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.

The osteogenic, cytotoxic, and antibacterial activities of polysaccharide (PS-SC) and flavonoid (F-SC) fractions isolated from the leaves extract of Saussurea controversa were studied in vitro. F-SC consists of the five quercetin glycosides in the ratio 2:8:10:1:4, which were isolated from the leaves extract of S. controversa and have been characterized previously. PS-SC was first isolated from the leaves extract of S. controversa and has been described. PS-SC consists in 30 compounds is characterized by a high degree of heterogeneity with a heterogeneity index of 19.74. The Mw and Mn of PS-SC were 108.6 and 5.5 kDa, respectively. Structural fragments are represented by galactose, arabinose, xylose, glucose, uronic acids, mannose, and rhamnose in a 10.1:3.3:2.2:2.1:1.7:0.9:0.5 molar ratio. F-SC as compared with PS-SC showed in vitro microbicidal (50 g/L) and better bacteriostatic (6.25 g/L versus 25 g/L of PS-SC) effects against the 24-h growth of Staphylococcus aureus strain 209 P and a 21-day absence of cytotoxicity on human adipose-derived multipotent mesenchymal stromal cells (hAMMSCs). Both fractions (PS-SC > F-SC) at doses of 10–50 mg/L stimulated differentiation of hAMMSCs into secreting osteoblasts accompanied by local mineralization of extracellular matrix. These fractions of S. controversa and especially F-SC, might be promising peroral drugs in the complex treatment of bone fractures and for prophylaxis of their infectious complications.

Calcium chelidonate [Ca(ChA)(H₂O)₃]_n was obtained by semi-synthesis using natural chelidonic acid. The structure of the molecular complex was determined by X-ray diffraction analysis. The asymmetric unit of [Ca(ChA)(H₂O)₃]_n includes chelidonic acid coordinated through three oxygen atoms, and three water ligands. The oxygen atoms of acid and oxygen atoms of water from each asymmetric unit are also coordinated to the calcium of another one, forming an infinite linear complex. Calcium geometry is close to the trigonal dodecahedron (D2d). The intra-complex hydrogen bonds additionally stabilize the linear species, which are parallel to the axis. In turn the linear species are packed into the 3D structure through mutual intercomplex hydrogen bonds. The osteogenic activity of the semi-synthetic CaChA was studied in vitro on 21-day hAMMSC culture and in vivo in mice using ectopic (subcutaneous) implantation of CaP-coated Ti plates saturated in vitro with syngeneic bone marrow. The enhanced extracellular matrix ECM mineralization in vitro and ectopic bone tissue formation in situ occurred while a water solution of calcium chelidonate at a dose of 10 mg/kg was used. The test substance promotes human adipose-derived multipotent mesenchymal stromal/stem cells (hAMMSCs), as well as mouse MSCs to differentiate into osteoblasts in vitro and in vivo, respectively. Calcium chelidonate is non-toxic and can stimulate osteoinductive processes.

Objective To analyze a profile of hypotensive drug therapy in patients with arterial hypertension (АH) aged 55–84 in a sample of urban population at a current period of time (2015–2017). Materials and Methods AH is a leader among risk factors of cardiovascular diseases (CVD) due to its high prevalence and serious prognosis. Despite the availability of effective hypotensive drugs and guidelines on AH treatment, 50% of patients do not achieve blood pressure (BP) goals. Knowledge about drug correction of AH in the Russian population is limited to clinical studies. Taking into account changing approaches in management of patients with AH, the population-based evaluation of hypotensive treatment if relevant. A random population sample of males and females aged 55-84 (n=3.898) was evaluated in Novosibirsk in 2015-2017 (international project, Health, Alcohol and Psychosocial Factors in Eastern Europe (HAPIEE)). AH was diagnosed in presence of systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg and/or treatment with hypotensive drugs within the recent two weeks. Regular intake of medication for 12 months was evaluated with coding according to the Anatomic Therapeutic Chemical Classification System (АТХ / АТС). Results In the population sample aged 55–84, AH prevalence was 80.9 %, and 21.1 % of persons with AH did not receive drug therapy. Hypotensive medicines included (total/as a part of combination therapy) angiotensin-converting enzyme (ACE) inhibitors (42.3 % / 25.3 %), angiotensin II receptor blockers (ARBs) (30.3 % / 18.9 %), diuretics (22.6 % / 20.4 %), calcium channel blockers (20.2 % / 16.1 %), and beta-blockers (34.7 % / 27.6 %). 45.7 % of people with AH received a combination therapy. Effective BP control was achieved in 23.4 % of AH patients and in 29.6 % of patients receiving a hypotensive therapy. In the group of ineffective BP control, the proportion of females was lower, AH duration was longer, and blood glucose was higher than in the group of effective control. Conclusion In the sample of urban population aged 55–84 in 2015–2017, each fourth participant with AH and each third participant using hypotensive drugs achieved effective BP control. The therapy profile in AH patients included recommended drug classes. However, combination therapy was used insufficiently (50% of AH patients). By frequency of use, ACE inhibitors were on the first place, beta-blockers were on the second place, ARBs were on the third place, diuretics were on the fourth place, and calcium channel blockers were on the fifth place, which differed from the guidelines (the difference from the recommended priority ranking is that the drugs taking the first places in the guidelines were in fact on the 3rd and 4th places in their actual frequency of use). 20% of persons with AH did not receive hypotensive therapy, which significantly contributed to the insufficient BP control in the population.

Five flavonoids were isolated from leaves of Saussurea controversa, one new flavonoid (5), three described for the first time from the genus Saussurea (1, 2, and 4), and one described previously (3). A number of flavonol glycosides can be easily isolated from the butanol fraction of the ethanol extract from S. controversa. As a result of separating these using column chromatography on silica gel and microcrystalline cellulose, five glycosides of quercetin were isolated in the proportional relationship of 2 (1): 8 (2): 10 (3): 1 (4): 4 (5). The structure of these substances was determined using the method of NMR by conducting various ¹H-¹H and ¹H-¹³C correlation spectroscopy experiments and by comparing their spectroscopic data with published values, 5,3^/,4^/-trihydroxyflavone-7-О-α-L-rhamnopyranoside-3-О-β-D-glucopyranosidе (1), 5,7,3^/,4^/-tetrahydroxyflavone-3-О-β-D-glucopyranoside-(1→6)-β-D-glucopyranoside-(1→6)-О-α-L-rhamnopyranoside (2), 5,7,3^/,4^/-tetrahydroxyflavone-3-О-β-D-glucopyranoside-(1→6)-О-α-L-rhamnopyranoside (3), 5,3^/,4^/-trihydroxyflavone-7-О-α-L-rhamnopyranoside-3-О-β-D-xylopyranoside (4), and 5,3^/,4^/-trihydroxyflavone-7-О-β-D-glucopyranoside-3-O-α-L-rhamnopyranoside-(1→2)-О-β-D-glucopyranoside (5). It was established for the first time that flavonol glycosides from S. controversa stimulate granulopoiesis and lymphopoiesis in the bone marrow of rats, and enhance the reparative process in the affected area in experimental osteomyelitis.