Selenium Supplementation May Decrease Thyroid Peroxidase Antibody Titer via Reducing Oxidative Stress in Euthyroid Patients with Autoimmune Thyroiditis.

OBJECTIVE: Selenium, as an antioxidant, has been implicated in the development of autoimmune thyroiditis (AIT). Many studies showed selenium supplementation could decrease thyroid autoantibodies in patients with AIT. However, the underlying mechanisms have not been well determined. Therefore, we performed a clinical study to investigate the possible mechanism of beneficial effects of selenium treatment on AIT patients. METHODS: Forty euthyroid patients with AIT were randomized into two groups. Group I was treated with 200 µg/day selenium supplementation, and group II received a placebo over a 3-month period. Thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), antithyroglobulin antibody (TgAb), malondialdehyde (MDA), total antioxidant capacity (TAC), and superoxide dismutase (SOD) were measured before and 3 months after treatments. Additionally, twenty healthy volunteers also served as a control group for the evaluation of such parameters in basic condition. RESULTS: Totally, 32 patients (group I, n = 18; group II, n = 14) completed the clinical study and were incorporated into the statistics. MDA level was higher and SOD activity and TAC were lower in patients compared to healthy individuals. After 3 months, TPOAb titer significantly decreased within group I (P < 0.001) but did not change within group II (P=0.001). There were also no statistically significant changes in TSH and TgAb titers within the two groups (all P > 0.05). Additionally, decreased MDA level (from 6.8 ± 1.3 nmol/ml to 4.9 ± 0.7 nmol/ml; P < 0.001) and increased TAC (from 10.0 ± 1.9 mmol/l to 12.9 ± 3.1 mmol/l; P=0.003) and SOD activity (from 72.3 ± 10.3 U/ml to 84.3 ± 13.2 U/ml; P=0.007) were simultaneously observed after 3 months' selenium treatment. Moreover, there was a negative correlation between TAC and TgAb/TPOAb and a positive correlation between MDA and TgAb/TPOAb in AIT patients. CONCLUSIONS: Our findings support the hypothesis that selenium treatment could decrease TPOAb titer via enforcing the defense against oxidative stress in euthyroid patients with AIT, which may be a potential underlying mechanism.

Peony-Glycyrrhiza Decoction for Antipsychotic-Related Hyperprolactinemia in Women With Schizophrenia: A Randomized Controlled Trial.

OBJECTIVES: An herbal preparation called peony-glycyrrhiza decoction (PGD) may have the potential in reducing antipsychotic-related hyperprolactinemia (hyperPRL). This double-blind, randomized placebo-controlled study aimed to reevaluate the efficacy of PGD against antipsychotic-related hyperPRL. METHODS: Ninety-nine schizophrenic women who were under antipsychotic therapy and had symptomatic hyperPRL were randomly assigned to additional treatment with placebo (n = 50) or PGD (n = 49, 45 g/d) for 16 weeks. The severity of hyperPRL, psychosis, and abnormal involuntary movements was assessed at baseline and weeks 8 and 16 using standard instruments including the Prolactin Related Adverse Event Questionnaire. Blood levels of prolactin (PRL) and related pituitary and sex hormones were measured at the same time points. RESULTS: Peony-glycyrrhiza decoction treatment produced a significantly greater reduction of the Prolactin Related Adverse Event Questionnaire score at weeks 8 and 16 and a greater improvement on abnormal involuntary movements at end point compared with placebo, without altering the severity of psychosis. The group treated with PGD showed significantly higher proportion of having overall improvement on hyperPRL symptoms (χ = 4.010, P = 0.045) and menstrual resumption (χ = 4.549, P = 0.033) at week 8 than placebo. Serum PRL levels were similar in the 2 groups. CONCLUSIONS: Peony-glycyrrhiza decoction is effective in reducing antipsychotic-related hyperPRL and abnormal involuntary movement symptoms, but no reduction in blood PRL concentrations was observed. The underlying mechanisms of PGD's effects need further investigation (trial registration of NCT01852331 at www.clinicaltrials.gov).

Repetitive transcranial magnetic stimulation ameliorates anxiety-like behavior and impaired sensorimotor gating in a rat model of post-traumatic stress disorder.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been employed for decades as a non-pharmacologic treatment for post-traumatic stress disorder (PTSD). Although a link has been suggested between PTSD and impaired sensorimotor gating (SG), studies assessing the effects of rTMS against PTSD or PTSD with impaired SG are scarce. AIM: To assess the benefit of rTMS in a rat model of PTSD. METHODS: Using a modified single prolonged stress (SPS&S) rat model of PTSD, behavioral parameters were acquired using open field test (OFT), elevated plus maze test (EPMT), and prepulse inhibition trial (PPI), with or without 7 days of high frequency (10Hz) rTMS treatment of SPS&S rats. RESULTS: Anxiety-like behavior, impaired SG and increased plasma level of cortisol were observed in SPS&S animals after stress for a prolonged time. Interestingly, rTMS administered immediately after stress prevented those impairment. CONCLUSION: Stress-induced anxiety-like behavior, increased plasma level of cortisol and impaired PPI occur after stress and high-frequency rTMS has the potential to ameliorate this behavior, suggesting that high frequency rTMS should be further evaluated for its use as a method for preventing PTSD.

Gastrodin ameliorates depression-like behaviors and up-regulates proliferation of hippocampal-derived neural stem cells in rats: involvement of its anti-inflammatory action.

Gastrodin (GAS), an active constituent of the Chinese herbal medicine tianma, has antidepressant-like activity in animals but no specific molecular mechanisms have been identified. In the present study, chronic unpredictable stress (CUS) was used to establish a rat depression model; The sucrose preference test, forced swim test and Morris water maze test were used to assess depression-like behaviors (anhedonia, behavioral despair, motor retardation, and poor spatial memory), and the proliferation of hippocampal stem cells was tested by BrdU immunohistochemistry. The stress and inflammatory responses were assayed by measuring IL-RA, NF-κB, and p-iκB expression by Western blot and IL-1ß production by ELISA. Direct and indirect effects of GAS on NSC viable cell number were examined in vitro by WST-1 and BrdU assays. It was found that GAS (200 mg/kg daily) reversed all tested depression-like behaviors in CUS model rats and up-regulated NSCs proliferation in the hippocampus. Enhanced expression of p-iκB, NF-κB, and IL-1ß by CUS was also reversed by GAS. Moreover, in vitro experiments revealed that GAS alone did not increase the viability of NSCs but protected them from IL-1ß-induced damage. These results support the antidepressant and neuroprotective effects of GAS, and GAS may reduce depression-like behaviors by protecting hippocampal NSCs against the proinflammatory cytokine IL-1ß.

Gastrodin ameliorates depressive-like behaviors and up-regulates the expression of BDNF in the hippocampus and hippocampal-derived astrocyte of rats.

Gastrodin (GAS), a main constituent of a Chinese herbal medicine Tian ma, has been shown to be effective in treating various mood disorders. The purpose of the present study was to assess the effects of GAS on alleviating depressive-like behaviors in a rat model of chronic unpredictable stress (CUS) and regulating the expression of BDNF in the hippocampus and hippocampal-derived astrocyte from Sprague-Dawley (SD) rats. Following CUS, rats were intraperitoneally administered gastrodin (50, 100, or 200 mg/kg daily) or vehicle for 2 weeks. Rats were then experienced sucrose preference test and forced swim test. The expressions of GFAP and BDNF in the hippocampus were evaluated. In addition, hippocampal astrocytes were isolated from neonatal SD rats and exposed to different concentrations of GAS (sham, 5, 10, 20, 50 and 100 µg/mL) for 48 and 72 h before the cell viability and the levels of pERK1/2 and BDNF were analyzed. Furthermore, the cell viability was also tested after exposure to serum-free condition that contain different concentrations of GAS for 48 and 72 h. GAS administration (100 and 200 mg/kg daily) reversed depressive-like behaviors in rats exposed to CUS paradigm and restored the expression of GFAP and BDNF in the hippocampus. Moreover, in vitro experiments revealed that GAS did not increase the cell viability of astrocytes but protected it from 72 h's serum-free damage at the dosage 20 µg/mL. Increased levels of ERK1/2 phosphorylation and BDNF protein were also observed after GAS (20 µg/mL) treatment for 72 h. These results indicate that gastrodin possesses antidepressant effect. The changes of the astrocyte activation and the level of BDNF may play a critical role in the pharmacological action of GAS.

Rhynchophylline attenuates LPS-induced pro-inflammatory responses through down-regulation of MAPK/NF-κB signaling pathways in primary microglia.

Excessive activation of microglial cells has been implicated in various types of neuroinflammation. Suppression of microglial activation would have therapeutic benefits, leading to the alleviation of the progression of neurodegeneration. In this study, the inhibitory effects of rhynchophylline (RIN), a tetracyclic oxindole alkaloid component isolated from Uncaria rhynchophylla (Miq.) Jacks., on the production of pro-inflammatory mediators were investigated in lipopolysaccharide (LPS)-stimulated microglia. The results showed that RIN markedly reduced the production of nitric oxide (NO), prostaglandins E(2) (PGE(2) ), monocyte chemoattractant protein (MCP-1), tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in LPS-activated microglia. The mRNA expression levels of iNOS and COX-2 were also depressed by RIN in a concentration-dependent manner. Further studies revealed that RIN blocked IκBα phosphorylation and degradation, inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs). In summary, these data suggest that RIN suppresses inflammatory responses of microglia and may act as a potential therapeutic agent for various neurodegenerative diseases involving neuroinflammation.

Free and Easy Wanderer Plus (FEWP), a polyherbal preparation, ameliorates PTSD-like behavior and cognitive impairments in stressed rats.

Free and Easy Wanderer Plus (FEWP) is a well-known traditional Chinese medicine that has been shown to be effective in treating various mood disorders. The purpose of the present study was to determine whether FEWP could ameliorate stress-associated behavior in rats. Following the exposure to enhanced single prolonged stress (ESPS) paradigm, consisting of 2-hr constraint, 20-min forced swimming, ether-induced loss of consciousness, and an electric foot shock, animals were administered orally with FEWP (2.5, 5, or 10mg/kg daily) or vehicle for 2 weeks. Animals were then tested in the open field, elevated plus-maze, and Morris water maze. ESPS exposure resulted in pronounced anxiety-like behavior, without impairing locomotor activity, as indicated by significant decreases of time spent and number of entries into open arms in the elevated plus-maze test, and unaltered distance traveled in the open field test compared to unexposed animals. ESPS-exposed animals also displayed marked cognitive impairments, with significant increases of distance traveled and the escape latency to the underwater platform, and a striking decrease of time spent in the target quadrant with and without the removal of the platform in the water maze test. However, repeated treatment with FEWP, particularly at higher doses, reversed the aforementioned behavioral values in the elevated plus-maze and water maze tests to the levels similar to unexposed animals. These results indicate that FEWP possesses anxiolytic and cognition-improving effects and may be an effective herbal preparation for the treatment of stress-associated conditions, such as posttraumatic stress disorder (PTSD).