Targeting HMGB1/PI3K/Akt and NF-κB/Nrf-2 signaling pathways by vildagliptin mitigates testosterone-induced benign prostate hyperplasia in rats.

Benign prostatic hyperplasia (BPH) is a prevalent illness in older adults. It is well-recognized that testosterone is essential in the onset of BPH. Vildagliptin (Vilda), a dipeptidyl peptidase-IV inhibitor, has been shown to have anti-inflammatory and antioxidant effects. In this study, we studied the effects of vildagliptin on testosterone-induced BPH in rats and its underlying mechanisms. Forty male Wistar rats were allocated into four groups (n = 10): CTRL, Vilda, BPH, and BPH + Vilda groups. Our results revealed that vildagliptin treatment considerably lessened the prostate weight, prostate index, serum levels of prostate-specific antigen, 5α-reductase activity, and DHT levels compared to the testosterone group. Furthermore, vildagliptin treatment inhibited the expression of HMGB1, PI3K/Akt/NF-κB, and TNF-α signaling pathways in the prostate tissue of diseased rats. Additionally, vildagliptin treatment increased the expression of Nrf-2 and HO-1, reduced GSH levels, and lowered MDA levels. Besides, vildagliptin noticeably scaled up the level of cleaved caspase-3 enzyme and, conversely, the protein expression of proliferating cell nuclear antigen (PCNA). Correspondingly, vildagliptin counteracts testosterone-induced histological irregularities in rats' prostates. These findings suggest that vildagliptin may be a potential prophylactic approach to avoid BPH.

Nanoformulated Recombinant Human Myelin Basic Protein and Rituximab Modulate Neuronal Perturbations in Experimental Autoimmune Encephalomyelitis in Mice.

Introduction: Rituximab (RTX) and recombinant human myelin basic protein (rhMBP) were proven to be effective in ameliorating the symptoms of multiple sclerosis (MS). In this study, a nanoformulation containing rhMBP with RTX on its surface (Nano-rhMBP-RTX) was prepared and investigated in comparison with other treatment groups to determine its potential neuro-protective effects on C57BL/6 mice after inducing experimental autoimmune encephalomyelitis (EAE). Methods: EAE was induced in the corresponding mice by injecting 100 µL of an emulsion containing complete Freund's adjuvant (CFA) and myelin oligodendrocyte glycoprotein (MOG). The subjects were weighed, scored and subjected to behavioural tests. After reaching a clinical score of 3, various treatments were given to corresponding EAE-induced and non-induced groups including rhMBP, RTX, empty nanoparticle prepared by poly (lactide-co-glycolide) (PLGA) or the prepared nanoformulation (Nano-rhMBP-RTX). At the end of the study, biochemical parameters were also determined as interferon-γ (IFN-γ), myeloperoxidase (MPO), interleukin-10 (IL-10), interleukin-4 (IL-4), tumor necrosis factor alpha (TNF-α), nuclear factor kappa B (NF-kB), brain derived neurotrophic factor (BDNF), 2', 3' cyclic nucleotide 3' phosphodiesterase (CNP) and transforming growth factor beta (TGF-ß) along with some histopathological analyses. Results: The results of the Nano-rhMBP-RTX group showed promising outcomes in terms of reducing the clinical scores, improving the behavioural responses associated with improved histopathological findings. Elevation in the levels of IL-4, CNP and TGF-ß was also noticed along with marked decline in the levels of NF-kB and TNF-α. Conclusion: Nano-rhMBP-RTX treated group ameliorated the adverse effects induced in the EAE model. The effectiveness of this formulation was demonstrated by the normalization of EAE-induced behavioral changes and aberrant levels of specific biochemical markers as well as reduced damage of hippocampal tissues and retaining higher levels of myelination.