ABSTRACT
Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide. The association between AD and other diseases such as diabetes is well-studied. In parallel, potential disease-modifying effects of therapeutic agents used for diabetes have been investigated in the context AD of. Metformin is a biguanide and the most commonly prescribed medication for type 2 diabetes Due to its pleiotropic properties, metformin's potential disease-modifying effects are widely studied on different pathophysiological plyers of AD such as amyloid-ß (Aß) production and clearance, tau phosphorylation, and neuroinflammation, in relevant in vitro and in vivo models. In this review, we summarize the relevant scientific literature on the effects of metformin on various aspects of AD pathophysiology.
Subject(s)
Alzheimer Disease/drug therapy , Brain/drug effects , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Metformin/therapeutic use , Alzheimer Disease/metabolism , Amyloid beta-Peptides/antagonists & inhibitors , Amyloid beta-Peptides/metabolism , Animals , Brain/metabolism , Diabetes Mellitus, Type 2/metabolism , Humans , Hypoglycemic Agents/pharmacology , Metformin/pharmacology , Phosphorylation/drug effects , Phosphorylation/physiology , Plaque, Amyloid/drug therapy , Plaque, Amyloid/metabolism , tau Proteins/antagonists & inhibitors , tau Proteins/metabolismABSTRACT
Introduction: Traditionally Prangos ferulacea root is being used as an effective wound healing agent especially for pus-filled wounds both in human and stocks in the western north of Iran. Regarding the subject we decided to study P. ferulacea roots essential oil (PFE) for its antimicrobial and wound healing activities. Methods: The in vitro wound healing activity of PFE was evaluated in the mouse fibroblast cell line L929 using MTT assay of cell viability and cytotoxicity indices. Scratch assay as an in vitro model of wound healing assay was also conducted in this study. Moreover, the type I collagen content was used as an indicator of progress in wound healing process using Sircol collagen assay. Besides, PFE was subjected to GC/MS to identify the chemical constituents, and antimicrobical property was also evaluated against S. aureus, S. epidermidis, E. coli, P. aeruginosa,S. paratyphi and C. albicans using agar dilution method. Results: GC/MS analysis showed that the monoterpene hydrocarbones dominated in PFE, amounting to a total percentage of 95.1% with the major constituents: ß-Phellandrene (32.1%), m-Tolualdehyde (26.2%), and δ-3-carene (25.8%). PFE inhibited the growth of S. aureus and P. aeruginusa with the MIC value of 20 µg/mL. In addition, at the second day of treatment, PFE at concentrations of 4 and 16 µg/mL significantly (P<0.001) enhanced the migration rate of L929 cells by 87.05±2.4 and 63.5±0.08 %, respectively. Moreover, the collagen production by L929 cells was increased greatly (P<0.001). Conclusion: It is proposed that the excellent antimicrobial activity along with the significant increase of migration rate and collagen production by fibroblast cells might be associated with the high content and synergistic effect of the monoterpens, corroborating the traditional usage of this plant as a wound healing agent.
ABSTRACT
The present study was planned to investigate the influence of polyethylene glycols (PEGs) on the activity and expression of P-glycoprotein (P-gp). Sub-toxic concentrations of PEGs in Caco-2 cells were determined using the MTT test assay. Then the measurement of Rhodamine-123 (Rho-123) uptake, a P-gp fluorescence substrate, in Caco-2 cells confronting PEG 400 (1% and 2% w/v), PEG 4000 (2% and 4% w/v), PEG 6000 (2% and 4% w/v), PEG 10000 (2% and 4% w/v), PEG 15000 (1% and 2% w/v), and PEG 35000 (2% and 4% w/v) overnight was taken to elucidate whether non-toxic concentrations of PEGs are able to impact P-gp activity. Furthermore, western blotting was carried out to investigate P-gp protein expression. The results showed that PEG 400 at concentrations of 1% (w/v) and 2% (w/v) and PEG 6000 at the concentration of 4% (w/v) are notably capable of blocking P-gp. Based on the obtained results it is concluded that the mentioned excipients could be used to obstruct P-gp efflux transporter in order to increase the bioavailability of co-administered substrate drug.
O presente estudo foi planejado para investigar a influência de polietileno glicóis sobre a atividade e expressão da P- glicoproteína (P-gp) . Concentrações sub-tóxicas de PGPs e em células Caco-2 foram determinadas por meio do ensaio de MTT. Em seguida, efetuou-se a a medida de captura de Rodamina-123 (Rho-123), um substrato fluorescente de P-gp, em células Caco-2, confrontando com PEG 400 (1% e 2% m/v), PEG 4000 (2% e 4% m/v) e PEG 6000 (2% e 4% m /v), PEG 10000 (2% e 4% w/v), PEG 15000 (1% e 2% m/v), e PEG 35000 (2% e 4% m/v). Essa medida foi efetuada durante a noite, para saber se as concentrações não tóxicas de excipientes são capazes de influenciar a actividade da P-gp. Além disso, realizou-se o western blotting para investigar a expressão da proteína P-gp. Os resultados mostraram que o PEG 400, nas concentrações de 1% (m/v) e 2% (m/v), e PEG 6000, na concentração de 4% (m/v) são capazes de bloquear P-gp. Com base nos resultados conclui-se que os excipientes mencionados poderiam ser utilizados para obstruir o efluxo por P-gp, a fim de aumentar a biodisponibilidade de do fármaco co-administrado.
