Investigation of the neuroprotective and neuritogenic effects of halotolerant Penicillium flavigenum-derived sorbicillin-like compounds on PC-12 Adh cells.

Parkinson's disease (PD) is an adult-onset neurodegenerative condition caused by oxidative stress and mitochondrial malfunction. In this study, the neuroprotective and neuritogenic activity of water fraction (Sw-fr) containing sorbicillin-like active metabolites of halotolerant P. flavigenum isolated from Salt Lake in Konya, Turkey were investigated on a 6-hydroxydopamine (6-OHDA)-induced PD in vitro PC-12 Adh cell model. Firstly, Sw-fr containing sorbicillin-like active metabolites were extracted from P. flavigenum and was compared with a sorbicillin standard by liquid chromatography-mass spectrometry (LC-MS). Then, the effects of non-cytotoxic concentrations of Sw-fr on the 6-OHDA-induced PD cell model were investigated via real-time cell proliferation analysis using the RTCA DP instrument. The effects of these concentrations on mitochondrial membrane integrity, caspase-3 were investigated by flow cytometry. Neurite outgrowth analysis and immunofluorescence staining were used to explore the neuritogenic effects of neuroprotective doses. By improving PC-12 Adh cell viability, decreasing reactive oxygen species production, and reducing apoptotic cell death, 1 and 10 µg/mL Sw-fr and sorbicillin standard proved neuroprotective against 6-OHDA-induced neurotoxicity. Furthermore, 1 and 10 µg/mL Sw-fr significantly induced neurite outgrowth. As a result, sorbicillin-like active metabolites containing Sw-fr were found to have neuroprotective and neuritogenic effects. Sorbicillin-like metabolites obtained from fungi may be novel natural medicines for neurodegenerative diseases. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10616-021-00498-9.

Clarithromycin-Loaded Poly (Lactic-co-glycolic Acid) (PLGA) Nanoparticles for Oral Administration: Effect of Polymer Molecular Weight and Surface Modification with Chitosan on Formulation, Nanoparticle Characterization and Antibacterial Effects.

Clarithromycin (CLR) is a member of the macrolide antibiotic group. CLR has low systemic oral bioavailability and is a drug of class II of the Biopharmaceutical Classification System. In many studies, using nanoparticles (NPs) as a drug delivery system has been shown to increase the effectiveness and bioavailability of active drug substances. This study describes the development and evaluation of poly (lactic-co-glycolic acid) (PLGA) NPs and chitosan (CS)-coated PLGA NPs for oral delivery of CLR. NPs were obtained by nanoprecipitation technique and characterized in detail, and the effect of three molecular weights (Mw1: 7.000-17.000, Mw2: 38.000-54.000, Mw3: 50.000-190.000) of PLGA and CS coating on particle size (PS), zeta potential (ZP), entrapment efficiency (EE%), and release properties etc. were elucidated. Gastrointestinal stability and cryoprotectant effect tests were performed on the NPs. The PS of the prepared NPs were in the range of 178 to 578 nm and they were affected by the Mw and CS coating. In surface-modified formulations with CS, the ZP of the NPs increased significantly to positive values. EE% varied from 62% to 85%, depending upon the Mw and CS coating. In vitro release studies of CLR-loaded NPs showed an extended release up to 144 h. Peppas-Sahlin and Weibull kinetic model was found to fit best for CLR release from NPs. By the broth microdilution test method, the antibacterial activity of the formulations was determined on Staphylococcus aureus (ATCC 25923), Listeria monocytogenes (ATCC 1911), and Klebsiella pneumoniae (ATCC 700603). The structures of the formulations were clarified by thermal (DSC), FT-IR, and 1H-NMR analysis. The results showed that PS, ZP, EE%, and dissolution rates of NPs were directly related to the Mw of PLGA and CS coating.

Cytotoxic Effects of Resveratrol, Rutin and Rosmarinic Acid on ARH-77 Human (Multiple Myeloma) Cell Line.

Multiple myeloma (MM) cancers are 10% of hematological cancers. Leukemia ARH-77 is a malignancy like MM with a worse course of disease and the survival rate from it is very low. Therefore, ARH-77 is a commonly used model for antitumor agent studies. Polyphenolic compounds, such as resveratrol, rutin and rosmarinic acid, have many protective roles, but there is no comparative study about these three polyphenolic compounds on ARH-77. In the present study, we investigated the cytotoxic effects of resveratrol, rutin and rosmarinic acid on ARH-77. Toxic concentration ranges were determined by the brine shrimp lethality test on Artemia salina. In addition, for determination of their cytotoxic effects, MTT and NR methods were used for ARH-77. Resveratrol caused significant reduction in both mitochondrial and lysosomal activities compared with the control group. Maximum inhibition values were detected on mitochondrial and lysosomal activity with 200 pM concentrations after 48 hours. After a 24 hours incubation period, rutin showed cytotoxic effects, particularly with 50, 100 and 200 lM concentrations. Rosmarinic acid also decreased the mitochondrial activity with the same concentrations. Resveratrol showed higher cytotoxic effects than rutin and rosmarinic acid. According to our study, polyphenolic compounds such as rutin, resveratrol and rosmarinic acid may hold promise in multiple myeloma treatment with further investigations.