Phytochemistry, Traditional Uses and Pharmacological Properties of Enhydra fluctuans Lour: a Comprehensive Review.

BACKGROUND: Enhydra fluctuans Lour, a tropical herb, commonly known as helencha or harkuch, belongs to the family Asteraceae. It is an edible semi-aquatic herbaceous vegetable plant with serrate leaves and grows commonly in different parts of the world. Enhydra fluctuans possesses potential pharmacological role against inflammation, cancer, diarrhea, microbial infection, diabetes, etc. Aim: This review aims to provide the most current information on the botanical characterization, distribution, traditional uses, chemical constituents, as well as the pharmacological activities of Enhydra fluctuans Lour. MATERIALS AND METHODS: The recently updated information on Enhydra fluctuans was gathered from scientific journals, books, and worldwide accepted scientific databases via a library and electronic search PubMed, Elsevier, Google Scholar, Springer, Scopus, Web of Science, Wiley online library. All of the full-text articles and abstracts related to Enhydra were screened. The most important and relevant articles were carefully chosen for study in this review. RESULTS: Crude extracts and isolated compounds of Enhydra fluctuans Lour have been reported to be pharmacologically active against cytoprotective, analgesic and anti-inflammatory, antimicrobial, anticancer, antidiarrheal, antihelmintic, CNS depressant, hepatoprotective, thrombolytic, antidiabetic, antioxidant, phagocytic and cytotoxic, and neuroprotective potential activities. DISCUSSION: Phytochemical analysis from different studies has reported Germacranolide, Sesquiterpene lactone, Flavonoid, Essential oil, Steroid, Diterpenoid, Melampolide, Sesquiterpene lactone, and Isoflavone glycoside as major compounds of Enhydra fluctuans Lour. CONCLUSION: However, more research is needed to explore the mode of action of bioactive components of the plant and its therapeutic capabilities.

Analgesic and CNS Depressant Activities of Sea Anemone Heteractis aurora Nematocyst Toxin.

Marine organisms are the excellent sources for biologically active compounds. Cnidarian venoms are potentially valuable materials used for biomedical research and drug development. The present work was carried out to analyse haemolytic, analgesic and CNS depressant activity of sea anemone Heteractis aurora. In haemolytic assay, among the five different RBC blood cells, the chicken blood exhibited maximum hemolytic activity of 64 Hemolytic Unit (HU). The maximum Analgesic Ratio (AR) of 5 recorded at 15 and 30 min interval and minimum was recorded after 45, 60 and 120 min time intervals. In jumping response activity, the maximum of 5 AR recorded at 15, 30 & 45 min and minimum was recorded at 90 & 120 min time intervals. The maximum decrease of depressant activity of 45.07% was determined in CNS depressant activity. Anti-inflammatory activity showed significant inhibition by crude extract of Heteractis aurora.

Isolation of compound and CNS depressant activities of Mikania scandens Willd with special emphasis to brain biogenic amines in mice.

Mikania scandens, a twining herb that grows as a weed in India and Bangladesh is used as vegetables and is a good source of vitamin A, C, B complex, mikanin, sesquiterpenes, betasitosterin, stigmasterol and friedelin. The present communication reports CNS depressant activities with special emphasis to brain biogenic amines in mice. Ethanol extract of leaves of M. scandens (EEMS) was prepared by Soxhalation and analyzed chemically. EEMS potentiated sleeping time induced by pentobarbitone, diazepam and meprobamate and showed significant reduction in the number of writhes and stretches. EEMS caused significant protection against pentylene tetrazole-induced convulsion and increased catecholamines and brain amino acids level significantly. Results showed that EEMS produced good CNS depressant effects in mice.

Analgesic, anti-inflammatory, and CNS depressant activities of new constituents of Nepeta clarkei.

Two new pentacyclic triterpenes named kirmanoic acid (1) and kurramanoic acid (2) have been isolated from the chloroform-soluble portion of the whole plant of Nepeta clarkei Hook. The structures of the two new compounds were assigned on the basis of their ¹H and ¹³C NMR spectra including two-dimensional NMR techniques such as COSY, HMQC, and HMBC experiments. Kirmanoic acid (1) was investigated for analgesic, anti-inflammatory, and CNS depressant activities. Interestingly kirmanoic acid (1) showed strong analgesic activity than standard drug in acetic induced writhing and formalin tests. Similarly kirmanoic acid (1) also showed strong anti-inflammatory activity than its standard drug. The gross behavioral study of kirmanoic acid (1) revealed that it exhibited mild CNS stimulant and muscle relaxant in the mice. Compound 1 showed a slight increase in Locomotor activity and possesses the antidepressant effect.

Neuropharmcological potential of methanolic extract and a triterpene isolated from Madhuca longifolia L leaves in mice.

The methanolic extract of M. longifolia (MLME) and a compound a triterpene, derivative of madhucic acid (dMA) isolated from the leaves of M. longifolia, were investigated for their possible neuropharmacological activities in mice using phenobarbitone induced sleeping time, spontaneous motor activity, marble burying test and Eddy's hot plate method. LD50 for MLME and dMA were 100 and 10 mg/kg of body weight, respectively. Both MLME and dMA (10 mg/kg and 2 mg/kg oral route respectively) exhibited significant increase in phenobarbitone induced sleeping time, greater reduction in spontaneous motor activity and marble burying activity, confirming their sedative nature. Both MLME and dMA also exhibited considerable antinociceptive activity in experimental animals. The results suggest that both MLME and dMA have CNS depressant activity in mice.

The anti-immobility effect of hyperoside on the forced swimming test in rats is mediated by the D2-like receptors activation.

The crude extracts of HYPERICUM species native to South Brazil showed analgesic and antidepressant-like effects in rodents. The chemical characterization of these species revealed that they are rich in flavonoids and phloroglucinol derivatives. In the present study a detailed investigation was performed on the activities of hyperoside (HYP), a common flavonoid in the genus HYPERICUM. Hyperoside was obtained from the aerial parts of H. CAPRIFOLIATUM by chromatographic procedures. Mice treated with single doses (10, 20 and 40 mg/kg i.p.) did not present signs of toxicity or weight loss. At 20 and 40 mg/kg i.p. the mice exploratory behavior in the open field test was reduced. At 20 mg/kg i. p. the pentobarbital sleeping time increased, but not the sleeping latency. No activity was found on the hot-plate (10 and 20 mg/kg i.p.) or in the acetic acid-induced writhing test (20 and 40 mg/kg p.o.). Nevertheless, an antidepressant-like effect in the forced swimming test in mice and rats was observed (HYP 10 and 20 mg/kg i.p. in mice; HYP 1.8 mg/kg/day p.o. in rats). The antidepressant-like effect in rats was prevented by the administration of sulpiride (50 mg/kg i.p.) a D2 antagonist. In conclusion, hyperoside was found to present a depressor effect on the central nervous system as well as an antidepressant-like effect in rodents which is, at least in part, mediated by the dopaminergic system.

Anticonvulsant activity of embelin isolated from Embelia ribes.

Anticonvulsant activity of embelin (2.5, 5 and 10mg/kg, i.p.) was studied. It showed a significant inhibition of the seizures induced by electroshock and pentylenetetrazole in a dose dependent manner and the activity was comparable to phenytoin and diazepam. Significant decrease in locomotion revealing its CNS depressant activity was observed. The findings suggest that embelin possess anticonvulsant activity against both grand mal and petit mal epilepsy.

Analgesic activity of Heliopsis longipes and its effect on the nervous system.

Heliopsis longipes S.F. Blake (Asteraceae: Heliantheae) (chilcuague) is used in Mexican traditional medicine against parasites and to alleviate tooth and muscle pains. Its biocide effect has already been experimentally demonstrated; however, its analgesic action and its action on the nervous system (NS) have not been investigated yet. The objectives of this study were to evaluate the analgesic action of affinin and the H. longipes root ethanol extract, as well as their effects on the NS using an animal model. The ethanol extract was obtained by maceration, and affinin was purified from it through chromatographic techniques. Chemical and thermal analgesia were used to assess their analgesic proprieties. Irwin's test was used to evaluate their stimulating or depressing effects. The ethanol extract and affinin displayed analgesic action similar to ketorolac and stimulating effect comparable to caffeine on the nervous system of adult mice.

Central effects of isolated fractions from the root of Petiveria alliacea L. (tipi) in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Petiveria alliacea L. (tipi) a shrub from Phytolaccaceae family is popularly used in folk medicine for treating a wide variety of disorders in South and Central America. AIM OF THE STUDY: To investigate the neuropharmacological properties on experimental animals. MATERIALS AND METHODS: The acetate (FA), hexanic (FH), hydroalcoholic (FHA) and precipitated hydroalcoholic (FHAppt) fractions from the root of tipi were studied to investigate its pharmacological properties in the classical behavioral models (open-field, elevated plus maze-EPM, rotarod, barbiturate-induced sleeping time, forced swimming and pentylenetetrazole (PTZ)-induced convulsions tests) using mice. These fractions were administered intraperitoneally and orally to female mice at single doses of 100 and 200mg/kg. RESULTS: All these fractions decreased the locomotor activity, rearing and grooming in the open-field test, suggesting a possible central depressant action. No significant effect was evident on motor coordination of the animals in the rotarod test. On EPM, all the fractions of tipi presented a significant reduction on the time of permanence in the open arms, indicating an absence of anxiolytic-like effect. In addition, the fractions increased the immobility time in the forced swimming test and potentiated pentobarbital-induced sleeping time in mice, confirmed a probable sedative and central depressant effect. Furthermore, the fractions increased the latency to the first convulsion and the lethal time of the PTZ-induced convulsions test in the animals, confirmed its popular use as anticonvulsant. CONCLUSION: Our results suggest that the fractions of P. alliacea L. contains biologically active substance(s) that might be acting in the CNS and have significant depressant and anticonvulsant potentials, supporting folk medicine use of this plant.

Central nervous system depressant activity of Russelia equisetiformis.

The central nervous system depressant activity of the crude methanol extract (REC) and fractions (RE1, RE2, and RE3) of Russelia equisetiformis were evaluated in mice using the following models: amphetamine-induced stereotypy, picrotoxin-induced convulsion and phenobarbitone sleeping time. At 200-400 mg/kg, REC significantly increased phenobarbitone-sleeping time [P < 0.05] in a dose- dependent manner and also reduced the sleep latency significantly [P < 0.05]. The fractions, at doses 1.5 mg/kg for RE1 and 20 mg/kg for RE2 and RE3 also significantly prolonged Phenobarbitone sleeping time and sleep latency [P < 0.05]. Picrotoxin-induced convulsion was not prevented by 100-400 mg/kg of REC but this dose range significantly prolonged seizure latency. A significant reduction [P < 0.05] in amphetamine-induced stereotype behavior was observed with 200 mg/kg REC, but there was no protection against amphetamine-induced mortality. The results of this study suggest that Russelia equisetiformis methanol extract possesses central nervous system depressant activities.

High-performance liquid chromatography of seized drugs at elevated pressure with 1.7 microm hybrid C18 stationary phase columns.

High-performance liquid chromatography (HPLC) separation of drugs at elevated pressure with 1.7 microm hybrid C18 stationary phase columns was investigated. This technique, which uses instrumentation engineered to handle the narrow peaks and high back pressures generated by 1.7 microm particle columns, provided significantly better resolution and/or faster analysis than conventional HPLC and capillary electrophoresis (CE). The use of 2mm internal diameter (i.d.) columns of 3-10 cm length has been evaluated for the separation of basic and neutral drugs, drug profiling, and general screening (including acidic drugs). For these applications, compared to conventional HPLC and CE, it provided up to 12x and 3x faster analyses, respectively. Precision was excellent for both isocratic and gradient analyses. For retention time and peak area, RSDs of < or =0.1% were obtainable. Fifteen anabolic steroids and esters were well separated in a 2.5 min gradient. For drug profiling, compared to HPLC and CE, approximately twice as many peaks were resolved. HPLC at elevated pressure is also well suited as a general screening technique. Twenty-four solutes of varying drug classes including narcotic analgesics, stimulants, depressants, hallucinogens, and anabolic steroids were fully separated in a 13.5 min gradient.

Analgesic, antiinflammatory and central depressor effects of the hydroalcoholic extract and fractions from Aeolanthus suaveolens.

This work studied antinociceptive, antiedematogenic and central depressor effects of the hydroalcoholic extract (HAE) from Aeolanthus suaveolens and its fractions: hexane (ASHAE-H), ethyl acetate (ASHAE-A), aqueous (ASHAE-E) and precipitate (ASHAE-PPT) in experimental models in mice. The highest activity in the writhing test was presented by ASHAE-A followed by ASHAE-PPT and ASHAE-E and the lowest by ASHAE-H. In the formalin test the effect was manifested at both phases, although more intensely at the 2nd phase of the response. In this test, the most active fraction was ASHAE-PPT causing inhibitions of the order of 76 and 90% of the 2nd phase of the test at the doses of 10 and 100 mg/kg i.p., respectively. Naloxone reversed the effects of ASHAE-PPT in both phases of the test, suggesting the participation of the opioid system in the antinociceptive effect. On the other hand, the HAE effect on both phases of the formalin test was only partially reversed by naloxone, suggesting that the extract presents more than one active compound, and at least one, of a polar nature, acting through the opioid system. HAE and ASHAE-PPT presented antiinflammatory activity and were very effective in decreasing the mouse paw edema induced by carrageenan. All fractions significantly decreased locomotor activity in the open field test in mice. However, only the nonpolar fractions presented myorelaxant activity as demonstrated by the rota rod test.

Analgesic, antiinflammatory and CNS depressant activities of sesquiterpenes and a flavonoid glycoside from Polygonum viscosum.

Analgesic, antiinflammatory and CNS depressant activities of four sesquiterpenes, viscosumic acid, viscozulenic acid, viscoazucine and viscoazulone, and a flavonoid glycoside, quercetin-3-O-(6''-feruloyl)-beta-D-galactopyranoside isolated form the aerial parts of Polygonum viscosum (Polygonaceae) have been assessed. All test compounds exhibited CNS depressant activity in open field test, all but viscoazulone showed analgesic activity in Eddy's hot plate test, all sesquiterpenes inhibited acetic acid induced abdominal writhing in mice, and all but viscoazucine and the flavonoid glycoside exhibited mild to moderate antiinflammatory effect on carrageenan induced rat paw edema.

Plants and the central nervous system.

This review article draws the attention to the many species of plants possessing activity on the central nervous system (CNS). In fact, they cover the whole spectrum of central activity such as psychoanaleptic, psycholeptic and psychodysleptic effects, and several of these plants are currently used in therapeutics to treat human ailments. Among the psychoanaleptic (stimulant) plants, those utilized by human beings to reduce body weight [Ephedra spp. (Ma Huang), Paullinia spp. (guaraná), Catha edulis Forssk. (khat)] and plants used to improve general health conditions (plant adaptogens) were scrutinized. Many species of hallucinogenic (psychodysleptic) plants are used by humans throughout the world to achieve states of mind distortions; among those, a few have been used for therapeutic purposes, such as Cannabis sativa L., Tabernanthe iboga Baill. and the mixture of Psychotria viridis Ruiz and Pav. and Banisteriopsis caapi (Spruce ex Griseb.) C.V. Morton. Plants showing central psycholeptic activities, such as analgesic or anxiolytic actions (Passiflora incarnata L., Valeriana spp. and Piper methysticum G. Forst.), were also analysed.Finally, the use of crude or semipurified extracts of such plants instead of the active substances seemingly responsible for their therapeutic effect is discussed.

Central nervous system depressant effect of Hoslundia opposita vahl.

The chloroform extract of the dried root of Hoslundia opposita has been evaluated for effects on the central nervous system (CNS). The extract significantly potentiated the phenobarbitone sleeping time in mice and produced a 60% protection against leptazol-induced convulsion. Neuropharmacological screening revealed CNS depression.

Microdialysis ethanol removal reflects probe recovery rather than local blood flow in skeletal muscle.

The present study compared the microdialysis ethanol outflow-inflow technique for estimating blood flow (BF) in skeletal muscle of humans with measurements by Doppler ultrasound of femoral artery inflow to the limb (BFFA). The microdialysis probes were inserted in the vastus lateralis muscle and perfused with a Ringer acetate solution containing ethanol, [2-3H]adenosine (Ado), and D-[14C(U)]glucose. BFFA at rest increased from 0.16 +/- 0.02 to 1.80 +/- 0.26 and 4.86 +/- 0.53 l/min with femoral artery infusion of Ado (AdoFA,i) at 125 and 1,000 microg . min-1 . l-1 thigh volume (low dose and high dose, respectively; P < 0.05) and to 3.79 +/- 0.37 and 6.13 +/- 0.65 l/min during one-legged, dynamic, thigh muscle exercise without and with high AdoFA,i, respectively (P < 0.05). The ethanol outflow-to-inflow ratio (38.3 +/- 2.3%) and the probe recoveries (PR) for [2-3H]Ado (35.4 +/- 1.6%) and for D-[14C(U)]glucose (15.9 +/- 1.1%) did not change with AdoFA,i at rest (P = not significant). During exercise without and with AdoFA,i, the ethanol outflow-to-inflow ratio decreased (P < 0.05) to a similar level of 17.5 +/- 3.4 and 20.6 +/- 3.2%, respectively (P = not significant), respectively, while the PR increased (P < 0.05) to a similar level (P = not significant) of 55.8 +/- 2.8 and 61.2 +/- 2. 5% for [2-3H]Ado and to 42.8 +/- 3.9 and 45.2 +/- 5.1% for D-[14C(U)]glucose. Whereas the ethanol outflow-to-inflow ratio and PR correlated inversely and positively, respectively, to the changes in BF during muscular contractions, neither of the ratio nor PR correlated to the AdoFA,i-induced BF increase. Thus the ethanol outflow-to-inflow ratio does not represent skeletal muscle BF but rather contraction-induced changes in molecular transport in the interstitium or over the microdialysis membrane.

Cardenolides from the methanolic extract of Nerium oleander leaves possessing central nervous system depressant activity in mice.

Two new cardenolides, 3 beta-O-(D-2-O-methyldigitalosyl)-14 beta-hydroxy-5 beta-carda-16,20(22)-dienolide (1) and 3 beta-hydroxy-8,14-epoxy-5 beta-carda-16,20(22)-dienolide (2), and two known cardenolides, 3 beta-O-(D-digitalosyl)-14 beta-hydroxy-16 beta-acetoxy-5 beta-card-20(22)-enolide (3) and 3 beta-O-(D-digitalosyl)-14 beta-hydroxy-5 beta-card-20(22)-enolide (4), have been isolated from the leaves of Nerium oleander following a bioactivity-directed isolation of the MeOH extract, which showed central nervous system (CNS) depressant activity in mice at a dosage of 50 mg/kg i.p. Their structures were established on the basis of chemical and spectral data. Compounds 1, 3, and 4 were found to exhibit sedation in mice at a dosage of 25 mg/kg, although 2 had no effect on the CNS of mice at a dosage of up to 50 mg/kg.

Compounds from the sea with actions on the cardiovascular and central nervous systems.

Recent efforts at probing into the oceans have produced evidence that marine invertebrates such as gorgonians and sponges offer a rich reserve of pharmacologically interesting molecules. Our investigations indicate that it is possible to obtain novel compounds both structurally and pharmacologically. For example, autonomium from a sponge is a dual adrenergic combined with cholinergic molecule, with a structure that may be considered a hybrid between a catecholamine and choline. Various terpenoids and indole derivatives from marine organisms have been found to possess activities on the central nervous system. Several peptides from sea anemones are cardiotonic and have initiated a new concept of chemical structure believed to be associated with cardiac activity. A number of closely related halogenated cyclic ethers are good inhibitors of drug metabolism. Thus, there seems little doubt that the sea warrants an extensive chemical and pharmacological examination.