RESUMEN
Grewia asiatica L. fruit natively called phalsa is a popular berry of Pakistan and widely consumed in the form of fresh juices and carbonated drinks in the summer season. The berry is enriched with antioxidants such as phenols, flavonoids, anthocyanins, and vitamin C. Scientifically, it is the least explored berry in terms of neuromodulatory activities, and therefore, in the designed study, chronically fed rats with the different dilutions (5%-30%) of fruit juice were subjected to behavioral assessment for anxiety, depression, and cognition (spatial memory) followed by biochemical analysis of isolated brains. Results revealed a prominent impact of 20 and 30% dilutions of fruit exudate as treated animals showed anxiolytic behavior to central zone (P < 0.05) of open field test (OFT) and open arms of elevated plus maze (EPM) (P < 0.05) in anxiety models. Overall, immobility of rats treated with a higher concentration of exudate in forced swim test (FST) was reduced (P < 0.05) presenting antidepressant-like activity. Moreover, in learning and memory experimental models, the treated animals reversed scopolamine-induced amnesic effects as evident from improved step-through latencies (P < 0.05 vs. scopolamine; passive avoidance test), spontaneous alternation behavior (P < 0.05 vs. scopolamine; Y-maze test), discrimination index (P < 0.05 vs. scopolamine; novel object recognition test), and escape latencies (P < 0.05 vs. scopolamine; Morris water maze). Biochemical studies of isolated brains from treated rats demonstrated significantly elevated levels of superoxide dismutase and glutathione peroxidase (P < 0.05), whereas levels of acetylcholinesterase and malondialdehyde level (P < 0.05) were reduced, indicating its potential to reduce oxidative damage in the brain and modulation with the cholinergic system. The outcomes of studies support the benefits of phytoconstituents possessed by G. asiatica fruit in the amelioration of neurological disorders that could be due to their antioxidative capacity or due to interaction with GABAergic, serotonergic, and cholinergic systems in the brain.
RESUMEN
There are many mechanisms of resistance, chemoresistance of HeLa cells to anti-cancer agents seems to be autophagy-mediated. While using very effective anti-cancers such as Doxorubicin and cisplatin, cells overcome the cytotoxicity of these drugs through promotion of what so-called cytoprotective autophagy. Here in this study, we sought to introduce a novel platinum-based compound PBC-II that possesses anti-cancer activity. Our data showed that PBC-II is able to induce apoptosis at relatively low concentrations, with no detectable reactive oxygen species (ROS). However, further experiments demonstrated that exposure of HeLa cells to PBC-II did not promote autophagy; rather, it resulted in accumulation of p62 and decrease in LC3-II levels. Autophagy was then promoted in HeLa cells pharmacologically by Doxorubicin and genetically by siRNA IL-10. In order to confirm promotion of autophagy in our model, we performed acridine orange staining to assess for autophagy under microscope as well as via flow cytometry. We then measured protein level of autophagy markers p62 and LC3 by western blot. Our data indicated that PBC-II interferes with therapy-induced autophagy. We also determined PI3K activity while co-incubation of PBC-II with autophagy inducers. It was clear that PI3K activation decreased when PBC-II was co-administered with autophagy inducers. Collectively, PBC-II exerts unique anti-proliferative effects associated with inhibition of autophagy, which indicates that PBC-II is potentially a promising agent to be used in resistant ovarian tumors.
