Phytotherapeutic Approach in the Management of Cisplatin Induced Vomiting; Neurochemical Considerations in Pigeon Vomit Model.

Cisplatin induced vomiting involves multiple mechanisms in its genesis and a single antiemetic agent do not cover both the phases (acute & delayed) of vomiting in clinics; necessitating the use of antiemetics in combination. Cannabis sativa and other selected plants have ethnopharmacological significance in relieving emesis. The aim of the present study was to investigate the intrinsic antiemetic profile of Cannabis sativa (CS), Bacopa monniera (BM, family Scrophulariaceae), and Zingiber officinale (ZO, family Zingiberaceae) in combinations against vomiting induced by highly emetogenic anticancer drug-cisplatin in pigeons. We have analysed the neurotransmitters which trigger the vomiting response centrally and peripherally. Electrochemical detector (ECD) was used for the quantification of neurotransmitters and their respective metabolites by high performance liquid chromatography in the brain stem (BS) and area postrema (AP) while peripherally in the small intestine. Cisplatin (7 mg/kg i.v.) induced reliable vomiting throughout the observation period (24 hrs). CS-HexFr (10 mg) + BM-MetFr (10 mg)-Combination 1, BM-ButFr (5 mg) + ZO-ActFr (25 mg)-Combination 2, ZO-ActFr (25 mg) + CS-HexFr (10 mg)-Combination 3, and CS-HexFr (10 mg) + BM-ButFr (5 mg)-Combination 4; provided ~30% (30 ± 1.1), 70% (12 ± 0.4; P < 0.01), 60% (19 ± 0.2; P < 0.05) and 90% (05 ± 0.1; P < 0.001) protection, respectively, against cisplatin induced vomiting as compared to cisplatin control. Standard MCP (30 mg) provided ~50% (23 ± 0.3) protection (P > 0.05). CS Hexane fraction (10 mg/kg), BM methanolic (10 mg/kg) and bacoside rich n-butanol fraction (5 mg/kg) and ZO acetone fraction (25 mg/kg) alone provided ~62%, 36%, 71%, and 44% protection, respectively, as compared to cisplatin control. The most effective and synergistic combination 4 was found to reduce 5HT and 5HIAA (P < 0.05-0.001) in all the brain areas area postrema (AP)+brain stem (BS) and intestine at the 3rd hour of cisplatin administration. In continuation, at the 18th of cisplatin administration reduction in dopamine (P < 0.001) in the AP and 5HT in the brain stem and intestine (P < 0.001) was observed. The said combination did not change the neurotransmitters basal levels and their respective metabolites any significantly. In conclusion, all the tested combinations offered protection against cisplatin induced vomiting to variable degrees, where combination 4 provided enhanced attenuation by antiserotonergic mechanism at the 3rd hour while a blended antidopaminergic and antiserotonergic mechanism at the 18th hour after cisplatin administration.

Neuroprotective effect of Bacopa monnieri against morphine-induced histopathological changes in the cerebellum of rats.

Opioid addiction is associated with oxidative cell injury in neuronal cells. In this study, Bacopa monnieri (L.), a reputed nootropic plant, was evaluated against morphine-induced histopathological changes in the cerebellum of rats. B. monnieri methanolic extract (mBME) (40 mg/kg, p.o) and ascorbic acid (50 mg/kg, i.p) were administered two hours before morphine (20 mg/kg, i.p) for 14 and 21 days. The in vitro antioxidant activity of mBME was determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical scavenging assay. Morphine produced vacuolization of basket and stellate cells and reduced the size of Purkinje cells in the cerebellum after 14 days. However, treatment for 21 days was associated with severe shrinkage of Purkinje cells with loss of their characteristic flask-shaped appearance as well as degeneration of basket, stellate and granule cells. Pretreatment with mBME and ascorbic acid for 14 and 21 days attenuated the morphine-induced histopathological changes in the cerebellum. The EC50 for the DPPH free-radical scavenging assay of mBME (39.06 µ/mL) as compared to ascorbic acid (30.25 µ/mL) and BHT (34.34 µ/mL) revealed that mBME strongly scavenged the free-radicals and thus possessed an efficient antioxidant propensity. These results concluded that B. monnieri having strong antioxidant activity exerted a protective effect against morphineinduced cerebellar toxicity.

Neuroprotective and Anti-Aging Potentials of Essential Oils from Aromatic and Medicinal Plants.

The use of essential oils (EOs) and their components is known since long in traditional medicine and aromatherapy for the management of various diseases, and is further increased in the recent times. The neuroprotective and anti-aging potentials of EOs and their possible mechanism of actions were evaluated by numerous researchers around the globe. Several clinically important EOs and their components from Nigella sativa, Acorus gramineus, Lavandula angustifolia, Eucalyptus globulus, Mentha piperita, Rosmarinus officinalis, Jasminum sambac, Piper nigrum and so many other plants are reported for neuroprotective effects. This review article was aimed to summarize the current finding on EOs tested against neurodegenerative disorders like Alzheimer disease (AD) and dementia. The effects of EOs on pathological targets of AD and dementia including amyloid deposition (Aß), neurofibrillary tangles (NFTs), cholinergic hypofunction, oxidative stress and glutamatergic abnormalities were focused. Furthermore, effects of EOs on other neurological disorders including anxiety, depression, cognitive hypofunction epilepsy and convulsions were also evaluated in detail. In conclusion, EOs were effective on several pathological targets and have improved cognitive performance in animal models and human subjects. Thus, EOs can be developed as multi-potent agents against neurological disorders with better efficacy, safety and cost effectiveness.

A bacosides containing Bacopa monnieri extract alleviates allodynia and hyperalgesia in the chronic constriction injury model of neuropathic pain in rats.

BACKGROUND: The current therapy of neuropathic pain is inadequate and is limited by the extent of pain relief and the occurrence of dose dependant side effects. Insufficient control of pain with conventional medications prompts the use of complementary and alternative medicine therapies by patients with neuropathic pain. This study therefore investigated a standardized methanolic extract of Bacopa monnieri, a widely reputed nootropic plant, for prospective antinociceptive effect in the chronic constriction injury (CCI) model of neuropathic pain. METHODS: Placement of four loose ligatures around the sciatic nerve produced partial denervation of the hindpaw in rats. Bacopa monnieri (40 and 80 mg/kg, p.o) and the positive control, gabapentin (75 mg/kg, i.p), were administered daily after CCI or sham surgery and the behavioral paradigms of static- and dynamic-allodynia (paw withdrawal threshold to von Frey filament stimulation [PWT] and paw withdrawal latency to light-brushing [PWL]), cold-allodynia (paw withdrawal duration [PWD] to acetone), heat- (PWL to heat-stimulus) and punctate-hyperalgesia (PWD to pin-prick) were assessed on days 3, 7, 14 and 21. RESULTS: CCI consistently generated static- (days 3-21), dynamic- (days 14-21) and cold-allodynia (days 3-21) plus heat- and mechano-hyperalgesia (days 3-21). The tested doses of Bacopa monnieri significantly attenuated the CCI-induced allodynia and hyperalgesia, exemplified by increased PWT (days 7-21), PWL to light brushing (days 14-21) and heat (days 7-21) as well as decreased PWD to pin prick and cold stimuli (days 3-21). The extract also counterbalanced the CCI-induced aberrations in the nociceptive behaviors by increasing the pain threshold to that of pre-surgery baseline. Gabapentin also afforded analogous beneficial behavioral profile but of higher magnitude. CONCLUSIONS: Our findings suggest that Bacopa monnieri can be used as adjuvant therapy for neuropathic pain conditions afflicted with allodynia and hyperalgesia.

Action of Bacopa monnieri to antagonize cisplatin-induced emesis in Suncus murinus (house musk shrew).

Bacopa monnieri (BM, family Scrophulariaceae) is used in several traditional systems of medicine for the management of epilepsy, depression, neuropathic pain, sleep disorders and memory deficits. The present study investigated the potential of BM methanol (BM-MetFr) and BM n-butanol fractions (BM-ButFr) to reduce chemotherapy-induced emesis in Suncus murinus (house musk shrew). Cisplatin (30 mg/kg, i.p.) reliably induced retching and/or vomiting over a 2 day period. BM-MetFr (10-40 mg/kg, s.c.) and BM-ButFr (5-20 mg/kg, s.c.) antagonized the retching and/or vomiting response by ∼59.4% (p < 0.05) and 78.9% (p < 0.05), respectively, while the 5-HT3 receptor antagonist, palonosetron (0.5 mg/kg, s.c.), reduced the response by ∼71% (p < 0.05). The free radical scavenger/antioxidant, N-(2-mercaptopropionyl)-glycine (30-300 mg/kg, s.c.) reduced the retching and/or vomiting response occurring on day one non-significantly by 44% (p > 0.05). In conclusion, the n-butanol fractions of BM have anti-emetic activity comparable with palonosetron and MPG. BM may be useful alone or in combination with other anti-emetic drugs for the treatment of chemotherapy-induced emesis in man.

Synthetic and natural antioxidants attenuate cisplatin-induced vomiting.

BACKGROUND: Synthetic and natural antioxidants including Bacopa monnieri (L.) Pennell (Scrophulariaceae) which also possess anti-dopaminergic properties, have been proposed to be useful for emetogenic chemotherapy. In this study, synthetic [N-(2-mercaptopropionyl) glycine (MPG), vitamin C (Vit-C)] and natural [grape seed proanthocyanidin (GP), B. monnieri n-butanolic fraction (BM-ButFr)] antioxidants and their combinations were evaluated against cisplatin-induced emesis in pigeons during a 24 h observation period. METHODS: Emesis was induced using cisplatin (7.0 mg/kg, i.v). MPG (10, 20, 30 mg/kg), Vit-C (100, 200, 300 mg/kg), GP (50, 100, 150 mg/kg) and BM-ButFr (5, 10, 20 mg/kg) and their combinations were administered i.m., 15 min before cisplatin administration. The number of vomiting bouts, retching, emetic latency and % weight loss were recorded to assess antiemetic potential. Antioxidant activity was evaluated by the DPPH free radical scavenging assay (FRSA). RESULTS: Significant attenuation of vomiting bouts, retching, % weight loss along with an increase in latency was produced by all the antioxidants and their combinations compared to cisplatin alone and this is the first report of this activity of GP in pigeons. Low EC50 values in the FRSA for MPG (67.66 µg/mL), Vit-C (69.42 µg/mL), GP (6.498 µg/mL) and BM-ButFr (55.61 µg/mL) compared to BHT standard (98.17 µg/mL) demonstrated their radical scavenging capacity. Correlation between the antioxidant activity and antiemetic efficacy disclosed a high degree of correlation for the tested antioxidants. CONCLUSION: The selected synthetic and natural antioxidants and their combinations were able to attenuate cisplatin-induced vomiting, which correlated with their potent in vitro antioxidant activity.

Molecularly Characterized Solvent Extracts and Saponins from Polygonum hydropiper L. Show High Anti-Angiogenic, Anti-Tumor, Brine Shrimp, and Fibroblast NIH/3T3 Cell Line Cytotoxicity.

Polygonum hydropiper is used as anti-cancer and anti-rheumatic agent in folk medicine. This study was designed to investigate the anti-angiogenic, anti-tumor, and cytotoxic potentials of different solvent extracts and isolated saponins. Samples were analyzed using GC, Gas Chromatography-Mass Spectrometry (GC-MS) to identify major and bioactive compounds. Quantitation of antiangiogenesis for the plant's samples including methanolic extract (Ph.Cr), its subsequent fractions; n-hexane (Ph.Hex), chloroform (Ph.Chf), ethyl acetate (Ph.EtAc), n-Butanol (Ph.Bt), aqueous (Ph.Aq), saponins (Ph.Sp) were performed using the chick embryo chorioallantoic membrane (CAM) assay. Potato disc anti-tumor assay was performed on Agrobacterium tumefaciens containing tumor inducing plasmid. Cytotoxicity was performed against Artemia salina and mouse embryonic fibroblast NIH/3T3 cell line following contact toxicity and MTT cells viability assays, respectively. The GC-MS analysis of Ph.Cr, Ph.Hex, Ph.Chf, Ph.Bt, and Ph.EtAc identified 126, 124, 153, 131, and 164 compounds, respectively. In anti-angiogenic assay, Ph.Chf, Ph.Sp, Ph.EtAc, and Ph.Cr exhibited highest activity with IC50 of 28.65, 19.21, 88.75, and 461.53 µg/ml, respectively. In anti-tumor assay, Ph.Sp, Ph.Chf, Ph.EtAc, and Ph.Cr were most potent with IC50 of 18.39, 73.81, 217.19, and 342.53 µg/ml, respectively. In MTT cells viability assay, Ph.Chf, Ph.EtAc, Ph.Sp were most active causing 79.00, 72.50, and 71.50% cytotoxicity, respectively, at 1000 µg/ml with the LD50 of 140, 160, and 175 µg/ml, respectively. In overall study, Ph.Chf and Ph.Sp have shown overwhelming results which signifies their potentials as sources of therapeutic agents against cancer.

Passiflora incarnata attenuation of neuropathic allodynia and vulvodynia apropos GABA-ergic and opioidergic antinociceptive and behavioural mechanisms.

BACKGROUND: Passiflora incarnata is widely used as an anxiolytic and sedative due to its putative GABAergic properties. Passiflora incarnata L. methanolic extract (PI-ME) was evaluated in an animal model of streptozotocin-induced diabetic neuropathic allodynia and vulvodynia in rats along with antinociceptive, anxiolytic and sedative activities in mice in order to examine possible underlying mechanisms. METHODS: PI-ME was tested preliminary for qualitative phytochemical analysis and then quantitatively by proximate and GC-MS analysis. The antinociceptive property was evaluated using the abdominal constriction assay and hot plate test. The anxiolytic activity was performed in a stair case model and sedative activity in an open field test. The antagonistic activities were evaluated using naloxone and/or pentylenetetrazole (PTZ). PI-ME was evaluated for prospective anti-allodynic and anti-vulvodynic properties in a rat model of streptozotocin induced neuropathic pain using the static and dynamic testing paradigms of mechanical allodynia and vulvodynia. RESULTS: GC-MS analysis revealed that PI-ME contained predominant quantities of oleamide (9-octadecenamide), palmitic acid (hexadecanoic acid) and 3-hydroxy-dodecanoic acid, among other active constituents. In the abdominal constriction assay and hot plate test, PI-ME produced dose dependant, naloxone and pentylenetetrazole reversible antinociception suggesting an involvement of opioidergic and GABAergic mechanisms. In the stair case test, PI-ME at 200 mg/kg increased the number of steps climbed while at 600 mg/kg a significant decrease was observed. The rearing incidence was diminished by PI-ME at all tested doses and in the open field test, PI-ME decreased locomotor activity to an extent that was analagous to diazepam. The effects of PI-ME were antagonized by PTZ in both the staircase and open field tests implicating GABAergic mechanisms in its anxiolytic and sedative activities. In the streptozotocin-induced neuropathic nociceptive model, PI-ME (200 and 300 mg/kg) exhibited static and dynamic anti-allodynic effects exemplified by an increase in paw withdrawal threshold and paw withdrawal latency. PI-ME relieved only the dynamic component of vulvodynia by increasing flinching response latency. CONCLUSIONS: These findings suggest that Passiflora incarnata might be useful for treating neuropathic pain. The antinociceptive and behavioural findings inferring that its activity may stem from underlying opioidergic and GABAergic mechanisms though a potential oleamide-sourced cannabimimetic involvement is also discussed.

Anti-emetic mechanisms of Zingiber officinale against cisplatin induced emesis in the pigeon; behavioral and neurochemical correlates.

BACKGROUND: Zingiber officinale (ZO, family Zingiberaceae) has been reported for its antiemetic activity against cancer chemotherapy induced emesis in animal models and in clinics. Current study was designed to investigate ZO for potential usefulness against cisplatin induced vomiting in pigeon and its effects on central and peripheral neurotransmitters involved in the act of vomiting. METHODS: Zingiber officinale acetone fraction (ZO-ActFr) was investigated for attenuation of emesis induced by cisplatin in healthy pigeons. Neurotransmitters DA, 5HT and their metabolites DOPAC, HVA and 5HIAA were analyzed using High Performance Liquid Chromatography system coupled with electrochemical detector in area postrema, brain stem and intestine. Antiemetic effect of ZO-ActFr was correlated with central and intestinal neurotransmitters levels in pigeon. RESULTS: Cisplatin (7 mg/kg i.v.) induced emesis without lethality upto the observation period. ZO-ActFr (25, 50 & 100 mg/kg) attenuated cisplatin induced emesis ~ 44.18%, 58.13% (P < 0.05) and 27.9%, respectively; the reference drug, metoclopramide (MCP; 30 mg/kg), produced ~ 48.83% reduction (P < 0.05). ZO-ActFr reduced (P < 0.05 - 0.001) 5-hydroxytryptamine (5HT) concentration in the area postrema, brain stem and intestine at 3(rd) hour of cisplatin administration, while at the 18(th) hour ZO treatments attenuated the dopamine upsurge (P < 0.001) caused by cisplatin in the area postrema and 5HT concentration (P < 0.01 - 0.001) in the brain stem and intestine. ZO treatments alone did not altered the basal neurotransmitters and their metabolites in the brain areas and intestine. CONCLUSION: The behavioral study verify the antiemetic profile of ZO against cisplatin induced emesis in the pigeon, where central and peripheral neural evidences advocate the involvement of serotonergic mechanism at initial time point (3(rd) hr), while the later time point (18(th) hr) is associated with serotonergic and dopaminergic component in the mediation of its antiemetic effect.

Heavy metals analysis, phytochemical, phytotoxic and anthelmintic investigations of crude methanolic extract, subsequent fractions and crude saponins from Polygonum hydropiper L.

BACKGROUND: Polygonum hydropiper L decoctions are traditionally used in the treatment of various ailments including inflammation, dyspepsia, diarrhea, menorrhagia, hemorrhoids, helminthiasis and CNS disorders. Present study was undertaken to investigate P. hydropiper L. for heavy metals content, phytoconstituents, Phytotoxic and anthelmintic activities to explore its toxicological and pharmacological potentials and rationalize its ethnomedicinal uses. METHODS: Plant crude powder, methanolic extract, fractions and soil samples were analyzed for heavy metals using atomic absorption spectrophotometer. Qualitative phytochemical analysis of the plant extracts was carried out for the existence of alkaloids, flavonoids, glycosides, anthraquinones, saponins, terpenoids, sterols and tannins. Radish seeds phytotoxicity assay was used to study phytotoxic action of plant extracts. Pheretima posthuma and Ascaridia galli were used to study anthelmintic potential of the plant using albendazole and levamisole HCl as standard drugs. RESULTS: Plant crude powder, methanolic extract (Ph.Cr), its subsequent fractions; n-hexane (Ph.Hex), chloroform (Ph.Chf), ethyl acetate (Ph.EtAc), n-Butanol (Ph.Bt), aqueous (Ph.Aq), saponins (Ph.Sp) and soil samples were found to contain copper (Cu), iron (Fe), chromium (Cr), zinc (Zn), lead (Pb), nickel (Ni), cadmium (Cd) and lead (Pb) in different concentrations. In crude powder of the plant, heavy metals concentrations were within WHO specified limits, whereas different fractions and soil samples exhibited high metals content. Ph.Cr was tested positive for the presence of alkaloids, flavonoids, saponins, tannins, triterpenoids and anthraquinone glycosides. Among different fractions Ph.EtAc, Ph.Sp, Ph.Chf and Ph.Bt were most effective causing 89.32, 89.25, 86.68 and 85.32% inhibition of seeds in phytotoxicity assay, with IC50 values of 50, 60, 35 and 100 µg/ml respectively. In anthelmintic study, Ph.Sp, Ph.Chf, Ph.EtAc and Ph.Cr were most effective against P. posthuma at 10 mg/ml concentration with an average death time of 50, 64.67, 68.67 and 71 minutes respectively. Ph.EtAc, Ph.Chf and Ph.Aq were most effective against A. galli with average death time of 7, 9 and 10 min respectively at 1 mg/ml concentration. CONCLUSIONS: Our findings indicate that P. hydropiper contains different heavy metals and secondary metabolites. Different fractions exhibited phytotoxic and anthelmintic activites comparable to control drugs, thus provide pharmacological basis for ethnomedicinal uses of this plant.

Attenuation of cisplatin-induced emetogenesis by standardized Bacopa monnieri extracts in the pigeon: behavioral and neurochemical correlations.

Nausea and vomiting are the most distressing and common side effects of cancer chemotherapy which often result in patient noncompliance. In the present study, standardized methanolic and n-butanolic fractions of Bacopa monnieri were evaluated against cisplatin-induced emesis in the pigeon in relation to their activity on central and intestinal neurotransmitters levels. Cisplatin (7.0 mg/kg, i. v.) induced reproducible emesis without lethality in healthy pigeons. The methanolic (10-40 mg/kg) and the bacoside-rich n-butanolic fractions of B. monnieri (5-20 mg/kg), as well as the antioxidant N-(2-mercaptopropionyl) glycine (10 mg/kg), attenuated cisplatin-induced emesis by 66.3% (p < 0.05), 71.6% (p < 0.001), and 76.5% (p < 0.001), respectively, where the standard antiemetic metoclopramide (30 mg/kg) produced a 48.9% reduction (p < 0.01). The methanolic and n-butanolic fractions of B. monnieri at all of the doses tested significantly reduced the serotonin concentration (p < 0.001) in the brain stem and intestine 3 h after cisplatin administration, while at the 18th h, B. monnieri treatments attenuated not only the dopamine upsurge in the area postrema and brain stem (p < 0.05-0.001), but also the intestinal 5-HT concentration (p < 0.01-0.001). B. monnieri treatments alone did not alter the basal neurotransmitters or their metabolites in the brain areas and intestine. The prolonged suppressive effect of B. monnieri treatments on the behavioral signs of cisplatin-induced emesis, the subsequent supportive neural evidence, and the safety and tolerability profile suggest that B. monnieri methanolic and bacoside-rich n-butanolic fractions might be a valuable adjunct in the treatment of emetogenic chemotherapy, and this warrants further study in other models of emesis.

Inhibitory effect of bacopasides on spontaneous morphine withdrawal induced depression in mice.

Bacopa monnieri is a perennial herb with a world known image as a nootropic. We investigated the effect of Bacopa monnieri methanolic extract (Mt Ext BM) 10, 20, and 30 mg/kg body weight (b.w) on acquisition and expression of morphine withdrawal induced depression in mice. Locally available Bacopa monnieri (BM) was screened for contents of Bacoside A3, Bacopasaponin C, and Bacopaside II using HPLC with UV. Morphine dependence was induced in mice using twice daily escalating chronic morphine treatments (20-65 mg/kg b.w) for eight consecutive days. Morphine withdrawal induced depression was assayed in animals using forced swimming test (FST), three days after last morphine injection. The HPLC analysis revealed that Mt-ext BM contained Bacoside A3 as major component, i.e. 4 µg in each mg of extract. The chronic treatment with Met Ext BM 10, 20, and 30 mg/kg b.w. dosing significantly inhibited opioid withdrawal induced depression in mice. These findings imply a newer potential role of Bacopa monnieri in the clinical management of opioid withdrawal induced depression which can be attributed to Bacoside A3.

Comparative evaluation of gastroulcerogenic potential of nitrogen isoforms of salicyl alcohol and aspirin in rats: biochemical and histological study.

The aim of the current study was to explore in vivo any relative gastroulcerogenic prospective propensity of newly synthesized nitrogen containing derivatives of salicyl alcohol; compound (I) [1-(2-hydroxybenzyl)piperidinium chloride], compound (II) [4-carbamoyl-1-(2-hydroxybenzyl)piperidinium chloride] and aspirin in albino rats. The experimental groups received the following oral treatments daily for 6 days: group I saline control; group II, standard (aspirin) treatment group [150 mg/kg of body weight]; group III, test (compound I) treatment group [100, 150 mg/kg]; group IV, test (compound II) treatment group [100, 150 mg/kg]. The results showed that in the case of the aspirin treated group and compound (I) [150 mg/kg], there was a significant increase in gastric volume, free acidity, total acidity, ulcer score and a decrease in gastric pH. Furthermore, histopathological examination of gastric mucosa of these treated groups revealed detectable morphological changes. Utilizing the same protocol, synthetic compound (I) [100 mg/kg] and (II) [100, 150 mg/kg] exhibited no statistically significant ulcerogenic or cytotoxic properties. A cyclooxygenase (COX) selectivity test indicated the preferential inhibition of COX-I and COX-II enzymes by compounds (I) and (II). This study therefore indicates that these synthetic compounds may possess reduced ulcerogenic potential and could be a functional substitute to aspirin.

Nature cures nature: Hypericum perforatum attenuates physical withdrawal signs in opium dependent rats.

CONTEXT: Hypericum perforatum Linn. (Hypericaceae) (St. John's wort) attenuates opium withdrawal signs. AIM: To explore the therapeutic potential of Hypericum perforatum in the management of opium-induced withdrawal syndrome. MATERIALS AND METHODS: The effect of the Hypericum perforatum hydro-ethanol extract was investigated for potential to reverse naloxone (0.25 mg/kg)-induced opium withdrawal physical signs. Rats received opium extract (80-650 mg/kg) twice daily for 8 days along with Hypericum perforatum (20 mg/kg, orally) twice daily in chronic treatment and the same single dose 1 h before induction of withdrawal syndrome in the acute treated group. RESULTS: Hypericum perforatum reduced stereotype jumps and wet dog shake number in the chronic treatment compared to the saline control group (F(2, 24) = 3.968, p < 0. 05) and (F(2, 24) = 3.689, p < 0.05), respectively. The plant extract in the acutely treated group reduced diarrhea (F(2, 24) = 4.850, p < 0. 05 vs. saline). It decreased rectal temperature by chronic treatment at 30 min (F(2, 24) = 4.88, p < 0.05), 60 min (F(2, 240 = 5.364, p < 0.01) and 120 min (F(2, 24) = 4.907, p < 0.05). DISCUSSION AND CONCLUSION: This study reveals that the extract of Hypericum perforatum attenuates some physical signs of opium withdrawal syndrome possibly through direct or indirect interaction with opioid receptors. Further study is needed to clarify its mechanism.

Evaluation of antidiabetic and antihyperlipidemic activity of Artemisia indica linn (aeriel parts) in Streptozotocin induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetes mellitus is a major metabolic disorder affecting a huge population all over the world. Artemisia species have been extensively used for the management of diabetes in folkloric medicine. The present study is designed to investigate the antidiabetic and antihyperlipidemic effects of aeriel parts of Artemisia indica. MATERIALS AND METHODS: Hydromethanolic crude extracts, chloroform, ethyl acetate and n-butanol fractions of aerial parts of Artemisia indica were tested for their antidiabetic potential in Streptozotocin (STZ) (50mg/kg, i.p.) induced diabetic Sprague-Dawley rats. Blood glucose level, body weight, serum lipid profile and activities of liver enzymes were determined. The extracts were further subjected to preliminary phytochemical analysis. RESULTS: A daily oral dose of hydromethanolic crude extracts (200 and 400mg/kg b.w.) and chloroform fraction (200mg/kg b.w.) of Artemisia indica for 15 days showed a significant reduction in blood glucose level which was comparable to that of the standard antidiabetic drug, glibenclamide (500 µg/kg, p.o.). Artemisia indica extracts also showed reduction in total cholesterol, triglycerides and low density lipoproteins as well as serum creatinine level, serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT) and alkaline phosphatase (ALP) in diabetic rats. CONCLUSION: According to the results Artemisia indica possesses hypoglycemic, antihyperlipidemic and valuable effects on liver and renal functions in diabetic rats, which seems to validate its traditional usage.

A Bacoside containing Bacopa monnieri extract reduces both morphine hyperactivity plus the elevated striatal dopamine and serotonin turnover.

Bacopa monnieri (BM) has been used in Ayurvedic medicine as a nootropic, anxiolytic, antiepileptic and antidepressant. An n-butanol extract of the plant (nBt-ext BM) was analysed and found to contain Bacoside A (Bacoside A3, Bacopaside II and Bacopasaponin C). The effects of the BM extract were then studied on morphine-induced hyperactivity as well as dopamine and serotonin turnover in the striatum since these parameters have a role in opioid sensitivity and dependence. Mice were pretreated with saline or nBt-ext BM (5, 10 and 15 mg/kg, orally), 60 min before morphine administration and locomotor activity was subsequently recorded. Immediately after testing, striatal tissues were analysed for dopamine (DA), serotonin (5HT) and their metabolites using HPLC coupled with electrochemical detection. The results indicated that nBt-ext BM significantly (p < 0.001) decreased locomotor activity in both the saline and morphine treated groups. Additionally, nBt-ext BM significantly lowered morphine-induced dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-H1AA) upsurges in the striatum but failed to affect DA, 5-HT and their metabolites in the saline treated group. These findings suggest that nBt-ext BM has an antidopaminergic/serotonergic effect and may have potential beneficial effects in the treatment of morphine dependence.

Effect of Bacopasides on acquisition and expression of morphine tolerance.

Opioids are extensively used for the management of both chronic malignant and non malignant pains. One major serious limitation associated with chronic use of opioids is the development of tolerance to its analgesic effect. The effect of Bacopa monnieri, a renowned ayurvedic medicine for acquisition and expression of morphine tolerance in mice, was investigated. Bacopa monnieri, n-Butanol fraction was analyzed on High performance liquid chromatography (HPLC), for Bacopaside A major components i.e. Bacoside A(3), Bacopaside ll and Bacosaponin C. Antinociceptive effect of n-Butanol extract of Bacopa monnieri (n Bt-ext BM) (5, 10 and 15 mg/kg) was assessed on hot plate. Effect of different doses of n Bt-ext BM on morphine antinociception was also assessed. n Bt-ext BM was also screened for development of tolerance to antinociceptive effect of Bacopa monnieri by administering 15 mg/kg n Bt-ext BM for seven days. Tolerance to morphine analgesia was induced in mice by administering intraperitoneally (I.P.) 20 mg/kg morphine twice daily for five days. Acute and Chronic administration of 5, 10 and 15 mg/kg n Bt-ext BM significantly reduced both expression and development of tolerance to morphine analgesia in mice. Additionally, Bacopa monnieri was found to enhance antinociceptive effect of morphine in intolerant animals. However, no tolerance to Bacopa monnieri antinociceptive effect was observed in seven days treatment schedule. These findings indicate effectiveness of Bacopa monnieri for management of morphine tolerance.

Terpenoid content of Valeriana wallichii extracts and antidepressant-like response profiles.

Three extracts of Valeriana wallichii DC (Valerianaceae) rhizome and fluoxetine were studied for antidepressant-like activity in two behavioral models, namely the forced swim test (FST) and the tail suspension test (TST). Fluoxetine as well as methanolic and aqueous extracts of V. wallichii induced monophasic dose-related decrements in immobility times in both tests. However, the aqueous-ethanolic fraction induced a biphasic dose-response profile since it produced a graded effect up to 200 mg/kg but the highest dose (250 mg/kg) was inactive in the FST. This extract also exhibited significantly reduced activity at 200 mg/kg compared to lower doses in the TST. The highest doses of aqueous-ethanolic extract also reduced locomotor activity which will have led to a negative functional interaction with antidepressant-like effects. Qualitative phytochemical analysis revealed that the aqueous-ethanolic extract of V. wallichii was the only separated rhizome fraction containing terpenoids. Furthermore, since the methanolic and aqueous extracts were active in the tests, it is suggested that the antidepressant-like action of this herbal plant is not contingent upon its terpenoid constituents.

Antispasmodic, bronchodilator and blood pressure lowering properties of Hypericum oblongifolium--possible mechanism of action.

The crude extract of Hypericum oblongifolium (Ho.Cr), which tested positive for flavonoids, saponins and tannins caused concentration-dependent (0.1-1.0 mg/mL) relaxation of spontaneous and high K(+) (80 mM)-induced contractions in isolated rabbit jejunum preparations, suggesting a Ca(++) antagonistic effect, which was confirmed when pretreatment of the tissue with Ho.Cr produced a rightward shift in the Ca(++) concentration-response curves, like that caused by verapamil. Ho.Cr relaxed carbachol (1 microM) and high K(+)-induced contractions in guinea pig tracheal preparations. It caused a dose-dependent (3-100 mg/kg) fall in arterial blood pressure of rats under anesthesia. In isolated guinea pig atria, Ho.Cr caused inhibition of both atrial force and rate of spontaneous contractions. When tested in rabbit aortic rings, Ho.Cr exhibited a vasodilator effect against phenylephrine (1 microM) and high K(+)-induced contractions. These results indicate that Ho.Cr possesses gastrointestinal, respiratory and cardiovascular inhibitory effects, mediated via a Ca(++) antagonist mechanism.

Adulterant profile of illicit street heroin and reduction of its precipitated physical dependence withdrawal syndrome by extracts of St John's wort (Hypericum perforatum).

The study evaluated the adulterants in a specimen of illicit street heroin supplied under strict control by the Pakistan Anti-Narcotic Force. It also examined the effects of Hypericum perforatum L. extracts on the naloxone-induced heroin withdrawal syndrome. The GC-MS analysis of the specimen showed that in addition to heroin (37.8%), the sample also contained caffeine (8.4%), phenobarbitone (12.7%), 6-acetyl codeine (5.3%), 6-acetyl morphine (10.9%) and noscapine (15.8%). Administration of the heroin to rats for 8 days induced physical withdrawal signs of abdominal constriction, diarrhoea and vocalization on touch after naloxone treatment. Aqueous Hypericum perforatum extracts (20 mg/kg twice daily chronically or as a single acute dose 90 min before naloxone) given orally to the heroin dependent rats attenuated abdominal constrictions both acutely and chronically while the hydroethanol and ethanol extracts were only effective in acutely treated animals. Diarrhoea was ameliorated by the hydroethanol and ethanol extracts following acute or chronic heroin treatment while the aqueous extract failed to show any effect. Vocalization on touch during withdrawal was reduced by all the extracts either chronically or acutely with the exception of chronic treatment with hydroethanol extracts. The findings suggest that Hypericum perforatum is capable of reducing the physical signs of opiate withdrawal.