The antidepressant effect of secoisolariciresinol, a lignan-type phytoestrogen constituent of flaxseed, on ovariectomized mice.

Secoisolariciresinol (SECO) is a natural lignan-type phytoestrogen constituent mainly found in flaxseed. It can be metabolized in vivo to mammalian lignans of enterodiol and enterolactone, which have been proven to be effective in relieving menopausal syndrome. Depression is one of the most common symptoms of menopausal syndrome, and is currently treated with estrogen replacement and antidepressant therapy. However, due to the serious side-effects of such agents, there are urgent needs for safer and more tolerable treatments. In this paper, using two classical depression models, the forced swimming test and the tail suspension test, we report the antidepressant effect of SECO on ovariectomized (OVX) mice by intragastric administration for 14 consecutive days at doses of 5, 10 and 20 mg/kg. The results showed that SECO (10 mg/kg) treatment could significantly reduce the duration of immobility of OVX mice in these two models compared with the control group (OVX mice + vehicle), which was similar to the positive control imipramine. In addition, SECO treatment could substantially increase brain monoamine (norepinephrine and dopamine) levels in OVX mice. The present studies showed that SECO can reverse depressive-like behavior and exhibit monoamine-enhancing effects.

Production of enterodiol from defatted flaxseeds through biotransformation by human intestinal bacteria.

BACKGROUND: The effects of enterolignans, e.g., enterodiol (END) and particularly its oxidation product, enterolactone (ENL), on prevention of hormone-dependent diseases, such as osteoporosis, cardiovascular diseases, hyperlipemia, breast cancer, colon cancer, prostate cancer and menopausal syndrome, have attracted much attention. To date, the main way to obtain END and ENL is chemical synthesis, which is expensive and inevitably leads to environmental pollution. To explore a more economic and eco-friendly production method, we explored biotransformation of enterolignans from precursors contained in defatted flaxseeds by human intestinal bacteria. RESULTS: We cultured fecal specimens from healthy young adults in media containing defatted flaxseeds and detected END from the culture supernatant. Following selection through successive subcultures of the fecal microbiota with defatted flaxseeds as the only carbon source, we obtained a bacterial consortium, designated as END-49, which contained the smallest number of bacterial types still capable of metabolizing defatted flaxseeds to produce END. Based on analysis with pulsed field gel electrophoresis, END-49 was found to consist of five genomically distinct bacterial lineages, designated Group I-V, with Group I strains dominating the culture. None of the individual Group I-V strains produced END, demonstrating that the biotransformation of substrates in defatted flaxseeds into END is a joint work by different members of the END-49 bacterial consortium. Interestingly, Group I strains produced secoisolariciresinol, an important intermediate of END production; 16S rRNA analysis of one Group I strain established its close relatedness with Klebsiella. Genomic analysis is under way to identify all members in END-49 involved in the biotransformation and the actual pathway leading to END-production. CONCLUSION: Biotransformation is a very economic, efficient and environmentally friendly way of mass-producing enterodiol from defatted flaxseeds.

[Antidepressant effect of acute administration with Jianyate Hao (JYTH) and its possible mechanism].

OBJECTIVE: Jianyate Hao (JYTH) , a traditional Chinese medicine formula, which has been used effectively to treat depression in the past ten years. The purpose of this study was to explore the antidepressant effect of acute administration with JYTH and its possible mechanism. METHOD: the animals behavioral despair models of depression, the tail suspension and forced swimming tests, were used to explore the antidepressant effects of JYTH. In addition, the locomotor activity test was used to detect the change of locomotor activity. The monoamine oxidase activity in the mouse brain was also determined by using fluorospectrophotometry. RESULT: JYTH (17.5, 35, 70 g x kg(-1), ig) could decrease the duration of immobility in both tail suspension and forced swimming tests, and the effect of JYTH (35 g x kg(-1) ig) was resembling imipramine (10 mg x kg(-1), ip) in relieving depression. And the effective doses (17.5, 35, 70 g x kg(-1), ig) did not alter locomotion activity. Moreover, JYTH (35 g x kg(-1), ig) was found to inhibit monoamine oxidase activity in the mouse brain. CONCLUSION: These findings suggest that JYTH exerts antidepressant effect in animals behavioral despair tests and the underlying mechamism may involve the inhibition monoamine oxidase activity in the mouse brain.

[Effects of jieyuwan on HPA axis and immune system in chronic stress models in rats].

OBJECTIVE: To observe the effects of jieyuwan on neuroendocrine-immune of chronic unpredictable stress rats, for identifing its mechanism of action. METHOD: Animals were randomly assigned to six groups: one non-stressed (control) group, one stressed group (CUS + vehicle) , three treatment groups (CUS + Jieyuwan 53, 106, 212 mg x kg(-1), respectively), and one group for imipramine (CUS + imipramine 10 mg x kg(-1)). We used the chronic unpredictable stress (CUS) test in rats to investigated the effects of chronic oral administration (21 days) of Jieyuwan and imipramine (ip) on the sucrose consumption, the relative weight of adrenal and thymus, the concentration of serum corticosterone, adrenocorticotropic hormone, TNF-alpha, IL-1beta measured by ELISA. RESULT: Our results showed that Sprague-Dawley rats subjected to CUS exhibited increased adrenal weight, reduction in thymus weight, less sucrose consumption, and synchronized with higher serum corticosterone, adrenocorticotropic hormone, TNF-alpha, IL-1beta concentration. Chronic treatment with Jieyuwan (53, 106, 212 mg x kg(-1), po, 21 days) could improve locomotion of stressed rat sucrose consumption, turn over the high levels of serum corticosterone, adrenocorticotropic hormone, TNF-alpha, IL-1beta concentration. CONCLUSION: The therapeutic actions of jieyuwan, in some degree, may be related with indirect or direct effects on HPA axis and immune system.

Antidepressant effects of curcumin in the forced swim test and olfactory bulbectomy models of depression in rats.

Curcuma longa is a major constituent of Xiaoyao-san, the traditional Chinese medicinal formula, which has been used to effectively manage stress and depression-related disorders in China. Curcumin is the active component of curcuma longa, and we hypothesized that curcumin would have an influence on depressive-like behaviors. The purpose of the present study was to confirm the putative antidepressant effect of chronic administrations of curcumin (1.25, 2.5, 5 and 10 mg/kg, p.o.) in the forced swimming test and bilateral olfactory bulbectomy (OB) models of depression in rats. In the first study, chronic treatment with curcumin (14 days) reduced the immobility time in the forced swimming test. In the second experiment, curcumin reversed the OB-induced behavioral abnormalities such as hyperactivity in the open field, as well as deficits in step-down passive avoidance. In addition, OB-induced low levels of serotonin (5-HT), noradrenaline (NA), high 5-hydroxyindoleacetic acid (5-HIAA) and 4-dihydroxyphenylacetic acid (DOPAC) in the hippocampus were observed, and were completely reversed by curcumin administration. A slight decrease in 5-HT, NA and dopamine (DA) levels was found in the frontal cortex of OB rats which was also reversed by curcumin treatment. These results confirm the antidepressant effects of curcumin in the forced swim and the OB models of depression in rats, and suggest that these antidepressant effects may be mediated by actions in the central monoaminergic neurotransmitter systems.

The effects of curcumin on depressive-like behaviors in mice.

Curcuma longa is a major constituent of Xiaoyao-san, the traditional Chinese medicinal formula, which has been used effectively to treat depression-related diseases in China. There is no information available about the antidepressant activity of curcumin, the active component of curcuma longa. In the present study, we analyzed the effects of curcumin on depressive-like behaviors in mice, using two animal models of depression. Our results showed that curcumin treatment at 5 and 10 mg/kg (p.o.) significantly reduced the duration of immobility in both the tail suspension and forced swimming tests. These doses that affected the immobile response did not affect locomotor activity. In addition, the neurochemical assays showed that curcumin produced a marked increase of serotonin and noradrenaline levels at 10 mg/kg in both the frontal cortex and hippocampus. Dopamine levels were also increased in the frontal cortex and the striatum. Moreover, curcumin was found to inhibit monoamine oxidase activity in the mouse brain. These findings suggest that the antidepressant-like effects of curcumin may involve the central monoaminergic neurotransmitter systems.

Tetrandrine, a bisbenzylisoquinoline alkaloid from Chinese herb Radix, augmented the hypnotic effect of pentobarbital through serotonergic system.

This is the first study of hypnotic activity of tetrandrine (a major component of Stephania tetrandrae) in mice by using synergism with pentobarbital as an index for the hypnotic effect. The results showed that tetrandrine potentiated pentobarbital (45 mg/kg, i.p.)-induced hypnosis significantly by reducing sleep latency and increasing sleeping time in a dose-dependent manner, and this effect was potentiated by 5-hydroxytryptophan (5-HTP). In the subhypnotic dosage of pentobarbital (28 mg/kg, i.p.)-treated mice, tetrandrine (60 and 30 mg/kg, p.o.) significantly increased the rate of sleep onset and also showed synergic effect with 5-HTP. Pretreatment of p-chlorophenylalanine (PCPA, 300 mg/kg, s.c.), an inhibitor of tryptophan hydroxylase, significantly decreased pentobarbital-induced sleeping time and tetrandrine abolished this effect. From these results, it should be presumed that serotonergic system may be involved in the augmentative effect of tetrandrine on pentobarbital-induced sleep.

Inhibitory effects of tetrandrine on the serum- and platelet-derived growth factor-BB-induced proliferation of rat aortic smooth muscle cells through inhibition of cell cycle progression, DNA synthesis, ERK1/2 activation and c-fos expression.

Tetrandrine (TET) is a well known naturally occurred nonspecific Ca(2+) channel blocker. It has long been used for the treatment of arrhythmia, hypertension, and occlusive cardiovascular disorders. The objective of the present study was to investigate the effect of TET on the proliferation of primary cultured rat aortic smooth muscle cells (RASMCs). TET significantly inhibited both 10% fetal bovine serum (FBS) and 50 ng/ml platelet-derived growth factor (PDGF)-BB-induced proliferation, [(3) H] ]thymidine incorporation into DNA, and p42/p44 mitogen-activated protein kinase (ERK1/2) phosphorylation at the concentration of 1.0 and 5.0 microM. Flow cytometry analysis of DNA content in synchronized cells revealed blocking of the FBS-inducible cell cycle progression by TET. In accordance with these findings, TET 5 microM caused a 48% decrease in the early elevation of c-fos expression induced after 10% FBS addition. Furthermore, in contrast to its distinguishable higher potency of Ca(2+) antagonistic activity, verapamil showed lower potent antiproliferative activities than TET. These results suggest that TET can exert antiproliferative effects against mitogenic stimuli for RASMCs in vitro by a mechanism that involves the MAPK pathway, altering cell cycle progression, and the inhibitory action cannot be limited to its Ca(2+) modulation.

Fangchinoline inhibits rat aortic vascular smooth muscle cell proliferation and cell cycle progression through inhibition of ERK1/2 activation and c-fos expression.

Fangchinoline (FAN; a plant alkaloid isolated from Stephania tetrandrae) is a nonspecific Ca(2+) channel blocker. The objective of the present study was to investigate the effect of FAN on the growth factor-induced proliferation of primary cultured rat aortic smooth muscle cells (RASMCs). FAN significantly inhibited both 5% fetal bovine serum (FBS)- and 50ng/mL platelet-derived growth factor (PDGF)-BB-induced proliferation, [3H]thymidine incorporation into DNA and phosphorylation of extracellular signal-regulated kinase 1/2. In accordance with these findings, FAN revealed blocking of the FBS-inducible progression through G(0)/G(1) to S phase of the cell cycle in synchronized cells and caused a 62% decrease in the early elevation of c-fos expression induced after 5% FBS addition. Furthermore, significant antiproliferative activity of FAN is observed at concentrations below those required to achieve significant inhibition of Ca(2+) channels by FAN. These results suggest that FAN reduced both FBS- and PDGF-BB-induced RASMCs proliferation by perturbing cell cycle progression. This antiproliferative effect of FAN is dependent on the MAP kinase pathway, but cannot be limited to its Ca(2+) modulation.

In vitro inhibitory effects of bergenin and norbergenin on bovine adrenal tyrosine hydroxylase.

The aqueous extract of Mallotus japonicus (Euphorbiaceae) showed an inhibitory effect on bovine adrenal tyrosine hydroxylase (TH), the rate-limiting enzyme in the biosynthesis of catecholamine. The present study was undertaken to investigate the effects of bergenin and norbergenin, constituents of the aqueous extract of Mallotus japonicus on bovine adrenal TH. Bergenin and norbergenin inhibited the TH activity by 29.0% and 53.4% at a concentration of 20 microg/mL, respectively, and exhibited noncompetitive inhibition of TH activity with the substrate l-tyrosine. The inhibition of TH activity and the inhibitory effect of norbergenin was more potent than that of bergenin. From these results, it is presumed that bergenin and norbergenin may be the active components of Mallotus japonicus in inhibiting TH, and these inhibitory effects may be partially responsible for the clinical use of Mallotus japonicus in treating peptic ulcer by reducing the availability of dopa/dopamine in vivo.