RESUMO
D-galactose (D-gal) administration was proven to induce cognitive impairment and aging in rodents' models. Geraniol (GNL) belongs to the acyclic isoprenoid monoterpenes. GNL reduces inflammation by changing important signaling pathways and cytokines, and thus it is plausible to be used as a medicine for treating disorders linked to inflammation. Herein, we examined the therapeutic effects of GNL on D-gal-induced oxidative stress and neuroinflammation-mediated memory loss in mice. The study was conducted using six groups of mice (6 mice per group). The first group received normal saline, then D-gal (150 mg/wt) dissolved in normal saline solution (0.9%, w/v) was given orally for 9 weeks to the second group. In the III group, from the second week until the 10th week, mice were treated orally (without anesthesia) with D-gal (150 mg/kg body wt) and GNL weekly twice (40 mg/kg body wt) four hours later. Mice in Group IV were treated with GNL from the second week up until the end of the experiment. For comparison of young versus elderly mice, 4 month old (Group V) and 16-month-old (Group VI) control mice were used. We evaluated the changes in antioxidant levels, PI3K/Akt levels, and Nrf2 levels. We also examined how D-gal and GNL treated pathological aging changes. Administration of GNL induced a significant increase in spatial learning and memory with spontaneously altered behavior. Enhancing anti-oxidant and anti-inflammatory effects and activating PI3K/Akt were the mechanisms that mediated this effect. Further, GNL treatment upregulated Nrf2 and HO-1 to reduce oxidative stress and apoptosis. This was confirmed using 99mTc-HMPAO brain flow gamma bioassays. Thus, our data suggested GNL as a promising agent for treating neuroinflammation-induced cognitive impairment.
Assuntos
Monoterpenos Acíclicos , Disfunção Cognitiva , Galactose , Humanos , Camundongos , Animais , Galactose/toxicidade , Proteínas Proto-Oncogênicas c-akt/metabolismo , Doenças Neuroinflamatórias , Fator 2 Relacionado a NF-E2/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Estresse Oxidativo , Envelhecimento/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Antioxidantes/farmacologia , Modelos Animais de Doenças , Inflamação/tratamento farmacológicoRESUMO
The potential of Alhagi maurorum (Boiss.) aqueous extract (AME), used in traditional medicine for treatment or prevention of urolithiasis, to dissolve calcium oxalate stones in vitro was evaluated. In order to determine the litholytic potential of the extract, Calcium oxalate urinary stones were incubated during 12 weeks under continuous shaking in the presence of AME, Rowanix or NaCl 9 g/mL solution were used as controls. After the incubation period, the residual weight of the treated calculi was determined and the rate of dissolution was calculated. The medium pH variation was measured and changes in the calcium oxalate crystals at the stone surface were assessed using a scanning electron microscope (SEM). The results showed a significant dissolution effect for the extract on the kidney calculi during the experimentation period. At the end of the experiment, the percentages of calculi weight decrease were 41.23, 4.97 and 55.67% for the extract, NaCl solution and Rowanix, respectively. Gas Chromatography analysis revealed mainly the presence of the following phyto-compounds: Cyclopropenone, 2,3-diphenyl; 1-Nonadecanol; methyl-alpha-D-mannopyranoside; cis-9-Hexadecenal. These compounds unarguably play crucial roles in the health care system especially in cancer treatment and many other diseases including urolithiasis. The urinary stone dissolution, independent of medium pH, could be attributed to formation of complexes between the phytochemical compounds in the extract and the calculi.