phosphatase (TRAP) assay. Caffeic acid regulated the osteogenic marker and upregulated the osteopontin, osteocalcin, and bone morphogenic proteins (BMP). Quantitative real time PCR and Western blot were used to quantify the mRNA and protein markers. It also regulated the matrix metalloprotease-2 (MMP-2) and cathepsin-K proteolytic markers in osteoclast cells. In addition, caffeic acid inhibited bone resorption in osteoclast cells. On the other hand, it upregulate osteoblast differentiation through stimulation of extracellular calcium concentrations osteoblast differentiation, respectively. The results also were confirmed through in silico docking of caffeic acid against cathepsin-B and cathepsin-K markers. These findings revealed that caffeic acid has a potential role in bone-metabolic disorder through its multifaceted effects on osteoblast and osteoclast regulations and controls osteoporosis.

Highlights

Osteoporosis is a metabolic bone disease characterized by low bone mass, imbalanced bone cell types that leads to osteoarthritis (OA)
This study represents the first report on the isolation of Caffeic acid (CAF) from T. stellata
These results showed that osteoclast markers negative regulated of boneregulated cells

Summary

Introduction

Osteoporosis is a metabolic bone disease characterized by low bone mass, imbalanced bone cell types that leads to osteoarthritis (OA). Osteoclast types of cells efficiently absorb the damaged bone cells and promote osteoconductivity, as in-growth around the bone; induction of osteogenic response promote progenitor cell differentiation and mineral storage in osteoblastic. Balances between osteoblast and osteoclast would be happened by bone marrow derived cells. Bone-marrow derived mesenchymal stem cells (BM-MSCs) are multipotent, differentiated into connective tissue, and develop into mature osteoblasts [2]. Osteoclasts are generated from precursor cells in presence of receptor activator of nuclear factor kappa-B ligand (RANKL) [4]. These inductions activate the inflammatory mediators which given back bone loss. Bone morphogenetic protein (BMP) and IL-10 are examples of osteogenic markers widely used in differentiation of mesenchymal stem cells into osteoblasts. Mitogen activated protein kinase (MAPK) regulates the osteoblast-specific transcription factors for differentiation process [5]

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