Naringenin improves depressive- and anxiety-like behaviors in mice exposed to repeated hypoxic stress through modulation of oxido-inflammatory mediators and NF-kB/BDNF expressions.

Oxidative and inflammatory signaling pathways have been identified as important targets for mitigating hypoxic stress-induced neurological complications. Thus, the effects of naringenin, a potent antioxidant, anti-inflammatory and neuroprotective bioflavonoid on hypoxic stress-induced depressive-like and anxiety-related behaviors in mice, and the underlying molecular mechanisms were evaluated in this study. Thirty-five male Swiss mice were distributed into 5 groups (n = 7). Mice in group I (non-stress control) and group 2 (stress-control) both had vehicle (5 % DMSO), while groups 3-5 received naringenin (10, 25 and 50 mg/kg), intraperitonally. Thirty minutes later, mice in groups 2-5 were subjected to 15 min hypoxic stress, daily for 14 days. Locomotor activity, anxiety and depression were evaluated on day 15. The mice brains were processed for malondialdehyde, glutathione, superoxide-dismutase (SOD), catalase, tumor necrosis factor-alpha (TNF-α) and interleukin-1ß assays. The serum corticosterone concentration and expressions of the brain immunopositive cells of inducible nitric oxide synthase (iNOS), nuclear factor kappa-B (NF-kB) and brain derived neurotrophic factor (BDNF) as well as histomorphological changes of the amygdala were also determined. Naringenin (25-50 mg/kg) ameliorated the hypolocomotion, depressive- and anxiety-like behaviors in hypoxic mice. The increased brain contents of malondialdehyde, TNF-α, interleukin-1ß, and decreased antioxidant (glutathione and SOD) status were attenuated by naringenin. Naringenin (10 mg/kg) increases BDNF expression but did not significantly (p < 0.05) alter corticosterone and catalase contents. The increased expressions of iNOS and NF-kB as well as loss of amygdala neuronal cells were reduced by naringenin (10 mg/kg). Overall, these findings suggest that naringenin improves depressive- and anxiety-like behaviors in mice exposed to hypoxic stress by modulating oxido-inflammatory insults and NF-kB/BDNF expressions.

Antinociceptive effects of methyl jasmonate in experimental animals.

Methyl jasmonate (MJ) is a chemical compound that has been postulated to play a role in plant wound and pathogen responses. While the anti-inflammatory property of MJ has been reported in literature, no studies have been carried out to describe its role in the modulation of pain. Thus, this present investigation sought to evaluate the antinociceptive activity of MJ in animal models of pain. The antinociceptive activity of MJ (10-50 mg/kg) administered intraperitoneally (i.p.) was screened using the acetic acid-induced writhing, tail immersion, formalin-induced paw licking and Randall-Selitto paw pressure tests in rodents. MJ demonstrated inhibitory activity against acetic acid-induced abdominal constrictions in mice. It further produced a significant suppression of the inflammatory pain associated with the second phase of the formalin test in mice. However, MJ did not inhibit the neurogenic pain associated with the first phase of the formalin test and also failed to alter the reaction time of mice to noxious heat in the tail immersion test. In the Randall-Selitto paw pressure test, MJ significantly prolonged the paw withdrawal latency in the inflamed hind paw but did not alter the pain response in the non-inflamed hind paw of rats. The acute toxicity test showed that MJ given i.p. was well tolerated by the animals, as no toxic symptoms or death were observed at a dose range of 100-300 mg/kg in mice. Behavioural changes (ataxia, sedation and hyperventilation) were only observed at higher doses of MJ (400 and 500 mg/kg). Taken together, these findings suggest that methyl jasmonate has antinociceptive activity and may serve as a therapeutic in the treatment of inflammatory pain.