Evolvosides C­E, flavonol-4'-O-triglycosides from evolvulus alsinoides and their anti-stress activity [corrected].

Phytochemical investigation of the n-butanol fraction of Evolvulus alsinoides (Linn.) led to the isolation of three new phenolic glycosides, evolvosides C, D and E (1-3) along with six known compounds (4-9). The structures of the compounds were elucidated on the basis of spectroscopic analysis, viz. 1D and 2D NMR experiments, chemical study, and comparison with literature data. Evolvoside C (1) was characterized as kaempferol 4'-O-ß-D-glucopyranosyl-(1→2)-α-L-rhamnopyranosyl-(1→6)-ß-D-glucopyranoside, whereas evolvosides D and E (2-3) were found to be mono and di-O-methyl derivatives of 1. The new compounds (1-3) represent rare triglycoside derivatives of flavonol at C-4'. The isolated compounds (1-6) were screened for acute stress-induced biochemical changes in male Sprague-Dawley rats at a dose of 40 mg/kg body weight. Compounds 1 and 2 displayed anti-stress effects by normalizing hyperglycemia, plasma corticosterone, plasma creatine kinase, and adrenal hypertrophy. Compounds 3 and 6 were also found to be effective in normalizing most of these stress parameters, whereas compounds 4 and 5 were ineffective in normalizing most of these effects.

Novel Ocimumoside A and B as anti-stress agents: modulation of brain monoamines and antioxidant systems in chronic unpredictable stress model in rats.

Therapies targeting central stress mechanisms are fundamental for the development of successful treatment strategies. Ocimum sanctum (OS) is an Indian medicinal plant traditionally used for the treatment of various stress-related conditions. Previously, we have isolated and characterized three OS compounds; Ocimarin, Ocimumoside A and Ocimumoside B. However, their role in modulating chronic stress-induced central changes is unexplored. Thus, in the present study the efficacy of these OS compounds have been evaluated on the chronic unpredictable stress (CUS)-induced alterations in the monoaminergic and antioxidant systems in the frontal cortex, striatum and hippocampus, along with the changes in the plasma corticosterone levels. CUS (two different types of stressors daily for seven days) resulted in a significant elevation of plasma corticosterone level, which was reversed to control levels by pretreatment with Ocimumoside A and B (40 mg/kg p.o.), while Ocimarin showed no effect. The levels of NA, DA and 5-HT were significantly decreased in all the three brain regions by CUS, with a selective increase of DA metabolites. A significant decrease in the glutathione (GSH) content, the activities of superoxide dismutase and catalase with a significant increase in the glutathione peroxidase activity and lipid peroxidation was observed in all the three regions of the brain by CUS. The OS compounds alone did not cause any significant change in the baseline values of these parameters. However, Ocimumoside A and B (40 mg/kg body p.o.) attenuated these CUS-induced alterations with an efficacy similar to that of standard anti-stress (Panax quinquefolium; 100 mg/kg p.o.) and antioxidant (Melatonin; 20 mg/kg i.p.) drugs. While, Ocimarin failed to modulate these CUS-induced alterations. Therefore, this is the first report which identified the anti-stress activity of novel Ocimumoside A and B at the level of central monoamines and antioxidant properties, implicating their therapeutic importance in the prevention of stress-related disorders.

Involvement of monoamines and proinflammatory cytokines in mediating the anti-stress effects of Panax quinquefolium.

Panax quinquefolium (PQ) is well acclaimed in literature for its effects on central and peripheral nervous system. The present study explores the effects of PQ on stress induced changes of corticosterone level in plasma, monoamines (NA, DA and 5-HT) and interleukin (IL-2 and IL-6) levels in cortex and hippocampus regions of brain and also indicate their possible roles in modulating stress. Mice subjected to chronic unpredictable stress (CUS, for 7 days) showed significant increase in plasma corticosterone level and depletion of noradrenaline (NA), dopamine (DA) and 5-hydroxytryptamine (5-HT) levels in cortex and hippocampal regions along with an increased level of IL-2 and IL-6 in the same areas. Aqueous suspension of PQ was administered daily at a dose of 100 and 200mg/kg p.o. prior to the stress regimen and its effects on selected stress markers in plasma and brain was evaluated. PQ at a dose of 200mg/kg p.o. was found to be effective in normalizing the CUS induced elevation of plasma corticosterone and IL-2, IL-6 levels in brain. Moreover, it was significantly effective in reinstating the CUS induced depletion of NA, DA and 5-HT in hippocampus, while NA and 5-HT in cortex of brain. However, PQ at a dose of 100mg/kg p.o. was found ineffective in regulating any of these CUS induced changes. Present study provides an insight into the possible role of PQ on hyperactive HPA axis in the regulation of immediate stress effectors like corticosterone, cytokines and brain monoamines. In this study, PQ has emerged as a potential therapeutic in the cure of stress related disorders and needs to be evaluated in clinical studies to ascertain its efficacy.

Constituents of Ocimum sanctum with antistress activity.

Three new compounds, ocimumosides A (1) and B (2) and ocimarin (3), were isolated from an extract of the leaves of holy basil (Ocimum sanctum), together with eight known substances, apigenin, apigenin-7-O-beta-D-glucopyranoside, apigenin-7-O-beta-D-glucuronic acid ( 4), apigenin-7- O-beta- d-glucuronic acid 6''-methyl ester, luteolin-7-O-beta-D-glucuronic acid 6''-methyl ester, luteolin-7-O-beta-D-glucopyranoside, luteolin-5-O-beta-D-glucopyranoside, and 4-allyl-1-O-beta-D-glucopyronosyl-2-hydroxybenzene (5), and two known cerebrosides. The structures of the new compounds were determined on the basis of extensive 1D and 2D NMR spectroscopic analysis. The new compounds (1- 3) and the known compounds 4 and 5 were screened at a dose of 40 mg/kg body weight for acute stress-induced biochemical changes in male Sprague-Dawley rats. Compound 1 displayed promising antistress effects by normalizing hyperglycemia, plasma corticosterone, plasma creatine kinase, and adrenal hypertrophy. Compounds 2 and 5 were also effective in normalizing most of these stress parameters. In contrast, compounds 3 and 4 were ineffective in normalizing any of these effects.

Anti-stress constituents of Evolvulus alsinoides: an ayurvedic crude drug.

Bioactivity-guided purification of n-BuOH soluble fraction from the ethanol extract of Evolvulus alsinoides resulted in the isolation of two new compounds, 2,3,4-trihydroxy-3-methylbutyl 3-[3-hydroxy-4-(2,3,4-trihydroxy-2-methylbutoxy)-phenyl]-2-propenoate (1) and 1,3-di-O-caffeoyl quinic acid methyl ester (2) along with six known compounds, caffeic acid (3), 6-methoxy-7-O-beta-glucopyranoside coumarin (4), 2-C-methyl erythritol (5), kaempferol-7-O-beta-glucopyranoside (6), kaempferol-3-O-beta-glucopyranoside (7) and quecetine-3-O-beta-glucopyranoside (8). The structure of new compounds 1 and 2 were elucidated by spectroscopic analysis, while known compounds were confirmed by direct comparison of their NMR data with those reported in literature. This is the first report of the presence of phenolic constituents in Evolvulus alsinoides. The isolated compounds 1-5 and 8 were screened for anti-stress activity in acute stress induced biochemical changes in adult male Sprague-Dawley rats. Stress exposure has resulted in significant increase of plasma glucose, adrenal gland weight, plasma creatine kinase (CK), and corticosterone levels. Compound 1 displayed most promising antistress effect by normalizing hyperglycemia, plasma corticosterone, CK and adrenal hypertrophy, while compounds 2 and 3 were also effective in normalizing most of these stress parameters, however compounds 4, 5 and 8 were ineffective in normalizing these parameters.

Effect of Bacopa monniera on stress induced changes in plasma corticosterone and brain monoamines in rats.

Bacopa monniera (BM) is well known for its neuropharmacological effects. Our previous studies indicated the adaptogenic effect of standardized extract of BM in various stress models. In the present study, effect of BM was evaluated on acute stress (AS) and chronic unpredictable stress (CUS) induced changes in plasma corticosterone and monoamines-noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in cortex and hippocampus regions of brain in rats. Panax root powder (Panax quinquefolium) was taken as standard. Subjecting animals to AS (immobilization for 150 min once only) and CUS (different stressors for 7 days) resulted in significant elevation in plasma corticosterone levels, which was significantly countered by treatment with BM at a dose of 40 and 80 mg/kg p.o. similar to the effects of Panax quinquefolium (PQ) at 100 mg/kg p.o. AS exposure significantly increased the levels of 5-HT and decreased NA content in both the brain regions while DA content was significantly increased in cortex and decreased in hippocampus regions. In CUS regimen, levels of NA, DA and 5-HT were significantly depleted in cortex and hippocampus regions of brain. Treatment with BM (40 and 80 mg/kg) attenuated the stress induced changes in levels of 5-HT and DA in cortex and hippocampus regions but was ineffective in normalizing the NA levels in AS model, whereas PQ treatment significantly reverted back the effects of stress. In CUS model, pretreatment with BM and PQ significantly elevated the levels of NA, DA and 5-HT levels in cortex and levels of NA and 5-HT in hippocampus regions. Hence, our study indicates that the adaptogenic activity of BM might be due to the normalization of stress induced alteration in plasma corticosterone and levels of monoamines like NA, 5-HT and DA in cortex and hippocampus regions of the brain, which are more vulnerable to stressful conditions analogous to the effects of PQ.

Adaptogenic and anti-amnesic properties of Evolvulus alsinoides in rodents.

Evolvulus alsinoides (EA) is well known for its memory enhancement, antiepileptic and immunomodulatory properties in the traditional Indian system of medicine, Ayurveda. In view of the increasing attention towards plants offering non-specific resistance (adaptogens) towards stress, we have evaluated crude ethanolic extract of EA for its adaptogenic and memory enhancing properties in rodents. Adaptogenic activity was assessed in rats subjected to acute and chronic unpredictable stress. Male Sprague-Dawley rats, weighing 180-200 g were immobilized for 150 min once only in acute stress (AS) model, whereas in chronic unpredictable stress (CUS) model rats were subjected to different types of stressors daily for 7 days. Stress exposure has induced gastric ulceration with increase in adrenal gland weight, plasma creatine kinase (CK), and corticosterone level in AS and CUS. However plasma glucose was increased only in AS. Rats were treated with graded doses of crude ethanolic extract of EA (100, 200 and 400 mg/kg p.o.) for 3 days and subjected to AS on 3 day after 45 min of last dose. In CUS, EA at a dose of 200 mg/kg p.o. found effective in acute studies was administered 45 min prior to stress regimen for 7 days. EA reduced the stress induced perturbations similar to Panax quinquefolium (PQ) (100 mg/kg p.o.), a well known adaptogen. EA (100 mg/kg) administered orally for 3 days in adult male Swiss mice, was effective in decreasing scopolamine induced deficit in passive avoidance test. The improvement in the peripheral stress markers and scopolamine induced dementia by EA in the present study indicates the adaptogenic and anti-amnesic properties of EA.

In vitro evaluation of antioxidant properties of Cocos nucifera Linn. water.

Tender Cocos nucifera L. (Palmacea) water (CW), variety Chandrasankara, was tested for its ability to scavenge free radicals, inhibit lipid peroxidation and protect hemoglobin from nitrite-induced oxidation. Fresh sample of CW scavenged 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenz-thiazoline-6-sulfonic acid) (ABTS) and superoxide radicals but promoted the production of hydroxyl radicals and increased lipid peroxidation. The activity was most significant for fresh samples of CW and diminished significantly upon heat, acid or alkali treatment or dialysis. Maturity of coconut drastically decreased the scavenging ability of CW against DPPH, ABTS and superoxide radicals. CW protected hemoglobin from nitrite-induced oxidation to methemoglobin when added before the autocatalytic stage of the oxidation. Acid, alkali or heat treated or dialyzed CW showed a decreased ability in protecting hemoglobin from oxidation. The scavenging ability and protection of hemoglobin from oxidation may be partly attributed to the ascorbic acid, which is an important constituent of CW. As CW is a rich source of vitamins, amino acids and enzymes, etc., more than one active principle maybe involved.