Melatonin exacerbates acute experimental autoimmune encephalomyelitis by enhancing the serum levels of lactate: A potential biomarker of multiple sclerosis progression.

Melatonin has a beneficial role in adult rat models of multiple sclerosis (MS). In this study, melatonin treatment (10 mg/kg/d) was investigated in young age (5-6 weeks old) Lewis rat model of acute experimental autoimmune encephalomyelitis (EAE) followed by assessing serum levels of lactate and melatonin. Results showed that clinical outcomes were exacerbated in melatonin- (neurological score = 6) vs PBS-treated EAE rats (score = 5). Melatonin caused a significant increase in serum IFN-γ, in comparison to PBS-treated EAE rats whereas no considerable change in IL-4 levels were found, although they were significantly lower than those of controls. The ratio of IFN-γ/IL-4, an indicator of Th-1/Th-2, was significantly higher in PBS- and melatonin- treated EAE rats, in comparison to controls. Moreover, results showed increased lymphocyte infiltration, activated astrocytes (GFAP+ cells) but also higher demyelinated plaques (MBP-deficient areas) in the lumbar spinal cord of melatonin-treated EAE rats. Finally, serum levels of lactate, but not melatonin, significantly increased in the melatonin group, compared to untreated EAE and normal rats. In conclusion, our results indicated a relationship between age and the development of EAE since a negative impact was found for melatonin on EAE recovery of young rats by enhancing IFN-γ, the ratio of Th1/Th2 cells, and astrocyte activation, which seems to delay the remyelination process. While melatonin levels decline in MS patients, lactate might be a potential diagnostic biomarker for prediction of disease progression. Early administration of melatonin in the acute phase of MS might be harmful and needs further investigations.

Hepatoprotective activity of aerial parts of Otostegia persica against carbon tetrachloride-induced liver damage in rats.

OBJECTIVE: To evaluate the hepatoprotective properties of Otostegia persica (O. persica) ethanol extract on carbon tetrachloride-induced liver damage in rats. MATERIALS AND METHODS: Fifty adult male Wistar rats were randomly divided into five groups. Group I served as normal control and was given only olive oil intraperitoneally (i.p.). Group II, III, IV, and V were administered CCl4 mixed with olive oil 1:1 (1 ml/kg) i.p., twice a week for 8 weeks. Group II was maintained as CCl4-intoxicated control (hepatotoxic group). Group III, IV, and V received O. persica extract at a dose of 40, 80, and 120 mg/kg for 8 weeks every 48 h orally, respectively. Biochemical parameters including aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin (TB), albumin (ALB), total protein (TP), and lipid peroxidation marker (Malonaldialdehyde, (MDA) were determined in serum. After 8 weeks, animals were sacrificed, livers dissected out, and evaluated for histomorphological changes. RESULTS: The administration of CCl4 increased AST, ALT, ALP, TB, and MDA in serum but it decreased TP , and ALB compared with normal control. Treatment with O. persica extract at three doses resulted in decreased enzyme markers, bilirubin levels, and lipid peroxidation marker (MDA) and increased TP and ALB compared with CCl4 group. The results of pathological study also support the hepatoprotective effects which were observed at doses of 80 and 120 mg/kg. CONCLUSION: The results of the present study indicate that ethanol extract of O. persica may have hepatoprotective effect which is probably due to its antioxidant property.

Anti-inflammatory Activity of Stachys Pilifera Benth.

BACKGROUND: Stachys pilifera Benth has long been used to treat infectious diseases as well as respiratory and rheumatoid disorders in Iranian folk medicine. Antioxidants, antitumor, and antimicrobial properties of the plant have been reported. OBJECTIVES: This experimental study was designed to evaluate systemic and topical anti-inflammatory effects of the hydro-alcoholic extract from aerial parts of Stachys pilifera (HESP). MATERIALS AND METHODS: Anti-inflammatory effects of HESP was studied in four well-known animal models of inflammation, including carrageenan- or formalin-induced paw edema in rat (thirteen groups, 6 rats per each group), and 12-O-tetradecanoylphorbol-13-acetate (TPA)- or xylene-induced ear edema in mouse (ten groups, 6 mice per each group). The rats received HESP (50-400 mg/ kg) orally 45 minutes before the subplantar injection of carrageenan or formalin. In TPA or xylene tests, HESP (1, 2.5, and 5 mg/ear) was applied topically simultaneous with these phlogistic agents on the ear mice. Finally, pathological examination of the inflamed tissues (paw and ear) was carried out. RESULTS: Acute toxicity study of the extract showed that no rats were killed at 5000 mg/kg (LD50 > 5000 mg/kg). The extract (100 and 200 mg/ kg) significantly suppressed carrageenan-induced paw edema 1, 2, 3, and 4 hours after carrageenan challenge in comparison with the control group (P < 0.001). The HESP (100 and 200 mg/kg) also produced a considerable antiedematogenic effect in the formalin test over a period of 24 hours (P < 0.01). Furthermore, topical administration of the HESP (1, 2.5, and 5 mg/ear) inhibited TPA- and xylene-induced ear edema in comparison with the control group (P < 0.001). The pathological analysis of the paws and ears revealed that HESP was capable of reducing tissue destruction, cellular infiltration, and subcutaneous edema induced by the indicated phlogistic agents. CONCLUSIONS: The present data confirmed systemic and topical anti-inflammatory effects of Stachys pilifera which is comparable to indomethacin.