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Huntington’s disease (HD) is a progressive neurodegenerative disorder. The pre-motor symptomatic stages of the disease are commonly characterized by cognitive problems including memory loss. 3-Nitropropionic acid (3-NPA) is a mitochondrial toxin that produces selective lesions in the brain similar to that of HD and was proven to cause memory impairment in rodents. Phytoestrogens have well-established neuroprotective and memory enhancing effects with fewer side effects in comparison to estrogens. This study investigated the potential neuroprotective and memory enhancing effect of genistein (5, 10 and 20 mg/kg), a phytoestrogen, in ovariectomized rats challenged with 3-NPA (20 mg/kg). These potential effects were compared to those of 17β-estradiol (2.5 mg/kg). Systemic administration of 3-NPA for 4 consecutive days impaired locomotor activity, decreased retention latencies in the passive avoidance task, decreased striatal, cortical and hippocampal ATP levels, increased oxidative stress, acetylcholinesterase (AChE) activity, cycloxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions. Pretreatment with genistein and 17β-estradiol attenuated locomotor hypoactivity, increased retention latencies in the passive avoidance task, increased ATP levels, improved the oxidative stress profile, attenuated the increase in AChE activity and decreased the expression of COX-2 and iNOS. Overall, the higher genistein dose (20 mg/kg) was the most effective. In conclusion, this study suggests neuroprotective and memory enhancing effects for genistein in a rat model of HD. These effects might be attributed to its antioxidant, anti-inflammatory and cholinesterase inhibitory activities.

Context: Solidago virgaurea L. (Asteraceae) is traditionally used as an anti-inflammatory for the treatment of various symptoms including cystitis. However, little is known concerning the constituents responsible for this activity and the mechanism of their action. Objective: To assess the anti-inflammatory activity of the phenolic-rich fraction of S. virgaurea aerial parts in rats, isolate and assess the activity of the major compounds present. Materials and methods: An HPLC method was developed for the analysis of the phenolic-rich fraction (EtFr). The in vivo anti-inflammatory activity of the EtFr and four isolated compounds (at 25 and 50 mg/kg) were assessed in adult male rats using the carrageenan-induced rat paw oedema model. The levels of the pro-inflammatory cytokines (TNF-a and IL-1b) were measured using ELISA. Results: 3,5-O-Dicaffeoylquinic acid (1), 3,4-O-dicaffeoylquinic acid (2), 3,4,5-O-tricaffeoylquinic acid (3) and 4,5-O-dicaffeoylquinic acid (4) were isolated from EtFr. Compound 3 (50 mg/kg) showed a highly significant activity in inhibiting the oedema volume after 3 h (88% of the activity of indomethacin at 10 mg/kg). The EtFr and the isolated compounds largely inhibited the excessive production of the inflammatory mediators TNF-a and IL-1b. Discussion and conclusion: This is the first report of 3,4,5-tri-O-caffeoylquinic acid (3) in Solidago species. The tricaffeoylquinic acid (3) showed a significantly higher activity than the other three dicaffeoylquinic acids (1, 2, 4) and indomethacin in reduction of TNF-a and IL-1b concentrations (8.44 ± 0.62 and 5.83 ± 0.57 pg/mL compared to 12.60 ± 1.30 and 52.91 ± 5.20 pg/mL induced by indomethacin, respectively). ARTICLE HISTORY

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