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Update on dietary supplements for depression.

When does an alternative therapy become mainstream? When enough studies show it's safe and effective. For mild to moderate depression, a handful of supplements seem headed in that direction.

Depression↗

[The influence of extraction method on the quality of the liquid extract of St John's wort].

The liquid extract of St John's wort was produced by methods of remaceration, percolation, and repercolation. Extraction by remaceration did not result in the complete extraction of herbal raw material; therefore, this method was rejected. Extraction by percolation requires the process of evaporation of the weak extract to take place, during which the active substances can decompose. This method was found to be not efficient. The liquid extract of St John's wort was produced by the complete-cycle repercolation: by dividing the raw material into unequal parts, and by dividing it into equal parts. It has been found that the highest concentration of hypericine, flavonoids and the dry remainder is obtained in the extract produced by repercolation with raw material divided into equal parts. The optimal method of extraction for St John's wort has been confirmed to be the complete-cycle repercolation with raw material divided into equal parts. In the course of the experiment, it was observed that the release of active substances from the raw material is influenced by the density of raw material filling. The optimal density of raw material filling has been found to be 0.11 g/cm3. The most suitable usage period was found to be 2 years.

Anthracenes↗

Effect of prototypical inducing agents on P-glycoprotein and CYP3A expression in mouse tissues.

P-glycoprotein (P-gp) and CYP3A have considerable overlap in inducers in vitro. Characterizing P-gp induction in vivo and potential coregulation with CYP3A are important goals for predicting drug interactions. This study examined P-gp expression in mouse tissues and potential coinduction with CYP3A following oral treatment with 1 of 7 prototypical inducing agents for 5 days. P-gp expression in brain or liver was not induced by any treatment as determined by Western blot, whereas dexamethasone, pregnenolone-16alpha-carbonitrile (PCN), St. John's wort (SJW), and rifampin induced hepatic CYP3A expression. In intestine, rifampin and SJW induced P-gp expression 3.7- and 1.6-fold and CYP3A 3.5- and 2.4-fold, respectively, whereas dexamethasone and PCN induced CYP3A only. These observations suggest that P-gp in mouse small intestine is inducible by some, but not all, CYP3A inducers, whereas P-gp expression in liver or brain is not readily induced. Intriguingly, rifampin and SJW, both activators of the human pregnane X receptor (PXR), induced CYP3A in both liver and intestine but induced P-gp only in intestine, whereas PCN, an activator of murine PXR, did not induce P-gp in any tissue. Rifampin disposition was evaluated, and hepatic exposure to rifampin was comparable to intestine; in contrast, brain concentrations were low. Overall, these observations demonstrate that P-gp induction in vivo is tissue-specific; furthermore, there is a disconnect between P-gp induction and CYP3A induction that is tissue- and inducer-dependent, suggesting that PXR activation alone is insufficient for P-gp induction in vivo. Tissue-specific factors and inducer pharmacokinetic/pharmacodynamic properties may underlie these observations.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

St John's wort and depression: slight efficacy at best, many drug interactions.

(1) St John's wort has been widely used for centuries as a herbal remedy. Dozens of trials, of variable quality, have examined the therapeutic value of St John's wort. Published meta-analyses show that St John's wort extracts are more effective than placebo in patients with mild and moderate depression. (2) Trials show that St John's wort is about as effective as tricyclic and serotonin reuptake inhibitor antidepressants. (3) There is insufficient evidence to determine the efficacy of St John's wort in patients with more severe depression. (4) Few, mostly minor adverse effects have been reported, but there may be a small risk of serotonin syndrome and cutaneous photosensitisation. (5) Some components of St John's wort interfere with CYP3A4, one of the main cytochrome P450 isoenzymes. CYP3A4 is involved in the metabolism of many commonly used drugs. St John's wort reduces the efficacy of several drug groups including: immunosuppressants (risk of graft rejection), oral contraceptives (risk of pregnancy), oral anticoagulants (risk of thrombosis), and HIV protease inhibitors. It can also reduce the bioavailability of digoxin. (6) In practice, St John's wort is an inappropriate treatment for severe depression. It is, however, an acceptable option for short-term management of transient depressed mood when there is no risk of drug interactions and when the patient is properly informed of this risk. (7) In short, the risk-benefit balance of St John's wort is no better than that of standard antidepressants, mainly because of the risk of drug interactions.

Antidepressive Agents↗

[Potential risks, adverse effects and drug interactions associated with herbal medicine in dental patients].

Herbal medicine is an increasingly common form of alternative therapy in the United States. Most herbal products are considered dietary supplements and thus are not regulated as medicines. They are marketed without prior approval of their efficacy and safety by the Food and Drug Administration (FDA). Some herbal medications have potentially harmful side effects as well as adverse interactions with conventional drugs. The adverse reactions involve all systems, age groups and severity. It is important for dentists and other health care providers to obtain adequate information as to what herbal medications their patients are taking. It is also necessary for professionals to acquire knowledge regarding herbal medications as to their use and to educate their patients about the risk-benefit and potential interactions these medications may have with over-the-counter and prescription drugs. The purpose of this article was to review the literature on the potential risks of commonly used herbal medications: Ginkgo Biloba, St. John's Wort, Ginseng, Echinacea, Saw Palmetto, Garlic, Kava and Ephedra.

Echinacea↗

Nelumbinis Semen reverses a decrease in 5-HT1A receptor binding induced by chronic mild stress, a depression-like symptom.

Depression is associated with a dysfunctional serotonin (5-hydroxytryptamine; 5-HT) system. More recently, several lines of evidence suggest that an important factor in the development of depression may be a deficit in the function and expression of 5-HT1A receptors. The present study assessed if Nelumbinis Semen (N.s.) had an anti-depression effect through reversing a decrease in 5-HT1A receptor binding in rats with depression-like symptoms induced by chronic mild stress. Using a 5-HT1A receptor binding assay, with a specific 5-HT1A receptor agonist, 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino) tetralin), the mechanism of the anti-depression effect of N.s. on rats was investigated, and the effects compared with two well-known antidepressants, Hyperium Perforatum (St. Johns Wort) and fluoxetine (Prozac). Animals were divided into five groups: the normal (N) group without chronic mild stress (CMS), the control (C) group under CMS for 8 weeks, the Nelumbinis Semen (N.s.) treatment group under CMS for 8 weeks, the Hyperium Perforatum (H.p.) treatment group under CMS for 8 weeks and finally, the fluoxetine (F) treatment group under CMS for 8 weeks. Each treatment was administered to rats during the last 4 weeks of the 8-week CMS. A sucrose intake test was performed to test the anti-depression effect of N.s. The N.s. treatment significantly reversed the decreased sucrose intake under CMS (P < 0.05 compared to control group under CMS). In the CA2 and CA3 regions of the hippocampus, both N.s. and H.p. reversed the CMS-induced decrease in 5-HT1A receptor binding. In the I to II regions of the frontal cortex, N.s. and H.p. also reversed the CMS-induced decrease in 5-HT1A receptor binding, and even showed a significant increase in 5-HT1A receptor binding compared to the F treatment group (N.s. vs. P, p < 0.05, H.p. vs. P, p < 0.05). However, in the hypothalamus, all treatments reversed the CMS-induced decrease in 5-HT1A receptor binding. This reversal effect of N.s. on the decrease in 5-HT1A receptor binding in the frontal cortex, hippocampus and hypothalamus of rat brains was very similar to that of H.p, but different from that of F. It is concluded that N.s. presents an anti-depression effect through enhancing 5-HT1A receptor binding.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Analysis of responses to St. John's Wort in the feline pulmonary vascular bed.

OBJECTIVE: To test the hypothesis that St. John's wort induces a depressor response in the feline pulmonary vascular bed and identify the pathways involved in the mediation or modulation of these effects. DESIGN: Prospective vehicle controlled study. SETTING: University research laboratory. SUBJECTS: Intact chest preparation; adult mongrel cats. INTERVENTIONS: In separate experiments, the effects of L-N5-(1-Iminoethyl) ornithine hydrochloride (L-NIO), a nitric oxide synthase inhibitor, glibenclamide, an ATP-sensitive K+ channel blocker, meclofenamate, a non-selective cyclo-oxygenase (COX) inhibitor, nicardipine, a calcium channel blocker, bicuculline, a GABAA receptor antagonist, and saclofen, a GABAB antagonist, were investigated on pulmonary arterial responses of St. John's wort (SJW), pinacidil, an ATP-sensitive K+ channel activator, bradykinin, an inducer of nitric oxide synthase, 3-aminopropyl (methyl) phosphinic acid, hydrochloride (SKF-97541), a GABAB receptor agonist and muscimol, a GABAA receptor agonist. MEASUREMENTS AND MAIN RESULTS: Lobar arterial perfusion pressure and systemic pressure were continuously monitored, electronically averaged and permanently recorded. Under elevated tone conditions in the isolated left lower lobe vascular bed of the cat, SJW induced a dose-dependent vasodepressor response that was not significantly altered after administration of L-NIO, glibenclamide, meclofenamate or saclofen. Responses to SJW were significantly reduced after administration of either nicardipine or bicuculline. When the calcium channel blocker nicardipine was administered in addition to the GABA blocker bicuculline, there was near complete attenuation of the SJW-induced vasodepressor responses. CONCLUSIONS: The results of the present study suggest that SJW has potent vasodepressor activity in the pulmonary vascular bed of the cat and that this response is mediated or modulated by both a calcium channel and GABA receptor sensitive pathway.

Acetylcholine↗

Depressive disorders.

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Antidepressive Agents, Second-Generation↗