Development and Characterization of Plant-derived Aristatoside C and Davisianoside B Saponin-loaded Phytosomes with Suppressed Hemolytic Activity.

Saponins are glycosides widely distributed in the plant kingdom and have many pharmacological activities. However, their tendency to bind to cell membranes can cause cell rupture, limiting their clinical use. In the previous study, aristatoside C and davisianoside B were isolated from Cephalaria species. Cytotoxicity assays showed that they are more active on A-549 cell lines than doxorubicin but caused hemolysis. In the current research, aristatoside C and davisianoside B were loaded to phytosomes called ALPs and DLPs respectively, and characterized for particle size, zeta potential, encapsulation efficiency, release kinetic, hemolytic activity, and cytotoxicity on A-549 cell line. DLPs maintained the cytotoxic activity of the free saponins against A-549 cells with IC50 of 9,64±0,02 µg/ml but dramatically reduced their hemolytic activity. Furthermore, temperature and time-dependent stability studies based on the size and zeta potential of ALPs and DLPs revealed that the phytosomes have sustained release properties over 2 weeks. Overall, DLPs displayed cytotoxicity against A-549 cells with minimal hemolysis and sustained release, highlighting their potential as nanotherapeutics for clinical applications.

Effects of biochar treatments on the elemental composition of tobacco (Nicotiana tabacum L.) leaves based on the priming period.

This study determined the effects of different doses of biochars (B) on Virginia tobacco (Nicotiana tabacum L.) cultivar, on first and second harvest dependent change in plant nutrients (N, P, K, Ca, Mg, Cl, Zn, Fe, Mn, Cu, and B), leaf color parameters (L*, a*, and b*), chlorophyll value (SPAD), electrolyte leakage (EL), crude ash, number of leaves, and plant height. Pot experiments were conducted with biochar treatments of 10 tons ha-1 (B1), 20 tons ha-1 (B2), 40 tons ha-1 (B3), and 80 tons ha-1 (B4). Tobacco leaf macroelement (N, P, K, Ca, and Mg) levels increased with increasing biochar doses. The highest values were obtained for B4 treatments (80 tons ha-1) and the lowest for control (B0) treatments. Microelements (Fe, Zn, Mn, and B) exhibited a non linear change, while Cl and Cu exhibited a linear change. Color parameters (L*, a*, and b*) for the first and second priming showed the highest L* and b* values for B2 and B3 treatments, respectively, and the highest a* values for the B2 treatment. Leaf SPAD values increased with increasing biochar doses; further, the obtained SPAD values were ordered as B4 > B3 > B2 > B1 > B0. Leaf electrolyte leakage values were 25.90 %-37.25 % in the first priming and 26.90 %-40.59 % in the second priming. For both the primings, the highest crude ash values (21.94 % and 19.05 %) were observed for the B4 treatments, whereas the lowest values (17.89 % and 17.01 %) were observed for the B0 treatments. the tallest plant height (121.9 cm) and the highest number of leaves (45.3) were determined in B4 applications. Overall, considering the nutrition and quality of tobacco, B2 application is recommended.

A hederagenin-type triterpene saponin, sumbulianoside a from Cephalaria sumbuliana and its potent immunomodulatory activity against seasonal flu virus H3N2.

A new hederagenin-type triterpene saponin; hederagenin 28-O-ß-D-galactopyranosyl-(1→6)-ß-D-glucopyranosyl ester named sumbulianoside A (1), together with twelve known saponins were isolated from the n-butanol extract of Cephalaria sumbuliana (Caprifoliaceae) from which, one known saponin, dipsacus saponin A (2) was isolated, for the first time from Cephalaria species. The structures of the isolated compounds were elucidated by 1 D and 2 D NMR and HRESIMS analyses. Cytotoxic activities were investigated on A549, Hela, PANC1, SHSY5Y cells and non-cancerous cell HEK293 by MTT method and immunomodulatory activities were evaluated against activated H3N2 seasonal virus in whole blood by measuring IL-4, IFN-γ, IL-1ß cytokine level with ELISA. According to the cytotoxicity results, compounds 1 and 2 did not possess significant cytotoxicity, while only compound 2 induced significant IL-4 production (** p<.001) against H3N2 showing a possible Th2 response and antibody production. All compounds had no effect on cytokine release (p > 0.5).

Increased cytotoxic potential of infrequent triterpenoid saponins of Cephalaria taurica obtained through alkaline hydrolysis.

Phytochemical investigations of the aerial parts of the plant Cephalaria taurica Szabó. (Caprifoliaceae) have resulted in the isolation of nine oleanane-type triterpenoid saponins, of which two still remain undescribed. The structures of tauricosides A and B were characterized based on NMR analysis, HRESIMS spectrometry, and chemical evaluations. The saponins tauricosides A and B have been rarely reported in the literature due to the presence of eight sugar moieties, and this is also the first report of saponins containing eight sugar moieties in the Caprifoliaceae family. The cytotoxic activities of tauricosides A and B, their undescribed prosapogenins, aglycone hederagenin, and n-butanol extract of C. taurica against the cancerous cells A-549, HeLa, PANC-1, and SH-SY5Y and the noncancerous HEK-293 cells were evaluated by the MTT method. Although tauricosides A and B and the crude n-butanol extract did not exhibit any activity at the tested concentrations on all the tested cells, after alkaline hydrolysis, the cytotoxic activity potential of the compounds was obviously improved. The most active compound, obtained after the alkaline hydrolysis of tauricoside B, showed a significant inhibitory effect, which was higher than that of the standard, commercially available drug doxorubicin, on the cancerous A-549, HeLa, PANC-1, and SH-SY5Y cells with IC50 values of 9.04, 8.75, 6.87, and 4.32 µM, respectively. In addition, prosapogenin, obtained after the alkaline hydrolysis of tauricoside A, exhibited considerable cytotoxic activity on the cancerous A-549, HeLa, PANC-1, and SH-SY5Y cells, with IC50 values of 13.19, 10.32, 11.91, and 7.49 µM, respectively. In conclusion, the alkaline hydrolysis of the saponins (tauricosides A and B) obviously improved their cytotoxic activity potential.

Immunomodulatory, hemolytic and cytotoxic activity potentials of triterpenoid saponins from eight Cephalaria species.

BACKGROUND: Saponins isolated from a number of plants possess a broad spectrum of biological and pharmacological activities by using in vitro and in vivo bioassays. The recent investigations and findings in biological activity studies of saponins have mostly focused on immunomodulatory, hemolytic and cytotoxic properties. HYPOTHESIS/PURPOSE: Considering the great potential of saponins as bioactive agents, we investigated the cytotoxic, hemolytic and immunomodulatory activities of nineteen triterpenoid saponins from the aerial parts of eight Cephalaria species from Turkey. STUDY DESIGN: The isolated oleanane type saponins from Cephalaria species were tested for their hemolytic, cytotoxic and immunomodulatory activities through anin vitro cell based assay systems. METHODS: HeLa, A549, and a normal cell line HEK293 were used for testing cytotoxicity using MTT method. Immunomodulatory activity was performed in stimulated whole blood cells by PMA plus ionomycin. Hemolytic activity was assessed on human erythrocytes. RESULTS: Aristatoside C (3) and davisianoside B (16) displayed significant inhibitory effects on cancerous A549 and HeLa cells, and non-cancerous HEK293 cells with IC50 values of 3.52 ± 0.11, 35.69 ± 0.50, 8.96 ± 0.62 µM and 4.08 ± 0.06, 11.74 ± 0.82, 20.43 ± 3.21 µM, respectively. Thirteen saponins out of the nineteen tested increased IL-1ß concentrations considerably, while six compounds changed IL-2 or IFN-γ levels slightly. Almost all of the saponins showed noticeable hemolysis in human erythrocyte cells based on the sugar units. CONCLUSION: In this study, almost all saponins with oleanolic acid as aglycones exhibited significant hemolysis, monodesmosidic saponins with hederagenin as aglycone were the most active compounds against lung cancer cells with greater activity than standard commercial chemotherapy drug doxorubicin and some of the hederagenin type saponins induced remarkable IL-1ß secretion.

Chemical constituents and biological activities of Dianthus elegans var. elegans.

Chemical investigation of the aerial parts of Dianthus elegans var. elegans afforded two previously undescribed saponins, named dianosides M-N (1-2), together with four oleanane-type triterpenoid glycosides (3-6). Their structures were elucidated as 3-O-α-L-arabinofuranosyl-16α-hydroxyolean-12-ene-23α, 28ß-dioic acid (1) and 3-O-α-L-arabinofuranosyl-(1 â†’ 3)-ß-D-glucopyranosyl 16α-hydroxyolean-12-ene-23α-oic acid, 28-O-ß-D-glucopyranosyl-(1 â†’ 6)-ß-D-glycosyl ester (2) by chemical and extensive spectroscopic methods including IR, 1D, 2D NMR and HRESIMS. Both of the saponins were evaluated for their cytotoxicities against HEK-293, A-549 and HeLa human cancer cells using the MTT method. All compounds showed no substantial cytotoxic activity against tested cell lines. However, dianosides M-N and the n-butanol fraction exhibited considerable haemolysis in human erythrocyte cells. The immunomodulatory properties of dianosides M-N were also evaluated in activated whole blood cells by PMA plus ionomycin. Dianosides M-N increased IL-1ß concentration significantly whereas the n-butanol fraction slightly augmented IL-1ß secretion. All compounds did not change IL-2 and IFN-γ levels considerably.

Immunomodulatory, hemolytic properties and cytotoxic activity potent of triterpenoid saponins from Cephalaria balansae.

Phytochemical investigations on n-butanol extract of Cephalaria balansae Raus. (Caprifoliaceae) led to the isolation of four previously undescribed triterpenoid saponins based on hederagenin type aglycone, namely, balansoides A-D, along with ten known compounds. Their structures were proposed based on 1D and 2D NMR spectroscopic data, HRESIMS analysis and chemical evidence as 3-O-α-L-rhamnopyranosyl-(1 â†’ 3)-ß-D-xylopyranosyl-(1 â†’ 3)-α-L-rhamnopyranosyl-(1 â†’ 2)-α-L-arabinopyranosyl hederagenin, 3-O-α-L-rhamnopyranosyl-(1 â†’ 3)-ß-D-xylopyranosyl-(1 â†’ 3)-α-L-rhamnopyranosyl-(1 â†’ 2)-α-L-arabinopyranosyl hederagenin 28-O-ß-D-glucopyranosyl ester, 3-O-α-L-rhamnopyranosyl-(1 â†’ 3)-ß-D-xylopyranosyl-(1 â†’ 3)-α-L-rhamnopyranosyl-(1 â†’ 2)-α-L-arabinopyranosyl hederagenin 28-O-ß-D-galactopyranosyl-(1 â†’ 6)-ß-D-glucopyranosyl ester and 3-O-α-L-rhamnopyranosyl-(1 â†’ 3)-ß-D-xylopyranosyl-(1 â†’ 3)-α-L-rhamnopyranosyl-(1 â†’ 2)-α-L-arabinopyranosyl hederagenin 28-O-ß-D-glucopyranosyl-(1 â†’ 6)-ß-D-glucopyranosyl ester. The four saponins were evaluated for their potential cytotoxic activity against HEK-293, A-549, HeLa cells and for hemolytic properties on human blood cells. Balansoide A displayed significant inhibitory effects on cancerous A-549 and HeLa cells, and non-cancerous HEK-293 cells with IC50 values of 12, 15 and 8 µM, respectively. Balansoides A-D together with n-butanol extract exhibited considerable hemolysis in human erythrocyte cells. Immunomodulatory properties of balansoides A-D were also evaluated in activated whole blood cells by PMA plus ionomycin. While balansoides A-C increased IL-1ß concentration with values of 1004.47, 991.57 and 966.50 pg/ml, only balansoide B augmented a slight IFN-γ secretion with value of 5219.14 pg/ml. None of the compounds changed IL-2 levels significantly.