Gentamicin (GNT) is the most frequently used aminoglycoside. However, its therapeutic efficacy is limited due to nephrotoxicity. Thus, the potential anticipatory effect of Diosmin (DIOS) against GNT-prompted kidney damage in rats together with the putative nephroprotective pathways were scrutinized. Four groups of rats were used: (1) control; (2) GNT only; (3) GNT plus DIOS; and (4) DIOS only. Nephrotoxicity was elucidated, and the microRNA-21 (miR-21) and microRNA-155 (miR-155) expression and Nrf2/HO-1 and p38-MAPK/NF-κB pathways were assessed. GNT provoked an upsurge in the relative kidney weight and serum level of urea, creatinine, and KIM-1. The MDA level was markedly boosted, with a decline in the level of TAC, SOD, HO-1, and Nrf2 expression in the renal tissue. Additionally, GNT exhibited a notable amplification in TNF-α, IL-1β, NF-κB p65, and p38-MAPK kidney levels. Moreover, caspase-3 and BAX expression were elevated, whereas the Bcl-2 level was reduced. Furthermore, GNT resulted in the down-regulation of miR-21 expression along with an up-regulation of the miR-155 expression. Histological examination revealed inflammation, degradation, and necrosis. GNT-provoked pathological abnormalities were reversed by DIOS treatment, which restored normal kidney architecture. Hence, regulating miR-21 and -155 expression and modulating Nrf2/HO-1 and p38-MAPK/NF-κB pathways could take a vital part in mediating the reno-protective effect of DIOS.

Alzheimer’s disease (AD) is a neurodegenerative disease (ND) that represents the principal cause of dementia. Effective treatment is still lacking. Without prevention, Alzheimer’s disease (AD) incidence is expected to triple within 30 years. The risk increases in highly polluted areas and is positively linked to chronic aluminum (Al) exposure. Canonical Wingless-Int (Wnt)/β-catenin pathway has been found to play a considerable role in ND pathogenesis. Resins ofBoswellia serrata (frankincense) have been used traditionally for their psychoactive activity, in addition to their memory-boosting effects. Boswellic acids (BA) are pentacyclic triterpenes. They have antioxidant, anti-inflammatory, antinociceptive, and immunomodulatory activities. This study aimed to elucidate the role of the Wnt/β-catenin pathway in BA protective activity against aluminum-induced Alzheimer’s disease. For 6 weeks, rats were treated daily with AlCl3 (100 mg/kg/i.p.) either alone or with BA (125 or 250 mg/kg PO). Results indicated that BA significantly improved learning and memory impairments induced by AlCl₃treatment. Moreover, BA treatment significantly decreased acetylcholinesterase levels and reduced amyloid-beta (Aβ) expression. In addition, BA ameliorated the increased expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), inhibited lipid peroxidation, and increased total antioxidants in the brain. Indeed, BA significantly suppressed AlCl₃-induced decrease of brain-derived neurotrophic factor, pGSK-3β (Ser 9), and β-catenin. BA (250 mg/kg) showed a significant protective effect compared to a lower dose. The results conclude that BA administration modulated the expression of Wnt/β-catenin pathway-related parameters, contributing to BA’s role against Al-induced Alzheimer’s disease.Graphical abstractEffect of Boswellic acids on AlCl₃-induced neurodegenerative changes. ChE cholinesterase, Ach acetylcholine, BDNF brain-derived neurotrophic factor, IL-1β interleukin-1β, TNF-α tumor necrosis factor-α