Hydroxychloroquine induces oxidative stress and impairs fracture healing in rats.

OBJECTIVES: The aim of this study was to investigate whether hydroxychloroquine sulfate (HCQS) induced oxidative stress and how it affected the union of bone fractures in an experimental rat model. MATERIALS AND METHODS: A total of 48 Wistar albino male rats were used. The rats were divided into six groups. To investigate the effects of oral administration of HCQS at varying doses between the third and sixth weeks, fracture healing processes were evaluated using radiography, histopathology, biochemistry, and dual-energy X-ray absorptiometry. The activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) were measured to analyze the relationship between HCQS and oxidative stress. RESULTS: Radiographic scores, alkaline phosphatase levels, callus/diaphysis ratio, callus development, and bone mineral density were significantly lower in rats given HCQS at three and six weeks compared to the control group (p<0.005). When oxidative stress parameters were compared among the groups, all antioxidant parameters were statistically significant, indicating that antioxidant systems played a role in peripheral blood, when HCQS was used (p<0.005). CONCLUSION: Oral HCQS intake impairs the fracture healing process by causing oxidative stress in rats. However, further biomolecular researches are needed to understand the underlying mechanism of these effects.

Investigation of Antimicrobial, Anti-Quorum Sensing, and Cytotoxic Activities of Flavonoids Isolated from Pulicaria armena Boiss. & Kotschy ex Boiss. (Asteraceae).

This is the first report on the separation and biological assessment of all metabolites derived from Pulicaria armena (Asteraceae) which is an endemic species narrowly distributed in the eastern part of Turkey. The phytochemical analysis of P. armena resulted in the identification of one simple phenolic glucoside together with eight flavon and flavonol derivatives whose chemical structures were elucidated by NMR experiments and by the comparison of the spectral data with the relevant literature. The screening of all molecules for their antimicrobial, anti-quorum sensing, and cytotoxic activities revealed the biological potential of some of the isolated compounds. Additionally, quorum sensing inhibitory activity of quercetagetin 5,7,3' trimethyl ether was supported by molecular docking studies in the active site of LasR which is the primary regulator of this cell-to-cell communication system in bacteria. Lastly, the critical molecular properties indicating drug-likeness of the compounds isolated from P. armena were predicted. As microbial infections can be a serious problem for cancer patients with compromised immune systems, this comprehensive phytochemical research on P. armena with its anti-quorum sensing and cytotoxic compounds can provide a new approach to the treatment.

Two new eudesmane-type sesquiterpene derivatives from Lecokia cretica (Lam.) DC.

Two new sesquiterpene glucosides, 1α,6ß,9ß-trihydroxy-eudesm-4(15)-en-1,6-O-ß-diglucopyranoside (1) and 1α,6ß,9ß-trihydroxy-eudesm-3-en-1,6-O-ß-diglucopyranoside (2) were obtained along with the 1α,6ß,9ß-trihydroxy-5,10-bis-epi-eudesm-3-en-6-O-ß-D-glucopyranoside (3), chlorogenic acid (4), luteolin 7-O-rutinoside (5) and luteolin 7-O- glucoside (6) from the whole plant parts of Lecokia cretica. Their structures were determined on the basis of 1 D, 2 D NMR and HRMS analyses. The in vitro cytotoxic activity of compounds 1-3 against human lung cancer cells (A549) and normal human lung cells (BEAS-2B) was determined using the MTT colorimetric assay. All the tested eudesmane derivatives were found to be inactive.

Isolation, Characterization and in Silico Studies of Secondary Metabolites from Jurinea macrocephala DC. with Antiproliferative Activity.

In the present work, cytotoxic potential of Jurinea macrocephala DC. (Asteraceae) was evaluated on A549 lung cancer and MCF-7 breast cancer cell lines. Isolation studies were carried out using various and repetitive chromatographic methods in order to determine the phytochemical profile of the extracts. These studies led to the identification of twelve compounds; four triterpenes (1-4) and eight flavonoids (5-12). Spectroscopic examination (1D and 2D NMR, ESI-MS) and comparison with relevant literature data were used to deduce the structures of all isolated molecules. To rationalize the obtained cytotoxicity data against breast cancer cell lines, the isolated compounds were docked into the binding site of aromatase, an important target enzyme for the treatment of breast cancer. Molecular docking studies revealed that flavonoids without sugar moieties (5-8) showed the best binding affinities. Overall, these mentioned compounds turned out to be also the most appropriate oral drug candidates after the calculation of their Lipinski parameters.

Icariin promotes early and late stages of fracture healing in rats.

OBJECTIVES: This study aims to evaluate the effects of locally applied icariin on bone fracture healing in femur fractured rat model. MATERIALS AND METHODS: The study included 64 male Sprague-Dawley rats (mean age 6 months; weighing, 280-490 g) in eight main study groups. Fracture healing process and level were evaluated with radiography, histopathology and dual energy X-ray absorptiometry to investigate the effects of local administration of icariin at varying doses, which is an exogenous osteo-inductive substance. Activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were measured in the peripheral blood in addition to glutathione (GSH) and myeloperoxidase (MPO) levels to investigate the effects of icariin on the oxidant-antioxidant systems. RESULTS: Radiological bone mineral density measurements and histopathological findings revealed that icariin improved all these parameters in the two healing periods tested. Superoxide dismutase activity decreased in association with local icariin application to the fractured side whereas GPx and GSH increased and MPO remained unchanged. Icariin increased the GPx and GSH levels which are responsible from scavenging hydroxyl radical and hydrogen peroxide. CONCLUSION: Locally administered icariin to the fracture accelerated bone healing by reducing the oxidative stress.

Phenylacylated-flavonoids from Peucedanum chryseum

ABSTRACT Phytochemical investigation of the methanol extract of the aerial parts of Peucedanum chryseum (Boiss. & Heldr.) D.F.Chamb., Apiaceae, led to the isolation of a dihydrofuranochromone, cimifugin (1); a phloroacetophenone glucoside, myrciaphenone A (2); and a flavonoid glycoside, afzelin (3) along with two phenylacylated-flavonoid glycosides: rugosaflavonoid C (4), and isoquercitrin 6"-O-p-hydroxybenzoate (5). The structures of compounds 1-5 were elucidated by extensive 1D- and 2D-NMR spectroscopic analysis in combination with MS experiments and comparison with the relevant literature. All compounds are reported for the first time from this species and compounds 2, 4, and 5 from the genus Peucedanum and from Apiaceae.