Chelidonic Acid and Its Derivatives from Saussurea Controversa: Isolation, Structural Elucidation and Influence on the Osteogenic Differentiation of Multipotent Mesenchymal Stromal Cells In Vitro

Abstract

4-oxo-4H-pyran-2.6-dicarboxylic acid (chelidonic acid, ChA) in the native state and in the complex with calcium [Ca(ChA)(H2O)3], named saucalchelin (CaChA), was isolated from the extract of Saussurea controversa leaves for the first time for the Asteraceae family. The structure of ChA was determined by NMR, MS and confirmed by X-ray analysis of its monomethyl ester, and CaChA was described by IR, ICP-MS, CHN analysis. The yield of ChA and CaChA was 45 mg/g and 70 mg/g of extract, respectively. The osteogenic activity of ChA, n-monobutyl ester of chelidonic acid, and CaChA has been studied in vitro in a 21-day culture of human adipose-derived multipotent mesenchymal stromal cells (hAMMSCs) in a standard nutrient medium without osteogenic supplements. CaChA significantly stimulated the growth of cell mass and differentiation of hAMMSCs into osteoblasts with subsequent mineralization of the culture and it may be a promising substance for accelerating bone tissue regeneration and engineering.

Comparative In Vitro Evaluation of Antibacterial and Osteogenic Activity of Polysaccharide and Flavonoid Fractions Isolated from the leaves of Saussurea controversa

“…However, the osteogenic action of these substances may be similar. Polysaccharides may enhance the expression of the ALP and matrix metallopeptidase 13 (collagenase 3) ( MMP13 ) gene from the early stage of differentiation, leading to maturation and mineralization of the collagenous extracellular matrix (ECM) [16]. Polysaccharides from Persimmon ( Diospyros kaki L.f.) leaves consisting of arabinose, galactose, glucose, mannose, and rhamnose have in vivo and in vitro anti-osteoporotic effects in a model of ovariectomy-induced bone loss via dose-dependent inhibition of osteoclast differentiation through down-regulated activator of nuclear factor-κB ligand (RANKL) [20].…”

“…Not only the basic structure of the flavone nucleus and the antioxidant and complexing properties of phenolic groups in the ring have a role in the osteogenic activity of F-SC, but also the number and nature of the bonds of sugar fragments [12,13]. The latter assumption is confirmed by the revealed osteogenic properties of polysaccharides, mainly consisting of sugar monoses and having different types of glycoside chains [16,17,37]. The composition of sugar fragments plays a decisive role in the activity of polysaccharides, and the degree of polymerization of the branch and the degree of branching determine the degree of activity.…”

“…S. controversa is a perennial plant of the Asteraceae family, growing mainly in the forest-steppe zone, in meadow-steppe phytocenoses, and on rocky slopes in Siberia, Buryatia, and the Far East. We have previously described some active substances isolated from S. controversa extract (native chelidonic acid and its complex with calcium) and their direct in vitro effect on osteogenic differentiation of human multipotent mesenchymal stromal cells (MMSCs) [16] promoting bone regeneration. Osteoprotective in vivo action of S. controversa extract, containing flavonoids and polysaccharides as predominant components, has been recently discovered in a rat model of experimental osteomyelitis caused by Staphylococcus aureus [17].…”

Costimulatory Effect of Rough Calcium Phosphate Coating and Blood Mononuclear Cells on Adipose-Derived Mesenchymal Stem Cells In Vitro as a Model of In Vivo Tissue Repair

“…Previously, PLA cells cultured with specific induction media from the StemPro ® Differentiation Kit (Thermo Fisher Scientific, Waltham, MA, USA) for 21 days showed multilineage differentiation into osteoblasts, chondrocytes, and adipocytes by selective staining [ 24 ]. Thus, the isolated cells constitute a pool of hAMSCs according to the recommendations of the International Society for Cellular Therapy (ISCT) and the International Federation for Adipose Therapeutics and Science (IFATS) [ 25 , 26 ].…”

Calcium Chelidonate: Semi-Synthesis, Crystallography, and Osteoinductive Activity In Vitro and In Vivo

“…It was revealed that Saussurea controversa DC (Asteraceae) contains a high concentration of chelidonic acid and can be a source for its isolation [ 32 ]. S. controversa also contains calcium chelidonate, which showed high osteogenic activity in vitro and enhanced osteogenic differentiation of mesenchymal stromal cells [ 32 ].…”