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Valeriana officinalis
Natural Encyclopaedia

Valerian

FAMILY: Valerianaceae.

HABITAT: It is common in damp undergrowth, at the edge of ditches and watercourses throughout Europe.

USED PART: the rhizome with the rootlets.

RECOMMENDED PHARMACEUTICAL PREPARATION: nebulised dry extract titrated in total sesquiterpene acids calculated as valerenic acid min. 0.42% (Italian Pharmacopoeia X). The daily dosage used in studies published in the literature is 4-6 mg/kg/day, divided into two doses, the last of which should be taken about 30 minutes before bedtime. The above-mentioned studies were done using the dry extract with the above-mentioned title for the most part.

CHEMICAL COMPOSITION: is a drug rich in substances of a terpenic nature, particularly sesquiterpenes and iridoids. The sesquiterpenes are acidic (valerenic acid, hydroxyvalerenic acid, acetoxyvalerenic acid), ketone (valeranone), alcoholic (maaliol, valerianol, kessyl alcohol) and aldehydic (valerenal) compounds. Valerenic acids are only present in Valeriana officinalis, but not in other species of the genus Valeriana. Iridoids are characteristic and typical of the species, and are lipophilic esters of triols derived from iridane. The potassium content ranges from 0.5 to 1.2 %, but these compounds are highly unstable and decompose rapidly, turning into unsaturated aldehydes such as baldrinal and isopropylbaldrinal. It also contains moderate amounts of essential oil, about 0.5 per cent of the dry drug weight, composed of both monoterpenes and sesquiterpenes.

THERAPEUTIC PROPERTIES:
Action on the central nervous system: is a drug active on the central nervous system, on which it exerts sedative and hypnoinductive action. In vivo studies in animal models actually show a decrease in locomotor activity, aggression and were generically tranquillising.
These properties have been attributed to valepotriates, but these are very labile compounds and are present in valerian extracts in very small quantities. Furthermore, they are destroyed by gastric juice, although the degradation products formed, such as baldrin, appear to have pharmacological activity on the central nervous system.
The sesquiterpenes also appear to have a central sedative action, possibly due in part to inhibition of GABA transaminase, which leads to an increase in this amino acid with potent sedative activity, and in part to the fact that these substances appear to be able to bind to brain receptors for benzodiazepines.
Studies have also been done on the ability of aqueous Valerian extract to influence the capture and/or release of GABA in synaptosomes isolated from the rat cerebral cortex. It has been noted that the drug inhibits capture and stimulates the release of GABA.
Very interesting is the observation that total valerian extract is able to compete with fluorodiazepam in binding to benzodiazepine receptors in the hamster brain. The intensity of this competition is about seven times greater for valepotriates and sesquiterpenes taken in isolation than for total valerian extract.
Even more recent data indicate that at low doses valerian promotes the binding of flunitrazepam to its receptors, while at higher doses it has an antagonistic effect on this binding.
Other data indicate that valerian stimulates GABA production by hippocampal cells and inhibits GABA recapture by synaptosomes.
Experiments in the rat have shown that sesquiterpenes, and in particular valerenic acid, significantly reduce the animal's motility through a depressant action on the central nervous system. This seems further confirmed by the fact that these substances enhance the central depressant action of barbiturates and prolong the sleep induced by these substances.
Also interesting is the observation that the Valerian phytocomplex may enhance the hypnotic action of melatonin on the central nervous system.
The effects on the central nervous system of the Valerian phytocomplex have also been compared to those of diazepam and chlorpromazine, and it has been noted that they are similar to those of these drugs, but their intensity is considerably less.
In this study, the action of valerian extract mediated by adenosine A1 receptors on postsynaptic potentials in pyramidal cells of the rat cingulate cortex was evaluated. It was observed that N(6)-cyclopentyladenosine (CPA, 0.01 - 10 muM), an A1 adenosine receptor agonist, inhibited postsynaptic potentials in a concentration-dependent manner. This inhibition was overridden by 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 0.1 muM), an adenosine A1 receptor antagonist. Valerian extract Ze 911 inhibited postsynaptic potentials in a concentration-dependent manner starting at a concentration of 0.1 mg/ml in the presence of an adenosine A2 receptor antagonist such as 1,3,7-trimethyl-8-(3-chlorostyril) xanthine (CSC, 0.2 muM). The maximum inhibition occurred at a concentration of 10 mg/ml was completely antagonised by DPCPX at a concentration of 0.1 muM. These data indicate that activation of the A1 adenosine receptor is involved in the pharmacological effect of valerian.
An in vitro study examined the effects of three valerian extracts (methanolic, ethanolic and ethylacetic) on postsynaptic potentials in cortical neurons of the cingulate cortex. It was seen that the methanolic extract induced a strong inhibition of the aforementioned potentials at concentrations between 0.1 and 15 mg/ml, while the ethanolic extract had very little effect. The inhibition induced by the methanolic extract was abolished by 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 0.1 microm), an A1 receptor antagonist for adenosine. The ethanolic extract increased postsynaptic potentials, and this effect was blocked by picrotoxin, a selective GABA-A receptor antagonist. The study indicates that the activation of A1 receptors for adenosine and GABA-A receptors is mediated by different compounds present in the valerian phytocomplex, and that both of these mechanisms are useful for the sedative and hypnoinductive action of this drug.
A study in the rat evaluated the effect of three different valerian extracts (45% methanol or 70% ethanol or 35% ethanol) on the central nervous system, particularly with regard to sedative and anxiolytic action. It was seen that even at very high doses of 500 mg/kg/day none of the extracts tested had a sedative action, but the methanolic and ethanolic 35% extracts exhibited a clear anxiolytic action at doses between 100 and 500 mg/kg/day. In addition, the 36% ethanol extract also showed antidepressant action in the forced swimming test. None of the extracts studied had a muscle relaxant action at the doses tested. The study indicates that the methanolic and especially the 35% ethanolic extract of valerian have a significant anxiolytic and partly also antidepressant action in the rat.
An in vitro study evaluated the antioxidant action of valerian on brain tissue. In particular, we examined the effect of this drug at concentrations between 0 and 60 mug/ml on lipoperoxidation induced by various pro-oxidants such as quinolinic acid, 3-nitropropionic acid, sodium nitroprusside, iron sulphate and Fe2+EDTA in a brain tissue homogenate. The effect of valerian on deoxyribose degradation and ROS production was also examined. Valerian extract was found to inhibit the formation of thiobarbituric acid caused by all the above-mentioned pro-oxidants in a concentration-dependent manner. It also caused a significant reduction in lipoperoxidation and deoxyribose degradation. ROS production was also inhibited by valerian extract. The study indicates that this extract reduces pro-oxidant-induced lipoperoxidation and ROS formation in brain tissue, and that this effect may be important in explaining valerian's pharmacological action on the CNS.

Spasmolytic action: Both valepotriates and sesquiterpenes are endowed with spasmolytic action on the smooth muscles of the gastrointestinal tract. Valepotriates and valeranone in the essential oil have been shown to cause a reduction in rhythmic contractions of the guinea pig ileum in vivo and reduce potassium- and BaCl2-induced contractions in vitro.
Valerian is also able to consistently reduce potassium-induced smooth muscle fibrocell contractions in vitro, even when the autonomic receptors are blocked by specific receptors, with an efficacy similar to that of papaverine in inhibiting BaCl2 contractions. Therefore, this drug relaxes smooth muscle probably acting as a musculotropic agent and not interacting with autonomic nervous system receptors.

Main indications: anxiety syndrome, sleep disorders.

Prevalent action: sedative-anxiolytic and hypnoinductive.

Other actions: visceral antispasmodic.

SIDE EFFECTS: Recently, some cases of delirium and supraventricular tachycardia-type cardiac complications with fibrillatory arrhythmias have been reported in patients taking high doses (900 mg/day) of titrated valerian dry extract for prolonged periods of time.

CONTRAINDICATIONS: At high doses it may cause moderate liver damage, with moderate elevation of transaminases and GT gamma.
At high doses (12 mg/kg) these substances can cause a delay in ossification in the foetus, without altering the duration and course of pregnancy. No significant changes were observed in the histological appearance of the animal's various organs and in the values of the haematochemical tests performed. It is therefore contraindicated during pregnancy and lactation. Do not administer in children under 6 years of age.

DRUG INTERACTIONS: Valerian should not be used in conjunction with barbiturates because excessive sedation may occur.
A study in the rat assessed whether the combination of valerian and haloperidol could induce alterations in liver and/or kidney function. Valerian alone had no toxic effect, while haloperidol alone reduced reduced glutathione levels in the liver but not in the kidney. The combination of the two substances caused an increase in lipoperoxidation and dichlorofluorescein-reactive substances in liver tissue, without altering the activity of endogenous antioxidant enzymes in the liver and kidney. Valerian and haloperidol alone did not alter the activity of the renal enzyme delta aminolevulinate dehydratase, whereas the two drugs in combination caused its inhibition. Plasma transaminase levels were higher in rats treated with haloperidol alone and even higher in those receiving combination therapy. The study indicates that valerian given together with haloperidol may potentiate its hepato- and nephrotoxic action (51).

TOXICOLOGICAL DATA: The acute toxicity of an ethanolic extract of valerian administered intraperitoneally to the rat is very low at 3.3 g/kg. Doses of 600 mg/kg also administered intraperitoneally for 45 consecutive days did not cause changes in the weight of the animals or in their blood and urinary biochemical parameters. The administration of 400 mg/kg of pure valerenic acid intraperitoneally to rats resulted in the death of 6 out of 7 animals due to the onset of convulsions.

 

It can be found in Vagonotte® e Vagonotte® Mel


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