Asiatic acid exerts an anti-psoriatic effect in the imiquimod-induced psoriasis model in mice.

Background: Psoriasis is a common skin disorder related to inflammation and immune response. However, many treatment modalities are present in the clinics, and drug conformity halts chronic treatment. Therefore, novel treatment options are still needed. In this study, the possible protective effect of asiatic acid is one of the active compounds present in Centella Asiatica, was investigated in the imiquimod-induced psoriasis murine model.Methods:Imiquimod (62.5 mg) was administered dorsal skin of the mice for 6 days. Animals were co-treated with low-dose (25 mg/kg, p.o.) and high-dose (100 mg/kg, p.o.) asiatic acid. The dorsal skin of the animals was daily scored for erythema, thickness, and scaling. At the end of the treatments, serum levels of IL-17A and IL-23 were determined by ELISA. Additionally, the dorsal skins of animals were histopathologically evaluated.Results: Asiatic acid (high-dose) prevented imiquimod-induced skin lesions and protected dermal integrity in addition decreasing mast cell infiltration due to the imiquimod. Furthermore, asiatic acid (high-dose) suppressed the imiquimod-induced increase in serum levels of IL-17A and IL-23.Conclusion: These results indicate that asiatic acid showed an anti-psoriatic effect in the imiquimod-induced psoriasis model via mediating IL-17A and IL-23 pathways. Because wound healing properties of asiatic acid are described, further investigations should be carried out to understand deeper mechanisms and possible use in dermatological pathologies such as psoriasis.

GLP-1 agonist liraglutide improves ouabain-induced mania and depressive state via GSK-3ß pathway.

Bipolar disorder (BD) is a severe mental illness characterized by aberrant mood changes between hypomania and mania or mixed states and depression. Metabolic changes also accompany disease progression and cause significant morbidity. Symptomatic treatment options are available, but asymptomatic patients and poor drug responders are significant problems. Based on the most common pharmacological agent that is used in the treatment, lithium and its main mechanisms of action, oxidative stress, and glycogen synthase kinase-3ß (GSK-3ß) signaling are extensively investigated. However, knowledge about the effects of compounds that positively affect oxidative stress and GSK-3ß signaling, such as glucagon-like peptide-1 (GLP-1) mimetics, liraglutide, is still missing. Therefore, in this study, we aimed to investigate the effects of liraglutide on the ouabain-induced bipolar disease model in rats. After intracerebroventricular single dose ouabain administration, animals were treated with 100, 200, and 400 µg/kg liraglutide (s.c.) and valproic acid (200 mg/kg, i.p.) for 10 d. The locomotion and depressive states of animals were assessed by an open field, forced swimming test, and sucrose preference tests. Serum total antioxidant (TAS) and oxidant states (TOS) and glutathione, malonyl dialdehyde (MDA) levels in the brain tissue were determined. GSK-3ß phosphorylation was evaluated by western blotting. Our results demonstrated that liraglutide attenuated ouabain-induced hyperlocomotion and depressive state. Additionally, liraglutide prevented oxidative stress after ouabain administration. Decreased GSK-3ß phosphorylation due to the ouabain insult was alleviated by liraglutide treatment. These findings indicate that the manic and depressive-like behaviors are ameliorated by liraglutide, which exerted antioxidant action, possibly improving GSK-3ß phosphorylation.

Role of TRPV1 channels on glycogen synthase kinase-3ß and oxidative stress in ouabain-induced bipolar disease.

Bipolar disorder (BD) is a multifactorial chronic and refractory disease characterized by manic, depressive, and mixed mood episodes. Although epidemiological, and pathophysiological studies demonstrated a strong correlation between bipolar disorder and oxidative stress, precise etiology is still missing. Recent studies suggested the possible role of transient receptor potential channels (TRP) in the BD but, current knowledge is limited. Therefore, the current study investigates the possible role of TRPV1 in the ouabain-induced model of BD. The model was created with intracerebroventricular single dose ouabain (10-3 M) administration. Animals were treated with capsaicin, capsazepine, and lithium for seven days. Mania and depressive-like states were investigated with open-field, sucrose preference, and elevated plus maze tests. Oxidative stress was assessed by measuring total antioxidant and oxidant states, spectrophotometrically. The phosphorylation Glycogen synthase kinase-3ß (GSK-3ß) evaluated by western blotting. Our results demonstrated that capsaicin dose-dependently inhibited the ouabain-induced hyperlocomotion and depression. Although capsazepine exacerbated behavioral impairment, it did not show a significant effect on the antioxidant and oxidant states, and the effects of capsazepine on behaviors were abolished by combination with capsaicin. Additionally, capsaicin potently prevented the ouabain-induced decrease in GSK-3ß phosphorylation. In contrast, capsazepine potentiated ouabain-induced decrease in GSK-3ß phosphorylation and combination with capsaicin, suppressed the effect of capsazepine on GSK-3ß phosphorylation. The effects of TRPV1 activation on oxidative stress and mania-like behaviors in the ouabain-induced BD model might be regulated by GSK-3ß phosphorylation.