RESUMEN

Depression is a common mood disorder and many patients do not respond to conventional pharmacotherapy or experience a variety of adverse effects. This work proposed that riparin I (RIP I) and riparin II (RIP II) present neuroprotective effects through modulation of astrocytes and microglia, resulting in the reversal of depressive-like behaviors. To verify our hypothesis and clarify the pathways underlying the effect of RIP I and RIP II on neuroinflammation, we used the chronic unpredictable mild stress (CUMS) depression model in mice. Male Swiss mice were exposed to stressors for 28 days. From 15 th to the 22 nd day, the animals received RIP I or RIP II (50 mg/kg) or fluoxetine (FLU, 10 mg/kg) or vehicle, by gavage. On the 29 th day, behavioral tests were performed. Expressions of microglia (ionized calcium-binding adaptor molecule-1 - Iba-1) and astrocyte (glial fibrillary acidic protein - GFAP) markers and levels of cytokines tumor necrosis factor alfa (TNF-α) and interleukin 1 beta (IL-1ß) were measured in the hippocampus. CUMS induced depressive-like behaviors and cognitive impairment, high TNF-α and IL-1ß levels, decreased GFAP, and increased Iba-1 expressions. RIP I and RIP II reversed these alterations. These results contribute to the understanding the mechanisms underlying the antidepressant effect of RIP I and RIP II, which may be related to neuroinflammatory suppression.

Asunto(s)

Antidepresivos , Astrocitos , Depresión , Modelos Animales de Enfermedad , Hipocampo , Microglía , Enfermedades Neuroinflamatorias , Estrés Psicológico , Animales , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Ratones , Masculino , Microglía/efectos de los fármacos , Microglía/metabolismo , Antidepresivos/farmacología , Depresión/tratamiento farmacológico , Depresión/metabolismo , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Enfermedades Neuroinflamatorias/metabolismo , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/complicaciones , Estrés Psicológico/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Fluoxetina/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-1beta/metabolismo , Fármacos Neuroprotectores/farmacología , Conducta Animal/efectos de los fármacos , Proteína Ácida Fibrilar de la Glía/metabolismo

RESUMEN

ABSTRACT The organic extracts from stems, roots and leaves of Tephrosia egregia Sandwith, Fabaceae, provided a new flavone, 5-hydroxy-8-(1",2"-epoxy-3"-hydroxy-3"-methylbutyl)-7-methoxyflavone (1), in addition to eleven known compounds: pongaflavone (2), praecansone B (3), 12a-hydroxyrotenone (4), praecansone A, 2',6'-dimethoxy-4',5'-(2",2"-dimethyl)-pyranochalcone, pongachalcone, maackiain, β-sistosterol and its glucoside, p-cumaric acid and cinnamic acid. The structures of all compounds were established on the basis of spectroscopic methods, mainly 1D and 2D NMR and HRESIMS, involving comparison with literature data. Cytotoxicity of compounds 1-4 was evaluated against AGP-01 (cancerous ascitic fluid), HCT-116 (colon adenocarcinoma), HL-60 (leukemia), PC-3 (prostate carcinoma), SF-295 (glioblastoma) and SKMEL 28 (melanoma) cell lines.