What Essential Oils Potentiate Amphetamine Locomotor Effects

The roots of the plant contain essential oil, rich in sesquiterpenes and coumarins. Jatamansone or valeranone (Fig. 5.240) is the principal sesquiterpene. Other sesquiterpenes include nardostachone (Fig. 5.241), dihydrojatamansin, jatamansinol, jatamansic acid, jatamansinone, jatamansinol, oroseolol, oroselone, seselin, valeranal, nardostachyin, nardosinone, spirojatamol, jatamol A and B, calarenol, seychellene, seychelane, coumarin: jatamansin or xanthogalin. A new sesquiterpene acid, nardin and new pyranocoumarin: 2', 2'-dimethyl-3'-methoxy-3', 4'-dihydropyranocoumarin have been reported. An alkaloid, actinidine has been reported (Fig. 21.1).

21.3 Ethnopharmacology

Hepatoprotective activity: Pretreatment of rats with 800 mg/kg body wt of the 50% ethanolic extract of N. jatamansi demonstrated significant hepatoprotective activity against thioacetamide induced hepatotoxicity. Marked reduction in raised levels of serum transaminase and alkaline phosphatase was observed. Pretreatment of the animals with the extract further resulted in an increase in survival of rats intoxicated with LD90 dose of the hepatotoxic drug.

Fig. 21.1 Structure of Actinidine.

Cardio protective and hypolipidemic activity: Rats administered doxorubicin (15 mg/kg, i.p.) showed myocardial damage that was manifested by the elevation of serum marker enzymes (lactate dehydrogenase, creatine phosphokinase, aspartate aminotransaminase and alanine aminotransaminase). The animals showed significant changes in the antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase) and lipid peroxidation levels. Pretreatment with N. jatamansi extract significantly prevented these alterations and restored the enzyme activity and lipid peroxides to near normal levels. Restoration of cellular normality accredits the N. jatamansi with a cytoprotective role in doxorubicin-induced cardiac damage.

In a study, ethanolic extract of N. jatamansi was studied in Wistar albino rats for cardio protective activity against doxorubicin induced myocardial injury. Doxorubicin is inhibitor of fatty oxidation in the heart and results in cardio toxicity. The rats treated with a single dose of doxorubicin (15 mg/kg) intraperitoneally showed an increase in serum and cardiac lipids (cholesterol, triglycerides, free fatty acids and phospholipids), along with a significant rise in serum low density lipoproteins, very low density lipoproteins and a drop in high density lipoproteins levels, resulting in alteration of serum and cardiac lipid metabolizing enzymes.

Pretreatment with an extract of N.jatamansi (500 mg/kg) orally for 7 d to doxorubicin induced rats showed a significant prevention in the lipid status with the activities of the lipid metabolizing enzymes. Histopathological observations were also in correlation with the biochemical parameters. These findings suggest that the protective and hypolipidemic effect of N. jatamansi against doxorubicin induced myocardial injury in rats could possibly be mediated through its anti lipid peroxidative properties.

A 50% ethanolic extract of Curcuma longa (tuber) and N. jatamansi (whole plant) elevated the HDL-cholesterol/total cholesterol ratio in triton-induced hyperlipidemic rats. There also was a reduction in the ratio of total cholesterol/phospholipids.

Nootropic activity: Acetyl cholinesterase inhibitory activity of methanolic and successive water extracts of N.jatamansi (rhizome), were investigated for acetyl cholinesterase inhibitory activity in vitro. Results indicated that methanolic extracts to be more active than water extracts. The IC (50) values obtained for methanolic and successive water extracts of N.jatamansi was 47.21mug/ml. These results partly substantiate the traditional use of N.jatamansi for improvement of cognition.

Anticonvulsant activity: Ethanol extract of the roots of N. jatamansi was studied for its anticonvulsant activity and neurotoxicity, alone and in combination with phenytoin in rats. The results demonstrated a significant increase in the seizure threshold by N. jatamansi root extract against maximal electroshock seizure model as indicated by a decrease in the extension/flexion ratio. However, the extract was ineffective against pentylenetetrazole-induced seizures. N. jatamansi root extract also showed minimal neurotoxicity against rotarod test at doses that increased the seizure threshold. Further, pretreatment of rats with phenytoin at a dose of 12.5, 25, 50 and 75 mg/kg in combination with 50mg/kg of N. jatamansi root extract resulted in a significant increase in the protective index of phenytoin from 3.63 to 13.18. The dose response studies of phenytoin alone and in combination with N. jatamansi extract on the serum levels of phenytoin clearly demonstrated the synergistic action of both the drugs.

Antidepressant activity: A 15-d treatment with an alcoholic root extract of N. jatamansi caused an overall increase in the levels of central monoamines and inhibitory amino acids, including a change in the levels of serotonin, 5-hydroxyindole acetic acid, gamma-amino butyric acid, and taurine in rat brain.

Antiparkinson's activity: Rats were treated with 200, 400, and 600 mg/kg body weight of N. jatamansi for 3 wk. On day 21, 2 microl of 6-OHDA (12 microg in 0.01% in ascorbic acid-saline) was infused into the right striatum, while the sham-operated group received 2 microl of vehicle. Three weeks after the 6-OHDA injection, the rats were tested for neurobehavioral activity and were scarified after 6 wk for the estimation of lipid peroxidation. The increase in drug-induced rotations and deficits in locomotor activity and muscular coordination due to 6-OHDA injections were significantly and dose-dependently restored by N. jatamansi. A significant decrease in the level of dopamine and its metabolites and an increase in the number of dopaminergic D2 receptors in striatum were observed after 6-OHDA injection, and both were significantly recovered following N. jatamansi treatment.

Neuroprotective activity: Pretreatment with an alcoholic extract of N. jatamansi dosed at 250 mg/kg of for 15 d protected rats against focal ischemia caused by middle cerebral artery occlusion. The protective effect may be associated with improving glutathione content, inhibiting lipid peroxidation, and activity on the Na+/K+ ATPase and catalase enzyme systems.

Nootropic activity: 1. Acetyl cholinesterase inhibitory activity of methanolic and successive water extracts of N.jatamansi (rhizome), were investigated for acetyl cholinesterase inhibitory activity in vitro. Results indicated that methanolic extracts to be more active than water extracts. The IC (50) values obtained for methanolic and successive water extracts of N.jatamansi was 47.21mug/ml. These results partly substantiate the traditional use of N.jatamansi for improvement of cognition.

2. The elevated plus maze and the passive avoidance paradigm were employed to evaluate learning and memory parameters. Three doses (50, 100, and 200 mg/kg, p.o.) of an ethanolic extract of N. jatamansi were administered for 8 successive days to both young and aged mice. The 200 mg/kg dose of N. jatmansi ethanolic extract significantly improved learning and memory in young mice and also reversed the amnesia induced by diazepam (1 mg/kg, i.p.) and scopolamine (0.4 mg/k& i.p.).

Furthermore, it also reversed aging-induced amnesia due to natural aging of mice. As scopolamine-induced amnesia was reversed, it is possible that the memory improvement may be because of facilitation of cholinergic transmission in the brain. Hence, N. jatamansi might prove to be a useful memory restorative agent in the treatment of dementia seen in elderly persons. The underlying mechanism of action can be attributed to its antioxidant property.

Antifungal activity: N. jatamansi essential oil demonstrated fungistatic activity against Aspergillus flavus, Aspergillus niger and Fusarium oxysporum.

21.4 Jatamansone (valeranone): Animal studies done on jatamansone have reported antioestrogenic, antiarrhythmic, antihypertensive, anticonvulsant, sedative and tranquilizing activities. In animal experiments, a limiting effect upon convulsant thresholds and a reduction of motor coordination ability traceable to the sequiterpene ketone, valeranone contained in the drug have been demonstrated. Jatamansone is anticonvulsive in effect without exhibiting neuroleptic characteristics.

Some experiments, typical for tranquillizers jatamansone prolonged barbiturate hypnosis, impaired rotarod performance, potentiate the body-temperature lowering activity of reserpine. Jatamansone exhibited anticonvulsant activity against electric shock and gastro protective actions. In toxicological studies on rats and mice an oral LD50 of greater than 3160 mg/kg was found, which suggests the possibility of a therapeutically useful dose ratio.

Preliminary clinical studies with jatamansone reported reduced incidence of aggressiveness, restlessness, stubbornness and insomnia. In a study conducted on hyperkinetic children, jatamasnone, D-amphetamine and chlorpromazine were compared for efficacy. Jatamasnone and amphetamine significantly improved behavior but amphetamine was better in reducing aggressiveness and restlessness. Children with mental retardation showed little response to any of the drugs. Jatamansone has fewer side effects than D-amphetamine and chlorpromazine.

21.5 Jatamansin: The coumarin: jatamansin is efficacious in internal treatment of varicose veins.

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