Two new compounds from endemic Centaurea paphlagonica (Bornm.) Wagenitz and their cytotoxic activities.

Centaurea paphlagonica (Bornm.) Wagenitz is an endemic plant in Turkey. Pyrocatechol, vanillic acid, 3,4-dihydroxy benzoic acid, 5-O-caffeoylshikimic acid, tamarixetin, chlorogenic acid methyl ester, quercetin, 1,3-dicaffeoylquinic acid, tamarixetin-7-O-ß-D-glucopyranoside, quercimetrin, daucosterin, paphlagonicanin B, tamarixetin-7-O-ß-rutinoside, rutin, chlorogenic acid, isoorientin, orientin, 3-O-feruloylquinic acid, quercetagetin-3-methyl ether 6-O-ß-glucopyranoside, diosmetin 6-C-ß-glucopyranoside, quercetagetin 4'-methyl ether 7-O-ß-glucopyranoside, paphlagonicanin A, nepetin, cirsiliol, desacylcynaropicrin, and 8α-O-(2',3'-dihydroxyisobutyryl) desacylcynaropicrin were isolated from both flower and aerial parts of C. paphlagonica. These compounds were identified using 1D and 2D NMR methods and ESI-MS. The MTT assay assessed the antiproliferative activities of all isolated (known and new compounds) compounds on Caco-2, LNCaP, A549, HeLa, and HEK-293 cell lines. The 8α-O-(2',3'-dihydroxyisobutyryl) desacylcynaropicrin demonstrated the highest activity against CaCo-2 and HeLa cancer cell lines.

Ferruginoside†D: A Novel Phenylethanoid from Verbascum leiocarpum.

A novel phenylethanoid, ferruginoside D, together with fourteen known compounds were isolated from the Verbascum leiocarpum for the first time. Chemical structures of isolated compounds were determined by spectroscopic analysis including HR-ESI-MS and NMR spectra. The antioxidant, α-glucosidase inhibitory properties, and antiproliferative activities against multiple cell lines (A172, C6, HeLa, A2780, SW620, HT29, Beas2B, RPE, and HSF) of the isolated compounds were evaluated in vitro. According to the results, iridoids, flavonoids (luteolin and apigenin), and phenylethanoids (poliumoside and isoverbascoside) with strong antiproliferative potential were also found to have cytostatic effects. Furthermore, the investigation revealed that compounds luteolin, poliumoside, verbascoside, isoverbascoside, ferruginoside C, ferruginoside D, and ursolic acid show potent alpha-glucosidase inhibitory activity, while compounds luteolin, verbascoside, and isoverbascoside exhibit substantial antioxidant activity. The new compound (ferruginoside D) was found moderately active against cancer cell lines, with strong alpha-glucosidase inhibitory activity, and moderate antioxidant properties.

Isolation, characterization and anticancer activity of secondary metabolites from Verbascum speciosum.

Herein, two iridoid glucosides aucubin (1) and ajugol (2), and two phenyl ethanoids, verbascoside (3) and poliumoside (4) were isolated from the methanol extract of the aerial parts of Verbascum speciosum and used to study about their anticancer activity for the first time. The structures of all compounds were elucidated using spectroscopic data (IR, 1D and 2D NMR, LC-TOF/MS). Antiproliferative activities of Aucubun (1) and Verbascoside (3) were tested against A-549 (human colon cancer), MDA-MD-453 (human breast cancer) and 3T3-L1 (mouse fibroblast)cell lines by XTT assay. In addition, the anticarcer mechanism of action of aucubin (1) was investigated on MDA-MB-453 cells for the first time. XTT result showed that both applied compounds exhibited antiproliferative effect at different dose ranges depending on the cancer type, as well as selectivity between cancer and healty cell lines. Flow cytometry analyzes revealed that aucubin (1) exerts its cytotoxic effect in MDA-MB-453 cells by directing cells to early apoptosis and inhibiting the P13K/AKT signaling pathway.

A Biochemical Approach for Hedysarum candidissimum from Turkey: Screening Phytochemicals, Evaluation of Biological Activites, and Molecular Docking Study.

This study was designed to screen the phytochemical composition and investigate the biological activities of Hedysarum candidissimum extracts and also support the results with molecular docking studies. LC/MS/MS analysis revealed the presence of 22 phytochemical constituents (mainly phenolic acids, flavonoids, and flavonoid glycosides) in the plant structure. The methanol extract exhibited the strongest antioxidant activity among all the extracts with its strong DPPH radical scavenging and iron reducing capacity, as well as high phenolic and flavonoid contents. Additionally, it was found to be the most promising acetylcholinesterase (AChE: IC50 : 93.26 µg/mL) and α-glycosidase (AG: IC50 : 28.57 µg/mL) inhibitory activities, supported by the major phenolics of the species through in silico studies. Ethyl acetate extract had the strongest cytotoxic effect on HT-29 (IC50 : 63.03 µg/mL) and MDA-MB-453 (IC50 : 95.36 µg/mL) cancer cell lines. Both extracts exhibited considerable apoptotic and anti-migrative effects on HT-29 cells. The investigations provide phyto-analytical and bio-pharmacological results which can be extended by in vivo studies in the future.

Phytochemical Content, Antidiabetic, Anticholinergic, and Antioxidant Activities of Endemic Lecokia cretica Extracts.

The aim of this work was to investigate the enzyme inhibition, antioxidant activity, and phenolic compounds of Lecokia cretica (Lam.) DC. Acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α-glycosidase enzymes were strongly inhibited by the L. cretica extracts. IC50 values for the three enzymes were found as 3.21 mg/mL, 2.1 mg/mL, and 2.07 mg/mL, respectively. Antioxidant activities were examined in both aqueous and ethanol (EtOH) extracts using CUPRAC, FRAP, and DPPH method. Also, the phenolic compounds of the endemic plant were identified and quantified by using HPLC/MS/MS. According to the results, the extracts have remarkable antioxidant activities. The most abundant phenolic acids of L. cretica in EtOH extract were determined as quinic acid (12.76 mg/kg of crude extract), chlorogenic acid (3.39 mg/kg), and malic acid (2.38 mg/kg).

Preliminary phytochemical analysis and evaluation of in vitro antioxidant, antiproliferative, antidiabetic, and anticholinergics effects of endemic Gypsophila taxa from Turkey.

The phenolic contents and antioxidant, anticancer, antidiabetic, and anticholinergic potentials of four endemic Gysophila taxa (G. pallida, G. arrosti, G. tuberculosa, and G. eriocalyx) were investigated. The HPLC analysis showed that methanol extracts of all the tested species were richer in phenolics than water extracts. 3,4-dihydroxybenzoic acid, p-hydroxybenzoic acid, vanillin, syringic acid, and p-coumaric acid were detected in all extracts. In parallel to the phenolic contents, methanol extracts displayed comparatively higher antioxidant activity than water extracts. Additionally, all extracts exhibited dose-dependent antiproliferative activity on the cancer cell lines with lower IC50 values changing from 0.170 to 1.805 mg/ml. Moreover, the extracts impressively inhibited the acetylcholinesterase (0.63-26.04), butyrylcholinesterase (3.66-10.73), and α-glycosidase (98.52-235.55) enzymes with very low IC50 (mg/ml) values. Together, the present results indicate that Gysophila taxa have various biological activities together with higher phenolic contents. Hence, these species hold good potential for use in the pharmaceutical industry. PRACTICAL APPLICATIONS: Gypsophila taxa having numerous biological activities have been used for different purpose in folk medicine as well as their use in the food industry. The obtained results of the current study indicated that the extracts of Gypsophila taxa are rich in phenolics and flavonoids with powerful antioxidant and antiproliferative activity against different type of cancer cell lines. In addition, the extracts obtained from these taxa showed notable antidiabetic and anticholinergics effects. Gypsophila taxa could be used as a natural material to develop anticancer, antidiabetic, and anticholinergic drugs.

The Effectiveness of Crataegus orientalis M Bieber. (Hawthorn) Extract Administration in Preventing Alveolar Bone Loss in Rats with Experimental Periodontitis.

The purpose of this animal study was to evaluate the effects of hawthorn (Crataeus orientalis M Bieber.) extract on serum oxidative status and alveolar bone loss in experimental periodontitis. Twenty-seven Wistar rats were assigned to one of the following groups: non- ligated+placebo (saline) (NL, n = 9), ligature only+placebo (saline) (LO, n = 9), and ligature and treated with hawthorn extract in saline (H, n = 9) (100 mg/kg orogastrically, once a day for 11 days). Periodontitis was induced by submerging a 4/0 silk ligature in the sulcus of the mandibular right first molars of rats, and the animals were sacrificed after 11 days. Micro-CT examinations were performed for linear and volumetric parameter assessment of alveolar bone. Periodontal tissues were histopathologically examined to assess the differences among the study groups. Levels of serum total antioxidant status (TAS)/total oxidant status (TOS), and oxidative stress index (OSI) were also analyzed. Alveolar bone loss was significantly reduced by hawthorn administration compared to LO group (p<0.05). The number of inflammatory cells and osteoclasts in the LO group was significantly higher than that of the NL and H groups (p< 0.05). The number of osteoblasts in the LO and H groups was significantly higher than that of the NL group (p<0.05). TOS and OSI levels were significantly reduced in H group compared to LO group (P <0.05) and TAS levels were similar in H and NL group (p< 0.05). Hawthorn extract showed inhibitory effect on periodontal inflammation and alveolar bone loss by regulating TAS, TOS and OSI levels in periodontal disease in rats when administered systemically.

Effect of sumac extract on serum oxidative status, RANKL/OPG system and alveolar bone loss in experimental periodontitis in rats.

OBJECTIVES: Sumac (Rhus coriaria L.) is widely used spice which has several properties such as antioxidant, anti-inflammatory and antimicrobial. The purpose of this animal study was to evaluate the effects of sumac extract on levels of receptor activator of nuclear factor-kappa B ligand (RANKL), osteoprotegerin (OPG) expression, serum oxidative status, and alveolar bone loss in experimental periodontitis. MATERIAL AND METHODS: Twenty-four Wistar rats were separated into three groups: non-ligated (NL, n=8), ligature only (LO, n=8), and ligature and treated with sumac extract (S, n=8) (20 mg/kg per day for 11 days). A 4/0 silk suture was placed around the mandibular right first molars subgingivally; after 11 days, the rats were sacrificed, and alveolar bone loss was histometrically measured. The detection of RANKL and OPG were immunohistochemically performed. Levels of serum total antioxidant status (TAS)/total oxidant status (TOS), and oxidative stress index (OSI) were also analyzed. RESULTS: Alveolar bone loss was significantly greater in the LO group compared to the S and NL groups (p<0.05). The number of inflammatory cell infiltrate (ICI) and osteoclasts in the LO group was significantly higher than that of the NL and S groups (p<0.05). The number of osteoblasts in the LO and S groups was significantly higher than that of the NL group (p<0.05). There were significantly more RANKL-positive cells in the LO group than in the S and NL groups (p<0.05). OPG-positive cells were higher in S group than in LO and NL groups (p<0.05). TOS and OSI levels were significantly reduced in S group compared to LO group (P<0.05) and TAS levels were similar in S and NL group (p>0.05). CONCLUSIONS: The present study showed that systemic administration of sumac extract may reduce alveolar bone loss by affecting RANKL/OPG balance, TOS and OSI levels in periodontal disease in rats.

Effect of sumac extract on serum oxidative status, RANKL/OPG system and alveolar bone loss in experimental periodontitis in rats

Objectives Sumac (Rhus coriaria L.) is widely used spice which has several properties such as antioxidant, anti-inflammatory and antimicrobial. The purpose of this animal study was to evaluate the effects of sumac extract on levels of receptor activator of nuclear factor-kappa B ligand (RANKL), osteoprotegerin (OPG) expression, serum oxidative status, and alveolar bone loss in experimental periodontitis. Material and Methods Twenty-four Wistar rats were separated into three groups: non-ligated (NL, n=8), ligature only (LO, n=8), and ligature and treated with sumac extract (S, n=8) (20 mg/kg per day for 11 days). A 4/0 silk suture was placed around the mandibular right first molars subgingivally; after 11 days, the rats were sacrificed, and alveolar bone loss was histometrically measured. The detection of RANKL and OPG were immunohistochemically performed. Levels of serum total antioxidant status (TAS)/total oxidant status (TOS), and oxidative stress index (OSI) were also analyzed. Results Alveolar bone loss was significantly greater in the LO group compared to the S and NL groups (p<0.05). The number of inflammatory cell infiltrate (ICI) and osteoclasts in the LO group was significantly higher than that of the NL and S groups (p<0.05). The number of osteoblasts in the LO and S groups was significantly higher than that of the NL group (p<0.05). There were significantly more RANKL-positive cells in the LO group than in the S and NL groups (p<0.05). OPG-positive cells were higher in S group than in LO and NL groups (p<0.05). TOS and OSI levels were significantly reduced in S group compared to LO group (P<0.05) and TAS levels were similar in S and NL group (p>0.05). Conclusions The present study showed that systemic administration of sumac extract may reduce alveolar bone loss by affecting RANKL/OPG balance, TOS and OSI levels in periodontal disease in rats. .