Nature against depression.

Depression is a major health problem currently recognized as a leading cause of morbidity worldwide. In the United States alone, depression affects approximately 20% of the population. With current medications suffering from major shortcomings that include slow onset of action, poor efficacy, and unwanted side effects, the search for new and improved antidepressants is ever increasing. In an effort to evade side effects, people have been resorting to popular traditional herbal medicines to relieve the symptoms of depression, and there is a need for more empirical knowledge about their use and effectiveness. This review provides an overview of the current knowledge state regarding a variety of natural plant products commonly used in depression. Herbal medicines discussed that have been used in clinical trials for the treatment of mild to moderate depression states include the popular St. John's wort, saffron, Rhodiola, lavender, Echium, and the Chinese formula banxia houpu. In addition, new emerging herbal products that have been studied in different animal models are discussed including Polygala tenuifolia, the traditional Chinese herbal SYJN formula, gan mai da zao, and Cannabis sativa constituents. A comprehensive review of the chemical, pharmacological, and clinical aspects of each of the reviewed products is provided. Finally, recent preclinical studies reporting the antidepressant action of marine-derived natural products are discussed at the end of the review.

Effect of cortisol and urea on flavin monooxygenase activity and expression in rainbow trout, Oncorhynchus mykiss.

Expression of flavin-containing monooxygenase(s) (FMO) correlates with salinity exposure in certain species of euryhaline fish, such as the rainbow trout, Oncorhynchus mykiss. The mechanism(s) by which salinity regulates FMO is unclear. Adult rainbow trout were infused through the dorsal aorta with either cortisol or urea. At 500 ng/ml, cortisol caused a significant increase in FMO-catalyzed thiourea oxidase activity in gill and liver microsomes. FMOI expression, however, was significantly increased by the high cortisol dose only in gill microsomes. The levels of TMAO and urea were not altered by cortisol. In the liver, urea infusion caused an increase in hepatic FMO activity. FMO expression and activity correlated with elevated tissue urea levels, but TMAO concentrations were not related. These results indicate that FMO expression and activity may be partially controlled by the osmoregulatory/stress hormone. cortisol, and concentrations of the organic osmolyte, urea, in the rainbow trout.

Characterization of salinity-enhanced toxicity of aldicarb to Japanese medaka: sexual and developmental differences.

The effects of salinity, gender, and development on the acute toxicity of aldicarb were examined in the euryhaline fish, Japanese medaka (Oryzias latipes). The 96-h median lethal concentrations (LC50s) at 1.5 parts per thousand (per thousand) salinity were not significantly different between adults and juveniles but larvae were significantly more sensitive to aldicarb. A two-week exposure to increased salinity significantly enhanced the toxicity of 0.5 ppm aldicarb to both sexually mature male and female medaka. After 48 h of aldicarb exposure, mortality significantly increased (p < 0.05) in males from 13+/-5.7% at 1.5 per thousand, salinity to 56+/-5.7% at 20 per thousand; in females mortality significantly increased (p < 0.01) from 17+/-5.7% to 76+/-5.6%. A time-course study was conducted in which muscle acetylcholinesterase (AChE) inhibition was monitored after exposure to aldicarb. In general, AChE in females was inhibited to a greater degree at 12.0 and 20.0 per thousand salinity regimens than AChE in males. Muscle AChE in females residing at 20.0 per thousand was inhibited 93+/-3.3% by 8 h of exposure to 0.95 ppm aldicarb, whereas in males the maximum inhibition was 80+/-7.4% after 8 h of exposure to 0.86 ppm aldicarb at 20 per thousand salinity. These results indicate that environmental factors, such as salinity, in addition to gender and development, have significant impacts on the acute toxicity of aldicarb to Japanese medaka.

Effects of the oxidant potassium permanganate on the expression of gill metallothionein mRNA and its relationship to sublethal whole animal endpoints in channel catfish.

Potassium permanganate is an oxidant heavily used in fish culture. The effects of this compound were examined utilizing molecular (Metallothionein) and whole animal endpoints following an 8-week exposure to nominal concentrations of 0.5 (daily) and 1.0 and 2.0 mg/L (on alternate days) of potassium permanganate (PM). In order to measure MT, a complementary DNA clone of metallothionein (MT) was cloned and sequenced from the liver of channel catfish treated with a single injection of cadmium chloride (10 mg/kg). The cDNA was obtained by reverse transcriptase polymerase chain reaction (RT-PCR), using 3' rapid amplification of cDNA ends (RACE) technique. No significant correlation was observed with gill MT expression or sublethal endpoints indicative of toxicity (weight, length, condition index [CI], or liver somatic index [LSI). MT mRNA expression in gill was significantly reduced only after 8 weeks in the 2.0 mg/L treatment. Decreases in CI were observed in males at all time points after 4 weeks, at the 2.0 mg/L treatment concentration, with a NOEC of 1 mg/L. Reductions in LSI that were not dose dependent were also observed in both males and females throughout the 8-week study and no consistent reduction in weight gain or length was observed. These data demonstrate that minimal changes in sublethal effects occur in fish following 0.5-2.0 mg/L PM treatment after 4 weeks, but recovery from adverse effects is observed by 8 weeks, suggesting that acute (typically less than 1 week) treatment of channel catfish with PM would not significantly affect fish health.

In vitro sulfoxidation of aldicarb by hepatic microsomes of channel catfish, Ictalurus punctatus.

The carbamate pesticide, aldicarb, demonstrates significant acute toxicity in mammals, birds, and fish, and is readily biotransformed by most organisms studied. Metabolic products of aldicarb include the more toxic sulfoxide and the less toxic sulfone as two of the major products. Both the cytochrome P450 (CYP) and the flavin monooxygenase systems (FMO) are involved in this process. This study examined the capacities of liver microsomes of male channel catfish (Ictalurus punctatus), which lack FMO, to biotransform aldicarb in vitro. In addition, the acetylcholinesterase inhibitory potencies of aldicarb and its sulfoxide and sulfone derivatives were determined. For metabolism studies, incubations of [14C]-aldicarb (0.1mM) were carried out for up to 15-90 min using 1.0 mg/mL of hepatic microsomal protein. Total NADPH- dependent biotransformation was low (< 3.0% conversion to polar metabolites), and was inhibited by carbon monoxide. The only metabolite detected was aldicarb sulfoxide (Kmapp = 53.8 +/- 25.3 microM; Vmaxapp = 0.040 +/- 0.007 nmol/min/mg). Treatment of fish with the CYP modulators beta-naphthoflavone (BNF, 50 mg/kg) and ethanol (EtOH, 1.0% aqueous) had no effect on sulfoxide production. No correlation existed between CYP isoform expression (determined by western blot) and aldicarb sulfoxidation rates, suggesting the involvement of an unmeasured CYP isoform or involvement of several isoforms with low specificity. This study indicates that a low rate of bioactivation of aldicarb to aldicarb sulfoxide may be responsible for the resistance of channel catfish to aldicarb toxicity relative to that of other piscine species.

Potential mechanisms of the enhancement of aldicarb toxicity to Japanese medaka, Oryzias latipes, at high salinity.

In an attempt to understand underlying mechanism(s) of salinity-induced aldicarb toxicity in Japanese medaka (Oryzias latipes), aldicarb uptake, biotransformation, and its effect on acetylcholinesterase (AChE) were examined. Salinity had no effect on aldicarb uptake. However, gill microsomal flavin-containing monooxygenase (FMO) activity and a 57-kDa FMO1-like protein increased as the salinity was raised from 0.15 to 2.0%. Sulfoxidation of 14C-aldicarb by liver and gill microsomal incubations showed ninefold and 1.8-fold increases, respectively, as the salinity was raised from 0.15 to 2.0%. Formation of aldicarb sulfoxide was not affected by incubation with carbon monoxide, indicating that cytochrome P450 (CYP450) was not a primary pathway in the formation of the sulfoxide. Muscle AChE activity showed no significant relationship with salinity, although the IC50 of aldicarb to muscle AChE differed significantly between 6.21 +/- 1. 253 and 2.97 +/- 0.597 microM for 0.15 and 2.0% salinity, respectively. Aldicarb sulfoxide was 40 times more potent than aldicarb in inhibiting muscle AChE in Japanese medaka. Based on these results, we conclude that salinity-induced enhancement of aldicarb toxicity to Japanese medaka might be partly attributed to the upregulation of FMO(s), which, in turn, increase the biotransformation of aldicarb to aldicarb sulfoxide, which is a more potent inhibitor of AChE than aldicarb. In addition, salinity also seems to potentiate the anticholinesterase activity of aldicarb (the parent) through an unknown mechanism.

Down regulation of hepatic flavin-containing monooxygenase activity by 17 beta-estradiol in rainbow trout (Oncorhynchus mykiss).

Expression of flavin-containing monooxygenase (FMO) activity has been shown to be directly correlated with salinity in euryhaline fish. Sex steroids play a significant role in osmoregulation in euryhaline fish. The effects of 17 beta-estradiol and testosterone on hepatic FMO activity (N,N-dimethylaniline N-oxygenase; thiourea S-oxygenase) and expression was examined in 6-month-old and 1-year-old rainbow trout (Oncorhynchus mykiss). Fish were treated with 3 mg/kg of each compound on days 1, 4, 7, 10, 13, and 15 with euthanasia on day 19. Treatment of 6-month-old and 1-year-old female rainbow trout with testosterone or estradiol significantly reduced FMO-catalyzed DMA N-oxygenase activity in liver. However, testosterone treatment failed to significantly alter thiourea S-oxidase in 1-year-old males, although 17 beta-estradiol significantly reduced FMO activity. These results parallel those of studies showing repressive effects of sex steroids on branchial chloride cells and Na+K+ATPase of salmonids and provide further evidence of a role for FMO in teleost osmoregulation.