the Indian Journal of Pharmacy最新文献

Objectives: In the present study, we tested the functional/pharmacological significance of dimethyl fumarate (DMF) in streptozotocin-induced diabetic neuropathy (DN) in rats and high glucose-exposed Neuro2a (N2a) cells.

Materials and methods: To evaluate the pharmacological effects of DMF on diabetic neuropathy, we assessed behavioral and functional parameters of peripheral neuropathy, oxidative stress markers, and target protein expression using immunohistochemistry/immunocytochemistry, and Western blotting in diabetic rats and hyperglycemic N2a cells.

Results: Diabetic rats exhibited hyperalgesia, allodynia, and compromised sensory and motor nerve conduction velocities in comparison to normal rats. Dorsal root ganglias of diabetic rats showed decreased antioxidant levels and increased pro-inflammatory transcription factors such as nuclear factor erythroid-related factor 2 and nuclear factor-kappa B, alongside reduced expression of the heat shock protein (HSP) 90. Administering DMF to diabetic rats for 2 weeks reversed these effects in a dose-dependent manner. We observed significant compromise in mitochondrial function, indicated by reduced mitochondrial membrane potential, increased free radical levels, and compromised mitochondrial complex activities in N2a cells exposed to elevated glucose levels. Conversely, DMF treatment restored mitochondrial function and augmented mitochondrial biogenesis through the upregulation of PGC-1α and improved chaperone activity by increasing the expression of HSP 60 and HSP 70.

Conclusions: Overall, DMF alleviated neurobehavioral deficits in DN rats and enhanced mitochondrial function and chaperone activity under hyperglycemic conditions in both diabetic rats and N2a cells.

Objectives: With the prevalence of Alzheimer's disease (AD) increasing exponentially, there has been a shift in the focus of drug discovery for AD from treating the symptoms to preventing the development of the disease. Several natural compounds are extensively studied as neuroprotectives in preventing disease progression. Helianthus annuus seed oil (HA) is widely used as cooking oil and is abundant in antioxidant activity. Therefore, we evaluated the effect of HA in mice model of scopolamine-induced amnesia and explored the potential underlying mechanisms.

Methods: Twenty-four male mice were administered orally with either distilled water (control and scopolamine groups) or treatment groups (HA 100 and HA 200 mg/kg) for 8 consecutive days. All groups, except the control group, received an intraperitoneal injection of scopolamine at a dose of 1 mg/kg. Subsequently, novel object recognition task for cognition assessment and open field tests for locomotory activity were performed. In addition, network analysis was performed to identify the key bioactives and targets of HA against AD. Further, the binding affinity of HA bioactives to the key targets was verified by molecular docking analysis.

Results: HA (100 mg/kg and 200 mg/kg) significantly ameliorated recognition memory compared to the scopolamine group, suggesting the protective effect of HA against cognitive impairment. Network analysis indicated that the key bioactives of HA, chlorogenic acid, and oleic acid act through multiple targets and pathways, particularly the mitogen-activated protein kinase (MAPK) pathway, to ameliorate AD symptoms. Importantly, chlorogenic acid showed good binding affinity with MAPKs, TP53, and EP300.

Conclusion: HA has therapeutic benefits in AD acting through the MAPK pathway. However, further studies need to be done to confirm the results derived and translate the potential use of HA as a dietary supplement for preventing AD.

Abstract: Polyamine synthesis and abnormal regulation of B cell differentiation occur concurrently in various diseases. We investigated whether putrescine could suppress germinal center B cell (GCB) differentiation by inducing reactive oxygen species (ROS) generation. The results of flow cytometry analysis revealed that putrescine did not affect B cell apoptosis and cell cycle. The results of RT-qPCR and western blotting revealed that putrescine could inhibit CD79a phosphorylation rather than total expression. Using an O2K high-resolution respirometer, we illustrated that putrescine increased the oxygen consumption rate in the basal mitochondrial respiration stage, ATP-coupled respiration stage, and maximum respiration stage. Similarly, it also elevated ROS generation across stages in B cells and reduced the proportion of GCB cells. Meanwhile, ROS scavenging by SOD could reverse such inhibitory effects on GCB cells. We concluded that putrescine could inhibit the differentiation of GCB cells by reducing CD79a phosphorylation and increasing ROS levels in GCB cells.